jonathan t. butcher, ph.d. · 3 by: michael h. teschner, esq. by: keir loiacono, esq. 4 600 south...

In The Matter Of:

St. Jude Medical Cardiology Division, Inc.vs.

The Board of Regents of the University of

Michigan

___________________________________________________

Jonathan T. Butcher, Ph.D.

December 2, 2013

___________________________________________________

Exh. 2031

University of Michigan Exhibit 2031 St. Jude Medical v. University of Michigan IPR 2013-00041

Jonathan T. Butcher, Ph.D. December 2, 2013

(312) 386-2000 www.merrillcorp.com/lawMerrill Corporation - Chicago

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UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

CASE IPR2013-00041

PATENT 5,746,775

ST. JUDE MEDICAL CARDIOLOGY :

DIVISION, INC., :

Petitioner, :

:

v. :

:

THE BOARD OF REGENTS OF THE :

UNIVERSITY OF MICHIGAN, :

Patent Owner. :

Transcript of the deposition of JONATHAN T.

BUTCHER, Ph.D., called for Oral Examination in the

above-captioned matter, said deposition taken by and

before SILVIA P. WAGE, a Certified Shorthand

Reporter, Certified Realtime Reporter, Registered

Professional Reporter, and Notary Public for the

State of New Jersey, New York, Pennsylvania and

Delaware, at the offices of LERNER DAVID LITTENBERG

KRUMHOLZ & MENTLIK, 600 South Avenue West, Third

Floor, Westfield, New Jersey, on Monday, December 2,

2013, commencing at 9:15 a.m.

JOB NO. 1803-198051



2 (Pages 2 to 5)

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1 A P P E A R A N C E S:2

LERNER DAVID LITTENBERG KRUMHOLZ & MENTLIK3 BY: MICHAEL H. TESCHNER, ESQ.

BY: KEIR LOIACONO, ESQ.4 600 South Avenue West

Westfield, New Jersey 070905 (908) 518-6313

[email protected] [email protected]

[email protected] Counsel for the Petitioner89 MARSHALL GERSTEIN BORUN, LLP

BY: MICHAEL R. WEINER, ESQ.10 BY: JENNIFER BURNETTE, ESQ.

233 South Wacker Drive11 6300 Willis tower

Chicago, Illinois 60606-635712 (312) 474-9560

[email protected] [email protected]

Counsel for the Patent Owner141516171819202122232425

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1 I N D E X2 WITNESS: JONATHAN T. BUTCHER, Ph.D. PAGE3 EXAMINATION BY MR. WEINER 5/291

EXAMINATION BY MR. TESCHNER 28745

E X H I B I T S6

EXHIBIT NO. DESCRIPTION PAGE7

Exhibit 1001 775 Levy Patent 678 Exhibit 1010 Dr. Kaplan's declaration 65

Exhibit 1016 Dr. Butcher's declaration 69 Exhibit 1019 Levy et al 1991 28

Exhibit 1020 Carpentier et al 1982 22010 Exhibit 1021 Golomb et al 1987 224

Exhibit 1023 Gonzalez-Lavin et al 1988 22511 Exhibit 1024 Kim et al 1986 229

Exhibit 1025 Han et al 1993 23712 Exhibit 1026 Levy et al 1983 101

Exhibit 1027 Okamura et al 1976 24013 Exhibit 1028 Shore et al 1983 244

Exhibit 1030 Ichikawa et al 1997 24514 Exhibit 1031 Muratov et al 2010 248

Exhibit 1032 Lu et al 2012 25115 Exhibit 1033 Gabbay et al 1982 254

Exhibit 1034 Gabbay et al 1983 25616 Exhibit 1035 Gabbay et al 1984 258

Exhibit 1036 Schryer et al 1986 26517 Exhibit 1037 Schoen et al 1985 266

Exhibit 1038 Jones et al 1982 26718 Exhibit 1039 Deck et al 1982 272

Exhibit 1070 St. Jude Inter Partes 1919 Review Exhibit Cliff Notes

Exhibit 1071 St. Jude vs. Michigan Inter 25420 Partes Review Declaration

and Document Outline21 Exhibit 2003 Shemin 1988 34

Exhibit 2005 Levy 1983 9022 Exhibit 2007 The Trifecta Valve by St. 278

Jude Medical23 Exhibit 2013 Kaplan Deposition 882425

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1 - - -2 DEPOSITION SUPPORT INDEX3 - - -45 Direction to Witness Not to Answer6 Page Line Page Line Page Line Page Line7 None8910 Request for Production of Documents11 Page Line Page Line Page Line Page Line12 None131415 Stipulations16 Page Line Page Line Page Line Page Line17 None181920 Motion to Strike21 Page Line Page Line Page Line Page Line22 87 11232425

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1 J O N A T H A N T. B U T C H E R, P h. D.,2 Cornell University, Department of Biomedical3 Engineering, 304 Weill Hall, Ithaca, New4 York 14853-7202, after having been duly5 sworn, was examined and testified as6 follows:7 EXAMINATION BY MR. WEINER:8 Q. Good morning, Dr. Butcher.9 A. Hi.10 Q. Would you state your name for the11 record, please.12 A. My name is Jonathan Talbot Butcher.13 Q. Dr. Butcher, I'm Michael Weiner. I'm14 here on behalf of the University of Michigan to ask15 you some questions today.16 Have you ever had your deposition taken17 before?18 A. No.19 Q. You understand that you're testifying20 under oath today?21 A. Yes.22 Q. And you understand that it's23 important that you give your answers out loud so24 that the court reporter will be able to write25 everything down?



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1 A. Yes.2 Q. Dr. Butcher, you've been retained by3 counsel for St. Jude Medical to serve as an expert4 witness; is that right?5 A. Yes.6 Q. Prior to this case, have you ever7 done any work for St. Jude Medical?8 A. No.9 Q. Have you ever served as an expert10 witness before in US Patent and Trademark11 proceedings?12 A. No.13 Q. Have you ever served as an expert14 witness in court litigation before?15 A. No.16 Q. I'd like to direct your attention to17 Exhibit 1016, which is your declaration.18 A. Okay. I think that's in this one.19 (There is a discussion off the record.)20 (Deposition Exhibit 1016, Dr. Butcher's21 declaration, was previously marked for22 identification.)23 MR. WEINER: We have a copy for the24 witness that we'll keep with the official record of25 the transcript.

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1 A. Okay, great.2 MR. WEINER: And a copy for counsel.3 A. I'll put this one back in, I guess.4 Q. Okay.5 A. So I don't get them all mixed up.6 Q. And, for the record, I understand,7 Dr. Butcher, you have work copies of your8 declaration with exhibits in front of you.9 A. I have -- I have some binders of the10 documents that are affiliated with the whole case11 and they're organized in different ways, yeah.12 Q. Okay. We'll plan to give you copies13 of any exhibits we ask you questions about.14 A. Great.15 Q. But if it's more convenient or16 comfortable for you to use your own copies, then17 feel free to do that as well.18 A. That would be great.19 Q. And do you recognize this as your20 declaration?21 A. I do.22 Q. Are you aware of any errors that need23 to be corrected in your declaration?24 A. I am not.25 Q. We'll have some more questions for

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1 you in a minute.2 Can you briefly describe your educational3 background?4 A. Yes. I have an undergraduate degree5 in mechanical engineering from the University of6 Virginia. I have a Masters in impact biomechanics7 from the same university. I have a Ph.D. in8 mechanical engineering from Georgia Tech and then I9 did a three-year post doctoral fellowship at the10 Medical University of South Carolina.11 Q. And what did you do during your post12 doc at South Carolina?13 A. So that post doc was joint between14 the Department of Pediatric Cardiology and15 Developmental Biology. So part of my research16 efforts were to understand the role of mechanical17 forces during embryonic heart valve development.18 And then on the clinical side I participated in19 grand rounds and clinical consult discussions.20 They, essentially, have these group sessions21 where the surgeons get together and they discuss22 cases to determine, you know, what to -- how to23 intervene, whether to intervene, what to do with the24 patient.25 Q. And that dealt with pediatric

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1 patients?2 A. Mostly, or adult cases that are3 follow-up from repeat surgical interventions of, you4 know, that they had since childhood.5 Q. Did the post doc involve any6 experience with calcification of tissues?7 A. During my post doc, we discussed, you8 know, these clinical cases which involved in some9 cases operations with patients that had calcified10 valves. The research material that I studied dealt11 with a hypothesis of calcification, that is, in12 terms of a reactivation of developmental signaling13 pathways. And we also used human tissue in some of14 the work.15 Q. You referred to dealing with16 calcified heart valves during your post doc.17 Were those implanted heart valves or natural18 heart valves?19 A. So they were both. So we would look20 at usually clinical presentations of the patient's,21 you know, ultrasound, CT scan, you know, findings22 where it was either there was a prosthetic valve23 that was implanted, some cases it could be24 mechanical valve or the patient's natural valve,25 sort of a mix. Like I said, the grand rounds were



4 (Pages 10 to 13)

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1 just what was going on that particular week of those2 particular class of patients that they were going to3 see.4 Q. According to your CV, you serve as a5 reviewer for a number of scientific publications; is6 that correct?7 A. Yes.8 Q. What are your responsibilities as a9 reviewer?10 A. So my responsibilities as a reviewer11 is to look at the article, the information that the12 document presents, understand its methodology,13 understand and interpret its results and compare14 those results with what was already known at the15 literature at that time and render a judgment16 whether or not I feel that the article teaches new17 information and is of sufficient impact for the18 particular readership of that journal.19 Q. And the journals for which you serve20 as a reviewer, do you serve on the editorial board21 for any of those publications?22 A. No.23 Q. What is the function of the editorial24 board in the peer review process?25 A. So the editorial board's job is to

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1 take the articles -- first, they make a decision2 whether the article should be reviewed in the first3 place, sort of a triage step. And once they do4 their job -- once they decide it's suitable to be5 reviewed, then they solicit reviewers and they find6 peers in the field that the article is about. And7 then once they get the reviews back from those8 peers, they integrate the information that those9 peers said and then they make their own judgment10 whether or not to accept required revisions or11 reject the article.12 Q. In your experience, would the13 editorial board select someone with particular14 experience in the subject matter of the article?15 A. Yes. I mean, all the articles that16 they ask me to review, I accept the ones, you know,17 I have the skill to review or I'm in that field.18 Rarely is somebody asking me to review an article19 that I don't possess that skill. I've never20 reviewed one for which I didn't because then it21 wouldn't really help me or them. And, you know...22 Q. And, if you feel you don't have the23 appropriate skills and experience, you would decline24 the request to review the article for publication?25 A. Yeah, I would decline.

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1 Q. How important is quantitative data2 for an article when you are reviewing an article for3 publication?4 A. I think quantitative data is very5 helpful to understand a variety of different results6 in an article. I mean, there's lots of different7 ways of obtaining results. I think quantitative8 data is good for that.9 Q. What kind of research are you10 currently engaged in?11 A. So my research at Cornell has three12 main thrusts. One of the thrusts is I try to13 understand embryonic heart and valve development as14 an engineering process. And my goal there is that15 if I can figure out how this tissue is put together16 and matured over such a short period of time and17 that procedure works well 99 percent of the time,18 that provides a great blueprint for engineering new19 living tissues. Furthermore, if I can compare the20 engineering that goes on in the 99 percent that goes21 well against the 1 percent for which it doesn't go22 well, I can, hopefully, identify strategies for23 understanding why those tissues fail in the first24 place but also how to rescue or revert that25 malformation.

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1 The second thrust of my research is to2 understand biological mechanisms of valve3 degeneration and disease and to try to design4 biologically based strategies to combat those5 processes. One of the things we like to do is6 utilize the information that we gain in the -- in my7 first thrust and try to explain some of those8 degenerative processes as, essentially, a9 reactivation of development signaling programs but10 now that microenvironment is not the same as in the11 embryo and so there could be pathogenic rather than12 developmental consequences.13 And the third thrust is associated with14 actually applying that information to design15 regenerative strategies for heart valve disease,16 which in my recent research involves fabricating new17 living heart valve replacements, in particular, for18 pediatric applications but also developing ways of19 differentiating stem cell populations towards20 autologous heart valve cells that one could actually21 utilize to populate a scaffold that somebody else22 might design.23 Other things that we try to do is what we24 call biohybrid strategies, which is to try to make a25 prosthetic more biologically active in a way that



5 (Pages 14 to 17)

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1 might promote better long-term function.2 Q. When you refer to "living heart valve3 replacements," is that something different than4 bioprosthetic heart valves?5 A. I would say that the distinction6 between those is getting less and less as the field7 progresses. It used to be back in the '70's just8 making a material mechanically durable was the only9 goal. But, as more knowledge is gained, it's become10 apparent that some of those processes induced11 biological changes that need to be dealt with as12 well. So the field, as it stands now, seeks to13 create more active beneficial properties in both14 that inevitably are incorporating living components15 of that technology.16 Q. Do you have graduate students who17 assist you in your research?18 A. Yes.19 Q. Do they prepare written reports of20 their work?21 A. Yes.22 Q. And do you review those written23 reports?24 A. Yes.25 Q. Do they also write articles to submit

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1 for publication?2 A. Yes.3 Q. And do you review drafts of those4 articles before publication?5 A. Yes.6 Q. Your CV lists 51 publications for7 which you are a named author, correct?8 A. I think it's more than that now. But9 I think at the time -- if I can look at my -- where10 my CV is. It's one of these exhibits.11 Q. I think it's Exhibit 1017.12 MR. TESCHNER: Yeah, it should be.13 A. I know that during this process we14 published a few other articles.15 MR. TESCHNER: 1017.16 THE WITNESS: 1017.17 A. Yeah, so here -- yeah, so 50 -- yeah,18 this one is currently 51. There is also a few book19 chapters and particular conference publications that20 for those fields represent, you know, the -- an21 authoritative record so, yeah.22 Q. Well, for those 51 publications, how23 many of those publications include quantitative24 data?25 A. Oh, I would say a fair amount of them

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1 do.2 Do you want me to go down the line and look3 through each one?4 Q. Well, can you estimate how many of5 the 51 include quantitative data?6 A. (No response.)7 Q. Let me put it this way. Do you think8 they all include quantitative data?9 A. I think in some form or another they10 all do. I can't say all of them include11 quantitative data, but I would say it's definitely12 closer that they all do then none of them and,13 certainly, it's more than half.14 Q. Okay. How important is quantitative15 data in your research?16 A. I would say it depends on the17 question that's asked. I mean, if I'm trying to ask18 the question if there's more of something than19 something else, I think quantitative data is very20 important. I think that if I'm trying to show21 somebody that something is present or if I'm trying22 to show that something is not present or if I'm23 trying to describe a biological feature, sometimes a24 picture is better. So I guess it really depends on25 what I'm trying to study.

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1 Q. And would that same approach apply2 when you're reviewing someone else's publication?3 A. Yeah, in general. Yeah, I would say4 that if I look for -- if somebody is making5 particular claims, I would look for data that6 support that claim.7 Q. What did you do to prepare for your8 deposition today?9 A. When you ask that question, do you10 mean like since I knew that I was going to be11 deposed or since I finished my declaration or all of12 the time up until that point?13 Q. Well, I was asking generally.14 But, when you prepared your declaration, you15 understood that it was possible or likely that you16 would have a deposition taken, right?17 A. Right.18 Q. And then at some point did you begin19 preparing for your actual deposition that we're20 having today?21 A. So, after I wrote the declaration, I22 think I took a breather for a while. And then once23 we realized when the actual date of the declaration24 was, so, you know, it was moved a couple weeks back,25 so I began to reread the documents, reread my



6 (Pages 18 to 21)

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1 declaration, reread, you know, to make sure that I2 could, to the best of my ability, recall the things3 that were in these documents. So, you know...4 Q. Okay. Well, other than your5 declaration and the cited exhibits to your6 declaration, is there anything else that you7 reviewed to prepare for your deposition?8 A. You're including in that the list of9 all the exhibits, right? What I mean is these10 exhibits are part of that, not just...11 Q. Okay.12 MR. WEINER: Maybe we should mark13 this as an exhibit.14 MS. BURNETTE: Okay.15 MR. TESCHNER: I think he was asking16 whether your question was the declaration or the17 declarations and the exhibits?18 A. Yeah, I don't know --19 MR. TESCHNER: I think that's what20 his question was. You're free to mark the list. Do21 what you want.22 A. What I meant is the binders -- these23 things in these binders were things that I was24 re-reviewing with the exception of, you know, the25 places where I put these little stars. Those are

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1 ones that I didn't really look at.2 Q. Alright. Well, let's take this one3 step at a time.4 A. Okay.5 MR. LOIACONO: I think the witness is6 referring to those documents. We should put them in7 the record.8 (There is a discussion off the record.)9 Q. Okay. Dr. Butcher --10 A. Yeah.11 Q. -- you provided a list of exhibits12 with some notations and I'm going to ask the court13 reporter to mark that -- our next exhibit number is14 1070.15 MS. BURNETTE: Yes, from the16 previously marked ones.17 (Deposition Exhibit 1070, St. Jude Inter18 Partes Review Exhibit Cliff Notes, was marked for19 identification.)20 A. Okay.21 Q. Okay. So 1070 is that the exhibit22 list that you prepared to keep track of the exhibits23 associated with your declaration?24 A. Yes.25 Q. Okay. And that looks like a two-page

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1 document.2 A. Uh-huh.3 Q. First page list exhibits in the 10004 series and then the second page lists exhibits in5 the 2000 series, correct?6 A. Yes.7 Q. And then there are a few asterisks8 that indicate -- it says, "a document I haven't9 studied."10 A. Yeah.11 Q. Now, I don't recall, the ones that12 are listed but have an asterisk that says weren't13 studied, were those listed in your declaration; has14 that been reviewed? No, your declaration list only15 the ones you did review?16 A. I'm fairly certain.17 MR. TESCHNER: Yes.18 MR. WEINER: Okay.19 Q. And the list that you prepared, those20 were intended to be a complete list of all the21 declarations -- I'm sorry, of all the exhibits22 submitted in the case?23 A. Yeah. That was my intention.24 Q. And the ones you didn't study, what25 was the reason for not studying those?

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1 A. I wasn't asked to.2 Q. And everything else without an3 asterisk, you were asked by counsel to review those?4 A. I probably should have listed also5 the CRC Chemical handbook excerpts now that I look6 at it. I didn't look at those either.7 So, I mean, most of these articles were8 cited by Schoen, the Schoen declaration or the9 patent owner. So I was, you know, trying to10 accumulate and figure out what was going on.11 Q. I see. And the CRC exhibit you were12 referring to, Exhibit No. 1013 and 1014?13 A. Yeah.14 Q. And those were associated with Dr.15 Paul Bohn's declaration?16 A. Yeah, I didn't review that. I just17 noticed that right now. I don't think there's any18 others.19 Q. Okay. Otherwise, it looks like these20 two pages, they just list a short title for each21 exhibit?22 A. Yeah. It's just the binders have23 numbers on them. So I don't know what they're24 actually about. I just have it figured out.25 Q. Okay. That makes sense; a lot of



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1 materials to keep track of.2 A. Yeah.3 Q. In connection with preparing for your4 deposition, you re-reviewed the exhibits that you5 had reviewed before; is that correct?6 A. Yeah. I mean, these -- this7 material, the things that I cited in my declaration,8 Schoen's declaration, the PO's -- I don't know what9 it's called -- response.10 Q. Okay. And did you also meet with11 counsel to prepare for your deposition?12 A. Yes.13 Q. And are you referring to Mr. Teschner14 you met with?15 A. Yes, Mr. Teschner was there.16 Q. And any other attorneys who you met17 with?18 A. Kier was there as well, as well as19 one partner was there for one part and then there20 was that one time in England with Ron.21 THE WITNESS: Is that what his name22 is -- Ron.23 Q. Ron Kreptz (phonetic) you met with24 him as well?25 A. Yeah, yeah.

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1 Q. So you met on more than one occasion2 with counsel to prepare for your deposition?3 A. Yes.4 Q. And just, roughly, how much time do5 you think you spent on that process?6 A. Meeting with counsel?7 Q. Meeting with counsel to prepare.8 A. Maybe 10 to 12 hours.9 Q. And, then in addition to the time10 with counsel, roughly, how much time did you spend11 on your own preparing?12 A. Oh, I would say, at least, 30 hours.13 Q. Other than meeting with counsel, is14 there anyone else you met with to prepare for your15 deposition?16 A. No.17 Q. What is calcification of tissue?18 A. Do you mean the clinical process, the19 clinical feature? I guess, I'm trying to figure out20 what...21 Q. Well, can you generally describe what22 the term refers to, to begin with, calcification of23 tissue?24 A. Okay. Calcification is a biological25 process by which calcium and phosphate ions

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1 accumulate within a tissue through several different2 avenues of nucleation. But, inevitably, these3 molecules aggregate and grow into crystals that4 acquire a hydroxy appetite level of crystallinity.5 They can be different sizes and affect the function6 of tissue.7 Q. Are there some calcium and phosphate8 ions present in normal healthy tissue?9 A. Calcium and phosphates are ions that10 are present in the body for a variety of very11 important bodily functions.12 Q. So tissue may have some calcium and13 phosphate ions without being considered calcified14 tissue?15 A. Yeah. I mean, calcium is inside16 cells. So they're a major signaling process. It's17 like their signaling currency, if you will.18 Q. So does that mean calcification would19 be an excessive amount of calcium ions in tissue?20 A. I mean, cells have their own way of21 regulating their calcium levels through different22 channels that they secrete and attract calcium ions,23 so they try to maintain a certain balance. When24 that balance is disrupted, it usually results in25 cell death. The death of the cell leads to,

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1 essentially, an explosion of calcium into the system2 and that can often serve as a nucleation site for3 the growth of calcium and calcium phosphate4 crystals.5 Q. Can you identify at what point6 calcium in tissue would be considered calcification;7 is there a certain numerical range?8 MR. TESCHNER: Object to form.9 A. I would say the features of10 calcification are detectable by different methods11 depending on the particular phase of the process12 that you're looking for. So, for instance, one can13 detect calcium very early in the process just14 looking at the formation of these crystals even15 inside the necrotic core of a cell. And one can16 also find calcification in histological sections17 much later where you have a nodule that can, you18 know, extend outside of a cell, include multiple19 cells, interact with different matrix fibers, et20 cetera, and then some that are grossly observable21 just on looking at the tissue itself.22 Q. And the calcification that's grossly23 observable, would that correspond to a higher24 concentration of calcium and phosphate ions or salts25 in the tissue?



8 (Pages 26 to 29)

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1 A. Not necessarily. I would say that2 it's more -- it's just larger, like a larger lesion3 is more grossly observable versus a smaller lesion.4 They're both calcification. It's just different5 sort of length scales.6 Q. I see. So there could be some7 calcification that's not observable with the naked8 eye but can be observable from other techniques?9 MR. TESCHNER: Objection to form.10 A. It depends -- it depends on the11 technique that one is -- or the scale that one is12 interested in identifying the calcification. So, if13 you're looking to see at a cellular level, you would14 use a cellular technique. And if you see it there,15 then it's there; likewise, if you are evaluating16 calcification at a tissue level and you look at this17 tissue level and see it there or not there.18 Q. What does extrinsic calcification19 refer to?20 A. I would say an extrinsic21 calcification process -- so, well, just to back up,22 I think that these terms have changed their meanings23 over the years, as people have become more aware of24 what the actual processes are. So terms that mean25 one thing, you know, in the '80's versus now mean

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1 different things or include more things.2 So, if you're asking me what that term meant3 at the time, it's probably easiest to go and, you4 know, go back to the documents for which they were,5 you know, first described. And I think Schoen6 described them. There's extrinsic and intrinsic7 calcification pathways. I just feel better8 repeating what they say, so I don't get it wrong if9 there is some comparison.10 Q. Sure, if you need to look at any11 document, that's fine. And, first, let's just12 clarify the relevant timeframe.13 A. Uh-huh.14 Q. In general, the relevant timeframe is15 October of 1993; is that your understanding?16 A. That's -- I think that's when the17 patent's filed and that's the relevant timeframe.18 So, if I remember correctly, I think that --19 Q. I think I can refer you to an20 exhibit.21 A. Okay, that would be easier, yeah.22 Q. Exhibit 1019, Levy 1991.23 A. Do you have it.24 Q. I have a copy of that, if you would25 like to refer to that.

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1 MR. WEINER: I guess I'll just2 mention to the court reporter this is Exhibit 10193 that was previously marked.4 (Deposition Exhibit 1019, Levy et al 1991,5 was previously marked for identification.)6 A. That's great.7 MR. WEINER: Copy for your counsel as8 well.9 MR. TESCHNER: Thank you.10 Q. And do you recognize Exhibit 1019?11 A. I do. I do recognize this, yes.12 Q. Okay. And Robert Levy is the first13 named author. There are several authors and it was14 published in 1991, right?15 A. That is correct.16 Q. And then, in particular, at Page 70917 of the publication, if you look at the left column,18 it's about two-thirds of the way down the page, it's19 the second full paragraph that starts,20 "morphological examination," and it's maybe a little21 more than halfway down that paragraph in the middle22 of the page. It says, "For example, extrinsic23 (surface oriented) calcific deposits occasionally24 occur."25 A. Okay.

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1 Q. And I think in the right-hand column2 on that page, the first full paragraph that begins,3 "An experimental ventricular assist."4 A. Alright.5 Q. About five lines down, there is a6 reference to extrinsic calcific lesions.7 A. Yeah, I don't know how the8 parenthesis of surface oriented defines extrinsic9 calcific deposits here, but I do see the use of the10 term is here.11 Q. Correct.12 A. I am familiar with each of these13 features of calcification, meaning, devitalized14 cells and related debris, as well as surface15 deposits that occur with mural thrombotic deposits16 or vegetations or fibrous tissue overgrowth.17 Q. Well, before we get into those18 details, do you know -- do you have a general19 understanding of what the term extrinsic20 calcification refers to?21 MR. TESCHNER: Objection to form.22 A. And, again, I think that the23 particular term extrinsic versus intrinsic, I mean,24 we discussed in the field now things like dystrophic25 versus osteogenic. And those terms have existed at



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1 those times as well. So I would say that -- I don't2 know if this article, in particular, discusses the3 intrinsic calcification pathway, you know, as a4 comparison to.5 Q. Well, is extrinsic calcification a6 term that you use in connection with your work?7 A. No.8 Q. And is it a term that you come across9 in publications in the field?10 A. Yes.11 Q. When you see that in publications,12 what is your understanding of what that refers to?13 A. Normally, when I come across it in14 publications, it's an older publication and they're15 usually describing the actual nature of the lesion,16 more specifically, like they do in this paper where17 they talk about the devitalized cells or within a18 lesion or something where it's, you know, associated19 with a matrix component, et cetera. They wouldn't20 just say, this is -- extrinsic calcification was21 found.22 Q. By a lesion do you mean a calcified23 area of tissue?24 A. Yeah. A lesion is a -- can also be a25 general term. But it's just sort of the region of

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1 affected tissue that contains the calcific region.2 Q. And does intrinsic calcification, as3 it's used in the field, generally, refer to lesions4 that are on the surface of the tissue?5 A. The way that Dr. Levy is describing6 it in this first paragraph you referred me to7 appears to associate it with surface lesions.8 However, the second paragraph that you referred me9 to, devitalized cells, and, you know -- where is the10 rest of that -- and related debris, I mean, that is11 something that also happens internally to the12 tissue. So that sort of is why I'm confused with13 the particular description.14 Q. Okay. Let's just -- we can put the15 publication aside for a minute. We may get back to16 that particular term in a little bit, but I think17 that answers the question.18 Do you consider yourself to be an expert in19 calcification of implanted tissue?20 A. Yes.21 Q. And can you generally describe what22 your experience is with calcification?23 A. Yes. So I study mechanisms of24 calcification in my research lab. We've been doing25 that since, essentially, my Ph.D. work, so over

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1 13 years. I mentor graduate students, post docs in2 this area. We publish papers in this area. I give3 presentations regarding this work and I participate4 in scientific meetings and in organizing committees5 or scientific bodies that are -- that associate6 themselves with understanding this process.7 Q. In your opinion, was calcification of8 implanted tissue considered to be a significant9 problem in October of 1993?10 A. Yes.11 Q. Does exposing tissue to12 glutaraldehyde tend to cause calcification of the13 tissue after implantation?14 A. Yes.15 Q. Was that something that was known in16 October of 1993?17 A. Yes.18 Q. What are the characteristics of a19 suitable animal model that can be used for20 calcification experiments?21 A. I would say there are lots of22 different animal models that are suitable. They23 come in different shapes and sizes depending on the24 experience of the research team that are using them,25 the financial resources available. But,

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1 fundamentally, the model that's utilized really just2 has to be able to recreate calcification in the3 tissue that you implant in it.4 Q. Are younger animals, generally,5 preferred for calcification testing?6 A. What do you mean by "preferred?"7 Q. Is a younger animal, generally, more8 suitable for calcification experiments than an older9 animal?10 A. No.11 Q. How about the rate at which animals12 would tend to calcify, is that a consideration in13 identifying an appropriate animal model?14 A. I imagine it could be one feature15 that one might consider if there are constraints of16 the experiments.17 Q. And why might that be an important18 feature?19 MR. TESCHNER: Objection to form.20 A. Well, I would say if you don't have21 significant amount of resources or time available,22 you may use an animal that would calcify quicker to23 get a comparison within the timeframe that you were24 hoping for.25 Q. For example, you generally wouldn't



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1 want to run an experiment that would run ten years2 that would show signs of calcification, right?3 A. Well, I guess, clinically you would4 hope that the experiment would take more than ten5 years to establish calcification. But I think in a6 basic research level, yeah, you would not want a7 ten-year experiment, certainly.8 Q. You would want to get results sooner9 than that, right?10 A. Yeah.11 Q. Let me direct your attention to12 another exhibit. It's been marked 2003.13 (Deposition Exhibit No. 2003, Shemin 1988,14 was marked for identification.)15 (There is a discussion off the record.)16 Q. Do you recognize Exhibit 2003?17 A. I do.18 Q. That's the Shemin article referring19 to the first named author from 1988?20 A. Yes.21 Q. In particular, I would like to direct22 your attention to Page 918 of the publication.23 A. Okay.24 Q. And I'm referring to the left column,25 first full paragraph that begins, "orthotopic

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1 experimental valve replacements."2 A. Yes.3 Q. And about seven or eight lines down4 the paragraph, there's a sentence that reads in5 part, "a model used to investigate the suitability6 of a new bioprosthetic valve configuration must use7 an immature subject of a species that potentiates8 calcification." Did I read that correctly?9 A. I'm trying to find it.10 Q. I'm sorry.11 A. It's in that --12 Q. You see --13 A. Ortho -- yeah, I do see that. It's14 an actual sentence.15 Q. No, part of a sentence six lines16 down. The whole sentence I think starts with the17 third line, "Since the durability."18 A. Okay. I see those words, yes.19 Q. Okay. And so I read that correctly?20 A. Yes.21 Q. And I was just reading part of the22 sentence for convenience. I wasn't intending to23 leave out any relevant context there. But, of24 course, you can take it in context there.25 Do you disagree with the Shemin authors that

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1 a model used to investigate the suitability of a2 bioprosthetic valve must use an immature subject of3 a species that potentiates calcification?4 A. I guess, the first statement that I5 would say was I would want to know what they were6 referring to with respect to suitability. So, in my7 analysis of this sentence, I'm thinking that they're8 looking for, you know, evaluating the suitability of9 a prosthetic valve for human implantation and their10 opinion is that that would be best achieved by using11 an immature version of a large animal model.12 Q. Okay. And I referred to young13 animals before.14 A. Okay.15 Q. Is that what Shemin is referring to16 as an "immature subject," young animal?17 A. I guess so, yeah.18 Q. Do you know why Shemin is referring19 to using an immature or young animal for20 calcification experiments?21 A. I think in his opinion that they22 potentiate calcification.23 Q. And by "potentiate calcification,"24 does that mean have a tendency to have calcification25 in implanted tissues?

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1 A. Yes. I think that he's saying if you2 implant tissue in this animal, it would calcify.3 Q. And, in general, do young animals4 calcify more quickly than older animals of the same5 species?6 A. I think on the whole that would be7 the case for the same -- you know, if you implant8 the same exact device in the same exact position in9 the same exact animal, if you put in it a younger10 species, it would tend to calcify quicker than in11 the adult version.12 Q. And is that why for human patients13 there's a greater concern about calcification of14 implanted devices for pediatric patients as opposed15 to adult patients?16 MR. TESCHNER: Objection to form.17 A. Are you referring to the nature of a18 pediatric person versus an adult person?19 Q. Well, let me break that up a little20 bit.21 A. Okay.22 Q. Is your understanding that a23 pediatric patient has a greater risk of24 calcification of implanted tissues as compared to an25 adult patient?



11 (Pages 38 to 41)

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1 A. I believe that a pediatric patient2 where you implant a bioprosthetic valve, they have a3 greater risk of calcification than an adult.4 Q. And is your understanding that that's5 common in other species as well, that young animals6 have a greater likelihood to a calcification of7 implanted tissues as opposed to older animals of the8 same species?9 A. I don't know about "likelihood," you10 know. It may, like I said, may be a question of11 timing.12 Q. What do you mean it's a question of13 timing?14 A. Well, in the case of humans, children15 are different than adults in the sense they're more16 metabolically active and growing. So that -- those17 are environmental stressors that increase the risk18 of calcification. I'm not saying that somehow that19 makes calcification form faster. I'm saying that20 the risk of that process occurring, you know, is21 greater in those conditions.22 Q. So for an implanted device in a child23 compared to a human over a given time period is it24 generally more likely that calcification would occur25 in a given time period in the child rather than in

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1 the adult?2 A. Yes, it is more likely that if you3 implant the same valve in a child versus an adult,4 that the valve would calcify after five, ten years5 in a child than it would in an adult.6 Q. And is that a pattern that's observed7 in other species as well with implanted devices?8 A. It's hard to say. You know, a lot of9 the studies that were done at this time, they10 utilize adults, they utilize juveniles. There are11 not many studies that I know of that directly12 compare the juvenile against the adult in the same13 study. So all of the models that people have used14 in the literature, the tissues calcify. When they15 actually look for the calcification, can often16 define when they decide calcification occurs. I17 would say that while there is evidence of people18 using adult animal models and juvenile animal19 models, that they have utilized similar time points20 regardless of which animal they're looking at.21 Q. According to Shemin, though, an22 immature animal must be used for such studies; is23 that correct?24 A. I mean, he says -- yeah, he says25 that. But, in terms of suitability, I don't know --

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1 I think he's arguing here for if you're going to2 implant this in a human, this valve, that you should3 evaluate it in an immature version of I'm guessing a4 large animal model. That's what I imagine he's5 saying here in terms of suitability.6 Q. Okay. And further down in the7 paragraph, the end of the paragraph, Shemin also8 states -- last sentence of the paragraph, "The dog9 is not generally considered to be a useful model for10 accelerated calcification." Did I read that11 correctly?12 A. Yes.13 Q. Do you agree with that statement?14 A. It's hard to agree or disagree with15 the phrase "generally considered" and "useful16 model." But, on the whole, I would disagree with17 the statement that the dog is not a useful model.18 Q. And do you disagree with his19 statement that the dog was not generally considered20 to be a useful model, at least, as of 1988?21 A. I disagree that the dog was -- so22 many negatives here.23 I disagree with the statement that the dog24 was not a useful model at the time for calcification25 studies.

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1 Q. So, in your opinion, as of 1988, you2 think the dog was a useful model for large animal3 calcification studies?4 A. Yes, it was a useful model, yes.5 Q. And are you surprised that Shemin6 said that the dog was not generally considered to be7 a useful model at that time?8 A. I mean, it's his opinion.9 Q. Are you aware of other researchers in10 the field that shared that opinion or shared that11 opinion at the time?12 A. I'm aware of lots of papers in the13 literature that advocated or utilized one model or14 another, meaning, a large animal, a small animal,15 different time points. I would say all of them were16 educating something of value, the process of17 calcification or risk of calcification of a18 particular implant design.19 I mean, I think, again, it comes down to20 which animal they had the best experience with, they21 had the most accessible to them and the resources22 to, you know, support the study.23 Q. Well, Shemin didn't say that dogs24 were not accessible for study, does he?25 A. No, he does not.



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1 Q. So his view that the dog is not2 generally considered to be a useful model doesn't3 have anything to do with the availability of dogs,4 does it?5 A. I mean, I don't know. In addition to6 being accessible, somebody has to have experience7 with it, too. I don't know why he's saying that8 it's not useful. Like I said, I think it's his9 opinion.10 Q. Why does he refer to accelerated11 calcification, what does that refer to?12 A. I think it goes back to the13 literature which used this juvenile model, which14 like in humans, the same implant, when you implant15 it in a -- same position in a juvenile species or,16 essentially, a child versus an adult, they had17 higher tendency of calcification in the juvenile or18 child.19 Q. In general, for calcification20 experiments, would it be preferable to use an animal21 model of an animal that calcify more quickly than a22 human subject?23 A. I think given the timeframe of trying24 to understand the process, not having to wait five25 years would be an advantage. So being able to look

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1 at it on a scale of months or sooner would be good.2 Q. So, if you're testing a heart valve,3 for example, you don't want to conduct a 20-year4 trial to determine if the valve would last 20 years,5 right?6 A. Well, unfortunately, that is sort of7 a requirement in general for convincing clinicians.8 I imagine they don't care what happened in a sheep.9 But I would say, you know, once you get that10 information, oh, this valves works for 17 years,11 that will be something that convinces a clinician.12 Me as a scientist, I don't need that information to13 try to understand the process of calcification.14 Q. By clinicians you refer to cardiac15 surgeon who would be implanting valves in a patient?16 A. Yeah.17 Q. And, in your opinion, a cardiac18 surgeon would not want to use a new valve until it's19 been on the market and used in humans for 17 or20 20 years?21 A. Well, I would say that -- I mean, I'm22 not saying that I know exactly how every valve is23 put together. But I imagine that there is an24 evolution of valve. For instance, it might be a25 valve that was around in the '60's that somebody is

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1 familiar with and they keep iterating on that2 process. So a surgeon is familiar with that valve3 if there is a, you know, version 1.2 that comes out,4 they will still be familiar with that valve and,5 therefore, more likely to use it.6 I would say that if it's a brand new valve,7 a whole new surgical procedure or whatever, I would8 imagine that it would be tough to convince a surgeon9 to switch.10 Q. When was the last time you became11 aware of a brand new valve for use in a surgical12 procedure that was offered for patients?13 MR. TESCHNER: Objection to form,14 outside of his declaration.15 A. Yeah. I mean, I work with or I16 collaborate with surgeons and, in my discussions17 with them, I don't remember being, you know, here is18 a new valve that has no history with any other valve19 process or valve design.20 Q. So what's the basis of your statement21 that surgeons would wait 17 to 20 years before22 waiting to use a new valve; is that just23 speculation?24 MR. TESCHNER: Objection, outside the25 scope.

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1 A. So my experience with the surgeons2 that I've worked with, they have a familiarity. I3 don't know how they get it. I don't know how they4 acquire that familiarity. They just like working5 with a particular valve, shape, you know, it must be6 how they put it in, how it's designed or whatever7 that they like. And when I have talked to them8 about other valves, one of the things they've9 mentioned is that familiarity.10 Now, I'm not, you know, going into anything11 about comparing designs. I have no idea. They12 might be familiar with a valve that's actually, I13 don't know, not optimal but I haven't actually14 studied that. I'm just telling you what my15 experience with my clinical colleagues have been.16 Q. You referred to large animal models17 and small animal models before.18 A. Uh-huh.19 Q. Can you briefly explain what the20 differences are between those types of animal21 models?22 A. Yeah. So a small animal model is23 generally an animal that's small enough to be able24 to be kept within a research facility vivarium that,25 you know, can be housed within like a normal



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1 building. It doesn't require large feed stalls and2 open areas for the animals to walk around in like a3 pasture, for instance. So small animals in the4 research facility that I use, for instance, includes5 mouse, rats and up to rabbits.6 Q. And, as far as calcification studies,7 are small animals used for subcutaneous experiments?8 A. Yes.9 Q. And that refers to tissues of10 interest that are implanted beneath the skin of the11 small animal?12 A. Yes.13 Q. And then at some point the tissues14 are retrieved from the animal and evaluated for15 calcification?16 A. Uh-huh.17 Q. And how does that differ from large18 animal studies for calcification?19 MR. TESCHNER: Objection to form.20 A. I would say in the large animal21 model, the materials are going to be implanted in22 the configuration that they're intended to be used23 in in the location where one would want to employ24 them whereas in the small animal model, it's usually25 the material itself is implanted to try to

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1 understand, you know, to test material2 configurations. One would -- if you're looking for3 the biological process, why spend all the money on a4 very expensive animal model, when you can do it in a5 much less expensive animal.6 Q. Would it be typical to do small7 animal studies first and move up to a larger animal8 if the results look promising?9 A. I imagine that's how I would do it.10 Q. And do you think your approach is11 typical to someone who works in this field?12 A. Well, so as an example -- I guess I13 shouldn't say as an example.14 It depends on the question. There are15 researchers who will, for instance, will evaluate a16 new engineered living valve, for instance. They17 would probably use an invitro bioreactor test to see18 how that valve performs under simulated blood flow19 conditions. And, if those results are promising,20 they may go directly to a large animal model and21 forgo a small animal model.22 Q. And, for the large animal testing,23 that device would be implanted directly into the24 circulatory system of the animal?25 A. Usually, there would -- I mean,

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1 especially, for a valve, if it's got to stop blood2 flow. If it's implanted somewhere else, it wouldn't3 do that.4 (There is a discussion off the record.)5 Q. And, likewise, for a vessel for6 implantation that was being tested, that would be7 implanted somewhere in the circulatory system of an8 animal?9 A. And I said somewhere where it can get10 blood flow.11 Q. Why does the FDA require juvenile12 sheep testing for bioprosthetic heart valves?13 A. I'm not really sure how they came to14 that decision as to why the sheep versus another15 animal model. I guess, if that's what you're trying16 to ask me.17 Q. I'm asking about -- if I understand18 you correctly, you're saying you really don't know19 why FDA requires sheep for testing?20 A. I'm going to say I wasn't present21 during the deliberations, so I can't tell you when22 they came up with it. I can tell you why I think23 they came up with the model.24 Q. Well, as far as timing, was that the25 required animal model as of October 1993?

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1 A. I haven't seen anything that2 establishes that date.3 Q. Is that requirement in effect today?4 A. The small animal model, the sheep,5 you mean?6 Q. Well, sheep is a large animal model,7 correct?8 A. Yes.9 Q. Well, let me back it up.10 Is it your understanding that the FDA11 requires juvenile sheep testing for bioprosthetic12 heart valves in order to get FDA approval of those13 valves?14 A. Yes.15 Q. And I asked you if you know why the16 FDA requires that. I'm still not sure if you have a17 response to that.18 A. I thought you were trying to ask me19 when.20 Q. I also asked when. And you're not21 sure of that, right?22 A. Yeah.23 Q. But, at least, as of today, that's24 your understanding as to the requirement?25 A. Uh-huh.



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1 Q. Do you know why FDA requires using2 juvenile sheep for such testing?3 A. My understanding is that the FDA4 needed to establish a uniform performance criteria5 to help integrate the amount of, you know, integrate6 the performance data for lots of different valve7 studies. And if you were using 20, 30 different8 animal models, it would be difficult to have a9 uniformed measure performance to evaluate the10 suitability for human implantation.11 My understanding of the sheep model is that12 it's one that is experimentally convenient and it's13 one that's widely available. And as we are learning14 more and more about, it becomes even better15 characterized.16 Q. Do you know why the FDA does not17 permit use of dogs for testing instead?18 A. No, I don't. I can speculate that19 they want to have one model.20 MR. TESCHNER: Counsel, when you --21 we've gone a little over an hour. When you reach a22 convenient place to break, just -- if you wouldn't23 mind.24 MR. WEINER: Okay.25 MR. TESCHNER: I don't want to

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1 interrupt you.2 MR. WEINER: Let me just ask one3 follow-up question and we can take a break.4 MR. TESCHNER: Yeah.5 Q. Is the purpose of the testing that we6 have been discussing for the FDA, is that to7 demonstrate safety and efficacy of the product?8 A. Yeah, for human implantation.9 Q. Isn't that the same thing that a10 researcher would want to determine if they were11 testing that product prior to making a submission12 for FDA approval?13 A. So I think there's a large life cycle14 of scientific discovery to clinical application and15 different animal models can be involved throughout16 that whole process. In fact, early discovery may17 not even involve an animal. It may just be cultured18 cells.19 MR. WEINER: Okay. Let's go off the20 record and take a break.21 (Recess taken 10:22 to 10:32 a.m.)22 Q. Dr. Butcher, getting back to the23 Shemin article, Exhibit 2003.24 A. Okay.25 Q. I'm talking about some of the text on

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1 Page 918.2 Shemin was published in the Journal of3 Thoracic and Cardiovascular Surgery; is that right?4 A. Yes.5 Q. Is that a journal you're familiar6 with?7 A. Yes.8 Q. Is this a peer reviewed scientific9 publication?10 A. Yes.11 Q. And I think you said before you12 disagree with the statement in Shemin that the dog13 model is not generally considered to be a useful14 model for accelerated calcification; is that right?15 A. Yes.16 Q. The fact that it's published in a17 peer reviewed scientific journal, does that mean the18 statement must be considered informative for19 calcification purposes?20 A. Well, it's in the discussion section21 of the article. And that's usually when people22 expound on the greater impacts of the research that23 they did.24 The nature of my disagreement with this25 particular article was that they didn't conduct the

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1 comparison in the study for which they're making the2 conclusion. But I also think that the statement,3 the dog is not generally considered to be a useful4 model, I mean, for accelerated calcification, I5 mean, there's enough vague terms in there to make me6 sort of think not much of the sentence.7 Q. You mean you're not sure what's meant8 by "generally"?9 A. Yeah, what generally or useful. It's10 not like he told me what areas he felt it was going11 to be a useful model versus not, so...12 Q. Well, he's talking about models for13 testing for calcification, right?14 A. Yeah. But when it says, not15 generally considered, I don't know if he means -- it16 sounds like there are special cases where it would17 be okay. So I don't -- like, I don't know enough18 about that sentence.19 Q. Okay. I'm just a little puzzled20 because in Paragraph 13 of your declaration, you21 stated the findings reported in Kaplan must be22 considered informative for calcification because23 they're published in a peer reviewed journal.24 A. So -- yeah.25 Q. If that's the case, why wouldn't that



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1 same standard apply to Shemin?2 A. I think I am applying the same3 standard in the sense that all of the results of4 the, you know, all the findings of the articles are5 informative. I think I mentioned that this comment6 is in the discussion section and the discussion7 section of an article is not presenting new results.8 So I would say that this article, Kaplan, all these9 other ones, they all teach the findings of their10 paper.11 Q. How is the discussion section of an12 article generally used for a scientific publication?13 A. It's usually used to bring the14 results of the findings of their particular study to15 relate it with works that are done in the literature16 and to give -- to offer their opinion about, you17 know, what people should do moving forward in the18 field.19 Q. If an investigator publishing an20 article believes that there was some significant21 discovery made, would that be discussed in the22 discussion section of the article?23 A. The discovery won't be revealed in24 the discussion section. The discovery would be, you25 know, would be presented in the results because it

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1 was part of their experiment.2 Q. Because the discussion section3 doesn't repeat the data that's written elsewhere in4 the article, right?5 A. No, it might repeat but it won't be6 the first place you see it.7 Q. But it would be the second place you8 see it if it's important?9 MR. TESCHNER: Objection to form.10 A. I don't think that in order for11 something to be important it needs to be discussed12 in the discussion. I'm not saying that -- what I'm13 trying to say is that the discussion takes the14 findings of the paper and tries to motivate the15 field, motivate new things, new avenues of research16 to try to compare and contrast their findings with17 others.18 Q. In your own scientific publications,19 if you think you have some important information to20 share, would you discuss that in the discussion21 section of the publication?22 A. I would discuss the impact of the23 results of my experiments in the discussion section.24 Q. Have you ever had experience testing25 an anti-calcification method?

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1 A. Yes.2 Q. What was the nature of the3 anti-calcification method or methods that you4 tested?5 A. So one example recently we had -- we6 looked at a biological process of calcification that7 discovered that the endothelial cells on the surface8 of the valves actively prevented calcification from9 forming and we conducted a series of experiments to10 ascertain that that chemical is nitric oxide. And11 so we tested how that chemical administered in a12 model system of calcification prohibited the13 formation of calcification in that system.14 Q. What was the nature of the model15 system you used?16 A. So, in that system, it was a17 combination of two things. So we used a three18 dimensional cell culture model. So this is a neo19 tissue that is made with the cells from the valve20 that when exposed to calcifying chemical environment21 will calcify like it does in the body. And we also22 tested actual valve leaflets in the same model.23 Q. By "valve leaflets" do you mean24 leaflets in substitute valves used for implantation25 in humans?

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1 A. Well, we got these leaflets from2 large animal models, so a pig, we got them from a3 pig model. And we also compared our findings4 against explanted human valve leaflets that were5 calcified.6 Q. How is your calcification of tissue7 being measured?8 A. The assessment of calcification can9 happen many different ways. I would say that the10 easiest way to assess calcification is through gross11 examination or histological examination. But you12 can also establish calcification via a variety of13 different quantitative methods like CT scan,14 densitometry, spectroscopy, et cetera.15 Q. By "gross examination" does that mean16 visual examination of the tissue?17 A. Yeah. So you can see calcification,18 if the calcification is present at that level, you19 can see it with your naked eye.20 Q. And "histological examination" would21 involve microscopic evaluation?22 A. Yeah, usually you would make a thin23 section of the tissue, look at it under a24 microscope. You can also stain it with various25 chemicals to reveal characteristics of the



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1 calcification process.2 Q. And the staining process, is that3 related to or part of a histological examination of4 tissue?5 A. It can be. There are lots of6 different ones that people will use.7 Q. Are there some situations in which8 calcification might be detected by histological9 examination but not by gross examination?10 A. I'm not aware of one.11 Q. Are there any situations in which12 calcification might be detectable by a quantitative13 method but not by a gross examination?14 A. I imagine there could be, yeah.15 Q. And would that apply to a situation16 where there might be a low level of calcification17 that hadn't developed to the point where it was18 observable by gross examination?19 A. Yeah, I would say that that kind of a20 method would detect calcification in a lower level.21 Q. Your answers about how calcification22 should be measured, would those be different as of23 October 1993 compared to today?24 A. We utilize a lot of the same25 approaches that were done in October 1993. I would

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1 say that those methods are still considered valid.2 There are lots of new technologies that have come on3 line that weren't available then. But, essentially,4 they give you the same information.5 Q. You referred to a densitometry6 measurement.7 A. Uh-huh.8 Q. Does that relate to using X-rays to9 study calcification?10 A. Yeah, it can, yeah.11 Q. And are you familiar with using X-ray12 studies for that purpose?13 A. Uh-huh.14 Q. Is it something that you use in your15 research?16 A. Yes.17 Q. And that was something that was used18 in October of 1993 as well?19 A. Not the method that I use.20 Q. But other types of X-ray studies for21 calcification were used in October 1993?22 A. Yes.23 Q. Have you ever performed histological24 evaluation for calcification?25 A. Yes.

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1 Q. Have you ever reviewed reports of2 histological examinations of calcification prepared3 by others?4 A. Yes.5 Q. What are you looking for in that kind6 of a report?7 A. I look for information that helps me8 determine whether -- I mean, it depends on actually9 what they're trying to claim, right. So if they're10 just trying to tell me that calcification is there,11 that's one thing. If they're trying to tell me what12 it associates with, how much is there, whatever,13 then I might want to see data that supports each of14 those statements.15 Q. Well, in the histological reports16 that you reviewed, do they generally report just17 yes, no on calcification, or do they include further18 detail?19 A. I would say that there are some20 papers are reviewed that are mainly interested with21 the presence of calcification and they will say,22 calcification is here, and they would present23 either -- you know, they might present like an image24 of the tissue showing, you know, something, or if25 they were interested in saying this tissue or this

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1 calcification starts at some cell fragment or2 whatever and progresses, they might have, you know,3 a series. I've seen people present quantitative4 information where the calcium is in the bar graph5 or, you know, just written in the text.6 Q. How are controls used in doing7 scientific studies?8 A. Controls are a condition where the9 environment is the same except for the application10 of the treatment or the -- I use "treatment" to11 refer to the thing that's not the same, so that you12 have the best chance of determining the difference13 between the treatment versus not the treatment14 condition without multiple additional variables.15 Q. So it gives you a baseline for16 comparison to see whether the treatment is effective17 or not effective for whatever you're trying to use18 it for?19 A. Yes.20 Q. Is using controls important in doing21 scientific studies?22 A. Yes.23 Q. Is using controls important in24 evaluating calcification of tissue?25 A. Yes.



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1 Q. Is using controls important in2 evaluating anti-calcification methods?3 A. Yes.4 Q. In doing scientific studies on5 animals, is it important to report the total number6 of specimens evaluated?7 A. It's certainly helpful. I would say8 that depending on what you're trying to claim, you9 know, there are other ways of doing that.10 From looking at patent claims all the time,11 maybe I look at that term differently.12 Q. What do you mean by what you're13 trying to claim in a scientific study?14 A. Oh, yeah. So if you're -- if you are15 making -- if you are making a statement about16 something being there, right, or a presence, that's17 different than trying to say a more or less. So, if18 you're trying to make a more or less statement,19 usually -- I mean, if it were me doing it, I would20 want to conduct a statistical, you know, comparison,21 in which case sample numbers are important and22 running, you know, statistical tests, et cetera.23 Q. In doing scientific studies on24 animals, is it important to report the number of25 specimens exhibiting an observed property?

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1 MR. TESCHNER: Objection to form.2 A. What do you mean by "important?"3 Q. In your opinion, is that something4 that you think is important in conducting scientific5 research and reporting on it?6 A. I think it's certainly helpful. I7 don't know if it's required.8 Q. Are those things you would look for9 in evaluating a publication on an animal study?10 A. You're talking about me?11 Q. Yeah.12 A. Yeah, if it were me, I would like to13 see -- I would like to see a whole host of details.14 I don't always get them. But I like to see them.15 Q. At Paragraph 27 of your declaration16 you discuss mobile and immobile tissue. Do you17 recall that?18 A. Let me look; yes.19 Q. Do you agree that calcification is20 most likely to occur at a junction between mobile21 and immobile tissue?22 A. I don't know if I would say "most23 likely." I do think that it's a place where it has24 a greater chance of occurring.25 Q. Has a greater chance of occurring

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1 than in the mobile portion of the tissue?2 A. Yes.3 Q. Or the immobile portion of the4 tissue?5 A. I would say the first one, the mobile6 portion. I don't know if I would say that it7 therefore will occur at a junction more than in the8 immobile portion.9 A lot of the annular sleeves of these valves10 can get calcified while the leaflets themselves are11 pretty free. And if you have a stinted valve that's12 already immobile, that was not as big a concern.13 Q. Is the annular sleeve located at the14 junction between the mobile and immobile tissue?15 A. I mean, parts of it is.16 Q. And is that an area where17 calcification is more likely to occur?18 MR. TESCHNER: Objection to form.19 A. You mean in a valve?20 Q. Well, you're talking about an annular21 sleeve that is part of a heart valve, right?22 A. Yeah. But the annular root is23 actually, you know, it's not like a line. It's a24 three-dimensional cylinder. So calcification can25 occur on that cylinder. It can also occur on the

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1 leaflets and attachment zones. I mean, there is a2 whole host of papers that find calcification3 occurring in lots of different regions. It depends4 on how the stint is designed, you know, how the5 leaflets are attached, whether they are attached,6 you know, pericardial valves have stitched leaflets7 versus a regular porcine root. I mean, there are a8 lot of different things that go into that.9 Q. I'd like to direct your attention to10 Exhibit 1010, Dr. Kaplan's declaration.11 A. Okay. Do you have that?12 (There is a discussion off the record.)13 (Deposition Exhibit No. 1010, Dr. Kaplan's14 declaration, was previously marked for15 identification.)16 Q. Do you recognize this exhibit 1010 --17 A. Dr. Kaplan's declaration, yes.18 Q. I see this has exhibits attached to19 it as well. There are 13 pages to the declaration20 as well as exhibits at the end.21 A. Uh-huh.22 Q. Did you review Dr. Kaplan's23 declaration as part of the process of preparing your24 own declaration?25 A. Yeah, yes, I did.



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1 Q. Do you know Dr. Kaplan, by the way?2 A. No.3 Q. Have you ever met her?4 A. No, I haven't.5 Q. Did you ever have any discussion with6 Dr. Kaplan?7 A. No.8 Q. Do you agree with everything in Dr.9 Kaplan's declaration?10 MR. TESCHNER: Objection to form.11 A. I mean, "everything?" I doubt I12 could say that. You know, if you might point me to13 something, I can...14 Q. I don't have anything in particular15 to point you to. It's 26 paragraphs long. I just16 want to know if you agreed with everything in there17 or if there's something in there that you disagree18 with.19 A. I mean, nothing comes to mind right20 now what I might disagree with.21 Q. Put that aside.22 A. Okay.23 Q. And I'd like to direct your attention24 to 1001. That's the 775 Patent.25 A. Okay. Is it okay if I keep these

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1 here?2 Q. Sure, put it aside or keep it handy,3 in case you need to refer to it later on.4 A. Great.5 MR. TESCHNER: Off the record for a6 second.7 (There is a discussion off the record.)8 (Deposition Exhibit 1001, 775 Levy Patent,9 was previously marked for identification.)10 MR. WEINER: Back on the record.11 Q. Alright. I'm handing you what's been12 previously marked Exhibit 1001. It's the Levy 77513 Patent.14 A. Okay.15 Q. Do you recognize this as the 77516 Patent? It has a cover page on the top of it with17 the exhibit number.18 A. Uh-huh, yes, I do.19 Q. Did you review this patent?20 A. I did.21 Q. Are you aware that the claims at22 issue in this case are directed to23 anti-calcification methods?24 A. I'm aware that -- so the claim 23, I25 think, is the dependent or the independent claim.

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1 And it says, "The method of making a calcification2 resistant biomaterial for use in interior of a human3 or animal." So I guess I would say that's what it4 relates to, more broadly.5 Q. Okay. Now, referring back to Dr.6 Kaplan's declaration, I do have something in7 particular to ask you about.8 A. Okay.9 Q. It's Paragraph 10.10 A. Mine? That's mine.11 (There is a discussion off the record.)12 A. Yes, here I am.13 Q. 1010 and it's Paragraph 10. It14 starts, "Despite my familiarity with patents."15 A. Yes.16 Q. The question I have is about halfway17 down. She states -- well, she refers to a period of18 ordinary skill in this art. You understand that to19 refer to the art pertaining to the 775 Patent, the20 Levy patent?21 A. Yes.22 Q. And she states, "I believe a person23 of ordinary skill in this art would have an advanced24 degree in a relevant discipline such as chemistry,25 biochemistry, biology and/or medicine and several

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1 years of practical experience."2 A. Yes.3 Q. Did I read that correctly?4 A. Yes.5 Q. Do you agree with that statement?6 A. Yes.7 Q. In your declaration, when you refer8 to what will be known or understood by a person of9 ordinary skill in the art or you abbreviate it10 PHOSITA, are you referring to what would be known or11 understood as of October of 1993?12 A. Yes.13 Q. Do you have ordinary skill in the art14 pertaining to the 775 Patent?15 A. Yes.16 Q. Do you have an advanced degree in17 chemistry, biochemistry, biology or medicine?18 A. I would say that I have an advanced19 degree in a relevant discipline. I think she was20 giving examples.21 Q. But your actual advanced degree is in22 mechanical engineering, right?23 A. Yes.24 Q. You think that's a relevant25 discipline to the art pertaining to the 775 Patent?



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1 A. Yes. The actual title of the, you2 know, the department which the degree is conferred3 does not necessarily describe the expertise that one4 develops in executing the dissertation.5 Q. What is several years of practical6 experience refer to in this standard?7 A. I would consider practical experience8 to be conducting research or clinical work involving9 calcification related science. So that can be basic10 science in a lab. That can be working on animal11 models. That could be as a surgeon evaluating12 prosthetic graphs.13 Q. In your view, would a person of14 ordinary skill in the art know what calcification15 means?16 A. Yes.17 Q. Would a person of ordinary skill in18 the art be able to explain what calcification means19 without speculating?20 MR. TESCHNER: Objection to form.21 A. I would say that they would be able22 to give you a general understanding of23 calcification. I think if you were to look at24 minutia of certain terms, I would say that, you25 know, like we were discussing earlier, you know,

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1 some of those have different meaning to different2 people, et cetera, but, certainly, they should be3 able to follow that discussion, you know, so you4 talk about it for a while.5 Q. They could, at least, generally6 describe what calcification refers to, right?7 A. Yes.8 Q. Would a person of ordinary skill in9 the art have experience evaluating calcification of10 tissue either quantitatively or qualitatively?11 A. When you say "experience," what do12 you mean, like actually performing the methodology?13 Q. Well, let's start with that.14 Would they have experience actually15 performing methodology of evaluating calcification?16 A. No, they don't need that.17 Q. Would they have experience in18 evaluating reports of calcification prepared by19 others?20 A. That certainly qualifies as -- that21 certainly qualifies as experience.22 Q. Is that the kind of experience you23 would expect someone of ordinary skill in the art to24 have had?25 A. Not necessarily because I think that

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1 -- I think that people who are skilled in the art2 need not be involved in the -- like need not have3 been involved in a peer review process to actually4 have acquired expertise.5 Q. Well, aside from a peer review6 process, how about their own work they would do in7 the field, is that experience that they would have8 had in connection with their own work?9 A. You mean like writing their own10 reports?11 Q. Performing their own research and12 writing their own reports, yes.13 A. Yeah. I would want to make sure that14 there's space in that definition to include the15 clinical side, you know, clinicians write reports.16 They may not be ones that they publish, but they17 have to communicate with their colleagues about18 cases, et cetera, even if they don't end up in a19 peer reviewed publication.20 Q. Would a person of ordinary skill in21 the art know how to perform a histological22 evaluation of tissue for calcification?23 A. No, they don't need to know how to do24 it.25 Q. Would a person of ordinary skill in

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1 the art be familiar with X-ray studies of2 calcification?3 A. They can be familiar. I don't -- do4 you mean like actually having to perform them or...5 Q. Would they be aware that X-ray6 studies are a technique that are used for evaluating7 calcification?8 A. I don't know if a person of ordinary9 skill needs to know the existence of every possible10 technique to evaluate calcification. But I think11 that knowing that one of those exist -- X-rays, for12 instance, is a method, would be something consistent13 with somebody of ordinary skill.14 Q. But a person of ordinary skill in the15 art might not know that X-ray methods are in16 existence for evaluating calcification?17 A. Well, for instance, they might not be18 aware of some new technique that came up or all the19 techniques that were used in antiquity up until now,20 but they would be aware of techniques that they21 could use to evaluate calcification.22 Q. Well, I wasn't asking if they were23 aware of everything.24 But would a person of ordinary skill be25 aware that X-ray techniques can be used and are used



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1 for evaluating calcification?2 A. I mean, generally, yeah, I would3 think they would know.4 Q. Would a person of ordinary skill in5 the art be familiar with quantitative methods of6 evaluating calcification?7 A. Not necessarily. I mean, I think,8 like I said, depending on what they're interested in9 doing, they only need to know methods to achieve the10 specific results that they're interested in.11 Whether that refers to a quantitative or qualitative12 assessment, you know, like I said, I don't think13 that they need to know every technique or even most14 of them.15 Q. Well, that's not exactly what I16 asked. I didn't ask if a person would know most17 techniques or every technique.18 A. Okay.19 Q. My question was, would a person of20 ordinary skill in the art, first of all, know that21 there are quantitative methods for quantifying22 calcification?23 A. I guess, yes.24 Q. And would a person of ordinary skill25 in the art be familiar, specifically, with at least

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1 some of those quantitative methods for evaluating2 calcification?3 A. What do you mean by "familiar," like4 aware they exist?5 Q. Yes.6 A. I don't know if they need to know of7 a specific number of methods.8 Q. At least one?9 A. I don't think they need to be10 familiar with any rather than just aware that11 they're there. I think if they are interested in12 understanding some quantitative aspect about13 calcification, they have to be able to know -- they14 have to be able to identify a quantitative method15 that they could use. So I'm not mandating -- I16 don't want to say that they have to use one or the17 other like one specific one.18 Q. I didn't ask about what they used.19 I was asking, a person of ordinary skill in20 the art, would they, at least, be able to identify21 by name or description, at least, some of the22 quantitative methods available for evaluating23 calcification?24 A. Yes, I think they would be able to25 articulate even if they don't know the actual name

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1 of the technique, the general, you know, yeah, the2 general method that they would want to do.3 Q. If I ask you that question, you could4 probably name several techniques right now, right?5 A. Yes.6 Q. And a person of ordinary skill in the7 art would, at least, be able to identify some of8 those methods?9 A. I think they could broadly describe10 some of those methods.11 Q. Would a person of ordinary skill in12 the art be familiar with scientific publications13 addressing quantitative methods of evaluating14 calcification?15 A. They would be familiar with the16 literature that discusses calcification.17 Q. Would a person of ordinary skill in18 the art be familiar with scientific literature19 addressing whether the dog is a suitable model for20 assessing calcification?21 A. You mean -- are you saying that the22 paper itself is designed to evaluate that question?23 Q. I wasn't asking about a particular24 paper.25 I was asking if a person of ordinary skill

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1 in the art would be familiar with, at least, some2 scientific literature that discusses whether or not3 dogs are a suitable model for evaluating4 calcification?5 MR. TESCHNER: Objection to form.6 A. I guess I wouldn't -- I guess I7 wouldn't say it that way. I would say persons of --8 person of ordinary skill in the art would be aware9 that there are multiple animal models that are used10 to evaluate calcification-related research.11 Q. And would a person of ordinary skill12 in the art be able to identify, at least, some of13 those animal models that potentially could be used?14 A. Yes, definitely the one they're15 working with.16 Q. Would they be familiar with more than17 one?18 A. They may be.19 Q. Maybe but not necessarily?20 A. Well, like I said, it depends on the21 questions that they're trying to ask. So they may22 be most familiar with small animal model and they23 can spend their whole lives studying in that small24 animal model and gaining meaningful scientific25 information. Whether they must be familiar with a



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1 particular large animal model, I don't know if they2 need to know of -- I think it's fair to say they3 should know that there are large animal models4 available and should be able to identify one5 because, certainly, humans are an ultimate, you6 know, the clinical end point.7 Q. Maybe I should have clarified this8 before, but I assume you discussed this with your9 counsel.10 Are you familiar with the concept of a11 person of ordinary skill in the art? I'm not asking12 about any particular researcher or person in the13 field, you understand that?14 A. So I have been -- I have been15 informed of the legal term. And I know in the16 Patent Owner's response there are a couple of -- I17 think in some of the early paragraphs they say some18 features about characteristics that establish19 somebody -- let me see if I can find them here.20 Yeah, factors considered in determining the21 level of ordinary skill in terms of -- include22 educational level, type of problems, prior art23 solutions, rapidity with --24 (There is a discussion off the record.)25 A. I should probably say the whole

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1 thing. So the factors --2 Q. Before you say that, can you explain3 what you're looking at?4 A. I am looking at the Patent Owner's5 opposition that's -- I don't know what...6 Q. It's not marked as an exhibit. It's7 Patent Owner's Opposition to Petition for Inter8 Partes Review, right?9 A. Right.10 Q. And you're referring to Page 6 of11 that?12 A. Yes, I am, Page 6. It says, "The13 factors considered in determining the level of14 ordinary skill in the art include the educational15 level of the inventor, the type of problems16 encountered in the art, prior art solutions to those17 problems, the rapidity with which innovations are18 made, the sophistication of the technology and the19 educational level of active workers in the field."20 Q. And you understand that person of21 ordinary skill in the art is a hypothetical person22 who has an ordinary skill level in the field, right?23 A. Yes.24 Q. Okay. Would a person of ordinary25 skill in the art be familiar with the scientific

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1 literature that addresses calcification?2 A. Yes.3 Q. How about a heart surgeon who4 implants bioprosthetic valves, in your opinion,5 would that person typically have ordinary skill in6 the art pertaining to the invention?7 A. I would say that there are two8 different types of surgeons. I would say there is a9 surgeon whose expertise is in, you know, maybe10 difficult patient anatomy or, you know, something11 like that and they're focused on that particular12 process. And there are surgeons who are clinician13 researchers who have an interest in not only14 implanting valves but evaluating their performance15 over longer term.16 I would say the surgeons that are focused on17 technique but not so much of the outcome of the18 valve or, you know, its design would not be19 considered somebody of ordinary skill whereas the20 clinicians that have an interest and are, you know,21 studying how those valves perform would be.22 Q. In your view, does Dr. Kaplan have23 ordinary skill in the art pertaining to the 77524 Patent?25 A. I think for the art that she

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1 classifies she does.2 Q. Well maybe my question wasn't clear.3 I'm not asking if she had ordinary skill in4 the art pertaining to something that she wrote5 about.6 The question is whether she has ordinary7 skill in the art pertaining to the 775 Patent?8 A. Yes, I understand --9 Q. That's what we've been talking about10 when I keeping asking --11 A. I understand that. The reason why I12 find it difficult to answer is that it seems as13 though one group -- one set of documents describe14 the art in one way and one set of documents describe15 the art in a different way.16 My opinion, the definition of the art lies17 closer to the description that Kaplan gives versus18 the description that the Patent Owner gives. And I19 think that Kaplan, as a director of a research lab20 of a major hospital conducting scientific research21 on implanted biomaterials, that qualifies her as22 somebody of ordinary skill in the art.23 Q. Did you review her deposition24 testimony in addition to her declaration?25 A. I did.



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1 Q. And, based on your review of her2 deposition testimony and her declaration, in your3 opinion, she has ordinary skill in the art4 pertaining to the 775 invention?5 A. (No response.)6 Q. I just want to make sure I understand7 your testimony.8 You're saying based on all those things,9 your opinion is that she does have ordinary skill in10 this art?11 MR. TESCHNER: Objection to form.12 Q. Is that correct?13 A. I would say, in my reading of her14 deposition, that she was asked about specific15 subsets of the art in which she admitted that she16 didn't know a lot about.17 Q. But she couldn't even explain what18 calcification means, right?19 A. I'd have to go back and look.20 Q. She said she had to speculate to21 answer that question.22 MR. TESCHNER: Objection to form.23 A. I think -- yeah, I would have to go24 back and look at what she said because I don't25 remember that part off the top of my head.

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1 Q. Okay. Well, let's take a look at2 that.3 A. This is her declaration, not her...4 Q. Right.5 MR. TESCHNER: Excuse me, counsel. I6 think the witness has a misunderstanding of what7 you've been asking.8 THE WITNESS: Maybe.9 MR. TESCHNER: And you can explain10 further. But you've been asking in the context of11 the 775 Patent. And the witness has been answering12 more broadly than the 775 Patent. I just think13 maybe you're missing each other.14 MR. WEINER: I'll clarify that.15 Q. You understand when I asked you about16 the level of the ordinary skill in the art17 pertaining to the 775 Patent?18 A. So when I read to you from the 77519 Patent the statement I said about preparation or the20 biomaterials for the implantation in humans, that's21 what I understand the art to be.22 Q. When you refer to Claim 23 of the23 patent, is that what you're talking about?24 A. Yes. Yeah, well, I think that25 statement is said again in the introduction or in

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1 the background of the patent, too. This invention2 relates generally to material -- I'm reading from3 Column 1 around Line 25 of the 775 Patent. It says,4 "This invention relates generally to materials which5 are resistant to in vivo calcification." So -- and6 then "suitable for implantation in a living being."7 So that is sort of the scope that I was considering.8 Q. Okay. And you were considering that9 the claims at issue relate to methods of10 anti-calcification treatments for biomaterials,11 right?12 A. Well, I said -- Claim 23 says, "a13 method of making a calcification resistant14 biomaterial for use in the interior of a human or15 animal."16 Q. And that's very similar to what you17 read from the background of invention, right?18 MR. TESCHNER: Objection.19 Q. More particularly, to a method of20 preparing calcification resistant biomaterials?21 A. Certainly, there's a more22 particularly. But I think that the general field is23 this larger organization. So, for instance, there24 is no group of people who -- there is no field of25 people who only study calcification. There is a

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1 subset of scientists that are interested in that2 within the broader area of, you know, artificial3 organs or cardiology.4 Q. You understand this is a hypothetical5 person, it's legal standard used for legal disputes6 such as the one that St. Jude Medical and the7 University of Michigan are engaged, right?8 A. I understand that the term ordinary9 skill in the art is a legal term.10 Q. It's not a term you use in connection11 with your research or interactions with colleagues,12 right?13 A. No.14 Q. Now, the questions I asked you15 before, I asked you several questions about what a16 person of ordinary skill in the art would know or17 understand.18 A. Uh-huh.19 Q. Having discussed now what the person20 of ordinary skill in the art refers to, do you stand21 by your testimony that you responded to my questions22 before, or do you want to revisit that?23 A. There was a lot of questions.24 Q. Well, I asked you several questions.25 I asked, in your view, would a person of ordinary



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1 skill in the art know what calcification means.2 A. Yes.3 Q. And you responded to that.4 When I asked you that question, you5 understood what I meant by a person of ordinary6 skill in the art pertaining to the 775 Patent,7 right?8 A. Yes.9 Q. Your counsel seemed to think you10 misunderstood what I meant by that and I just wanted11 to clarify with you just to see whether that was the12 case.13 A. So what you just said, I think, I14 agree with in terms of I understand what the legal15 term means, I have -- my opinion of the art which we16 just said and my statement about the background and17 whatever of the person having ordinary skill in the18 art would know.19 Q. Okay. And you think that Dr. Kaplan20 has ordinary skill in that art?21 A. Well, I think that in the broader22 context she does. I think that she definitely does23 not know as much as some people.24 Q. That's not what I asked you. I25 didn't ask you if she was an expert. I didn't ask

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1 you if she was a leading person in the field. I2 didn't ask if she knows as much as you.3 I asked you is Dr. Kaplan a person of4 ordinary skill in the art pertaining to the 7755 patent?6 MR. TESCHNER: Objection to form.7 And you don't need to raise your voice.8 A. I think she is somebody of ordinary9 skill in the art of biomaterial implantation for10 humans.11 MR. WEINER: Move to strike as not12 responsive. Could you read back the last question13 please.14 (Whereupon, the question is read back as15 follows:16 "Question: That's not what I asked you. I17 didn't ask you if she was an expert. I didn't ask18 you if she was a leading person in the field. I19 didn't ask if she knows as much as you.20 I asked you is Dr. Kaplan a person of21 ordinary skill in the art pertaining to the 77522 patent?")23 A. Yes.24 Q. I'd like to direct your attention to25 Dr. Kaplan's transcript, Exhibit 2013.

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1 A. Do I have that?2 (Deposition Exhibit 2013, Kaplan Deposition,3 was previously marked for identification.)4 Q. For you, copy to your counsel.5 Do you recognize this exhibit, 2013?6 A. Yes.7 Q. And you reviewed this transcript in8 connection with preparing your declaration?9 A. Yes.10 Q. Okay. I'd like to direct your11 attention to Pages 31 and 32.12 A. Is that of this or of the...13 Q. Let me clarify that. It's a little14 confusing.15 There are page numbers on the bottom. I was16 referring to the actual transcript pages and they're17 kind of copied four to one.18 A. Okay.19 Q. It's actually marked Page 9 of the20 exhibit but upper right-hand corner 31 and the lower21 right-hand corner of that page is 32.22 A. Okay.23 Q. So, in particular, starting at Page24 31/Line 10. Let me just read this into the record25 so it's clear what I'm talking about.

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1 Starting on the left-hand side, "Question:2 I see, Dr. Kaplan. I asked you a couple of times3 about calcification. Can you describe what4 calcification of tissue refers to?5 Answer: I don't think that I can describe6 in it detail. But I do know that a lot of -- a lot7 of problems and a lot of concerns were erased from8 long time ago about calcification of the products9 which are implantable.10 Question: Okay. Well, you said you can't11 describe it in detail. Can you provide a general12 description of what calcification of tissues refers13 to?14 Answer: I don't want to speculate because15 if I don't know details, I might be wrong.16 Question: I want to make sure I understand17 your testimony. Are you saying in order to give a18 general description of calcification of tissue you19 would have to speculate?20 Answer: To some degree because I am not an21 expert in calcification."22 Now, having reviewed that testimony, is it23 still your view that Dr. Kaplan has ordinary skill24 in the art pertaining to the 775 Patent?25 A. Yes.



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1 Q. Okay. I'd like to direct your2 attention now to Exhibit 2005.3 (Deposition Exhibit 2005, Levy 1983, was4 marked for identification.)5 (There is a discussion off the record.)6 Q. I'm sorry, it looks like we didn't7 bring an extra copy of that.8 Do you have a copy in your binder that we9 can look at?10 MR. LOIACONO: What was the Exhibit11 number?12 MR. WEINER: 2005.13 MR. TESCHNER: Do you want us just to14 make copies of that?15 MR. LOIACONO: Go off the record.16 (Recess taken 11:25 to 11:33 a.m.)17 Q. I'd like to direct your attention to18 Exhibit 2005.19 A. Okay, thank you.20 Q. And do you recognize Exhibit 2005?21 A. Yes.22 Q. It's the Levy 1983 publication?23 A. Uh-huh.24 Q. Okay. Put that aside for just a25 second.

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1 A. Okay.2 Q. And I'm going to refer to that in a3 second, but I want to refer you to your declaration4 at Paragraph 51.5 A. Okay.6 Q. Okay. And that's Exhibit 1016, your7 declaration.8 Okay, Paragraph 51. In Paragraph 51, you9 state that Levy 1983 provides no quantitative data,10 right?11 A. I say that it -- yes, no quantitative12 data, only data that Dr. Schoen admits is13 semi-quantitative.14 Q. Okay. And now let's look back at15 Levy 1983, Exhibit 2005. Let's start with the16 abstract right at the beginning of Exhibit 2005.17 A. Uh-huh.18 Q. In your declaration you stated that19 the article is devoid of truly quantitative data.20 Let me see if I can find that.21 Right. That's just after the part that was22 in Paragraph 51. You said -- actually, I might have23 misread that. That relates to Shemin 1988 was24 devoid.25 But your declaration states that there is no

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1 quantitative data?2 MR. TESCHNER: I'm sorry, could you3 point to where?4 A. It says Carpentier 1982 and Levy5 1983.6 Q. Both coauthored by the inventor, Dr.7 Levy, provide no quantitative date, only data that8 Mr. Schoen admits is semi-quantitative, right?9 A. I'm trying to remember if there is10 another 1983 paper from Levy that is in here.11 Q. Why don't you take a look at Appendix12 A to your declaration, that's the materials13 reviewed; is there something else that you might14 have been referring to there?15 A. I'm just making sure. I was looking16 at this one.17 Q. Okay.18 A. 1070.19 Q. That's fine as well.20 A. Yeah.21 Q. And what we've marked Exhibit 1070,22 on the second page, that's the same abbreviation you23 used for Exhibit 2005, it says, "Levy 1983"?24 A. Yeah. So there's also Exhibit 1026.25 That's Levy et al 1983. And I think that one -- I

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1 don't know if that...2 It's also 1983.3 Q. Okay. Do you know which Levy article4 you were referring to?5 A. Well, that's what I'm trying to6 remember here.7 MR. TESCHNER: Take your time and8 refer to them, if you know.9 Q. I mean, if you're not sure, we can10 look at both of them.11 A. Yeah, I don't think there...12 I'm allowed to ask?13 Q. Yeah.14 (There is a discussion off the record.)15 MR. TESCHNER: If you don't recall,16 then answer that question that way. But go through17 the two of them and see if it refreshes your18 recollection. And if you can answer the question or19 if you can't answer the question, say so.20 Q. Let's start with Exhibit 2005.21 A. Okay.22 Q. That's the Levy 1983 publication that23 you reviewed, right?24 A. Yeah.25 Q. If you start with the abstract, the



25 (Pages 94 to 97)

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1 abstract does report quantitative data, doesn't it?2 MR. TESCHNER: Objection to form.3 A. I see quantified information in the4 abstract.5 Q. Well, in particular, it has6 concentrations of calcium in the tissue and7 micrograms per milligram of dried tissue, right,8 several data points reported for amount of calcium?9 A. Yeah, I see that.10 Q. That's quantitative data, right?11 A. Yeah.12 Q. And let's take a look at Page 145,13 left-hand column, right, under the heading, "mineral14 analysis."15 A. Why am I not seeing it?16 Q. Page 145.17 A. Yes.18 Q. And the first sentence reads in part,19 "Calcium was determined by atomic absorption20 spectroscopy using a Perkin Elmer model 603," and it21 goes on from there.22 A. I see that.23 Q. And does that describe how24 quantitative data was taken for amount of calcium in25 the samples?

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1 A. This describes the method that was2 used to acquire the data.3 Q. Right. To acquire quantitative data4 for calcium ion concentration, right?5 A. Yeah.6 Q. Well, let's take a look at the rest7 of the article. How about Table 1 that's on Page8 148, do you see any quantitative data there?9 A. Yes, I do.10 Q. And, in fact, it has calcium amounts11 reported in micrograms per milligram?12 A. Yes.13 Q. Both for un-implanted tissue and 3, 714 14 and 21 days?15 A. Yes.16 Q. How about Table 3 that's on Page 8,17 do you see any quantitative data there?18 A. Yes.19 Q. Likewise, that has calcium20 concentrations in micrograms per milligram, right?21 A. Yes.22 Q. And how about Table 4, do you see the23 same thing there?24 A. I do.25 Q. It's not the same. It's different

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1 data, but it's also calcium concentrations and2 micrograms per milligram?3 A. Some of it is the same data but, yes.4 Q. Okay. And let's take a look back at5 your declaration, Paragraph 49.6 A. Uh-huh.7 Q. Now, this one -- Paragraph 49,8 specifically, refers to Levy 1983 and it refers to9 2005, right?10 A. Yes.11 Q. And it refers to Table 4. It says12 Table 4 provides the relevant data comparing13 calcification in young and old animals, right?14 A. Yes.15 Q. And it goes on to say a little bit16 more about that and then the last sentence of17 Paragraph 49 says, "Furthermore, the author does not18 provide a baseline calcium level of the aged mice to19 complete the data set and eliminate the alternative20 hypothesis that age mice were just as relatively21 sensitive to calcification as young mice."22 A. Yes.23 Q. Did I read that correctly?24 A. Yes.25 Q. Where did you get the idea that mice

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1 were tested?2 A. Oh, that should be rats. I'm sorry.3 Q. You're aware that rats are a standard4 small animal model used for subcutaneous5 experiments, right?6 A. Yes.7 Q. You understand that mice are8 generally not used for those experiments?9 A. I'm not aware that they can't be10 used, but I am aware that they generally are not11 used.12 Q. And you've never seen a study that13 refers to mice?14 A. No. There are mice studies used all15 the time to evaluate calcification.16 Q. But certainly not in this study?17 A. No, no.18 Q. What did you mean, the author does19 not provide a baseline calcium level of the aged --20 I understand that to mean rats.21 A. So let me go back here. So, in Table22 1, they utilize an un-implanted control of the23 material that's from this young mouse, however old24 it is, and then they implant and investigate for 3,25 7, 14 and 21 days.



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1 In Table 4, they compare the three-week and2 eight-month and their statistical analysis only3 looks at eight-month against the three-week but they4 did not test the statistical comparison of the5 eight-month against the un-implanted control, which,6 you know, assuming these data sets are normally7 distributed in order to do their statistics would8 also be significantly different, meaning, the9 eight-month old also calcifies. But the10 un-implanted control, the exact same data is11 utilized in both table sets. So you have an12 un-implanted version of the -- of one set but don't13 have -- you don't have an earlier time point with14 which to assess the calcification rate of the15 eight-month old explant.16 Q. I don't know if I followed you.17 Wasn't the same un-implanted tissue the18 control for both experiments, both in the three-week19 rats and eight-month old rats?20 A. I mean, it's the same exact data.21 Q. Well, the same exact data for the22 three-week old explants and then there was different23 data for eight-month old explants showing a lower24 degree of calcification for the older animals,25 right?

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1 A. Yeah. But this data is done after a2 certain amount of time of implantation. And I am3 not seeing what that time point is.4 Q. I asked you about your declaration.5 You said the author does not provide a baseline6 calcium level of the aged rats. What does that7 mean?8 A. Well, I'm referring to Table 1 where9 you can clearly see the progression of calcification10 over time where -- for the young implants, whereas11 in Table 4 there is not that similar progression of12 the eight-month old explants.13 Q. So there is some quantitative data in14 Table 4 but you think there should have been more?15 A. I'm saying to effectively tell me16 that I can analyze -- I cannot use the eight-month17 old explants to analyze calcification. I can't say18 that with this table. I'm saying that both the19 eight-month calcify and the three-week old calcify.20 Q. What do you mean by a baseline21 calcium level of the aged mice? I don't know what22 that means. The baseline is of the tissue that's23 implanted, not of the mice or rats.24 A. Well, I meant rats and I understand25 it's...

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1 What I mean is that to say that I can better2 utilize a young model versus an old model, animal3 model, I would want to look at the progression of4 calcification in both models. And so, while they do5 provide that information in Table 1 for the young6 model, they don't do that for the old one. So the7 eight-month old model could be just as relatively8 sensitive, meaning, you know, same degree of change,9 let's say.10 Q. Ideally, you would want to see more11 data points there; is that what you're saying?12 A. I would like -- not more data points13 of the same condition. I would like to see more14 conditions.15 Q. Over different times?16 A. I would like -- yeah.17 MR. TESCHNER: Objection to the form18 of the question.19 A. I would say that it would be better20 if that information -- those additional time points21 were present.22 Q. Then in Paragraph 51 of your23 declaration you said it was ironic that this article24 lacked quantitative data and that the Patent Owner25 argued the importance of Kaplan's omission of

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1 quantitative data, correct?2 MR. TESCHNER: Objection. We haven't3 established that that's the article that he was4 referring to.5 A. I mean, I think when I read, you6 know, not only my declaration in Paragraph 49, I'm7 talking about data. So I don't think that this 19838 article is not that one. Because I can clearly see9 there is quantitative data there.10 Q. But that's the article that talked11 about eight-month old aged rats, right?12 A. Yes.13 Q. And Paragraph 49 was clearly14 referring to Exhibit 2005?15 A. Yes, it was so, yeah.16 Q. So let's take a look at the other17 Levy article from the same year, that's18 Exhibit 1026.19 (Deposition Exhibit 1026, Levy et al 1983,20 was previously marked for identification.)21 (There is a discussion off the record.)22 Q. This has been previously marked as23 Exhibit 1026.24 MR. TESCHNER: Thank you, counsel.25 Q. Okay. Do you recognize Exhibit 1026?



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1 A. Yes.2 Q. That's another Levy article from3 1983, right?4 A. Uh-huh.5 Q. Actually, it says, accepted for6 publication 1982. Does it say it was published in7 '83 somewhere?8 A. It says on the top of Page 188,9 "August 1983."10 Q. I see.11 A. Yeah.12 Q. Do you see any quantitative data13 reported in this article?14 A. Yes.15 Q. For example, Page 190 there is a16 table that reports calcium in animals per milligram17 protein?18 A. Uh-huh.19 Q. Quantitative data with un-implanted20 and several different measurements were taken. And21 then on Page 188, right-hand column under22 "biochemical procedures," it states that the samples23 were assayed for calcium content by atomic24 absorption. And it's about three-quarters of the25 way down that paragraph under "biochemical

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1 procedures."2 A. Yes.3 Q. So do you think this was the article4 you were referring to when you said Levy 1983 has no5 quantitative data?6 A. I don't -- I would not look at this7 article and say there is no quantitative data in it.8 Q. But you said it in your declaration.9 A. I did.10 Q. You said it multiple times and you11 said it was ironic.12 A. I did.13 Q. Do you understand that St. Jude is14 relying on your testimony in support of its efforts15 to invalidate the University of Michigan's 77516 Patent?17 A. I do.18 Q. You understand that St. Jude has been19 charged with infringement of that patent?20 MR. TESCHNER: Objection, outside the21 scope.22 A. Yeah, I don't know all the legal23 details. I was really only asked to understand this24 information.25 Q. Okay. And are you aware that St.

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1 Jude has been charged with patent infringement of2 the 775 Patent?3 MR. TESCHNER: Objection, outside the4 scope.5 A. I, actually, don't know, like I said,6 the actual case terms or even what that means.7 Q. Okay. Are you aware that St. Jude8 has been charged with breach of contract for failing9 to pay royalties for a legends agreement under the10 775 Patent?11 MR. TESCHNER: Objection, outside the12 scope.13 A. Like I said, I wouldn't know what14 that means, even if I were.15 Q. Okay. You understand that your16 declaration is sworn testimony that's used by the17 Patent Office just as a court would use live18 testimony at a trial?19 A. I do.20 Q. And do you agree that your testimony21 includes incorrect testimony about the Levy 198322 publication, whichever one you're talking about?23 A. The Levy article I'm talking about24 here is not either of those two articles.25 Q. Well, which article were you talking

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1 about then? Take whatever time you need to look2 through your exhibit list and declaration because I3 would like to find that out.4 A. It might be one that was coauthored5 by him. Because I know that was something that I6 was interested in.7 Q. Well, Dr. Levy was interested in it8 too and he was interested in your testimony about9 his article. That definitely got his attention.10 MR. TESCHNER: Just take your time11 and look through whatever you need to to answer the12 question.13 (There is a discussion off the record.)14 A. So I'm reviewing back to the15 Carpentier 1982 and that paper is also coauthored by16 Levy and that material does not contain quantitative17 data regarding calcification.18 Q. But Paragraph 51 refers separately to19 Carpentier 1982 and a Levy 1983.20 The question is, what did you mean by Levy21 1982?22 MR. TESCHNER: Excuse me, counsel.23 While he's looking, what paragraph of his24 declaration were you questioning on primarily?25 THE WITNESS: It's 51.



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1 MR. WEINER: 51.2 MR. TESCHNER: Thank you.3 MR. WEINER: 49, specifically, refers4 to Exhibit 2005.5 MR. TESCHNER: Right.6 MR. WEINER: And then 51.7 MR. TESCHNER: Thank you.8 (There is a discussion off the record.)9 Q. Dr. Butcher, I don't want to cut10 short your time in reviewing the information, but11 have you looked at every exhibit that was cited in12 your declaration?13 A. Well, the problem is I didn't cite14 something in Paragraph 51. So I don't -- I'm15 confused as to what article I was referring to.16 Q. But, in Paragraph 49, you were17 referring to Levy 1983 and you provided the Exhibit18 number.19 A. Yeah, I mean, that information I20 think I discussed in Paragraph 49.21 Q. Right. And then 51, two paragraphs22 later, you refer to Levy 1983. It doesn't have a23 citation to an exhibit.24 But have you now reviewed all the exhibits25 that were attached to your declaration, as we sit

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1 here?2 A. Yeah, I looked at all the ones in3 this binder.4 Q. And there is no 1983 Levy article5 that lacks quantitative data, is there?6 A. I don't see an article with a7 coauthor or author Levy from 1983 here that lacks8 that data.9 Q. You did not intentionally make any10 incorrect statements in your declaration about Levy11 1983, did you?12 A. I didn't -- no, I did not intend to13 make an incorrect statement.14 Q. But you did, in fact, make an15 incorrect statement about Levy 1983, right?16 A. If that reference -- I don't know if17 that reference is one of these here. That's what18 I'm trying to say.19 Q. Well, I don't think any of us can20 answer what you were thinking when you wrote21 something down in your declaration criticizing Dr.22 Levy's articles and saying it was ironic that they23 were lacking data.24 I think it's ironic that you say it's ironic25 that his article lacks data.

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1 MR. TESCHNER: Argumentative. I2 object.3 Q. There is no such --4 MR. TESCHNER: You're badgering the5 witness and unnecessarily. If you have a question,6 ask the question.7 Q. Well, in view of your incorrect8 statements, do you think you owe an apology to Dr.9 Levy, Dr. Schoen, the other coauthors and the10 University of Michigan?11 MR. TESCHNER: Argumentative. I12 object to that.13 You don't need to answer that question.14 MR. WEINER: Are you instructing your15 witness not to answer?16 MR. TESCHNER: I'm not instructing17 him. I'm saying he doesn't have to answer.18 Q. Please answer the question.19 A. I don't want to answer that question.20 Q. Based on your counsel's advice not to21 answer the question?22 MR. TESCHNER: I didn't advise him23 not to answer. I said, I object as argumentative.24 MR. WEINER: And the rules do not25 permit you to instruct your witness not to answer

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1 except to preserve a privilege.2 MR. TESCHNER: And I did not instruct3 him not to answer.4 Q. Are you refusing to answer the5 question?6 A. Huh?7 MR. TESCHNER: No, go ahead.8 THE WITNESS: Oh.9 A. The question of whether I should owe10 him an apology -- I'm saying I'm not sure which11 article that was. And right now I can't remember12 what it is.13 Q. Okay. But you're sure you said in14 multiple paragraphs that Dr. Levy's article was15 deficient for lacking quantitative data, right?16 A. I said that in multiple places?17 Q. 49 and 51.18 A. I don't think in 49 I suggested that19 it was lacking quantitative data. I said there was20 something missing that I would like to see, but that21 doesn't mean it didn't have quantitative data. I22 wanted to see additional control. All I had to say23 -- I'm not saying this article is deficient. I'm24 saying that the standards of what is sufficient is25 determined differently than what was argued, in my



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1 opinion.2 Q. But it's not because the articles3 that you found have all kinds of quantitative data,4 don't they, and Dr. Levy did meet that standard and5 exceeded that standard, didn't he?6 MR. TESCHNER: Objection to form and7 asked and answered.8 A. I'm not criticizing the scientific9 utility of Levy's article. I think it's excellent.10 I'm saying that the level of scientific detail in11 one article does not create a minimum standard that12 all other articles need to follow in order to be13 teachable.14 Q. Uh-huh. But you incorrectly stated15 that Dr. Levy provides no quantitative data, didn't16 you?17 A. In Paragraph 51 I make a statement18 about an article that I cannot remember where it is19 or which one it was and I do not see that article in20 this here.21 Q. Okay. Let's move on to something22 else.23 Are you familiar with the Hope Heart24 Institute?25 A. I mean, vaguely I'm familiar with the

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1 institute.2 Q. Were you familiar with it before3 being retained to work on this case for St. Jude?4 A. I had heard about it before.5 Q. And, in your declaration, in6 Paragraph 22, you stated that it would be difficult7 to imagine that a research group at the Hope Heart8 Institute would mistake calcification for something9 else, right?10 A. You said paragraph what?11 Q. 22.12 A. Yes, yes, I say that.13 Q. And let me direct you to Paragraph 4514 of your declaration. Referring to Dr. Kaplan and15 her research team about halfway down the paragraph,16 you state, "They would clearly know what17 calcification looked like and the ramifications of18 an incorrect diagnosis." Did I read that correctly?19 A. Yes.20 Q. Would it be difficult for you to21 imagine that a researcher at Hope Heart Institute22 would not be able to describe what's meant by23 calcification?24 A. I mean, I imagine there could be25 somebody at the institute that wasn't, you know,

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1 that's involved in a completely different area of2 research.3 Q. How about Dr. Kaplan, didn't we look4 at her testimony before where she said she couldn't5 answer that question without speculating?6 A. Well, I said here that there is a7 research team involved. So I think that in this8 scientific contribution, there's a number of9 individuals that are involved in generating this10 information.11 Q. So maybe Dr. Kaplan couldn't do that12 but you're saying somebody else on the team probably13 could --14 MR. TESCHNER: Objection to form.15 Q. -- describe what calcification is?16 MR. TESCHNER: Objection to form.17 A. I think that Kaplan -- well, I can't18 speculate who was doing which. But, you know, in19 terms of -- I don't know who the other people on the20 study -- on the particular study, what their21 particular contribution to the paper was. I don't22 know.23 Q. But you're assuming someone on the24 team knew what calcification was?25 A. Yes.

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1 Q. And you're assuming someone on the2 team could identify if a tissue sample had3 calcification?4 A. Yes.5 Q. And do you realize that in Dr.6 Kaplan's testimony she also admitted that she could7 not personally identify if the tissue on the lab8 bench in front of her had calcification?9 A. Could you point me to where she said10 that?11 Q. Sure. Her transcript, that's12 Exhibit 2013. Take a look at Pages 37 to 38.13 A. This is the other -- the quadrant14 Page 37?15 Q. Right, exactly. Let me just read the16 testimony into the record to make sure the record is17 clear. It's Page 37 beginning at Line 12.18 "Question: If you had a heart valve in19 front of you in your laboratory, would you be able20 to evaluate whether that heart valve had signs of21 calcification?22 Answer: No. I never worked with heart23 valve.24 Question: If you had another tissue, say a25 vessel that had been implanted and then removed from



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1 an animal in front of you in a laboratory, would you2 be able to tell if that vessel had any signs of3 calcification?4 Answer: What I would do in this case, I5 would give it to analysis in the histology lab.6 Question: And you'd rely on a histologist7 to do the evaluation?8 Answer: Definitely.9 Question: You wouldn't be able to evaluate10 it on your own?11 Answer: No. It is definitely not to the12 degree which lab is supposed to do it, can do it. I13 can see some -- that it has some hardening or14 whatever, something unusual on the vessels, but I15 cannot prove if it's calcification or something16 different.17 Question: So you might be able to identify18 some hardening, but you wouldn't necessarily be able19 to tell whether that was caused by calcification?20 Answer: No. And I definitely wouldn't be21 able to the degree level of calcification."22 Did I read that correctly?23 A. Yeah, you repeated her words.24 Q. You find that testimony surprising25 from a researcher at the Hope Heart Institute?

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1 A. I would think that referring samples2 to a histological lab would be a reasonable3 procedure to evaluate calcification.4 Q. That's not what I asked, though.5 Do you find that testimony surprising from a6 researcher at the -- a researcher who is the lead7 author of an article that you say discloses8 information about calcification?9 A. I don't find it unusual that the10 first author of the study doesn't know how to11 perform the methodology to evaluate calcification.12 Q. Or recognize calcification in the13 tissue if it was sitting right in front of her?14 A. It may not be to that level when they15 were evaluating it. So, no, I don't find that...16 Q. I didn't ask you about level. She17 said she couldn't identify if a tissue sample in18 front of her had calcification or not.19 A. Yeah, I would say it's difficult for20 anybody to do that depending on how, you know, how21 far along calcification is. You know, there are22 different levels of evaluating calcification. There23 is a gross level, you know, all the way down to24 mineral levels.25 Q. And her article doesn't give any

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1 information at all about how calcification was2 identified, does it?3 A. I didn't say that, did I?4 Q. No.5 A. What did I say?6 Q. I'm -- you can review your testimony,7 if you like, but I was asking if you agree with that8 statement.9 A. I think -- I think that she did10 provide information with respect to calcification of11 the vessel. She used -- they used histology and SEM12 and TEM. Let's see if I can find a particular13 paragraph. Let me use my exhibit, if that helps.14 Q. You're referring to Exhibit 1018?15 A. 1018.16 Q. -- 1985?17 A. Well, I was referring first to my18 declaration because you were talking about what I19 said.20 Q. Okay, that's fine. Let's keep that21 exhibit aside and...22 A. Okay.23 MR. TESCHNER: Take your time to24 review your declaration.25 A. So the relevant text in my

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1 declaration refers to from, essentially, Paragraphs2 35 through -- well, 35 through probably 47.3 But, in terms of excerpts that have4 information, they discussed -- in Paragraph 36, they5 discussed the stability and configuration of the6 structure of the vessel wall and flow surface was7 confirmed by histological evaluation which revealed8 no change in the SEM and TEM performance of the9 graft after storage --10 (There is a discussion off the record.)11 A. So let me say, however they found12 that the behavior of grafts kept in 50 percent ethyl13 alcohol remained constant for up to two years of14 storage. That's Exhibit 1009.15 Stability of the configuration and structure16 of the vessel wall and flow surface was confirmed by17 histological evaluation which revealed no change in18 the SEM and TEM performance of the grafts after19 storage in alcohol. And then they go onto test with20 a short-term in vivo experiment, at which point they21 find that both the treatments and the control22 performed similarly and then they do longer term23 implants and they say that they report calcification24 was detected in some grafts stored in the -- .6525 glutaraldehyde following three-week implantation in



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1 the canine experimental model. Importantly, they2 determined that this phenomena was not seen in the3 vessels stored in ethyl alcohol. Histopathologic4 studies of the retrieved prostheses that had been5 stored in 50 percent alcohol revealed neither6 calcification nor untoward effects.7 Q. Okay. I see where you're reading8 that in Paragraph 38 and you quoted something from9 Kaplan's article. I'm going to ask you some10 questions about that a little later on.11 A. Okay.12 Q. The portion you quoted doesn't say13 anything about how calcification was measured other14 than what's detected, does it?15 A. It describes how they detected16 calcification, correct. They did not measure the17 quantity of calcification.18 Q. The portion you quoted simply says19 calcification was detected. The part you quoted20 from her article says nothing about how21 calcification was detected or by whom, correct?22 A. It does not say by whom. The methods23 that they used in their paper -- I don't know if I24 have that paper with me.25 Q. 1018.

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1 A. 1018?2 Q. Yeah.3 (There is a discussion off the record.)4 A. So, in the method section, they say5 that the grafts were evaluated by thrombus-free6 surface scoring, which expresses a percentage of7 surface free from thrombus and histological8 examination, which with attention paid to flow9 surface configuration structural stability of the10 preserved graft and perigraft tissue reaction.11 Q. You're reading from the abstract?12 A. I'm sorry. I'm reading from Page 4913 of the Kaplan paper, which is exhibit --14 Q. It's 1018, right?15 A. Oh, 1018, yes.16 Q. And where were you reading from?17 A. I'm sorry. It's Page 49.18 Q. Which column?19 A. It's the first column, it's right20 above the results word.21 Q. Okay. And where did you start22 reading, "the grafts were evaluated"?23 A. Yes.24 Q. And where was there a reference to25 calcification in that paragraph you were reading

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1 from?2 A. So the -- "both the surface3 configuration and structural stability of the4 preserved graft includes among other things whether5 calcification is present."6 Q. Okay. But the word calcification is7 not there in the part that you pointed to?8 A. The word calcification is not9 present.10 Q. Alright. And the question was, does11 Kaplan provide any information about how12 calcification was measured?13 MR. TESCHNER: Objection, asked and14 answered.15 Q. Okay. And you're pointing to a part16 of the paper that doesn't mention calcification, did17 I understand your testimony correctly?18 A. I was saying that they were using an19 examination approach that can detect a wide variety20 of things to determine if a wide variety of things21 were present. They didn't need to mention all22 possible outcomes of that particular method could23 detect.24 Q. Okay. This article is published in25 the Journal of Surgical Research --

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1 A. Yes.2 Q. -- is that right?3 Are you familiar with that journal?4 A. Yes.5 Q. Were you familiar with the journal6 prior to your work for St. Jude Medical on this7 case?8 A. Yes.9 Q. Is it a publication that you consult10 in connection with your own work?11 A. I imagine, highly likely, that I12 would have either read or cited an article from this13 journal.14 Q. Have you ever submitted an article to15 this journal for publication?16 A. No.17 Q. You consider this to be a respected18 publication?19 A. Yes.20 Q. Do you know who reviewed Dr. Kaplan's21 article prior to publication?22 A. No.23 Q. Do you know if the article was24 reviewed by a member of the editorial board prior to25 acceptance for publication?



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1 A. My understanding -- my knowledge of2 peer review makes it inconsistent that somebody from3 the editorial board did not review this article.4 Q. By that do you mean your expectation5 is a member of the editorial board did review the6 article?7 A. Well, when an article is submitted to8 a journal for peer review, the first place it goes9 is to an editor and then the editor decides whether10 to send it out. So I don't know if the editor11 conducted an exhaustive review or just did a triage12 but they, at least, do the triage and their final13 determination after accumulating the peer review14 reports.15 Q. And, typically, they would submit16 that to a reviewer who has appropriate background to17 review the article?18 A. Yes.19 Q. Do you know if the reviewer of the20 article was an expert on calcification?21 A. I don't know who the reviewers were.22 Q. Do you know if the reviewer was23 knowledgeable about calcification?24 A. I still don't know -- I don't know25 who they picked to be reviewers.

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1 Q. But you drew conclusions based on the2 fact -- you referred to the editorial board in your3 testimony and you seem to draw conclusions based on4 the fact all these prestigious people are on the5 editorial board, therefore, you give more weight to6 the article?7 A. What I'm saying is that the editorial8 board contains people who had ordinary skill in the9 art and therefore --10 Q. The art pertaining to the 775 Patent?11 A. Yes. And they would know -- well,12 the art pertaining to the article and what the13 article was trying to teach and this group of people14 -- I don't know which one was selected. I don't15 know who their peers are, the peers that they16 particularly chose. But it's their job to evaluate17 the article and all the information which it18 contains.19 Q. Do you know if anybody on the20 editorial board has ordinary skill in the art21 pertaining to the 775 Patent?22 A. Yes.23 Q. And who, in particular, do you think24 has ordinary skill in the art pertaining to the 77525 Patent?

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1 A. Christopher Zarins. He's the editor.2 Q. Okay. Are you familiar with Dr.3 Zarins?4 A. Yes.5 Q. Okay. Anybody else on the editorial6 board who you're familiar with?7 A. I'd have to look more in-depth at8 whatever it is that they were looking at.9 Q. But you don't know if Dr. Zarins ever10 saw this article before publication, do you?11 A. I couldn't tell you if he did.12 Q. If you were on the editorial board,13 what qualifications would you look for for a14 reviewer for this article?15 A. Somebody who had expertise in the16 areas that the article was teaching. So this17 article was -- I mean -- I can -- I mean, the18 article.19 So I would look for people who knew about20 glutaraldehyde preparation, people who knew about21 evaluating small diameter vascular grafts. I would22 look at people who understood the complications and23 consequences of bioprosthetics, yeah.24 Q. But you wouldn't necessarily look for25 an expert in calcification, would you?

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1 A. Well, I think that calcification is2 contained within several of those different areas3 that I just mentioned. I don't know if somebody4 would only know just one single small thing because5 that's not really a field. It's just a subject6 among -- or not even a subject, you know, an7 experimental end point among lots of things.8 Q. But you look for peer reviewers who9 had expertise in the primary subject matter of the10 article?11 A. Each article has, in my experience12 and in this experience and lots of these other13 articles, there are a variety of areas that the14 information touches on and so reviewers would be15 asked to encompass those areas to review the16 articles.17 Q. What do you understand to be the18 primary purpose of the study reported in the19 article?20 A. In my reading of this article, the21 research team's objectives were to develop an22 optimized preparation strategy for canine carotid23 arteries to be used as a small diameter vascular24 graft and they evaluated a whole litany of different25 possible processing steps, although beginning from



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1 the anesthetization agent for removing the vessel to2 the level of glutaraldehyde required for fixation,3 all the way to the best way to -- the best way to4 store the material and its in vivo consequences of5 that preparation.6 Q. Do you know if canine carotid7 arteries have ever been implanted in a human8 patient?9 A. I do not know.10 Q. You're not aware of that ever having11 been done, right?12 A. I'm not aware of that ever having13 been done.14 MR. TESCHNER: Counsel, we've gone --15 it's after 12:30. If there is a convenient time,16 again, I don't want to interrupt your questioning.17 MR. WEINER: I think this is fine.18 Take a break now.19 MR. TESCHNER: For lunch?20 MR. WEINER: Okay.21 (Lunch recess taken 12:36 to 1:25 p.m.)22 MR. WEINER: I'd like to go back on23 the record.24 Q. Okay. Dr. Butcher, we were talking25 about the Kaplan article, Exhibit 1018.

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1 A. Yes.2 Q. Have you ever seen Kaplan cited in3 another scientific article?4 A. This article is cited 14 times.5 Q. And how do you know that?6 A. When I was first directed to look at7 the article, when I looked for articles, Google8 Scholar is one of the ways you can look for articles9 and it says "cited by" underneath it.10 Q. Before working on this case for St.11 Jude Medical, had you come across Kaplan12 Exhibit 1018?13 A. No.14 Q. Had you come across any of the 1415 articles that reference Kaplan?16 A. I don't remember because I didn't17 look at each of those articles.18 (There is a discussion off the record.)19 (Recess taken at 1:26 to 1:29 p.m.)20 MR. WEINER: Back on the record.21 Q. Is that number of citations what you22 would expect for a scientific publication from 1985?23 A. So there's a quantity called an24 impact factor that takes into consideration the25 number of citations that a journal article has.

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1 Journals are ranked by the number of average2 citations an article has. I'm not familiar with3 what this journal's impact factor was in 1985.4 But I do know that 14 citations is on par5 with the average number of citations in the top6 journal in the cardiology field just in circulation.7 Q. Over the same period of time since8 1985?9 A. I was just saying now. I don't think10 they -- I don't know if there is historical data11 available.12 Q. I have a question about a statement13 you made in Paragraph 10 of your declaration.14 A. Okay.15 Q. It's under No. 3 in the list. It16 says after three, "Whatever calcification17 characteristics sheep exhibit for heart valves does18 not inform one on what to expect for blood vessels19 in dogs." Did I read that correctly?20 A. Yes.21 Q. And what did you mean by that22 statement?23 A. I meant that how a heart valve, an24 implanted heart valve, performs in sheep does not25 establish requirements for how materials must behave

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1 when implanted in dogs.2 Q. Well, your statement in the3 declaration doesn't refer to "requirements." It4 says that it does not inform one on what to expect5 for blood vessels in dogs.6 What does he mean by that?7 A. Well, it was my understanding of the8 term "expect" that the Patent Owner was using in9 their declaration expectation, meaning, if something10 didn't occur, then it wasn't reliable.11 Q. Well, if you had a situation where12 you had information about calcification13 characteristics for blood vessels implanted in dogs,14 would that inform one on what to expect for15 calcification of heart valves implanted in sheep?16 A. Certainly not a requirement, no.17 Q. I'm confused about why you're18 referring to "a requirement." I didn't ask you19 anything about "a requirement."20 A. Oh, well, when I think about21 expectation in just thinking about it the way that I22 interpret the Patent Owner using the term,23 expectation as, essentially, if X doesn't happen,24 then information is unreliable, meaning, X must25 happen or else something is wrong. I think an



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1 expectation to me refers to if you were to do the2 same study many, many times, you should get the same3 study, same sheep, whatever, usually get that4 average response.5 So I would say that blood vessel performance6 is a different experiment or different implantation7 cite, different material than a heart valve in a8 sheep. So you've got like three different9 conditions that are different in both those10 situations.11 Q. So getting back to the statement of12 your declaration. So are you saying if you had13 calcification data for sheep -- let me restate that.14 If you had calcification data for heart15 valves implanted in sheep, are you saying that that16 would not be predictive of what would be likely to17 occur for calcification of blood vessels implanted18 in dogs?19 MR. TESCHNER: Objection to form.20 A. What I was saying -- what I am saying21 is that that information does not give me an22 understanding of what the requirements for23 performance or how it should behave, statements like24 that, in a dog.25 Q. And, again, if you had information

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1 about blood vessels implanted in dogs, would that2 provide any useful information about what would be3 likely to occur for heart valves implanted in sheep4 as far as calcification?5 MR. TESCHNER: Excuse me. Could you6 read the question back.7 (Whereupon, the question is read back as8 follows:9 "Question: And, again, if you had10 information about blood vessels implanted in dogs,11 would that provide any useful information about what12 would be likely to occur for heart valves implanted13 in sheep as far as calcification?")14 A. I think it would provide useful15 information. I don't think it defines requirements16 of behavior. But I think you can learn something.17 Q. You're just saying that the different18 animal models might have differences in outcome; is19 that what you're saying?20 MR. TESCHNER: Objection to form.21 A. I would say that different animal22 models, different implantation sites -- I mean, I23 say right here, right underneath that sentence, I24 said, tissue implanted in a variety of animals25 including sheep and dogs are known at time to

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1 calcify at weeks rather than three to four months.2 But other places in my declaration I say there are a3 lot of animal models that are used, they calcify,4 you can learn information from all of them, but you5 can't necessarily take one set of information and6 make it sacrosanct for other scientific studies.7 Q. Okay. I'd like to direct your8 attention to Paragraph 36 of your declaration. And9 Paragraph 36 refers to the most significant findings10 from Kaplan; is that right?11 A. Yes.12 Q. And, in particular, Paragraph 3613 states in part, "The most significant findings from14 Kaplan are learned from head to head comparison of15 their glutaraldehyde fixed tissue exposed to either16 additional glutaraldehyde or 50 percent ethanol."17 Did I read that correctly?18 A. Yes.19 Q. The Kaplan article reports that20 vascular grafts stored in glutaraldehyde remain21 stable for seven months, correct?22 A. Let me find that specific place in23 the article, just so we're on the same page here.24 Q. Okay. And, from Paragraph 36, it25 looks like you're referring to Page 52?

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1 A. Yes.2 Q. And you further note in Paragraph 363 that Kaplan also reported at Page 52 that the grafts4 stored in 50 percent ethanol remain constant for up5 to two years of storage, right?6 A. Yes.7 Q. And, based on this difference, Kaplan8 concluded that storage in ethanol was more9 advantageous than storage in glutaraldehyde,10 correct?11 A. She didn't make that conclusion then.12 Q. Oh, she didn't?13 A. I don't think so.14 Q. I'd like to direct your attention to15 Page 52. It's the last paragraph in the first16 column.17 A. I'm just trying to find it, that's18 all.19 Q. I was trying to direct your attention20 to what I was looking at. Page 52, the last21 paragraph of the first column and then it continues22 onto the second column.23 A. Yes, I see that. Uh-huh.24 Q. And, just to put that in context,25 that's in the paragraph that starts, "The behavior



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1 of the grafts kept in 50 percent ethyl alcohol2 remain constant for up to two years of storage."3 And then it states, "Stability of the configuration4 and structure of the vessel wall and flow surface5 was confirmed by histological evaluation, which6 revealed no change in the SEM and TEM performance of7 the grafts after storage in alcohol. Comparison of8 grafts stored in alcohol and in .65 percent GA9 demonstrated that storage in ethyl alcohol was more10 advantageous than storage in GA."11 A. Yes.12 Q. Did I read that correctly?13 A. Yes.14 Q. So is it correct that Kaplan15 concluded that storage in ethanol was more16 advantageous than storage in GA based on the data17 from two years of storage in ethanol?18 A. Not only that information.19 Q. Because there's something else20 referred to in that paragraph that we discussed?21 A. There's more data that is taken into22 consideration about the performance of ethanol and23 glutaraldehyde. But, in this particular paragraph,24 she's referring to that data set.25 Q. The data set concerning two years of

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1 storage?2 A. Yes.3 Q. And those observations concerning two4 years of storage have nothing to do with5 calcification of tissue, right?6 A. These observations, no.7 Q. Right. These observations relate to8 un-implanted grafts, right?9 A. Right.10 Q. And Kaplan did not observe any11 calcification of un-implanted grafts that were12 stored for two years, right?13 A. Right.14 Q. And you would not expect that, right?15 A. No.16 Q. Calcification is associated with17 grafts that have --18 A. Have been implanted.19 Q. -- been implanted in animals, right,20 not just been stored?21 A. (No response.)22 Q. So determining that the grafts had23 storage for two years in ethanol does not provide24 any information about whether the grafts might25 calcify after being implanted in an animal, right?

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1 A. In my reading of this article, I2 think it led them to hypothesize that one of those3 two storage methods would be better.4 Q. But, at least, in the paragraph that5 we read --6 A. Yeah, up to that point they had not7 performed that experiment.8 MR. TESCHNER: Let him ask his9 question.10 THE WITNESS: I'm sorry.11 MR. TESCHNER: That's alright.12 Q. Okay. And then going onto Paragraph13 37 of your declaration, you state, "These results14 led them to hypothesize that 50 percent of the15 ethanol was the preferred medium to subject16 glutaraldehyde treated tissue for storage." Did I17 rad that correctly?18 A. Yes.19 Q. And by these results are you20 referring to the results that we just discussed, the21 results concerning two years of storage?22 A. Yes.23 Q. And you go onto say in your24 declaration that, "In test of this hypothesis with25 in vivo experimentation in dogs.

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1 A. Yes.2 Q. So that would be the first part of3 the experimentation in which there was a possibility4 of observing calcification after in vivo5 implantation, correct?6 A. This would be the best time that they7 could find calcification by in vivo implantation.8 Q. Okay. You wouldn't expect any9 calcification of preserved grafts before10 implantation in an animal, would you?11 A. I mean, maybe if there was something12 particular about the chemical environment because we13 do research all the time with particular14 pro-calcific biochemicals that one can put in a15 material and they can nucleate calcification under16 certain circumstances.17 Q. Okay. That wouldn't apply to a18 glutaraldehyde fixed tissue, would it?19 A. No, I don't think in this case that20 they had those in there.21 Q. And then at the end of Paragraph 3722 -- let me just read this into the record. I have a23 question about the last sentence. It says, "Their24 first series of short permanent (six-hour) in vivo25 implantation experiments found no difference between



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1 storage methods in terms of graft patentcy,2 biomechanical pulsatility (palpation of the vessel3 wall under flow), and tendency for coagulation."4 Did I read that correctly?5 A. Yes.6 Q. And then there's a citation, "see7 id.," referring to Kaplan at Page 52.8 A. Uh-huh.9 Q. Where does Kaplan refer to10 biomechanical pulsatility tests at Page 52?11 A. So there's a TFS score. I think that12 that's -- let's see. They have the methods that13 they utilized in -- let's see.14 Q. TSF refers to thrombus-free surface15 score?16 A. I'm looking at the information. I17 guess I'm talking before I should...18 MR. TESCHNER: Why don't you...19 A. Let me just...20 So, if you look at Page 49, where it talks21 about patentcy, it's defining patentcy, patentcy of22 the graft, so it's about the middle of the last23 paragraph above results in 49. "Patentcy of the24 graft was assessed by palpating the pulse proximally25 and distally and by noting blood flow through the

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1 graft after transecting the vessel distal to the2 prosthesis," and then, "the graphs were evaluated by3 thrombus-free surface scoring, which expresses the4 percentage of surface free from thrombus and5 histological examination," et cetera.6 Q. Okay.7 A. So that's what the patent meant.8 Q. So when Kaplan describes at Page 499 palpating the pulse proximally and distally, is that10 what you called biomechanical pulsatility testing?11 A. Yes.12 Q. Okay. Getting back to Page 52, where13 was there a reference on Page 52 to the14 biomechanical pulsatility testing?15 A. Oh, it's all wrapped up in the term16 patentness, as they defined it.17 Q. Okay. So reading on Page 52 the18 right-hand column, beginning of the first full19 paragraph, it's under the heading, "Biological20 evaluation of the prepared grafts, Kaplan states,21 the results of testing in acute six-hour controlled22 low flow studies demonstrated excellent patentcy23 rates of 100 percent and average TFS values of 8324 and 100 percent at 25 and 50 mils per minute25 respectively." Did I read that correctly?

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1 A. Yes.2 Q. And is that what you were referring3 to in Paragraph 37 as far as the testing of the4 six-hour in vivo experiments?5 A. Yes. So they have patentcy and then6 I said this biomechanical pulsatility and tendency7 for coagulation.8 Now, the patentcy that they define, okay,9 they have additional information that's gained in10 their methodology than what other people might use11 just to look at patentcy. So patentcy can be simply12 determined as, do I see flow coming out the other13 side that I push in. But when they actually are14 looking at pulsatility of this graft, the graft15 actually expands and contracts and palpating means16 you're actually squeezing the graft. So that is --17 that's actually a biomechanical readout of the way18 that that graft is expanding and contracting.19 Q. But isn't that what Kaplan refers to20 as excellent patentcy rates of over 100 percent?21 A. Yes.22 Q. Okay. Well, why in Paragraph 37 do23 you refer to graft patentcy and biomechanical24 pulsatility separately, aren't those both referring25 to the same test?

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1 A. Yes. But I think that this2 information, as she is generating, actually offers3 more than just simple patentcy -- simple blood flow4 information.5 Q. Okay. But, on Page 52, where you6 cite it, Kaplan, it just says excellent patentcy7 rates?8 A. Yeah, I'm using her definition but9 I'm trying to -- I was emphasizing that her10 particular definition included this, you know, more11 information.12 Q. And then as you state in Paragraph 3813 of your declaration, "Kaplan then described14 analyzing longer term implantation," correct?15 A. Uh-huh.16 Q. By "longer term" this refers to17 implants placed in dogs for 21, 56 and 112 days,18 right?19 A. Well, in Paragraph 38, I'm discussing20 the 3 week, the 21-day experiments.21 Q. Okay. Now, Table 3 -- I'm sorry,22 Table 2 on Page 53 --23 A. Yes.24 Q. -- Kaplan reports that 11 grafts were25 implanted for 21 days or 3 weeks, right?



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1 A. Yes.2 Q. Kaplan reports that 10 grafts were3 implanted for 56 days, right?4 A. Yes.5 Q. And Kaplan further reports that 56 grafts were implanted for 112 days, right?7 A. Yes.8 Q. And then referring back to Page 52,9 Kaplan reports that all 21, 56 and 112-day implants10 were 100 percent patent, right?11 A. Yes.12 Q. What does that mean?13 A. I think that when I read that, that14 means that just like they used their definition15 here, that they had -- where I read it, they had the16 same blood flows going through them. They had the17 similar biomechanical pulsatility, you know.18 Q. That there was unimpeded flow coming19 through the vessel; is that what it means?20 A. However they were defining it, yes.21 Q. And Kaplan further reports that TFS22 scores for all of the grafts were 98 to 100 percent.23 A. Uh-huh.24 Q. What does that mean?25 A. This was a thrombus-free surface

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1 scoring which expresses the percentage of surface2 free from thrombus. So there is a reference that3 they cite, Reference 10, that further defines it.4 My interpretation is that they just look at5 the entire surface area of the graft and they6 determine what percentage of it has thrombus.7 Q. And thrombus refers to blood clotting8 on the surface?9 A. Just adhesion of blood components.10 Q. And the patentcy and TFS scores are11 also reported in Table 2 on Page 53, right?12 A. Yes.13 Q. And then going back to Page 52,14 reading along in that paragraph, first full15 paragraph in the right-hand column, Kaplan discusses16 calcification and states, "Calcification was17 detected in some grafts stored in 0.65 percent GA18 following three weeks implantation in the canine19 experimental model." Did I read that correctly?20 A. Yes.21 Q. The statement about 3 weeks22 implantation refers to the 11 grafts implanted for23 21 days, right?24 A. Yes.25 Q. Of the 11 grafts implanted for

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1 21 days, how many were stored in glutaraldehyde?2 A. I don't know.3 Q. Why not?4 A. The authors didn't give that5 information.6 Q. It was some number of the 11 grafts,7 right?8 A. Some of the 11 grafts.9 Q. Could it be just one?10 A. No.11 Q. Could it be just two?12 A. Possible.13 Q. Could it be nine?14 A. Unlikely.15 Q. Nine is still some of eleven, right?16 A. No. I would consider some to be more17 than one but probably less than half.18 Q. Some is more than one and less than19 half?20 A. Yeah.21 Q. Is that the way you used the term22 "some" in scientific publications that you read?23 A. Yeah. If I was to use "some," that's24 what it would mean.25 Q. Of the 11 grafts implanted for

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1 21 days, how many were stored in ethanol?2 A. I don't know. It doesn't say. It3 just says that none of the ones that were, so this4 same kind of plural involved.5 Q. So there were also some grafts stored6 in ethanol?7 A. There are, at least, some stored in8 glutaraldehyde because all of the some calcified.9 The remainder of the some of that particular testing10 condition didn't calcify and then you have another11 group that are stored in ethyl alcohol, none of12 which calcified.13 Q. But you don't know how many were14 stored in ethyl alcohol?15 A. No.16 Q. Could it have been just one?17 A. No.18 Q. Just two?19 A. It's possible.20 Q. Possible just two in ethanol?21 A. I find it unlikely they would design22 a study where they put nine in one category and two23 in another.24 Q. Do you find it unlikely that they25 published an article that fails to state how many



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1 were still living in either condition?2 A. The article was peer reviewed.3 Q. If you were reviewing it, would you4 have questions about that?5 A. If it were me reviewing it, I would6 like to see more information.7 Q. Of the 11 grafts stored for 21 days8 -- I'm sorry, let me restate that.9 In the 11 grafts implanted for 21 days, how10 many were stored in glutaraldehyde and did not have11 any observable calcification?12 A. However many that weren't part of the13 some that did.14 Q. So some had calcification, some did15 not?16 A. Uh-huh.17 Q. Does the article report how18 calcification was detected?19 A. They used histopathological studies,20 like I said, as a broader analysis of lots of21 different things that they could have found.22 Q. And where does the article say that23 histopathological studies revealed calcification?24 A. Well, at the end -- or the first full25 paragraph, on the second column on Page 52, it says,

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1 "Histopathologic studies of the retrieved prosthesis2 that have been stored in 50 percent alcohol revealed3 neither calcification nor other untoward effects."4 And they further describe the pathological5 -- they use the second -- the paragraph after this6 they further describe the structural composition of7 the blood vessels.8 Q. But the next paragraph doesn't say9 about inspecting for calcification, does it?10 A. No. I think they were clarifying11 what the vessels actually looked like.12 Q. Well, let's see. The next paragraph13 refers to -- it says, "Histologically the patent14 grafts were shown to have," and it goes on.15 What does the "patent grafts" refer to?16 A. In my reading, it's referring to the17 grafts stored in 50 percent alcohol.18 Q. Okay. But Kaplan also reports that19 all the grafts were 100 patent.20 A. Yes, Kaplan refers to grafts as a21 hundred percent patent.22 Q. Table 2, all the 21-day grafts a23 hundred percent patent, all the 56-day grafts a24 hundred percent patent, all the 112-day grafts were25 a hundred percent patent?

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1 A. So, in my reading of the article,2 there is an experimental progression that Kaplan is3 moving through and describing results from, which I4 tried to more specifically delineate in my5 declaration.6 Q. I want to make sure I understand7 this.8 All the grafts were reported to be patent,9 but you think when Kaplan refers to the patent10 grafts, Kaplan really means only some of the patent11 grafts?12 A. I think she's referring to the grafts13 that she was describing right above in the previous14 sentence.15 Q. You think she's referring to just the16 grafts that were stored in ethanol?17 A. Yes.18 Q. Even though that paragraph doesn't19 say she was referring to the grafts stored in20 ethanol?21 A. Yes.22 Q. Do you think the patent grafts is the23 way to refer to grafts that were stored in ethanol?24 A. I would have used different words.25 Q. You think it's an ambiguous

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1 statement?2 A. It could be -- it could be seen as3 ambiguous.4 Q. Or it could be seen as unambiguous5 referring to all the grafts?6 A. I'm saying that one could interpret7 it -- I'm saying when I read it, I interpret it the8 way that I did. And you know...9 Q. Just above that, the sentence that10 says, "Histological pathologic studies of the11 retrieved prostheses that have been stored in 5012 percent ethanol revealed neither calcification nor13 other untoward effects." What does the "untoward14 effects" refer to?15 A. Like I said, in their methods, when16 they evaluate tissue histopathologically, there's a17 lot of different things that could have happened18 with the tissue. So listing all the possible things19 that could have happened would have probably taken a20 lot of words. So I think that they were, basically,21 saying here that -- no other untoward effects means22 any of the histopathological features that they23 would surmise could happen in such an experiment24 didn't happen, instead these valves -- excuse me,25 these grafts looked the way they did in the



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1 subsequent paragraph.2 Q. But you don't know how many vessels3 that refers to, right?4 A. Not for 21 days.5 Q. It refers to the vessels stored in6 50 percent alcohol?7 A. Yes.8 Q. We don't know how many vessels were9 stored in 50 percent alcohol?10 A. No, we don't.11 Q. Now, just above that sentence it12 says, "This phenomena was not seen in the vessels13 stored in ethyl alcohol." And by that Kaplan is14 saying calcification was not observed in the grafts15 seen in ethanol?16 A. Yes.17 Q. And then she repeats, "The18 histopathologic studies of the retrieved prosthesis19 stored in 50 percent ethanol revealed no20 calcification."21 A. Yes.22 Q. Why does Kaplan report two times that23 there were no calcification of the vessels stored in24 ethanol?25 A. I have no idea.

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1 Q. Wouldn't it have been better for2 Kaplan to report this one time than to state the3 number of vessels stored in ethanol?4 MR. TESCHNER: Objection to form.5 A. I would have written it differently.6 Q. Kaplan doesn't say anything about the7 calcification of the 56-day grafts, does it?8 A. It says something about the lack of9 calcification in these subsequent grafts.10 Q. And where do you see that reported?11 A. It's my understanding of their12 results that they -- once they found the information13 at three weeks, the subsequent experiments are14 conducted -- follow on to that for 56 and 112 days15 and none of those grafts have glutaraldehyde fixed16 tissue in them.17 Q. So your understanding is that after18 21 days Kaplan ceased doing any work with grafts19 that were stored in glutaraldehyde?20 A. Yes.21 Q. And how do you come to that22 conclusion?23 A. Because once they found the feature24 that the ethyl alcohol provided the lack of25 calcification, the subsequent experiments tried to

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1 test how long that performance or the preservation2 of that graft extends outward for.3 Q. But Kaplan doesn't say that anywhere?4 A. Well, they say -- she mentions that5 the preserved graft structure remained intact and6 stable and the preserved original endothelium still7 present after 112 days of implantation. That's all8 in that paragraph, the one after the 50 percent.9 Q. First, you're reading the preserved10 grafts to refer to preserved grafts that were stored11 in ethanol?12 A. Yeah. So, in the abstract, they say13 that the ethyl alcohol was chosen as a storage14 solution because it maintained the best physical15 chemical and histological characteristics of the16 grafts. And so my reading of that choice is at the17 end of this experiment and then the subsequent18 experiments are designed to see how far out that19 performance lasts.20 Q. Where does the abstract refer to21 calcification?22 A. The term is contained within the23 "maintain the best histological characteristics of24 the graft." If there was calcification, you25 wouldn't have a best characteristic.

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1 Q. If you observed it?2 A. What do you mean if I observed it?3 Q. If Kaplan says calcification was not4 detected in the graft stored in ethyl alcohol, she5 didn't say there was no calcification?6 A. Well, I mean, she used7 histopathological methods to determine if8 calcification among other things were there.9 Q. She didn't use it herself?10 A. Well, right, the team did, right,11 right.12 Q. Right. Because Dr. Kaplan couldn't13 really tell if the histological study revealed14 calcification, right?15 MR. TESCHNER: Objection,16 mischaracterizes the record.17 Q. She couldn't do that?18 A. I think she relied on other people to19 perform that assay.20 Q. But you don't know who she relied on?21 A. No. I imagine it's one of the team22 in her institute.23 Q. So you're reading on Page 5224 "preserved graft," you read that to read preserved25 grafts stored in ethanol?



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1 A. Uh-huh.2 Q. Even though all the grafts were3 preserved, whether they were stored in ethanol or4 not, right?5 A. Well, her -- their objective was to6 figure out the best preservation method, which7 included a whole bunch of other things in addition8 to glutaraldehyde fixation, all the way out to the9 best storage media. So that was their sum total10 preparation strategy. And that's why, I think --11 that's why when I read this, that sum total is what12 they were evaluating in these longer term13 implantation studies.14 Q. But the only detailed provided by15 Kaplan of the calcification was the calcification16 was detected in some of the 21-day grafts?17 A. Yes.18 Q. And, as far as ethanol, it could have19 just been two grafts that were stored in ethanol and20 did not have detectable calcification?21 A. Can you --22 Q. Isn't that what you said?23 MR. TESCHNER: Objection to form.24 Q. For the grafts stored in ethanol, you25 said there could have only been two?

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1 A. It may have been as few as two. But,2 if you have 11 grafts and you divide them, let's3 say, 6 in glutaraldehyde and 5 in ethanol, you have4 2 out of 6 that calcify in glutaraldehyde and 0 out5 of 5.6 Q. Right. It could be 6 and 5, it could7 be 7 and 4, it could be 8 and 3, you don't know,8 right, you don't know how they were split up between9 storage in ethanol and glutaraldehyde?10 MR. TESCHNER: Objection to form.11 A. I would say that just the presence of12 calcification detected in a set of samples is13 sufficient at the time to rule out a treatment in14 lots of literature. So if I was to see some in one15 treatment and none in another, I'm going to reject16 the some in favor of the none.17 Q. Based on two samples in micrograms18 you would reach that conclusion?19 MR. TESCHNER: Objection to form.20 A. I would probably want to follow on21 that information in -- you know, especially, if I22 was going to do this in valves, I would probably23 repeat the study in valves and test it out, you24 know, et cetera.25 Q. Are you aware of anyone repeating

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1 this study in valves or any other tissues?2 A. To determine -- well, isn't that what3 the Levy patent does?4 Q. Are you saying the Levy patent copied5 what was in this publication?6 A. I have no idea whether they copied7 it. I'm just saying if the Levy patent does the8 same test, meaning, exposes, you know, preserved9 grafts to ethanol and runs an experiment, it sounds10 like it would be consistent with evaluating that.11 Q. Well, that's not what I asked you,12 though.13 A. Okay.14 Q. If you were doing a scientific study15 that built on some other scientific research and did16 further testing, you would publish a paper and you17 would cite that earlier work, right?18 A. Yes.19 Q. Are you aware of anyone doing that20 ever with respect to Kaplan?21 A. Like I said, I didn't look at those22 other articles. So I don't recall anybody citing23 Kaplan and having done that work.24 Q. In your opinion, are you saying a25 person of ordinary skill in the art would understand

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1 that all the 56 and 112-day grafts were stored in2 ethanol?3 A. Yes.4 Q. So, of the 56 and 112-day studies,5 there were no grafts stored in glutaraldehyde?6 A. No.7 Q. Are you saying there was no controls8 used for those experiments?9 A. I would say at that point it turned10 into a time course study, meaning --11 Q. Are you saying there was no control12 used for the 56 and 112-day studies?13 A. No. I would say that the 3-week time14 point represented the baseline for which to compare15 against the 56 and 112.16 Q. So, in order to compare performance17 of ethanol stored grafts at 56 and 112-day studies,18 wouldn't it be an appropriate scientific approach to19 use grafts that were not stored in ethanol for20 comparison purposes?21 A. I would say with these animal model22 studies there's limited resources and so sometimes23 you have to kind of double dip with how you can24 utilize the animals to the most effect.25 Q. What do you mean by that?



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1 A. So an animal that serves as a2 comparison condition for one experiment could then3 be utilized as a control, the same data could be4 utilized as a control for another experiment.5 Q. In this case, you don't know how many6 controls there were for 21 days, just some?7 A. Well, the only number that we do know8 is that the some of the glutaraldehyde preserved9 grafts calcified but none of the ethanol. So I10 don't know.11 Q. So there were some grafts stored in12 glutaraldehyde, we don't know how many, and some13 subset of those calcified?14 A. Uh-huh.15 Q. We don't know how many?16 A. Right.17 Q. So maybe just one?18 A. Well, what we're talking about now,19 we're talking about the ethanol stored graft as the20 control for the time course of 56 and 112-day.21 Q. No. I was talking -- those are the22 experimental. That's what Kaplan you're saying was23 trying to demonstrate, that ethanol was effective as24 a storage medium for prohibiting calcification and25 there was no control because there was no comparison

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1 to glutaraldehyde stored grafts for the same time2 periods?3 MR. TESCHNER: Objection to form.4 A. So what I was saying was that there5 were two different experiments. There was the6 21-day side-by-side comparison and then there is a7 time course experiment that utilized new 56 and 1128 day data sets and the 3-week time point from the9 previous experiment.10 Q. And you think that's -- the11 three-week glutaraldehyde stored tissues of unknown12 number, you think that was an appropriate control13 for the 56 and 112-day studies?14 A. I would say that that -- that data15 set wasn't used in the time course study, but it was16 used in the side-by-side comparison. So it's saying17 it's sort of like a different data set.18 Q. But there was no side-by-side19 comparison of that data in this article, right?20 MR. TESCHNER: Objection to form.21 A. The three-week data is a side-by-side22 comparison. The 56 and 112 days did not do23 side-by-side comparisons. They did a time course.24 That was part of a time course.25 Q. And where is the time course

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1 reported?2 A. Well, it's reported in the fact that3 they took their experiments out to 56 and 112 days.4 So, I mean, that's my understanding of this5 information in that paragraph on 52 where they say6 that the structure was still present and still7 stable after 112 days of implantation.8 Q. If the dog model was a reliable model9 for calcification at 21 days, wouldn't all of the10 glutaraldehyde stored grafts have calcified in11 21 days?12 A. No.13 Q. Why not?14 A. All of them don't need to.15 Q. What do you mean they don't need to?16 A. Well, for different experimental17 studies, there's often situations where a number of18 the test samples calcify and a number of them don't.19 So I wouldn't -- I wouldn't expect that all of them20 would have to.21 Q. Why wouldn't you expect them all to22 calcify in the same time period?23 A. Because I think it's, you know, a24 statistical -- probably a statistical distribution.25 Q. You think you get different results

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1 from one animal to another?2 A. I guess I don't understand what you3 mean by that.4 Q. You test two animals of the same5 conditions and sometimes you get the same results?6 A. Now, we're talking about two7 different animals like two different species or what8 are we...9 Q. Well, Kaplan reported she used10 mongrel dogs, right?11 A. Yes.12 Q. So each experiment was performed on a13 different specimen of a dog?14 A. Yes, right, different specimen of the15 dog.16 Q. And would you expect some variation17 in the way one dog specimen would respond to another18 dog specimen?19 A. I suppose it's possible. A lot of20 people use a lot of different type of sheep, but21 they get the same responses.22 Q. And Kaplan doesn't report how many23 grafts calcified after 21 days, just some?24 A. Right, some of the grafts calcified25 in glutaraldehyde but none in ethanol.



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1 Q. These earlier calcification results2 in 21 days, could that have been a result of3 circumstances such as infection, thrombus or suture4 damage in the implants?5 A. No.6 Q. Do you think infection can cause7 calcification?8 A. Infection of a certain type in a9 valve leaflet has been known to be a site of10 calcification.11 Q. You think infection in an implanted12 vessel can cause calcification?13 A. I'm not aware of a study that14 reported that. I would say that an infection would15 be easily detectable histopathologically.16 Q. How about thrombus, couldn't that17 have caused earlier calcification?18 A. Well, these grafts didn't have19 thrombus. But I do think in valves --20 Q. I think Kaplan reported that there21 was no thrombus, did it?22 A. Well, this TSF value, that's the23 thrombus-free surface, I mean, we're talking about24 99.5, 99.0, and 98.0.25 Q. Those are the mean values, right?

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1 A. Sure.2 Q. An average?3 A. An average of 99.5 percent.4 Q. Some were higher, some were lower?5 A. Well, a hundred percent is the6 highest. So I can't --7 Q. Right. Like patentcy rate was a8 hundred percent. When it's a hundred percent,9 Kaplan knows how to write a hundred percent, right?10 A. Right.11 Q. But, for mean TSF score, there are12 less than 100 percent?13 A. Right.14 Q. Less than 100 percent means there was15 some thrombus present and observed, right?16 A. I don't know if it's actual -- so the17 way that they -- let me make sure that I understand18 exactly what they're referring to. Yeah, I would19 have to go back to look at the Reference 10 to20 determine that exclusively.21 But I would say that based on the way that22 they write it here, there's a potential for point23 whatever it is an average of .5 percent of the24 surface to have some sort of thrombus on it.25 Q. So there could have been a relatively

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1 small area of thrombus on some of these vessels, in2 fact, there must have been because the score was3 less than 100 percent?4 MR. TESCHNER: Objection to form.5 A. I don't know where they analyzed the6 histology versus the thrombus. But I do know when7 you process tissues for histology, very rarely, in8 fact, I can't remember certainly a time where I've9 done it that a surface-adhered thrombus would10 actually survive that whole process.11 Q. Survive what process? I don't know12 if I followed you.13 A. So, when you look at the surface of a14 blood vessel you just take out of an animal, it15 could have, you know, some amount of blood16 components on that surface area. But then when you17 process this for histological evaluation, you've got18 to go through a whole bunch of Xylene rinses and19 adding paraformaldehyde, et cetera. So if the20 thrombus was sufficient to have embedded21 calcification within it, I would think that it could22 survive the actual histology processing point so you23 could see it in the, you know, in the histology. I24 don't see how that happens, if it's just something25 floating around on the surface.

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1 Q. And where does Kaplan report that2 histology reports show that there was not a small3 amount of thrombus formation on that?4 A. I would characterize that as an5 untoward effect.6 Q. What if it was a small amount of7 thrombus, wouldn't that have been -- let me restate8 that.9 Couldn't there be a small amount of thrombus10 that promoted early calcification?11 A. I don't read this article as12 indicating that as possible. I mean, we're talking13 about .5 percent of the surface area. And they,14 specifically, state that there is no untoward15 effects.16 Q. Well, how about the grafts that were17 stored in ethanol, I mean, you're saying there were18 no untoward effects in the vessels stored in19 ethanol, but I don't think that Kaplan says that20 about the vessels stored in glutaraldehyde?21 A. They did detect calcification in the22 grafts stored.23 Q. Right. And the question is whether24 that calcification might have been associated with25 some of the thrombus in those vessels.



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1 A. So what I'm saying is that I find it2 difficult that surface thrombus would survive that3 process to then end up being detected by4 calcification, just my experience using histology.5 Q. But there was thrombus detected in6 the 21-day grafts?7 A. I know. But what I'm saying is that8 that process you open up the valve -- excuse me.9 You open up the blood vessel and you look at it10 right after you implant it on the dog and you see is11 there blood components still present and then you12 take it and process it histologically so --13 Q. Right. And some of those vessels14 were processed histologically and revealed15 calcification?16 A. Right.17 Q. And the question is, does Kaplan18 address the question of whether that calcification19 in the glutaraldehyde stored grafts might have been20 associated with thrombus?21 A. She does not, specifically, state22 that.23 Q. And isn't it possible that the24 calcification for the glutaraldehyde grafts of25 unknown number could have been associated with

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1 thrombus?2 A. In my opinion, I find it extremely3 unlikely given the amount of surface that's free and4 the nature of surface thrombus.5 Q. But it's possible?6 A. It's never happened when I've done7 it.8 Q. Have you ever done a calcification9 experiment on blood vessels implanted in dogs?10 A. No.11 MR. TESCHNER: Excuse me, counsel. I12 have to break. Would you give me two minutes13 literally?14 MR. WEINER: Sure.15 (Recess taken 2:22 to 2:27 p.m.)16 Q. Is it possible that the earlier17 calcification observed in the glutaraldehyde stored18 grafts was associated with suture damage to the19 tissue from the implants?20 A. No.21 Q. Why do you say that?22 A. Because they say that they discussed23 the perigraft region in the bottom of 52 and the top24 of Page 53.25 (There is a discussion off the record.)

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1 Q. "The perigraft of all prostheses2 appeared to be normal connective tissue with very3 mild cellular infiltration. There was no4 hyperplasia at the anastomosis." I'm not quite sure5 what that all means. Could you explain that?6 A. Yeah. So the anastomosis are the7 suture regions where the one vessel is attached to8 another.9 And the perigraft region refers to that10 section of tissue that is generally considered11 involved with that particular line. Actually, I12 don't know if the perigraft here refers to the13 midsection of the graft. I think they might be14 referring to the midsection there, whereas the15 anastomosis of what I said right there. It's hard16 -- well, it seems to be here or there but...17 Q. I'm confused because before you said18 the deep patent grafts refers to the ethanol stored19 grafts.20 A. Uh-huh.21 Q. And now you're saying in the same22 paragraph that this is not referring to just the23 ethanol stored grafts.24 A. No, I'm saying that this is25 consistent with being -- referring to the ethanol

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1 grafts.2 Q. Oh, okay. So the ethanol grafts3 showed that there was no suture damage; is that what4 you're saying by the anastomosis?5 A. I don't know if they're referring to6 any suture damage. I mean, there is lot of things7 that can happen at these anastomosis --8 Q. Well, my --9 A. -- that aren't suture related.10 Q. -- question is whether the11 calcification of the glutaraldehyde grafts could12 have been associated with suture damage?13 A. No.14 Q. And you said, no. And now I'm asking15 why and now you're referring to this discussion of16 the ethanol stored grafts.17 Where does Kaplan say there was no suture18 damage in the glutaraldehyde stored grafts?19 A. I don't think that they were20 discussing the glutaraldehyde in this particular21 circumstance.22 Q. Right. So where did Kaplan describe23 that the glutaraldehyde grafts had no suture damage,24 and, if not, maybe there was suture damage25 associated?



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1 A. I mean, that's not how I read it.2 Q. How did you read it?3 A. I read it --4 Q. Histologically the patent graft --5 does that whole paragraph refer to ethanol stored6 grafts?7 A. So, when I evaluate calcification of8 a material, I would look at the region that's most9 associated with the tissue and not whatever other10 potential attachment regions. You know, I would11 understand that, but I would know that, you know,12 there's other things going on like a suture, for13 instance.14 But so, for instance, when I read research15 that looks at blood vessels, blood vessel grafts,16 they will make comments about the attachment region,17 the anastomosis, and they will make comments about18 how the blood vessel performed usually in the19 midsection of the vessel.20 Q. And isn't there a risk of the21 anastomosis causing an increased presence of22 calcification in the region of the sutures?23 A. In the region of the sutures? I24 mean, I'm familiar with the possibility of25 inflammation and pannus overgrowth. Whether there

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1 is calcification that's there -- I mean, there is a2 lot of other things, right, there is the suture3 material itself, there are lots of different suture4 materials that may or may not calcify.5 Q. I asked more of a general question.6 Are you aware of the phenomena that suture7 damage can result in increased occurrence of8 calcification?9 A. What I'm saying is that I am aware10 that the different suture materials themselves can11 be a contributor to calcification in a region.12 Q. And this article says nothing at all13 about the materials used for suturing, right?14 A. It did say that they used a -- they15 put in a six-centimeter graft and it was interposed16 end to end with a running 70 or 80 prolene suture.17 Q. And what does that tell you about the18 calcification caused by the suturing?19 A. I don't know enough about prolene to20 make a conclusion about that.21 Q. But you know in some cases sutures22 can cause calcification?23 A. I know some materials can. I don't24 know -- I don't remember if prolene was one of them.25 Q. And your interpretation of this

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1 paragraph that refers to the patent grafts, you're2 saying the entire paragraph refers to just the3 ethanol stored grafts?4 A. I am referring to the histological5 description here as referring to the ethanol stored6 grafts.7 Q. "Histologically the patent grafts8 were shown to have only 1 to 2 millimeters of very9 thin smooth pannus that extended from the host10 carotid to cover the suture line." So that refers11 to ethanol stored grafts, right?12 A. Yes.13 Q. "These graft surfaces were extremely14 clean." Does that refer to the ethanol stored15 grafts or to all graft surfaces?16 A. I'm saying that this information17 which is referring to the follow on experimentation,18 there were only ethanol grafts being done.19 Q. That's your assumption, even though20 that's not reported anywhere?21 A. That's how I read it.22 Q. Right. So the question is the23 sentence that begins, "The graft surfaces," what24 grafts does that refer to?25 A. I'm saying that's referring to the

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1 grafts that were part of this time course study.2 Q. You mean the 21-day grafts are3 included?4 A. I'm referring to the ethanol treated5 grafts at 56 and 112 days but, as part of that time6 course, the 21 days was the first observation.7 Q. Let me get this straight.8 "The patent grafts," that refers to the9 ethanol stored grafts that were implanted for 56 and10 112 days, or does it mean something else?11 A. It refers to -- these -- this12 sentence -- this, you know, region of text we're13 talking about refers to the 50 percent alcohol14 stored prostheses as stated in the sentence above15 it.16 Q. Well, the last sentence of the17 paragraph above it says, "Histopathologic studies of18 the retrieved prostheses that have been stored at 5019 percent alcohol revealed neither calcification or20 other untoward effects."21 A. Yes.22 Q. So Kaplan, certainly, is capable of23 identifying grafts that were stored in 50 percent24 ethanol using understandable language, right?25 A. Uh-huh.



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1 Q. But the next paragraph you're saying2 instead of indicating whether they were stored in3 ethanol, Kaplan refers to those grafts stored in4 ethanol by saying "the patent grafts"?5 A. Yes. She was referring to the6 50 percent alcohol.7 Q. Right. Even though all grafts were8 patent whether stored in ethanol or glutaraldehyde,9 correct?10 A. Well, at these time points, all11 grafts were ethanol grafts.12 Q. Right. At all time points examined13 by Kaplan, all grafts were patent as reported in14 Table 2, 21, 56, 112-day grafts all had a patentcy15 rate of 100 percent?16 A. Yes.17 Q. Now, you're saying the paragraph that18 begins, "Histologically, the patent grafts," I19 thought you said that referred to the whole time20 period, 21, 56 and 112 days?21 A. Well, I'm saying they're referring to22 the 50 percent alcohol grafts.23 Q. Okay. So "the patent grafts" means24 the 50 percent ethanol grafts whether stored for 21,25 56 or 112 days?

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1 A. Yes.2 Q. And "the patent grafts" excludes the3 patent grafts that were stored in ethanol -- let me4 rephrase.5 "The patent grafts" excludes the patent6 grafts that were stored in glutaraldehyde, that's7 how you interpret it?8 A. I think they're here describing the9 alcohol stored grafts.10 Q. Right. Even though the word alcohol11 does not appear in that sentence or in this12 paragraph?13 MR. TESCHNER: Objection to form.14 A. I'm just going off of the previous15 sentence.16 Q. The previous sentence says,17 "ethanol," in the previous paragraph, but the next18 paragraph doesn't say ethanol even once, right?19 A. I don't see the word ethanol in that20 paragraph.21 Q. It's not there. But "the patent22 grafts" means the patent grafts stored in ethanol?23 A. Yes.24 Q. And then the next sentence in that25 paragraph says, "The graft surfaces." And you're

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1 saying "the graft surfaces" refers to the graft2 surfaces of the grafts stored in ethanol?3 A. Yes.4 Q. And the next sentence says, "The5 preserved graft structure," refers only to the6 structure of the preserved grafts that were stored7 in ethanol, right?8 A. Yes.9 Q. It doesn't refer to the preserved10 grafts that were stored in glutaraldehyde?11 A. No.12 Q. You're reading a lot of information13 into this paragraph, aren't you?14 MR. TESCHNER: Objection.15 A. This is how I interpret their16 experiments based on reading the paper. So the sum17 total of the results as they're being presented to18 me lead to that progression.19 Q. And then the paragraph goes onto say,20 "The preserved graft structure including the21 internal elastic lamina, a muscular layer and the22 collagenous fibrous adventitia remained intact and23 appeared to be stable." Did I read that correctly?24 A. Yes.25 Q. And, as stated in Paragraph 41 of

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1 your declaration, is it your position that this2 statement means that there was no calcification of3 the 56 and 112-day implants?4 A. I said that this description -- this5 result would be incompatible with the presence of6 calcification.7 Q. So Kaplan does not state whether the8 56 or 112-day implants were evaluated for9 calcification, does she -- I'm sorry, do the10 authors?11 MR. TESCHNER: Objection to form.12 Q. Let me restate that.13 Kaplan does not state whether the 56 or14 112-day implants were evaluated for calcification,15 right?16 A. She states what they look like and17 what they look like cannot look like that if there's18 calcification present.19 Q. Is it possible that there's some20 amount of calcification present and the tissue would21 still maintain stable internal elastic lamina,22 muscular layer and collagenous fibrous adventitia?23 A. Not at the level that they're24 analyzing.25 Q. What level are they analyzing?



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1 A. The histopathological level.2 Q. In a paper that reports3 histopathological analysis, wouldn't you expect some4 photographs or other information about the results?5 MR. TESCHNER: Objection to form.6 A. If it were me writing this article, I7 would probably show a picture.8 Q. Do you think this level of detail is9 appropriate for a scientific publication?10 A. Which level, the level of Kaplan?11 Q. The level of Kaplan.12 A. Yes, certainly at the time.13 Q. In 1985 you think there was a level14 of detail used for reporting histopathological15 reports?16 A. I would say now there is a different17 level required.18 Q. But, in articles from this time in19 the '80's or say October 1993, you wouldn't find20 quite a bit more detail in histopathological results21 that were reported?22 MR. TESCHNER: Objection to form.23 A. I think that you would find articles24 that have more information in some regions than25 others, but they would all inform on those different

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1 region areas.2 Q. But this is not the type of approach3 you would use in articles that you were writing?4 MR. TESCHNER: Objection to form.5 A. The articles that I write have -- you6 know, with this digital age now, we have7 supplemental methods and results where you have the8 ability to incorporate, in fact, much more data than9 was actually even presented in the article itself.10 I have published papers where my supplemental11 results are two and three times the length of the12 actual article.13 Q. Wouldn't it have been easier to say,14 no calcification was observed, instead of saying15 that the tissue maintained stable internal elastic16 lamina, muscular layer and collagenous fibrous17 adventitia?18 A. I mean, I don't presume to know why19 they wrote it the way they did. I do know that20 articles at the time had significant figure and word21 count limitations, so...22 Q. So you think Kaplan didn't mention23 the calcification was tested because of a word count24 limitation?25 A. No. I'm not saying that.

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1 Q. Isn't that what you just said?2 MR. TESCHNER: Objection.3 A. I'm saying that I don't know why she4 didn't say what she said. I don't know why she said5 it the way she did.6 Q. This thing is pretty short. Was it7 like three pages of text?8 MR. TESCHNER: Objection to form.9 A. Science articles are typically three10 pages.11 Q. Yeah. So you don't know why Kaplan12 wouldn't have simply stated no calcification had13 been observed, if that was simply the case?14 A. I think she thought that was15 sufficient.16 Q. "Sufficient" for what purpose?17 A. Peer review.18 Q. Paragraph 43 of your declaration, you19 state in part, "The primary feature of calcification20 that informs clinical decisions is its presence or21 absence."22 By "clinical decisions" do you mean23 decisions concerning treatment of human patients?24 A. Yes, the presence of calcification is25 a primary feature that informs a clinical decision.

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1 Q. And by "clinical decision" do you2 mean decisions concerning treatment of human3 patients?4 A. I think it includes human patients.5 I do think also in animal models that are intended6 to be a surrogate for human implantation that7 presence or absence is also important.8 Q. So by clinical decisions do you mean9 decisions concerning treatment of human or animal10 patients?11 A. Well, I don't mean animal patients in12 the sense of actually, you know, restoring some13 sheep with valve disease. I mean an animal model14 that is intended to be, you know, the final step15 before human implantation, is trying to be as human16 as possible. That, you know, for instance, for like17 FDA approval, the presence or absence of18 calcification will be the primary feature that19 informs the decision.20 Q. If you were testing an21 anti-calcification treatment and animal testing did22 not show clinical failure at 21 days, would you23 consider the treatment to be effective?24 A. What do you mean by "effective?"25 Q. Well, what do you understand to be



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1 the meaning of an effective anti-calcification2 treatment?3 MR. TESCHNER: Object as to form.4 Objection to form.5 A. So I would say that that information6 would be encouraging to repeat in a follow-on study7 with an animal or, you know, in the valve that I8 want or whatever the material that I want. In an9 animal model that -- certainly, I can't use it in10 patients unless I follow FDA approval requirements.11 So I would have to go through that method.12 Q. So, if you had results from 21 days,13 you would think that further testing was required?14 A. Certainly, before implanting in15 humans.16 Q. And, even before deciding whether it17 was worth pursuing additional research so that you18 could implant it in humans, you would want to do19 additional testing after 21 days, right?20 A. So, if I saw this paper, I would say,21 I'm going to repeat this in valves because this is a22 blood vessel and I want to make sure that the23 teaching here will work for my particular valve.24 Q. Right. But, to your knowledge, no25 one ever did that with respect to Kaplan's paper,

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1 right?2 A. The only thing that I've ever come3 across so far is the material presented in the 7754 Patent.5 Q. And, in the course of your work and6 your studies, you never came across any studies or7 reports of work at which somebody did follow-up8 research concerning the results reported in Kaplan?9 A. Meaning, testing ethanol as --10 Q. Yes.11 A. I am not aware of anything.12 Q. And you checked Google Scholar and13 you didn't find any articles that found any of that14 type of --15 A. Well, I found 14 articles, but I16 didn't look at them.17 Q. Okay. And, if you were doing18 research and you had some results after 21 days, you19 said you would do some follow-up studies maybe in a20 valve?21 A. Uh-huh.22 Q. Would you use controls for those23 studies?24 A. Yes.25 Q. By "controls," meaning, some animals

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1 tested without the anti-calcification treatment that2 was being tested and some with?3 A. It depends. If I was running a time4 course study and I wanted to see how long the5 treatment would last, I would use multiple time6 points of explantation and look at the trend and see7 how that material performed.8 Q. Are clinical complications for a9 patient more likely to occur in an implanted10 bioprosthetic device if there is more calcification11 rather than less?12 MR. TESCHNER: Objection to form.13 A. I mean, it really depends on where it14 is.15 Q. For the same location.16 A. The same location? I mean, so there17 could be two locations that have more and less that18 are still not serious enough to say explant and, you19 know, replace the tissue. But there could be a20 small amount in a different location that would be,21 you know, of more concern. So I don't know how to22 answer that question.23 Q. You said before there was a normal24 amount of calcium that could be present in healthy25 tissue, right?

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1 A. Yeah, there's calcium flowing around2 everywhere.3 Q. That's not the same as calcification?4 A. No.5 Q. Is it possible to have a small degree6 of calcification in an implanted device that would7 not result in any clinical problems for a patient?8 MR. TESCHNER: Objection, outside the9 scope.10 A. I don't want to speculate per se. I11 will say that clinicians can find calcification in12 natural valves and bioprosthetic valves and, you13 know, I don't know what makes -- I don't know what14 their decision making process is.15 Q. But, in a human patient, you would16 never test for the amount of calcification in the17 valve unless there was a failure, right?18 A. You could try to --19 MR. TESCHNER: Objection, outside the20 scope.21 Just wait for me to make an objection. Go22 ahead.23 A. I mean, you could try to evaluate it24 noninvasively, but you would have to ultimately25 remove the tissue to try to see if there's



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1 calcification there.2 Q. Which most patients wouldn't3 appreciate that if they had a heart beating with a4 valve implanted in it, right?5 A. Right.6 Q. Page 46 of your declaration, you7 refer --8 A. You mean paragraph?9 Q. Yeah, Paragraph 46, at the end of10 that paragraph you refer to, quote, "The undeniable11 fact that calcification was reported by Kaplan."12 Did I read that correctly?13 A. Yes.14 Q. Do you agree that it is an undeniable15 fact that Kaplan did not report whether16 calcification was observed for 56-day implants?17 MR. TESCHNER: Objection to form.18 A. There was a lot of negatives in19 there. I'm trying to understand. Can you repeat20 that?21 Q. Do you agree that it is an undeniable22 fact that Kaplan did not report whether23 calcification was observed for 56-day implants?24 MR. TESCHNER: Same objection.25 A. My reading of the article is that

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1 that information was conveyed. I did not see the2 specific sentence that you just referred to.3 Q. In your opinion, it was implied but4 it was not stated?5 A. I mean --6 MR. TESCHNER: Objection to form.7 A. I guess I don't know what you mean by8 "implied." I mean, that the information -- yeah, I9 mean, the information gives you that conclusion,10 whether or not they state it using the specific11 words you just indicated.12 Q. Okay. I did not ask about "the13 specific words."14 But Kaplan does not expressly state anywhere15 whether calcification was observed for 56-day16 implants?17 MR. TESCHNER: Objection to form and18 asked and answered.19 A. What I see is that the20 histopathological structure is preserved and it's21 incompatible with the presence of calcification.22 Q. Do you agree that it is an undeniable23 fact that Kaplan reported that some glutaraldehyde24 stored implants had calcification?25 A. She reported that some of the grafts

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1 stored in glutaraldehyde calcified after three2 weeks.3 Q. And some did not?4 A. The rest did not.5 Q. Kaplan does not state that 50 percent6 ethanol prevents calcification, does it?7 A. She said retrieved prosthesis that8 stored in 50 percent alcohol revealed neither9 calcification nor other untoward effects.10 Q. Kaplan does not report that ethanol11 has any anti-calcification effect, does it?12 A. I mean, when I read that, that's what13 I conclude, that it does.14 Q. Would you expect that early15 calcification at 21 days would be consistent among16 the tested animals?17 A. The tested animals? Which tested18 animals?19 Q. Kaplan tested dogs, right?20 A. Uh-huh.21 Q. Would you expect that early22 calcification at 21 days would be consistent among23 the tested animals?24 MR. TESCHNER: Objection to form.25 A. Do you mean its presence, the type,

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1 the size? I mean, I don't know what you mean.2 Q. Kaplan reported that calcification3 was detected in some grafts stored in4 glutaraldehyde?5 A. Yes. So I think that she was6 focusing on its presence. I don't know whether7 there was more or less. It just exceeded the8 threshold.9 Q. But only for some of the animals with10 vessels stored in glutaraldehyde?11 A. Yes, some of the glutaraldehyde12 treated animals.13 Q. If you were running a calcification14 study, wouldn't you run the study long enough to15 obtain consistent results?16 A. I mean, I think her three-week data17 is long enough to determine that finding. I think18 if it were me, I would follow this up with19 additional study, like I said, four valves. And, if20 I was trying to save my money knowing what the FDA21 requires, I would use juvenile sheep.22 Q. Based on calcification of immobile23 small diameter vascular grafts in dogs, does this24 provide any information about how other types of25 tissues might be expected to calcify?



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1 MR. TESCHNER: Could you read that2 back please.3 (Whereupon, the question is read back as4 follows:5 "Question: Based on calcification of6 immobile small diameter vascular grafts in dogs,7 does this provide any information about how other8 types of tissues might be expected to calcify?")9 MR. TESCHNER: Objection to form.10 A. When you say tissues and calcify, do11 you mean the same blood vessel material, or are you12 saying different tissues used as blood vessels? I13 know which --14 Q. I mean, other types of tissues,15 generally, not the same tissue, not the same blood16 vessels, not carotid arteries from dogs.17 A. So you're saying anything like18 skin --19 Q. It doesn't provide any information20 about how other types of tissues might be expected21 to calcify?22 A. I mean, I wouldn't use the term23 "expected" again. But I would say that it does24 provide information.25 Q. Predictive information?

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1 A. It tells me enough to say that if I2 was interested in preventing calcification, this is3 an experiment worth doing.4 Q. So on Paragraph 23 --5 A. This is my declaration?6 Q. -- of your declaration, you refer to7 Shemin 1988 and Hoffman 1993 and you state, "Both8 articles test the calcification of bioprosthetic9 valves in juvenile sheep, which offers no10 authoritative requirements for the calcification11 response of an immobile small diameter vascular12 graft in dogs."13 A. Right.14 Q. What do you mean by "authoritative15 requirements"?16 A. What I mean is they don't identify17 what must happen in some other experimental18 condition for it to be scientifically useful.19 Q. You don't think the information is20 scientifically useful for any purpose?21 A. Repeat that.22 Q. Are you saying that the information23 is not scientifically useful for any purpose?24 A. You mean the data in Shemin and25 Hoffman?

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1 Q. Yes.2 A. No, I think Shemin and Hoffman are3 scientifically useful, absolutely.4 Q. But just not for predicting what5 might happen with small immobile vessels implanted6 in dogs?7 A. So I think there is a difference8 between offering insight and mandating an9 authoritative requirement.10 Q. I'm still kind of puzzled to your11 reference to "authoritative requirements." I mean,12 what is that referring to?13 A. It refers back to the Patent Owner's14 use of the word standard and expect. I mean, I was15 trying to be more clear with, at least, my16 interpretation of those terms. So saying that17 something must happen or I throw it out is very18 different than saying, in this system the average19 response should look like this, you know, those are20 two different things.21 Q. Referring back to the Kaplan article22 in the discussion section that's from Pages 53 to23 54, Kaplan does not mention anything about24 calcification in this section, does it?25 MR. TESCHNER: Take time to review

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1 it, if you need.2 A. Okay. So I've reviewed the3 discussion again. And your question was what?4 Sorry.5 MR. WEINER: Can you read that back.6 (Whereupon, the question is read back as7 follows:8 "Question: Referring back to the Kaplan9 article in the discussion section that's from Pages10 53 to 54, Kaplan does not mention anything about11 calcification in this section, does it?")12 A. I mean, like I said before with the13 discussion section, often you're extending the14 results or extending the finding into what, you15 know, should happen next or what -- how this study16 impacts the area. I mean, they did talk about the17 canine carotid arteries, this is in -- near18 two-thirds of the way down on the left column. It19 says, canine carotid arteries --20 Q. Which page are you on?21 A. 53. "Canine carotid arteries22 preserved by the described method possess good23 handling and suture properties, do not require24 preclotting and have a flow surface that resembles25 the norm in smoothness," yada, yada, yada.



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1 MR. TESCHNER: Slow down.2 A. I mean, the idea is that they are3 discussing the, you know, the sum total of their4 preparation approach that they derive in this5 article, which includes everything from the initial6 anesthetization procedure all the way to the storage7 media.8 Q. There is nothing about calcification?9 A. Well, in their results, they said10 that this method doesn't calcify.11 Q. I'm talking about the discussion12 section.13 A. Oh.14 Q. Didn't you say that the discussion15 section has information about areas for further16 research, what would happen next?17 A. Yeah, that's something that you can18 add in or you mention in discussion.19 Q. Is that something that's generally20 included in the discussion; isn't that what you21 said?22 MR. TESCHNER: Objection to form. It23 mischaracterizes the prior testimony.24 A. I think I said that in the discussion25 section you extend your findings, you elaborate on

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1 what one can do next.2 Q. Right. And the discussion of Kaplan3 concerning what one could do next, there is no4 mention of calcification, there is no suggestion of5 any further experiments on calcification?6 A. I mean, they discuss continuing this7 in longer term work.8 Q. Well, if I missed something, please9 point it out.10 Where does the discussion section mention11 calcification or refer to a suggestion that you12 continue studies concerning calcification?13 A. Does it need to? I don't know --14 Q. I'm asking you whether it does.15 Whether it needs to or not is a different question.16 MR. TESCHNER: Objection to form.17 A. There are a lot of different18 directions that one could take and a limited amount19 of space. So I don't know why they chose what20 directions that they did choose.21 Q. You think the discussion was limited22 to two columns only, you don't think Kaplan ran out23 of space?24 A. No, I think the whole document is25 limited by space. I mean, most of the document is

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1 results.2 Q. And you think Kaplan would have3 reported more on calcification but they ran out of4 space?5 A. No, I don't think so. I don't know6 why they didn't talk about it.7 Q. I don't know why you didn't mention8 it if you don't think it had anything to do with it.9 A. All I'm saying is there's a lot of10 different directions and lot of different ways11 because there are so many different things that they12 did in this paper. Evaluating -- you know, all the13 way from, like I said, how to anesthetize, what14 levels of time to cross link the tissue. I mean,15 there's a lot of different things to talk about. So16 I don't know -- I don't know which of those things17 should have been, you know, or which ones were more18 important.19 Q. But you agree that calcification is20 not mentioned anywhere in the discussion?21 A. The word calcification is not in the22 discussion.23 Q. Is there any reference to24 calcification using any other language in the25 discussion?

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1 A. I think that they reference the2 performance of their arteries in the discussion and3 expound upon the value of that performance.4 Q. And are you referring to just the5 portion of the paragraph that you referred to before6 beginning, "Canine carotid arteries preserved by the7 described method possessed good handling and8 suturing properties"?9 A. Well, there's that and there's also10 the -- the stabilization, the enhanced stabilization11 conditions. So this is in the second or the first12 full paragraph of 53.13 Q. Okay. Well, let's take this one step14 at a time.15 So, first, in the left column on 53, it16 says, "Canine carotid arteries preserved by the17 described method possess good handling and suturing18 properties, do not require preclotting, have a flow19 surface that resembles the norm in smoothness, can20 be obtained in adequate length, can be sized to the21 desired 4 millimeter diameter and curved to shape22 and possess a wall thickness that is relatively23 close to that of the target coronary vessels."24 I see a lot of information there, but I25 don't see any information about calcification.



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1 A. So their preservation method that2 they present in this establishes a lot, a lot more3 than just a calcification or a limited -- a reduced4 amount of calcification. There is the ability to5 preserve wall geometry. There is ability to resist6 tissue degradation. There is preservation of7 internal tissue structures. There is a lot in8 there.9 Q. Calcification was not a focus of the10 research, would you agree with that?11 A. I don't know if when they started out12 designing or started out they knew what they were13 going to find in their animal implantation studies.14 Q. Aside from this portion of the15 discussion, where else do you think there is some16 reference to calcification in the discussion17 section?18 MR. TESCHNER: Objection to form.19 A. I am focusing my analysis of the20 discussion on the performance of their preservation21 method, which includes this ethanol storage step or22 exposure step, as well as all of the other things23 that they had subjected this tissue to.24 So, in that first full paragraph on Page 53,25 they talk about how their preservation method -- so

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1 -- maintains stabilization and it says, "In our2 experiments, this stabilized condition remains3 constant at about two years of grafts stored in4 50 percent alcohol."5 Q. Okay. And that statement has nothing6 to do with calcification, correct?7 A. That particular statement does not8 mention calcification.9 Q. Right. It doesn't mention it has10 anything to do with calcification?11 A. Right.12 Q. It has to do with storage for two13 years on un-implanted tissue?14 A. Yes.15 Q. I asked you where is calcification.16 Why are you pointing out that has nothing to do with17 calcification?18 MR. TESCHNER: Objection to form and19 don't badger the witness.20 A. I'm saying that I'm referring -- so21 because they did so many different things in22 addition to finding that their method doesn't result23 in calcification. They're discussing all of those24 different features.25 Q. Okay. Maybe my question was unclear.

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1 I'm not asking you about everything else they did.2 I'm asking you where is calcification mentioned in3 the discussion. It's not the sentence that you4 referred to before, "In our experiment, the5 stabilized condition remained constant at about two6 years for grafts stored in 50 percent ethyl7 alcohol."8 Do you agree that has zero to do with9 calcification?10 A. That particular statement doesn't11 have -- is not a value of calcification.12 Q. Has nothing to do with calcification?13 A. Yes.14 Q. Okay. Where in the discussion is15 there something that does relate to calcification?16 A. I mean, it's just part of the process17 for optimizing prosthesis for small vessel use.18 Q. Do you have a particular language19 that you are referring to?20 A. I mean that's in the first sentence21 of their discussion.22 Q. Okay. That says, "Many types of23 graft material have been investigated in an attempt24 to develop the optimal prosthesis for small vessel25 use."

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1 A. Right.2 Q. So does that tell you anything about3 ethanol having an anti-calcification effect?4 A. No.5 Q. Okay. Where is there something in6 the discussion section that has information about7 ethanol having an anti-calcification effect?8 A. They don't use that language.9 Q. They don't use the word -- well, you10 referred to -- we referred to 50 percent ethanol in11 connection with storage, so there is a reference to12 ethyl alcohol.13 Is there any other reference to ethyl14 alcohol concerning calcification?15 A. I would say in the end of the last16 sentence where they're talking about their17 preservation, it says -- I mean, but this processing18 technique includes the ethanol storage, so...19 Q. You're referring to Page 54. What20 language?21 A. Yeah. So the last sentence says,22 "The excellent physical properties and low23 thrombogenicity of the GA process canine carotid24 artery make it a potentially worthy xenograph backup25 for the autogenous saphenous vein in aortocoronary



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1 bypass, if our continuing work shows it to have2 long-term durability and an acceptable level of3 antigenicity."4 So my interpretation of that first sentence5 and the last sentence says that the features that6 are important for use in a small vessel graft, their7 data establishes that this is a promising approach8 that they will continue in long-term studies.9 Q. Promising approach for many reasons10 but among the reasons cited is not calcification?11 A. They don't use that text, no. I'm12 not trying to say therefore there's something in13 there. I understand --14 Q. Is there something in there or not?15 That's the question. Is there something in there or16 not concerning calcification?17 A. So my interpretation of the18 discussion when they refer to their processing and19 techniques includes the sum total of the things they20 were doing, in addition to the ethanol processing.21 The fact that they don't discuss the impact of the22 calcification results in the discussion does not23 negate the calcification results occurred.24 Q. What about the abstract, does the25 abstract say anything about calcification?

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1 A. The -- it does in the sense that the2 ethanol alcohol -- there is a sentence -- that's the3 second sentence from the end. "Ethyl alcohol was4 chosen as the storage solution because it maintained5 the best physical chemical and histological6 characteristics of the graft."7 So when I see that point, if I were to read8 on in the article, that would include calcification.9 Q. You're not aware of any follow-up10 studies performed by the Hope Heart Institute or11 other researchers concerning Kaplan's observations12 regarding the use of ethanol for storage of tissue?13 A. No.14 Q. Why don't you think those studies15 ever occurred?16 A. I mean, I have no idea.17 Q. Calcification of glutaraldehyde18 pretreated tissue is a significant problem, right?19 A. Uh-huh.20 Q. And at the time that the Kaplan21 article was published, there was a need for an22 anti-calcification method, right?23 A. Yes.24 MR. TESCHNER: Objection, outside the25 scope.

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1 A. Oh.2 Q. In your view, did Kaplan make an3 important discovery regarding the use of ethanol?4 A. I don't know what "discovery" means.5 Is that a legal term, are we talking about patent6 legal term or are we talking science because7 science, yes.8 Q. I was just using it in sort of its9 ordinary use.10 A. Oh, I don't know. I think, yes, they11 made a discovery of an effect of ethanol.12 Q. And you think this was an important13 discovery?14 A. It seems to be.15 Q. And this was reported in a reputable16 scientific journal?17 A. Yes.18 Q. Does the fact that there were no19 follow-up studies mean that others in the field may20 not have viewed Kaplan the same way that you are now21 reading Kaplan?22 A. No, it means that I don't know if23 there were follow-up studies done.24 Q. You think it's possible there were25 follow-up studies that you haven't been told about?

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1 A. Haven't been told about?2 Q. That you weren't aware of. You know3 there were no follow-up studies, right?4 MR. TESCHNER: Objection to form.5 A. I don't know, honestly. Like I said,6 I didn't look at the other 14 articles and what they7 had in them.8 Q. Okay. I have a question for you9 about Paragraph 35 of your declaration.10 A. Alright.11 Q. Okay. And I'm referring to the12 second part of it that goes onto Page 19.13 A. Okay.14 Q. And let me just read this into the15 record. Your declaration states, "Unless ethanol16 exerted an influence, it should have calcified at17 the same rate as the GA pretreated tissue stored in18 the additional GA." Did I read that correctly?19 A. Yes.20 Q. And you were referring to the21 glutaraldehyde stored tissue compared to the ethanol22 stored tissues that Kaplan tested, right?23 A. Yes.24 Q. What is the same rate of25 calcification that you're referring to?



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1 A. Well, in this context, I was2 referring to the fact that they identified its3 presence at three weeks implantation.4 Q. Kaplan does not report any rate of5 calcification, does it?6 A. No. I -- that's what I meant, I take7 that to mean in this case.8 Q. I don't really follow that.9 What does rate of calcification mean? Same10 rate, what does that mean?11 A. It means, in this case, the time at12 which I explant the tissue from the time I implant13 the tissue.14 Q. 21 days?15 A. In this case, yes.16 Q. And you say, "Unless ethanol exerted17 an influence, it should have also calcified after18 21 days"; is that what you mean?19 A. If ethanol had no effect, the grafts20 that were stored in ethanol should have also21 calcified at 21 days.22 Q. And Kaplan does not report how many23 grafts were stored in ethanol?24 A. No.25 Q. Kaplan does not report how many

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1 grafts were stored in glutaraldehyde?2 A. Well, there is, at least, plurals of3 both of those and some for the glutaraldehyde. So4 there is information about numbers.5 Q. And only some of the glutaraldehyde6 stored grafts were observed to have calcification?7 A. Yes.8 Q. Not all?9 A. No.10 Q. So even the glutaraldehyde stored11 grafts did not calcify at the same rate?12 A. Well, it's a statistical feature. So13 that experiment you're identifying the numbers that14 calcified, the numbers that don't. So it's a15 statistical process of -- it's a binary event of16 one's and zeros.17 Q. But Kaplan doesn't report any numbers18 as to how many calcified and how were stored in19 ethanol?20 A. Well, she uses numerical language.21 Q. Numerical language of 11 total, some22 of which were stored in ethanol, some of it in GA.23 Some of the GA stored calcified, some didn't?24 A. Yes.25 Q. There's no rate reported anywhere?

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1 A. Well, the rate is like I said, from2 the time it was implanted to three weeks.3 Q. And what do you mean by "rate," the4 speed?5 A. I just think the time at which it6 takes the implant starting at zero to go to that7 point.8 Q. Okay. The rate was three weeks to9 calcification; is that what you mean by rate,10 21 days?11 A. Well, they had additional time points12 with the ethanol, you know, 56, 112.13 Q. And, for the GA, they didn't have any14 additional time points?15 A. No.16 Q. And, for the GA, the rate of17 calcification over 21 days could have been only 1018 percent?19 A. Let me try the math in my head. If I20 design the experiment and had to use the word some,21 et cetera, let's say six were in glutaraldehyde and22 five in ethanol, you have two out of six that23 calcifies.24 Q. I'm not asking about a hypothetical25 experiment that you might design. I have no doubt

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1 if you design an experiment, it would have2 quantitative information, it would have results that3 were understandable.4 I'm asking you about what Kaplan reported.5 A. Yeah.6 Q. According to what Kaplan reported,7 some grafts were stored in GA and some of those8 grafts had calcification observed after 21 days.9 A. Yeah.10 Q. But you don't know what the rate is11 of calcification in terms of the percentage of those12 GA stored grafts that did, in fact, calcify in13 21 days?14 A. I mean, I thought in that previous15 question you gave me a number of grafts. So I was16 trying to do that out in my head.17 Q. I'm talking about what's reported in18 Kaplan. I'm not adding any numbers that weren't19 there.20 A. So Kaplan reports the total number21 and Kaplan reports a division into two groups and22 then Kaplan reports a subset of glutaraldehyde that23 calcifies, subset that don't and none in the ethanol24 case.25 Q. And what was the rate of



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1 calcification of the GA stored grafts over 21 days?2 A. I mean, the way to say it is the3 rate.4 Q. Yes. There were some but it was less5 than a hundred percent right, not all?6 MR. TESCHNER: Objection to form.7 A. So the three -- however some was,8 that number calcified. So I would expect if ethanol9 had no effect, that a similar level or some would10 have calcified in that group, too.11 Q. But I'm asking about the GA stored12 grafts.13 A. Uh-huh.14 Q. What percentage of the GA stored15 grafts calcified in 21 days?16 A. I don't know.17 Q. You don't know because Kaplan doesn't18 provide that information?19 A. No. But I can infer a minimum.20 Q. What's a minimum?21 A. I mean, I would say the absolute22 minimum would be if you had -- so, if you have 1123 grafts and you implant for some strange reason 9 in24 glutaraldehyde and 2 in ethanol, you would have to25 have, at least, 2 calcify in the glutaraldehyde and

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1 0 in the ethanol's. So that's 20 -- what is that2 22 percent, something like that.3 Q. The minimum would be two out of nine4 calcified; is that what you're saying?5 A. That's a wildly -- you know, I don't6 know anyone who would design an experiment like7 that. But, yeah, I think that would be the minimum.8 Q. Do you know anyone who would design9 an experiment and not report any of the numbers in10 the paper?11 MR. TESCHNER: Objection to form.12 A. I mean, I don't presume to know why13 they wrote the paper they way they did. If it was14 me --15 Q. Nobody in your lab would write a16 paper like that?17 MR. TESCHNER: Objection.18 A. I would not write the paper this way.19 Q. So the way you interpret Kaplan, the20 minimum amount of calcification that was observed21 for the GA stored grafts would be two out of nine?22 A. No. I mean, I interpret Kaplan to be23 some either six in glutaraldehyde and five in24 ethanol or the other way around, of which, at least,25 two of the glutaraldehyde treated ones calcified.

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1 That's how I would interpret it.2 Q. You're saying the minimum would be3 two out of six?4 A. In the way I read it, that would be.5 But the absolute possible, you know, world, the6 minimum would be two out of nine.7 Q. So either two out of six or two out8 of nine.9 And what would be the maximum amount of10 observed calcification that was observed by Kaplan?11 A. So I would say some is less than12 half. So, if there was nine grafts implanted, four13 of them would have calcified and five wouldn't.14 Q. So the maximum you think that could15 have been observed would have been four out of nine?16 A. Yeah, four out of nine.17 Q. If there was consistent reliable data18 from the 21-day dog study, wouldn't you expect that19 all of the GA stored grafts would have calcified?20 A. No.21 Q. Why not?22 A. Because calcification is -- detection23 of calcification in implants is often reported as a24 binary event of which you have a number of samples25 that don't and a number of samples that do under a

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1 condition. So it's routinely referred to as, you2 know, six out of eight, five out of seven. So, in3 that sense, it's perfectly reasonable to not see a4 hundred percent.5 Q. Have you ever seen a calcification6 study that reports its results by using the term7 some without having any numerical information?8 MR. TESCHNER: Objection to form.9 A. I mean, I can't recall every paper I10 ever read. But I would not refer to -- I would not11 write some and leave it with just that. I do know12 that at the time reporting of results via describing13 features, such as some occurring, this didn't14 happen, et cetera, was common. But I think that15 certainly today with, like I said, the supplemental16 information, peer reviewers would want to see17 something.18 Q. Okay. Well, I think after we take a19 break, we'll take a look at some of the articles20 that you cited in your declaration. I'd like to see21 kind of the comparison between the type of details22 that's included in that publication versus what you23 observed in Kaplan.24 MR. WEINER: You want to take a quick25 break now?



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1 MR. TESCHNER: Sure.2 (Recess taken 3:25 to 3:39 p.m.)3 MR. WEINER: Back on the record.4 Q. Dr. Butcher, on your opinion -- the5 Kaplan article reports that the authors concluded6 that ethanol was affective as an anti-calcification7 treatment for glutaraldehyde pretreated tissue for8 use in implantation in an animal; is that right?9 A. Yes.10 Q. And, in your view, the authors of the11 Kaplan article drew this conclusion based on a study12 of 21-day implants in adult mongrel dogs, right?13 A. They had more information than that.14 I interpret it based on the total of their 56, 11215 days.16 Q. In your view, after making17 observation at 21 days, the Kaplan authors ceased18 doing any further experimentation with non-ethanol19 stored tissue, right?20 A. Right.21 Q. Other than Kaplan, of the 20 articles22 that you cited in your declaration, that is, at23 least, Exhibits 1019 to 21, 1023 to 28, 1030 to 40,24 which of these articles describe calcification25 experiments in which the authors used an adult dog

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1 model to test for calcification after 21 days of2 implantation?3 MR. TESCHNER: Objection to form.4 You can go through and review, if you need.5 THE WITNESS: Okay.6 A. Well, I have looked at some of these7 things, but I'll go back to my...8 So, in my declaration, I did cite papers of9 calcification occurring faster or of a time that is10 consistent with that timeline.11 Q. I'm just not asking if there were any12 observations earlier than 21 days. I'm asking if13 there was any experiment that was designed for14 21 days or fewer of implantation.15 A. I certainly did find papers of16 studies where valves were, you know, valves were17 explanted in that same time period or timeframe, for18 instance, even earlier than 21 days.19 Q. Well, there was some animals that20 died very early and the valves were taken out at21 that time, right?22 MR. TESCHNER: Objection to form.23 A. Well, they were -- the animals were24 sacrificed prior to their death. So, for instance,25 in Paragraph 26, I cite Hoffman 1993 that show that

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1 prosthesis valves implanted for 7, 10 and 18 days,2 when they were explanted the valves were heavily3 calcified.4 Q. Right. They were sacrificed early5 because of severe mitral regurgitation, right?6 A. Yeah. But that's why they were --7 that's why they had the regurgitation because the8 valves were heavily calcified.9 Q. Do you know if the early10 calcification was caused by infection or thrombus or11 some other complication?12 A. So they determined that the animals13 were all well in the early post-operative period. I14 think there were other animals that they used -- let15 me look again. 2004.16 (There is a discussion off the record.)17 Q. What's the exhibit number on that?18 A. It's 2004.19 MR. TESCHNER: Again, so the record20 is clear, the reference in 26 to Hoffman, there is a21 typographical error. It should be Hoffman '93, I22 think, instead of '97.23 THE WITNESS: Oh, is that what it24 says? Oh, I thought it said '93.25 Q. Paragraph 26 you refer to Hoffman

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1 '93?2 MR. TESCHNER: I think so. I don't3 think there is a Hoffman '97.4 A. It's Page 97. That's the thing5 there.6 So they mention that the animals were well7 until early postoperative period and then developed8 severe mitral regurgitation.9 Q. Well, Hoffman reports that four valve10 implants were tested, right, on Page 97 right under11 the results?12 A. Oh, yes. One animal died early from13 a pneumothorax.14 Q. And is that an infection?15 A. No. It's -- I mean, it could be16 caused by a lot of different things. I knew it17 better when I was doing my crash testing research.18 It's -- I would have to look up the term to tell you19 exactly what it is. But it's something that can be20 caused by blunt trauma. So it's like -- it's part21 of the operative -- consequence of the operation.22 Q. Of the three animals that were23 sacrificed at 7, 10 and 18 days, they all had24 heavily calcified valves?25 A. Yes.



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1 Q. Would you expect that this early2 calcification may have been the result of an3 infection?4 A. No.5 Q. Do you agree that infections may6 promote early calcification?7 A. Yes.8 Q. And why do you think that these9 animals did not suffer from infections that caused10 the early calcification?11 A. Because they would have reported it.12 And they said that the animals were well. So if13 they had an infection, they would not be well.14 Q. They were well sometime before seven15 days after the surgery, right, because the first one16 of those three was --17 A. Yeah, sometimes --18 Q. -- sacrificed at seven days?19 A. So they were well and then they20 developed severe mitral regurgitation.21 Q. Okay. And is there any discussion of22 what caused that early calcification?23 A. I think that -- let's see here.24 MR. TESCHNER: Take whatever time you25 need to refresh your recollection to answer the

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1 question.2 Q. The tested valves were polymer3 covered, polyurethane?4 MR. TESCHNER: Excuse me. There is a5 pending question. Why don't you let him answer that6 first.7 MR. WEINER: Okay.8 A. I'm trying to find where they say why9 their valves calcified. Is there a section you can10 point me to?11 Q. Let me ask you this.12 These were polyurethane material valves,13 right?14 A. I see in the paragraph above the15 materials and methods on Page 96, it says, "The aim16 of the study was to evaluate the vivo performance of17 the porous polyurethane silicone composite18 material."19 Q. So this doesn't address20 glutaraldehyde pretreated bioprosthetic materials,21 right?22 A. I don't know if they actually treated23 this with -- let's see. It doesn't appear that this24 material was treated with glutaraldehyde.25 Q. And under the conclusions on Page 98,

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1 the first sentence states, "The porous silicone2 coated polyurethane material was not able to3 withstand the stresses experienced by a complete4 heart valve prosthesis," that sentence reads in5 part. Did I read that correctly?6 A. Yes. But it was also able to perform7 as a patch placed in the anterior leaflet of the8 mitral valve.9 Q. So this article has nothing to do10 with glutaraldehyde pretreated materials, right?11 A. It has to do with calcification.12 Q. It has nothing to do with13 calcification of glutaraldehyde fixed bioprosthetic14 materials, right?15 A. So calcification is a process that16 can happen in lots of different materials biological17 and processed. So this particular article was not18 looking at a glutaraldehyde treated valve.19 Q. Okay. Let me direct your attention20 to another article you cited, Carpentier 1982.21 That's Exhibit 1020.22 (Deposition Exhibit 1020, Carpentier et al23 1982, was previously marked for identification.)24 Q. I have a copy for you.25 A. Oh.

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1 Q. Okay. Do you recognize this article?2 A. Yes.3 Q. And Carpentier reports tests4 performed on young rabbits, right?5 A. Let me make sure. Control and6 treated tissues for subcutaneously implanted in the7 growing rabbit.8 Q. And these tests involve subcutaneous9 implants testing for calcification at one to10 four weeks?11 A. Yes.12 Q. Carpentier does not report on testing13 of dogs, right?14 A. No.15 Q. At Paragraph 48 of your declaration,16 you state that this article lacks detail on the17 amount of calcification observed, right?18 A. Let me look. I say that it lacks19 similar experimental detail to be considered20 reliable by the standards that PO sets.21 Q. It has a lot more information than22 the Kaplan article, right?23 MR. TESCHNER: Objection to form.24 Q. A lot more details on calcification25 measurements than the Kaplan article, right?



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1 A. It has more detail on calcification.2 Q. For example, at Page 321 it states,3 "The degree of calcification was determined on a4 scale of 0, 1, 2 and 3 using Von Kossa's stained5 tissue sections." Did I read that correctly?6 A. Yes.7 Q. And Carpentier goes on to say that,8 "The validity of this model was established by9 histological and chemical similarities found between10 explants in the animal model and vales explanted11 from the human," right?12 A. Yes.13 Q. Are you familiar with Von Kossa14 staining?15 A. Yes.16 Q. And have you used Von Kossa staining?17 A. Yes.18 Q. What is it used for?19 A. It's to determine the amount of20 phosphate present in a tissue lesion.21 Q. Is this a stain that calcification22 researchers often use to detect calcification?23 A. It is one that they use.24 Q. Did Kaplan use this stain to detect25 calcification?

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1 A. I don't know.2 Q. Kaplan didn't say anything about3 using this stain, right?4 A. Kaplan did not mention which stains5 they used.6 Q. Did Kaplan mention if any stains were7 used?8 A. Kaplan mentioned a histopathological9 analysis. I'm not familiar with what exactly that10 entails at their institution.11 Q. I would like to direct your attention12 to Exhibit 1021.13 A. Shall I keep this around?14 Q. You can keep that to the side. It's15 Golomb 1986.16 A. What was it 1021.17 Q. Right. I don't think I've shown that18 to you yet. I'll get a copy for you.19 (There is a discussion off the record.)20 Q. Sorry about that. We're missing that21 one. I'm going to have to -- we'll pull a copy and22 maybe we can get one from your counsel, but we can23 wait until after the break or something.24 A. Okay.25 Q. Let's go to Exhibit 1023.

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1 (There is a discussion off the record.)2 Q. Sorry about that. We'll go back to3 1021.4 A. Okay.5 (Deposition Exhibit 1021, Golomb et al 1987,6 was previously marked for identification.)7 Q. Do you recognize Exhibit 1021, Golomb8 1986?9 A. Yes.10 Q. Golomb reports on test performed on11 young rats, right?12 A. Yes.13 Q. And, in particular, on Page 123,14 right-hand column under "calcification studies," it15 states that three-week old male weanlings were used?16 A. Yes.17 Q. Does weanlings refer to young rats?18 A. It refers to the stage that the rat19 is now able to feed itself.20 Q. Do you know why weanlings were used21 for the tests?22 A. I think they just chose young animals23 and if you go too young and they're not feeding on24 their own -- I don't know what the consequences are25 for this particular study. But that's what the term

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1 means.2 Q. This article doesn't report on any3 testing of dogs, does it?4 A. I don't know if they discuss a study5 in dogs, you know, within their references.6 Q. They don't report on any testing of7 dogs that they performed, right?8 A. Yeah, this group did not report or9 did not perform experiments on dogs in this paper.10 Q. Do you know why they used young rats?11 A. Because it's a model of calcification12 or an animal model that calcifies.13 Q. And why are young rats used as an14 animal model for calcification?15 A. Because when you implant materials in16 them, they will calcify when -- you know, they will17 have calcified when you explant them.18 Q. They calcify at a fairly fast rate?19 A. They calcify in this study on the20 order of days.21 Q. Okay. Let's go to Exhibit 1023.22 (Deposition Exhibit 1023, Gonzalez-Lavin et23 al 1988, was previously marked for identification.)24 Q. And that was Gonzalez-Lavin 1998.25 A. Uh-huh.



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1 Q. Gonzalez-Lavin reports on testing of2 dogs for calcification, right?3 A. Yes.4 Q. In particular, mongrel puppies were5 used, right?6 A. Six-month old.7 Q. And why do you think they used8 six-month old mongrel puppies instead of adult dogs?9 A. Let's see. So they say in their10 discussion that the animal model is similar from the11 metabolic point of view to that of children in need12 of these procedures.13 Q. And what do they mean by that?14 A. I imagine that they mean that a15 growing child and a growing dog would share the16 similarity of growing, whatever that means.17 Q. And do the growing children tend to18 have calcification problems more rapidly than adult19 humans?20 A. For the same valve, yes, for21 bioprosthetic valve anyway.22 Q. And is that the same for puppies as23 compared to adult dogs, puppies would tend to24 calcify at a more rapid rate?25 A. I'm not sure if I know of a study

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1 that compares puppies and adult dogs. So I don't2 know if that age difference or feature has been3 tested.4 Q. According to the article, the mean5 time for implantation was 117 days; is that correct?6 A. Yes. It ranges from 12 to 174 days.7 Q. Why do the researchers use a mean8 time of 117 days if only 21 days was needed to draw9 conclusions?10 MR. TESCHNER: Objection to form.11 A. Why was 21 days needed?12 Q. Why was more than 21 days needed?13 A. I don't know why they chose 117 days.14 It's clearly a wide range of days that they15 examined. I think -- to speculate, I think they16 were interested in a time course.17 Q. This article reports on quantitative18 measurements of calcification in milligrams per19 gram, correct, as shown in Tables 2 and 3?20 A. Yes.21 Q. Why did the articles include this22 quantitative data?23 MR. TESCHNER: Objection.24 A. I think they wanted to compare the25 magnitudes of calcification between the different

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1 groups.2 Q. I thought you said the most important3 feature of calcification was its presence or4 absence.5 A. It is.6 Q. So why didn't they just report7 presence or absence?8 A. I think they were trying to indicate9 that there was more or less in one of the groups10 among the present material.11 Q. Reporting this quantitative data,12 isn't that inconsistent with the position that the13 most important thing about calcification is its14 presence or absence?15 A. No.16 Q. Why not?17 A. Because you can establish presence18 through a lot of different assays, quantitative,19 semi-quantitative, qualitative.20 Q. But quantitative shows you how much21 is present, right?22 A. Quantitative can show you -- I would23 use a quantitative assay to show that there was more24 calcification in one group than another.25 Q. Okay. Let's go to Exhibit 1024.

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1 (Deposition Exhibit 1024, Kim et al 1986,2 was previously marked for identification.)3 Q. It's Kim 1986.4 Okay. Do you recognize Exhibit 1024?5 A. Yes.6 Q. Kim 1986 reports on testing of dogs7 for calcification, right?8 A. Yes.9 Q. This article does not report on10 testing of implanted valves or any kind of a11 prosthesis, right?12 A. No.13 Q. The article has nothing to do with14 calcification of glutaraldehyde fixed materials,15 right?16 MR. TESCHNER: Objection to form.17 A. I don't think there is a difference18 in calcification process between, you know, these19 different environments. There are certainly20 different features that might bring it about, but21 the progression of calcification is the same.22 Q. The article reports on testing of old23 dogs.24 A. Uh-huh.25 Q. That refers to senescent canine



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1 aortic valves, right?2 A. Yes. Let me make sure that's aortic3 valves. I don't remember if it's...4 Okay, yes.5 Q. And the article reports on testing of6 12 or 16-year old dogs, right?7 A. As well as five -- a two-year-old8 male Beagle was used as a control.9 Q. Right. That was a control because it10 was just a short time interval as compared to the11 older dogs that were tested, right?12 A. I don't think there was a time13 interval. I think it was just the age of the14 animal.15 Q. But they were looking for senescent16 changes in the valve, right, that's calcification17 that occurs over a long period of time, right?18 A. I don't -- the question -- I'm trying19 to understand what you mean by "over a long period20 of time."21 Q. Let me restate the question.22 The article does not provide any information23 on a suitable model for accelerated calcification24 models, right?25 MR. TESCHNER: Objection to form.

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1 A. I don't think that was the -- yeah, I2 mean -- you mean they're trying to test the3 prosthetic valve in this article?4 Q. They weren't trying to test a5 prosthetic valve, right?6 A. No, they weren't evaluating7 prosthetic valve in...8 Q. They were testing for calcification9 that occurred in old dogs, right?10 A. They were trying to describe the11 calcification process that occurred in these12 animals.13 Q. Okay. At Paragraph 4 of your14 declaration, you refer to the discussion section15 with reviewers section of this article, right?16 MR. TESCHNER: Excuse me. Did you17 say Paragraph 4?18 MR. WEINER: I'm sorry, Paragraph 44.19 MR. TESCHNER: Thank you. Sorry.20 A. Yeah. I was...21 Q. Now, in Paragraph 44, are you saying22 that the authors were just trying to establish the23 presence or absence of calcification?24 A. They were trying to describe the25 process of calcification in dogs.

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1 Q. I was asking what you were referring2 to in Paragraph 44.3 MR. TESCHNER: Objection to form.4 Q. Let me take this one step at a time.5 In Paragraph 44 you refer to the discussion6 in the reviewers section?7 A. Yes.8 Q. You said, "A perfect example of this9 is found in the comments following the Kim article10 of 1986"?11 A. Yes.12 Q. "The researchers were directly asked13 about how their work on calcification could be14 quantified."15 A. Yes.16 Q. Okay. Now, the discussion section17 addresses measurement of a calcium to phosphate18 ratio, right?19 A. This is a different kind of20 discussion section than a typical journal article.21 This is actually discussion with the actual22 reviewers.23 Q. Okay. But the reviewers were24 discussing a measurement of a calcium to phosphorus25 ratio, right?

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1 A. Yes.2 Q. They weren't discussing the merits of3 a quantitative measurement of calcification, were4 they?5 A. I'm unclear if that's what they were6 trying to get at with their question.7 Q. Well, for example, 1154, right-hand8 column, "Authors," "An ideal CA to P ratio of9 appetite may occasionally be obtained by X-ray10 analysis of pure aggregates of needle shaped11 crystals especially the experimental12 calcifications."13 Aren't they talking about a calcium to14 phosphate ratio measurement?15 A. Can you point me -- is that --16 Q. Discussion with reviewers section.17 A. Yeah, yeah.18 Q. You see "authors" halfway down the19 page?20 A. Yeah.21 Q. "An ideal CA to P ration of22 appetite."23 A. Uh-huh.24 Q. They're discussing a measurement of25 the calcium to phosphorus ratio, right?



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1 A. Right, right.2 Q. They were not discussing the merits3 of having a quantitative measurement of4 calcification?5 A. I think they were asking him6 questions about this particular ratio.7 Q. Okay. And Kim actually includes much8 more detail in the article than just saying9 calcification was present, right?10 A. Yes, Kim includes more detail.11 Q. Right. For example, the last full12 paragraph on Page 1152, right-hand column, "The mode13 of calcification of CDP referring to cellular14 degradation products appeared complex. The calcific15 deposits were seen in the lumens as well in16 apposition to the surface of the membranous CDP,"17 and goes on there with quite a bit of detail about18 calcification, right?19 A. Uh-huh.20 Q. And Kim -- this discussion goes on to21 the next page and to 1154 and then on 1153 Kim22 includes six figures that appear to be photographs23 of microscopic images showing signs of24 calcification, right?25 A. Yes.

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1 Q. Kaplan had nowhere near this level of2 detail of analysis of calcification, did it?3 A. It did not have the same level of4 detail.5 Q. Nowhere near this level of detail,6 right?7 MR. TESCHNER: Objection to form.8 A. I guess I don't know -- I mean, I9 don't know what you mean by "nowhere near," like...10 Q. Quite a bit more detail than Kim.11 A. Yes.12 Q. So why did you say in Paragraph 44 of13 your declaration that the Kim authors concluded that14 establishing the presence of calcification was all15 that was necessary?16 A. Because that's what Kim said.17 Q. No, Kim did not say that.18 MR. TESCHNER: Objection.19 Q. Kim was talking about calcium to20 phosphorus ratio.21 Where did Kim say that establishing the22 presence of calcification was all that was23 necessary?24 A. Well, it says at the end of that25 paragraph, "The analysis was meant not to confirm

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1 the type of crystalline deposits but the presence of2 calcification."3 Q. But that wasn't the context of4 discussing the calcium to phosphorus ratio, right?5 A. Well, that paragraph discusses the6 difficulties -- the technical limitations of7 establishing calcium to phosphate ratios at this8 time. And they said that -- it says, Therefore, the9 determination of a calcium phosphate ratio requires10 a comprehensive study including statistical11 analysis, such an extensive analysis would not. The12 purpose of this study, the analysis was meant not to13 confirm the type of crystalline deposits but the14 presence of calcification."15 Q. But Kim includes much more16 information than just the presence of calcification,17 right?18 MR. TESCHNER: Objection, asked and19 answered.20 A. I think Kim includes information21 that, you know, says the same thing, presence of22 calcification.23 Q. Yeah. But if Kim thought an article24 should only report the presence of calcification,25 Kim didn't follow his own advice because his article

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1 reports a lot more information than just presence or2 absence, right?3 MR. TESCHNER: Objection to form.4 A. I think all of the data is reporting5 the presence. I don't know what you're asking for.6 Like, 27 pictures of the same crime scene describes7 the crime scene.8 Q. But Kaplan didn't have any9 photographs of the crime scene, did it?10 A. She didn't provide a picture11 description of the crime scene.12 Q. Or a numerical description?13 A. No, but a textual one.14 Q. Let's go to Exhibit 1025.15 (Deposition Exhibit No. 1025, Han et al16 1993, was previously marked for identification.)17 Q. Han 1993.18 Okay. Do you recognize Exhibit 1025?19 A. Yes.20 Q. Han reports on testing of dogs having21 implanted polyurethane coated valves, right?22 A. That looked likes a combination of23 materials.24 Q. Combination of materials including25 polyurethane coating?



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1 A. Yes, right.2 Q. The study doesn't involve3 glutaraldehyde pretreated tissue, does it?4 A. No.5 Q. The study does not involve any6 anti-calcification treatment, does it?7 A. They were utilizing the coating as an8 anti-calcification treatment of polyurethane.9 Q. Where does it say the coating was an10 anti-calcification treatment?11 A. So it says -- the paragraph above the12 materials and methods, it says, "To further13 investigate the correlation between blood14 compatibility and biostability as well as15 anti-calcification in implanted polymers, PU, PEO16 SO3 was applied as a coating material over polymer17 hard valves and vascular grafts and the biological18 responses were evaluated in a vivo canine19 ventricular pulmonary shunt system."20 Q. The focus of the study was on blood21 compatibility of the materials, right?22 A. As well as anti-calcification.23 Q. And the researchers evaluated24 thrombus crack formation and surface morphology of25 the retrieved implants, right?

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1 A. As well as calcium analysis.2 Q. Right. They did quantitative tests3 for calcium analysis, right?4 A. Yes.5 Q. Of the three dogs that were tested,6 they survived from between 14 to 39 days, right?7 A. Yes.8 Q. Do you think dogs were selected for9 the study because they're good model for testing for10 thrombosis?11 A. I don't think it says why they chose12 the dog.13 Q. Do you have an understanding of why14 they likely chose the dog?15 A. There are several reasons why they16 could have chose the dog. And their experience with17 the dog model could be the biggest factor.18 Q. Okay. Let's go to Exhibit 1026.19 That's Levy 1982.20 (There is a discussion off the record.)21 Q. Okay. Do you have that?22 A. Yes.23 Q. And this article reports on testing24 of glutaraldehyde pretreated valves implanted in25 calves, right?

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1 A. Yes.2 Q. And the article reports that sheep3 have also been used for such testing?4 A. I see that it does.5 Q. The article doesn't say anything6 about using dogs for calcification testing, does it?7 A. I have to look here. They refer to a8 lot of other studies in the references that I don't9 know off the top of my head whether they used dogs10 or not. But I'm looking at the text that they give11 and I don't see the word dog or canine in it.12 Q. The article does report quantitative13 measurements of calcification, right?14 A. Yes.15 Q. Okay. Let's go to Exhibit 1027.16 (Deposition Exhibit No. 1027, Okamura et al17 1976, was previously marked for identification.)18 Q. It's Okamura. So Okamura 197619 reports on testing of glutaraldehyde pretreated20 valves implanted in dogs, right?21 A. Yes.22 Q. And the results are reported on Page23 180. It states that of 30 dogs tested, only 824 survived 1 month or longer, right?25 A. I have to do the math here because

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1 they have a couple of groups. It looks like there2 are ten animals that survived.3 Q. Let's see. It says, among 304 animals, 21 received an aortic valve heterograft and5 9 received a pulmonary graft heterograft, right?6 A. Yes.7 Q. In the aortic group that was of 218 animals, 11 died at operation or within 48 hours.9 A. Uh-huh.10 Q. And then 5 dogs died of massive11 thrombosis between 1 and 29 days afterwards.12 A. Yeah.13 Q. And another five dogs survived one14 month or longer.15 A. Right. And in the next paragraph, it16 says, "In the pulmonary group, there were four17 immediate deaths and the remaining five animals18 survived more than one month."19 Q. Does the high death rate for the dogs20 following the surgery mean dogs may not have been21 the best model for the testing that was performed?22 MR. TESCHNER: Objection to form.23 A. What do you mean by "best?"24 Q. Most useful in providing information.25 A. I mean, all these animal models



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1 provide information. You know, as I say in my2 declaration, some animals might have peculiarities3 about them that require some expertise or skill or4 experience to work with and some groups had them and5 some groups didn't. So they worked on one animal6 model or a different one.7 Q. The article reports at Page 184 that8 there was a high incidence of thrombosis within the9 early period; is that correct?10 A. Can you point -- you said on 184?11 Q. 184, right-hand column, the first12 full paragraph, "However the high incidence of13 thrombosis."14 A. Okay. I mean, I notice that -- this15 is in the discussion section. I noticed that in the16 results that they find that there were bleeding17 events in that early period and then animals that18 didn't have those.19 Q. Back at 180, Okamura reports that the20 animals that survived the early problems, the21 remaining three animals were put down from 141 to22 183 days afterwards. Do you see that, the end of23 the first paragraph under results?24 A. Uh-huh.25 Q. Why did Okamura conduct these longer

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1 term tests from 141 to 183 days of implantation?2 A. I don't know.3 Q. Do you think 21 days would have been4 long enough?5 A. To see calcification in a valve? I6 mean, I don't know think that the 21 days of the7 blood vessel, as I said, informs what must happen in8 a valve in a dog or a sheep, for that matter, what9 must happen. I would say it's not -- it wouldn't be10 out of the realm of possibility.11 Q. The possibility that you get the12 results you need in 21 days?13 A. No. I would say it wouldn't be an14 unusual finding. I would say that -- I wouldn't15 know from conducting the -- either study what must16 happen in the other one.17 Q. But doesn't Okamura report that the18 early calcification was related to thrombosis?19 A. Can you say where that was?20 Q. Well, that paragraph we were looking21 at on 184, "However the high incidence of thrombosis22 and calcification deposition on the aortic cusps23 within the early period must be recognized as a very24 serious problem."25 A. I wouldn't say that they're implying

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1 that they happen coincidently or as a result of each2 other. I mean, those could be two features.3 Q. Okay. Let's go to 1028.4 (Deposition Exhibit 1028, Shore et al 1983,5 was previously marked for identification.)6 Q. That's Shore 1983.7 A. Uh-huh.8 Q. And Shore reports on testing of9 glutaraldehyde pretreated tissue implanted in eight10 mongrel dogs, right?11 MR. TESCHNER: Take time to read it12 again, if you need.13 A. They say in there a statement that,14 the objective or the experimental study was designed15 to examine method of cordal replacement using16 glutaraldehyde preserved pericardium.17 I was looking to see if they had mentioned18 the glutaraldehyde preservation strategy, but I19 didn't find it. So I was -- that's what I was...20 Q. But the testing's about21 glutaraldehyde fixed materials, right?22 A. Yes.23 Q. And of the eight dogs tested, two24 died too quickly for study of the implants, right?25 Just under results on Page 133, six out of eight

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1 dogs survived, two died before restudy because they2 suffered bacterial endocarditis?3 A. Yes, I see that. I just didn't -- I4 was trying to figure out restudy. But I see where5 that -- it made me think they had a study.6 Yeah, it says the valve was then tested with7 the heart beating, the aorta cross-plant and aortic8 group perfused and then they restudied them again in9 implantation. So they got something from them, but10 they didn't do the longer term study.11 Q. And the dogs that survived were12 electively sacrificed 3 months to 18 months after13 surgery, right?14 A. Yes.15 Q. And then the eighth dog survived, at16 least, two years after surgery, right?17 A. Yes.18 Q. Why did the authors wait 3 to19 18 months before sacrificing the dogs for testing?20 A. I have no idea.21 Q. Let's go to Exhibit 1030.22 (Deposition Exhibit 1030, Ichikawa et al23 1997, was previously marked for identification.)24 A. Presumably, they had an expectation25 of calcium formation at that time or some



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1 performance of the end points, but I couldn't tell2 you specifically what they were looking for.3 Q. Okay. Exhibit 1030, do you recognize4 it? Ichikawa 1997.5 A. Yes.6 Q. And Ichikawa reports on testing of7 vascular grafts implanted in eight young dogs,8 right? If you look at Page 225, bottom of the9 left-hand column, "implantation of the conduit." It10 says, "eight young mongrel dogs age less than one11 year."12 A. Yes, I see that. I was trying to13 figure out -- you said "the conduit." So the bovine14 jugular vein.15 MR. TESCHNER: Take as much time as16 you need to review it.17 THE WITNESS: Uh-huh.18 Q. So the graft was a bovine jugular19 vein?20 A. Yes.21 Q. Why did the authors use young dogs22 for the testing?23 A. Can you point me somewhere they say24 why they did it, at least, to save me time?25 Q. I don't know if it says why. I'm

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1 just asking if you know, in your experience, why2 they would select that animal model?3 A. Maybe they had more experience with4 that animal.5 Q. The minimum time for implantation6 used by the authors was six months, right? If you7 look in the abstract, it says 5 grafts were8 retrieved on day 182, other 3 grafts on days 196,9 375 and 385 respectively.10 A. Yes, I see that.11 Q. So, for some of the grafts, the12 authors waited more than one year before sacrificing13 the dogs and evaluating the grafts, right?14 A. Yes.15 Q. Do you know why the authors took so16 much time for the experiments?17 A. Sometimes in a time course study you18 want to see how far out the material can perform.19 But other times it's limited by how much resources20 you have available because it's an expensive study.21 Q. Why do you think they didn't do any22 testing at 21 days?23 A. I don't presume what their particular24 impacts were or study end points were. I think they25 just didn't.

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1 Q. Okay. Let's go to Exhibit 1031.2 (Deposition Exhibit No. 1031, Muratov et al3 2010, was previously marked for identification.)4 A. Thank you.5 (There is a discussion off the record.)6 Q. Okay. You recognize Exhibit 1031 as7 Muratov 2010?8 A. Yes.9 Q. Muratov reports on heart valve10 allografts implanted in adult mongrel dogs; is that11 right?12 A. I'm not sure I see the animal -- yes.13 Q. And the animals were sacrificed and14 tested four months after implantation?15 A. Yes.16 Q. And the researchers included17 quantitative data on calcification, right, on Page18 411?19 A. Yes.20 Q. The paper reports that the untreated21 grafts had a maximum amount of calcium detected of22 about 5.2 milligrams per gram; is that right?23 A. No, I think that was the average for24 group one after explantation.25 Q. Well, on Page 411, under Section 324,

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1 the content of mineralized calcium and explanted2 allografts, that's what I was referring to.3 A. Yeah, it says for Group 1 was .4 plus4 or minus .3 milligrams per gram before implantation5 and 5.2 plus or minus .9 milligrams or grams. So6 the maximum was probably something higher.7 Q. Well, it's 5.2 plus or minus .9, so8 the maximum would have been 6.1?9 A. I mean, that's a standard deviation.10 So the single value that was part of that11 distribution could be even higher than that.12 Q. Do those kind of numbers indicate13 calcification?14 A. They indicate the amount of15 mineralized calcium.16 Q. Does that sound like an amount of17 calcium that indicates a normal level?18 MR. TESCHNER: Objection to form.19 A. So there's lots of papers that we've20 been going over that report calcification magnitudes21 or magnitudes of mineralized calcium. Some which22 are in the hundred milligrams per gram. And this is23 at 5 milligrams per gram. I think the situation24 here was they were trying to compare the amount of25 calcium in the two groups and they found a



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1 statistical difference between them.2 Q. But all the numbers are pretty low3 compared to other reports of calcification we've4 seen in other articles, right?5 MR. TESCHNER: Objection to form.6 A. I mean, this is a different tissue.7 So I'm not aware of why the numbers of one study8 come to bear in the comparison of these two9 materials. The information sort of is what it is.10 Q. You don't think the information11 indicates that the numbers are relatively low for an12 amount of calcium that would be described as13 calcification?14 MR. TESCHNER: Objection to form.15 A. I'm not aware that this group16 conducted a comparison between the magnitude17 quantification and say a histological inspection to18 see if there was some relationship and, therefore,19 you know, threshold cutoff magnitude.20 Q. Do the low numbers indicate that the21 animal model may not have been suitable?22 MR. TESCHNER: Objection to form.23 A. No.24 Q. Are you familiar with the journal in25 which this article appears, Interactive

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1 Cardiovascular and Thoracic Surgery?2 A. I've come across in it my research.3 I have not submitted an article to it.4 Q. Are the articles in this journal peer5 reviewed before publication?6 A. My understanding is that's a7 requirement for incorporation into certain databases8 that I use to read literature.9 Q. Is this a publication that you10 consult in connection with your own work?11 A. I use pretty much every article that12 I would see in those databases.13 Q. And articles from this publication14 are included in the databases that you consult?15 A. That's where I found this article.16 Q. Okay. Let's go to Exhibit 1032.17 (Deposition Exhibit No. 1032, Lu et al 2012,18 was previously marked for identification.)19 Q. Okay. Do you recognize Exhibit 103220 as Lu 2012?21 A. Yes.22 Q. And Lu 2012 reports on implantation23 of bovine jugular veins implanted in young mongrel24 dogs, right? If you look at Page 2645, bottom of25 the left-hand column where it refers to young

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1 mongrel dogs.2 MR. TESCHNER: Take whatever time you3 need to review it, if you need.4 A. Yes, I see that.5 Q. And the article reports that the6 implants were tested after one year had passed?7 A. Well, they had pre-ethanol and8 post-ethanol treatment conditions, too.9 Q. And at what times were those tested?10 A. The pre and post?11 Q. Uh-huh.12 A. I mean, I assume it means or I13 interpret this to mean that the tissue was processed14 up until the step that they used the ethanol and15 they test it and then they continue through that16 until that's completed and then they test it again.17 I'm not sure -- so it looks like there's a series of18 this dehydration and ethanols and then cured for19 three days and then -- like there is a number of20 different time points or time steps. I'm not sure21 -- it seems to me they would have done once before22 that and once after that. I don't know exactly how23 long it took them to do each of, you know, the24 graded rinses.25 Q. After implantation they didn't do

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1 testing after one year had passed, right?2 A. It looks like their experiment was3 designed to evaluate at a one year time point.4 Q. Why did they wait a full year?5 A. Let's see if I see that. I'm not6 sure why they waited one year or they tried a7 one-year time point.8 Q. The article reports on quantitative9 testing for calcification, right? If you look at10 2151, you'll see some graphs of the results.11 A. Okay. I saw Table 1 first. So I'm12 -- they have a -- yes, I see that.13 Q. Why do you think they did14 quantitative testing?15 A. I think they were interested in16 comparing the magnitude of calcium content in the17 photo-oxidated group against the -- whatever the PCA18 group is. I don't remember what that stands for.19 Q. Why didn't they just report the20 presence or absence of calcification instead?21 A. I think they were interested in22 comparing which of these had more calcium in them.23 MR. WEINER: Okay. Why don't we take24 a quick break here.25 MR. TESCHNER: Sure.



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1 (Recess taken 4:49 to 5:08 p.m.)2 (Deposition Exhibit No. 1071, St. Jude vs.3 Michigan Inter Partes Review Declaration and4 Document Outline, was marked for identification.)5 MR. WEINER: Back on the record.6 Q. Okay. The court reporter also marked7 Exhibit 1071. Do you recognize this as your summary8 of your declaration?9 A. Yeah.10 Q. You had that in front of you and we11 had it marked so that the record is complete. I12 don't have any questions about that for you now.13 I would like to direct your attention to14 Exhibit 1033, Gabbay 1982.15 (Deposition Exhibit No. 1033, Gabbay et al16 1982, was previously marked for identification.)17 Q. And do you recognize this as Gabbay18 1982?19 A. Let me make sure; yes.20 Q. Okay. Gabbay 1982 reports on testing21 of a glutaraldehyde pretreated valve implanted in22 dogs, right?23 A. I'm just looking for the24 glutaraldehyde particulars.25 Q. Look at Page 412 under "Materials and

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1 Methods." It says the bovine pericardium has been2 treated with glutaraldehyde.3 A. Right. I just didn't see the4 percentage. It's usually what I look for.5 Q. Okay. Why do you look for the6 percentage?7 A. Just because it's usually a number8 that is easier to spot than words, but it usually9 defines more about the glutaraldehyde treatment10 procedure.11 Q. Gabbay reports, for example, at the12 bottom of Page 416 that 21 dogs were used for13 testing, right?14 A. Yes.15 Q. And, of the 21 dogs tested, 10 died16 in less than 1 month due to bleeding and infections,17 right?18 A. Yes.19 Q. Gabbay also reported that two dogs20 died of endocarditis at two and a half and three21 months?22 A. I'm looking for that part.23 Q. That's on Page 418, a couple of lines24 down.25 A. Yes, I see that.

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1 Q. The article reports that of the2 remaining dogs, 3 were sacrificed at 6, 7 and3 13 months, right?4 A. Yes.5 Q. Why did the authors wait, at least,6 six months before sacrificing and testing the dogs?7 A. I don't know. Did they say why they8 wait that long? Yeah, I don't think they make that9 clear in the paper.10 Q. Okay. And it's not clear to you from11 reading the paper why they waited that long?12 A. I think seven months is a time point13 to evaluate the performance of an implanted14 prosthetic valve.15 Q. I'd like to direct your attention to16 Exhibit 1034.17 (Deposition Exhibit 1034, Gabbay et al 1983,18 was previously marked for identification.)19 Q. Now, Exhibit 1034 is another Gabbay20 article. That's Gabbay 1983, right?21 A. Yes.22 Q. Do you agree that Exhibit 1034 is23 virtually identical to Exhibit 1033 in that it's,24 essentially, the same text in a different25 publication?

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1 MR. TESCHNER: Objection to form.2 A. I don't think these papers are3 identical.4 Q. Does the text appear to be virtually5 identical reporting on the same work?6 A. It looks like they include additional7 animals in the '83 paper and they have some8 durability information in Table 3 that's new.9 Figure 10 is new. I haven't looked through all of10 the tests to see. It looks like this copy is also11 missing the references and page, you know...12 Q. Exhibit 1034 you're referring to?13 A. The '83 article is missing.14 MR. LOIACONO: The exhibit stamp is15 in the lower right-hand corner.16 A. Oh, I'm sorry; 1034.17 Q. 1034, okay. What I provided is I18 think the way we received it. It goes up to Page19 657.20 A. I mean, I see a Reference 37 here.21 So there's, at least, 37 references in this article.22 Q. Okay.23 A. So I found this article because it24 was cited by one of the articles in PO. So --25 Q. Cited in the Patent Owner's



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1 application brief?2 A. Yeah. I don't think I found this in3 the databases that I normally look at.4 Q. Okay. Let's go on to Exhibit 1035.5 (Deposition Exhibit 1035, Gabbay et al 1984,6 was previously marked for identification.)7 Q. Exhibit 1035 is another Gabbay8 article, Gabbay 1984. Do you recognize that?9 A. Yes.10 Q. This appears to be a publication that11 reports on work related to what was reported in12 Exhibits 1033 and 1034; is that right?13 A. Yes.14 Q. In addition, Exhibit 1035 also15 includes studies performed on weanling sheep in16 addition to dogs, right?17 A. Yes.18 Q. Why did Gabbay use the sheep testing19 in addition to the dog testing?20 A. As far as I can tell, they used it21 because it was another model for testing22 bioprosthetic valves.23 Q. Do you agree that Gabbay reported24 that sheep are a better model than dogs for25 implanted cardiac valves?

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1 A. I don't know where it says that.2 Q. Well, let me direct your attention to3 Page 449 under canine experiments.4 A. Okay.5 Q. And Gabbay states, "Despite the6 tendency for infection, thrombosis and bleeding7 described by others as drawbacks to the use of dogs8 for experimental cardiac operations, we have9 developed routines that allow us to achieve10 satisfactory results."11 And then about halfway down the page under,12 "sheep experiments," and there Gabbay states,13 "Another series of experiments were carried out14 using weanling sheep less than six months old which15 have been demonstrated to be an excellent animal16 model for testing bioprosthetic valves."17 A. Okay.18 Q. Do you read that as saying sheep are19 superior to dogs as an animal model?20 A. No.21 Q. Okay. It doesn't say that the canine22 model is superior, right?23 A. No.24 Q. Sorry, let me restate that.25 It doesn't say the canine model is excellent

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1 does it?2 A. No.3 Q. It says "satisfactory?"4 A. Yeah. I believe in this paper they5 actually say that they have gained useful data from6 both animal models.7 Q. Well, it does say "satisfactory"8 referring to the dog testing, right, "satisfactory9 results"?10 A. Yes.11 Q. But it doesn't say excellent in12 referring to the canine data, right?13 A. Well, I don't know if they actually14 say that the sheep is excellent. They're saying15 that it's been reported by others. I think they say16 that they have useful data from both. I'm trying to17 find that.18 Q. Okay. Let's look at 454.19 A. Okay.20 Q. 454 in the right-hand column about21 halfway down the page, you see the text that begins,22 "Therefore some investigators"?23 A. Yes.24 Q. And let me just read that portion.25 "Therefore some investigators have started to use

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1 different animals such as young sheep for the2 testing of biological valves. Sheep represent an3 excellent alternative to dogs since they are less4 prone to infection and tolerate open heart5 operations much better and since morphologic changes6 in biological valves seem appear to be similar to7 those occurring in human beings."8 A. Okay.9 Q. Do you read that as saying that sheep10 are preferable to using dogs?11 A. No. I mean, I think they say right12 below that, "We have gained useful in vivo13 experience from both sheep and dogs and we plan to14 keep the five current canine survivors alive as long15 as possible so that as the initial insertions are16 performed on the human beings, they'll be animals17 alive with one or two years duration of insertion."18 So it seems to me that they can gain information19 from both models.20 Q. Do you agree that infection may cause21 calcification of implanted valves?22 A. It depends on the infection.23 Q. Well, you see at the bottom of Page24 454, the right-hand column Gabbay states, "Infection25 however is known to favor calcium deposition and



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1 tissue valves." Do you agree with that statement?2 A. Yes.3 Q. 454, the last full sentence on the4 page.5 A. Okay. I agree that lesions due to6 valve endocarditis can have calcific deposits in7 them.8 Q. Do you agree with what Gabbay says9 that an infection, however, is known to favor10 calcium deposition on tissue valves?11 A. I don't know if he's referring here12 only to valve endocarditis or, say, a general13 infection. I don't know if he's saying that. I14 think he's saying -- my understanding of infection15 induced calcification refers to an endocarditis with16 a lesion on the valve leaflet itself.17 Q. So, in your view, does an18 endocarditis infection tend to cause calcification?19 A. I think that calcium deposits can20 associate with those lesions. I don't know if the21 infection itself causes -- I wouldn't say that22 infection itself causes calcification.23 Q. When Gabbay says, infection, however,24 is known to favor calcium deposition and tissue25 valve, does Gabbay mean infection causes calcium

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1 deposition or calcification?2 A. I think he's saying -- I like the3 word "favor." It's a word that implies that it is4 an environmental feature that favors calcification.5 Q. Does that mean if there was an6 infection, you would be more likely to observe7 calcification?8 A. It's hard to say without knowing what9 else is going on.10 Q. I'm asking what your understanding is11 of what Gabbay said by "favor."12 A. Oh. I think if all other things are13 being equal, the presence of an endocarditis lesion14 on the surface of a valve, that particular region15 has a higher chance of having calcification than one16 that doesn't.17 Q. But Gabbay doesn't, specifically, say18 endocarditis, Gabbay just says "infection," right?19 A. I have to look back to see what -- if20 there were infections that he was describing.21 So, in his pathological findings in 451, at22 the bottom, it says three valves were found to have23 acute endocarditis. So then in another one it says24 that there was a feature of healed endocarditis but25 other valves that didn't.

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1 Q. So, in your view, are you saying that2 infection on Page 454 refers, specifically, to3 endocarditis?4 A. I don't know if I can make a claim to5 what exactly the infections that he was referring6 to. I would interpret what he was saying as an7 endocarditis lesion.8 Q. If he was referring to a specific9 type of infection, why wouldn't the authors just say10 that?11 A. I don't know.12 Q. How about Exhibit 1033, I have a13 question for you about one of the other Gabbay14 exhibits you looked at.15 A. 1033?16 Q. 1033.17 (There is a discussion off the record.)18 Q. And in particular Page 418.19 A. Okay.20 Q. And I'm going to read the21 parenthetical sentence that bridges 418 to 419. "It22 is known that biologic valves can calcify early if23 infected." Do you agree with that?24 A. Yes, if the valves were infected.25 Q. Is that the same thing as

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1 endocarditis?2 A. Endocarditis is a very common3 infection that occurs in valves and they mention4 endocarditis in this paper, too.5 Q. Other than endocarditis, are there6 other types of infections of valves that can cause7 calcification?8 A. I mean, I would have to look for9 different ones. I mean, there are rheumatic10 infections. There are -- I mean, there are11 different types of systemic infections.12 Q. I'm not asking you to identify all13 those. I'm just asking if there are other types of14 infections to heart valves that can cause15 calcification.16 A. Oh, this is the primary one that I'm17 aware of.18 Q. Okay. Referring to endocarditis?19 A. Yeah.20 Q. Let's go to Exhibit 1036.21 (Deposition Exhibit No. 1036, Schryer et al22 1986, was previously marked for identification.)23 Q. Do you recognize Exhibit 1036 as24 Schryer 1986?25 A. Yes.



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1 Q. And Schryer reports on testing of2 subcutaneous implants of glutaraldehyde pretreated3 tissue in young rats; is that correct?4 A. Glutaraldehyde fixed tissue in young5 rats, yes.6 Q. Schryer does not say anything about7 use of dogs for calcification experiments, does it?8 MR. TESCHNER: Look at whatever you9 need to.10 A. I haven't studied their references.11 But it does not look like they studied dogs.12 Q. Let's go to Exhibit 1037.13 (Deposition Exhibit No. 1037, Schoen et al14 1985, was previously marked for identification.)15 Q. Do you recognize Exhibit 1037 as16 Schoen 1985?17 A. Yes.18 Q. Schoen 1985 reports on testing of19 implanted glutaraldehyde pretreated valves both20 subcutaneous implants in rats and replacement valves21 implanted in calves; is that correct?22 A. Let's see; yes.23 Q. Schoen 1985 does not say anything24 about using dogs for such testing, does it?25 A. Again, I haven't or I'm not able to

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1 study the references to see whether they look at2 dogs. But this study doesn't use dogs. From my3 memory -- well, I don't know. I can't speculate. I4 know, at least, one group that they cited do use5 dogs but...6 Q. I'm only asking about the article,7 not about all the 34 references that are cited.8 A. That's right. It's hard for me --9 yeah, they don't use dogs for this study.10 Q. Okay. Schoen 1985 does report11 quantitative data for calcification, right?12 A. Yes.13 Q. Go to Exhibit 1038.14 (Deposition Exhibit 1038, Jones et al 1982,15 was previously marked for identification.)16 Q. Do you recognize Exhibit 1038 as17 Jones 1982?18 A. Yes.19 Q. And Jones 1982 reports on testing of20 bioprosthetic valves implanted in sheep, right?21 A. I see the two different types of22 sheep. I'm looking for the bioprosthetic23 information. If you could help me...24 Q. On Page 277, it refers to tricuspid25 valve implantation and on 279 it refers to mitral

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1 valve implantation.2 A. Right. I was just looking for like3 what they were implanting. I mean, I see it4 discusses in Table 1 76 bioprosthetic valves. I was5 just looking for, you know, what the valve was.6 Q. Well, if you look at Page 282, the7 text at the beginning of the -- of the first line on8 that page refers to bioprosthesis, right?9 A. Uh-huh, right. I just didn't know if10 it was a pericardial valve or aortic valve or11 jugular vein.12 Q. The implants used in Jones 1982 were13 tested after three to six months of implantation,14 right? If you look at Page 285, it refers to15 terminal elective study.16 A. I think that's -- well, they said --17 terminal elective studies, where is that? Oh.18 I mean, they report data from one to19 six months, so -- in both the tricuspid and mitral20 valves. I think they had an average of three21 months.22 Q. Well, if you look at top of the Page23 286, it says that of the 55 sheep that had undergone24 implantation of bioprosthetic valves in the mitral25 position, 35, 64 percent survived from 1 to

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1 6 months.2 A. Uh-huh.3 Q. 20 sheep died within 4 days after4 operation, 18 sheep died 1 to 5 months after -- from5 cardiopulmonary problems, infection of the6 bioprosthetic valves in late pericardial tamponade,7 right?8 A. Yeah. There were a number of9 different early deaths.10 Q. So it looks like those would be the11 studies that were done earlier than three months12 were due to premature deaths in the animals?13 A. Well, if you look at the statistics14 of the surviving sheep, right, like so, for15 instance, pathologic observations for the sheep16 surviving 1 or more months, it's 76 sheep and it's a17 mean of 4.2 plus or minus 1.7 months.18 So, if you look at that distribution, that19 means there must have been -- I forget how many but20 valves that were in a period earlier, much earlier21 than three months. So one standard deviation below22 that mean is 2.5 months. Two standard deviations23 is, you know .8 months.24 Q. Referring to Page 289, it's the full25 paragraph that begins with "Dogs have also been



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1 used."2 A. Okay.3 Q. Jones reports here that dogs are not4 suitable for such studies because their heart valves5 are too small during, quote, "their juvenile period6 of life," end quote; is that true?7 A. I'm looking for that. Where is...8 Q. It's the sentence that says, "The9 small tricuspid and mitral annular sizes of dogs10 during their juvenile period of life make the11 intracardiac implantation of clinically available12 valvular bioprosthesis technical difficult in this13 species."14 A. Okay.15 Q. Why does Jones refer to the juvenile16 period of life for the dogs?17 A. I think he's telling people if they18 want to use a juvenile dog, it's technically19 challenging to implant a valvular -- a clinically20 available valvular prosthesis in it because it's21 smaller.22 Q. Why wouldn't they just use an older23 dog?24 A. I don't know if they're telling you25 not to.

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1 Q. Jones reports that sheep are an2 excellent laboratory model for such studies, right?3 A. I'm looking.4 Q. Next paragraph after the one you just5 looked at.6 A. Sorry; yes.7 Q. Is Jones reporting here that sheep8 are a better animal model for such study than dogs?9 A. I don't see where they say that.10 Q. Well, they do describe sheep as being11 an excellent model, right?12 A. Yes.13 Q. Do they describe dogs as being an14 excellent model?15 A. No.16 Q. Do you interpret that to mean that17 dogs are a better model than sheep?18 A. I don't interpret the word "better"19 meaning to be that you can't use one or the other.20 Q. I didn't ask you could use one or the21 other.22 I asked if Jones is reporting that sheep are23 a better animal model than dogs?24 A. I think Jones is reporting sheep is25 an excellent animal model and dogs are also an

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1 animal model.2 Q. Right. But he doesn't say that dogs3 are also an excellent animal model, does he?4 A. No, he doesn't.5 Q. Let's go to Exhibit 1039.6 (Deposition Exhibit No. 1039, Deck et al7 1982, was previously marked for identification.)8 Q. Do you recognize Exhibit 1039 as Deck9 1982?10 A. Yes.11 Q. Deck reports on testing of12 bioprosthetic valves implanted in young calves,13 right?14 A. Yes.15 Q. Pages 297 to 98, beginning at the16 bottom of 297, Deck reports that calcification was17 revealed by radiography as early as four weeks after18 implantation; is that right?19 A. On Page 297?20 Q. Right. It's the last sentence on 29721 going over to 298, "In porcine valves radiography22 revealed calcification as early as four weeks after23 implantation." And then continuing to read the rest24 of the sentence, "even though it was not apparent25 visually until several weeks later."

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1 A. So these are porcine valves. So, for2 the porcine valves, that's the same. The3 pericardial ones they were able to observe4 calcification after four weeks.5 Q. Does this tell you that, at least,6 for porcine valves early visual observations may7 fail to reveal calcification that was already8 present but not visible?9 MR. TESCHNER: Objection to the form10 of the question.11 A. I think there are multiple methods to12 determine calcification depending on the level of13 how you want to see it. So, in this case, they used14 gross examination and -- I guess, or radiography.15 Q. But do you agree that Deck is16 reporting that, at least, for porcine valves there17 may be calcification that is detectable by18 radiography but not apparent by visual observation?19 MR. TESCHNER: Objection to form.20 A. The paper does say that for porcine21 valves radiography revealed calcification as early22 as four weeks, even though it wasn't apparent23 visually until several weeks later.24 Q. If they had only been doing a visual25 observation, they would have missed the



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1 calcification present at that time, right?2 MR. TESCHNER: Objection to form.3 A. Yeah, I think they were using4 multiple methods to detect it. So I don't know if5 their visual information, that information also6 refers to the aortic wall because it looks like7 that's much more calcified.8 Q. You do not cite any of your own9 studies in your declaration, did you?10 A. No.11 Q. Have you ever used dogs for a12 calcification study?13 A. I have used tissue from dogs in14 calcification studies.15 Q. Have you ever used tissue implanted16 in dogs for calcification studies?17 A. No.18 Q. Other than Exhibit 1018, you do not19 cite any other publications of Dr. Kaplan, right?20 A. No.21 Q. Why not?22 A. My objective was to utilize the23 articles that were cited or utilized in the24 declaration or response of the Patent Owner and25 Schoen.

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1 Q. You did your own searching for2 articles, though, right?3 A. Yes.4 Q. You didn't find anything relevant5 authored by Dr. Kaplan?6 A. I mainly focused on the authors, you7 know, the articles authored by Schoen, articles8 authored by -- so I didn't find any other articles9 for Kaplan.10 Q. And you did not find any other11 articles for any scientists at the Hope Heart12 Institute as well?13 A. I can't say for sure whether the14 authors in the papers that I looked at were at one15 point part of the Hope Heart Institute.16 Q. You didn't cite anything that17 indicated that one of the researchers was at the18 Hope Heart Institute, right?19 A. You mean at the time of writing the20 article?21 Q. At the time of writing or22 publication.23 A. I don't know if I could know whether24 they were at the Hope Heart Institute. Certainly, I25 would know if they were listed as that was their

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1 affiliation in the article itself.2 But what I'm saying is, I think, you asked3 also at the time of the invention and some of the4 articles I cited were much later. So I don't know.5 Q. Well, in connectin with the articles,6 I was really asking at the time of the articles.7 A. Okay.8 Q. You didn't cite any articles that9 indicated that one of the authors was affiliated10 with the Hope Heart Institute, right?11 A. I don't recall any.12 Q. Other than Exhibit 1018, the Kaplan13 article, you didn't cite any other publication that14 reports on testing for calcification of implants in15 adult dogs only after 21 or fewer days, right?16 MR. TESCHNER: Take whatever time you17 need to answer the question.18 A. So the Han article was looking at19 prosthetic grafts that were implanted in dogs,20 mongrel dogs.21 Q. What's the Exhibit number on there?22 A. 25, 1025, sorry. And they utilized23 --24 Q. We talked about that before. So25 those were not glutaraldehyde --

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1 A. Right.2 Q. -- fixed, right?3 A. Right.4 Q. And those dogs -- the experimental5 model wasn't intending to test the 21 or fewer days,6 the dogs simply did not survive 21 days, right?7 MR. TESCHNER: Objection to form.8 A. It says survival periods were 14, 249 and 39 days.10 Q. So they tested them early because11 they didn't last any longer?12 A. The Okamura paper that's 1027 is --13 they look at dogs -- they have a dog that they find14 calcification in 41 days.15 Q. Again, those are dogs that died16 prematurely, right?17 MR. TESCHNER: Objection to form.18 A. Well, a lung infection is not valve19 related, so...20 Q. The experimental model was not to21 sacrifice the dogs at 21 days or fewer, they had22 just tested dogs that had died prematurely, right,23 the dogs that survived were kept, at least,24 141 days?25 A. The remaining three, yeah.



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1 Q. Let's see if we can direct your2 attention to Exhibit 2007.3 (Deposition Exhibit 2007, The Trifecta Valve4 by St. Jude Medical, was marked for identification.)5 Q. And before I get to that, let me6 confirm...7 You testified before that the primary8 feature of calcification is its presence or absence,9 right?10 A. Yes.11 Q. Okay. If that's the case, why did we12 see so much quantitative data reported in the13 publications that you cited in your declaration?14 MR. TESCHNER: Objection, that's15 outside the scope of his direct.16 Q. Maybe I handed that to you too early.17 You don't need to refer to the exhibit to answer18 that.19 A. Uh-huh. Didn't I already answer20 that?21 Q. You might have. I'm just a little22 puzzled by it.23 If the primary feature of calcification is24 its presence or absence, why did these researchers25 spend so much time generating quantitative data?

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1 A. It may have been that they were2 trying to compare across different groups of3 experimental models or experimental conditions.4 Q. Now, I have a question for you about5 Exhibit 2007. Do you recognize that as St. Jude6 Medical's Trifecta valve brochure?7 A. Is this called a brochure?8 Q. Well, maybe that's not the best word9 for it.10 A. I don't know. I just haven't looked11 at it.12 MR. TESCHNER: I object. This13 exhibit is outside of his scope. He indicated14 earlier that this is not a document he reviewed.15 Q. In particular, why don't you take a16 look at Page 10 of the Exhibit, 10 at the bottom of17 the page.18 A. Exhibit Page 10?19 Q. Exhibit Page 10. And you see Figure20 12 at the top of that page?21 A. Yes.22 Q. What is shown in that figure?23 MR. TESCHNER: Objection, outside the24 scope of his direct.25 A. I see a graph with two bars and I see

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1 a line across the top of the bar.2 Q. And the line at the top, is it3 80 milligrams calcium per gram, right?4 MR. TESCHNER: Same objection.5 A. That's what it says.6 Q. And the text states that,7 "80 milligrams calcium per gram tissue is similar to8 what is encountered clinically in failed specimens."9 Did I read that correctly?10 MR. TESCHNER: Same objection.11 A. It looks like the information that12 was gained to establish that was from 1999 study.13 Q. And do you agree that 80 milligrams14 calcium per gram corresponds to clinical failure of15 implanted valves?16 A. I have no idea --17 MR. TESCHNER: Same objection.18 A. -- if that is what a clinically19 failed specimen...20 Q. What is shown by the two bar graphs,21 the two bars on that graph?22 A. It looks like one of them says23 Trifecta valves with Linx AC Technology.24 Q. Do you know what Linx AC Technology25 refers to?

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1 A. No.2 Q. Do you understand that refers to the3 invention claimed in the 775 Patent?4 MR. TESCHNER: He just answered that5 question. He answered, no.6 Q. And then the right-hand graph says,7 "Trifecta control valve," right?8 A. Yes.9 MR. TESCHNER: Objection, outside the10 scope of his direct.11 Q. How much calcium is indicated in12 those two graphs?13 MR. TESCHNER: Same objection.14 A. The text doesn't say, specifically,15 but it looks to me like they have a statistically16 similar amount that hovers around 20 milligrams per17 gram.18 Q. Do you know why St. Jude includes19 quantitative information in this document?20 MR. TESCHNER: Same objection.21 A. I imagine the FDA requires it.22 Q. Do you agree that an appropriate23 analysis for calcification includes a quantitative24 analysis, a histology study and an X-ray analysis?25 MR. TESCHNER: Object to the form of



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1 the question.2 A. I disagree that it requires all of3 those.4 Q. Now, do you see that this document5 states -- you see the text beginning at "A6 combination"?7 A. Okay.8 Q. It states, "A combination of all9 three methods, ICP, AES, histology and X-ray, is10 vital to comprehensively assess bioprosthetic heart11 valves calcification."12 MR. TESCHNER: Objection, outside the13 scope of his direct.14 A. I see that sentence.15 Q. Do you agree with that sentence?16 A. For a comprehensive assessment, sure.17 Every method you could possibly apply would be18 sufficient to establish a comprehensive assessment.19 Q. Do you think St. Jude is not aware20 that the most important feature of calcification is21 its presence or absence?22 MR. TESCHNER: Objection to the form23 of the question.24 A. I don't know if St. Jude is aware of25 that or not.

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1 Q. Alright. Going back to your2 declaration, Paragraph 47.3 A. Okay.4 Q. Towards the end of that paragraph5 your declaration states that, "The lack of6 additional information in Kaplan would inspire a7 person of ordinary skill in the art to confirm their8 findings perhaps with other techniques and perhaps9 with a different tissue or animal model." Did I10 read that correctly?11 A. Yes.12 Q. Are you aware of any follow-up13 studies that anyone performed to confirm what was14 reported in Kaplan?15 A. I mean, I think I answered this16 before, that although the 775 Patent does not cite17 Kaplan, it looks like it conducted a similar study.18 I have not been aware of a study that cited Kaplan19 that performed a follow-on study.20 Q. Are you aware of any researcher that21 was inspired by Kaplan to do a follow-up study?22 A. Not that they've told me.23 Q. And actual fact, as far as you know,24 no one was inspired by Kaplan to do anything, right?25 MR. TESCHNER: Objection, form,

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1 argumentative.2 A. I do not know who else was aware of3 Kaplan at the time. But a person of ordinary skill4 in the art had Kaplan available to them.5 MR. WEINER: Okay. Let's go off the6 record.7 (There is a discussion off the record.)8 (Recess taken 6:01 to 6:06 p.m.)9 Q. A couple more questions.10 Dr. Butcher, in your declaration, you11 referred to NIH funding for Dr. Kaplan's article or12 Kaplan Exhibit 1018, right?13 A. Yes.14 Q. In particular, Kaplan refers to the15 NIH grant and provides the number of the grant.16 Have you seen the NIH grant paperwork?17 A. No.18 Q. Did you try to get a copy of it?19 A. There are ways of looking up grant20 information. I was unsuccessful. I think it had to21 do with the shutdown.22 Q. Okay. So you don't know if this23 grant provides for funding for calcification24 studies?25 A. No.

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1 Q. You don't know if the grant indicates2 that dogs are to be used for calcification studies?3 A. I find it difficult that they could4 perform a study as expensive as this supported by5 that grant without the approval of the NIH.6 Q. But you don't know that?7 A. Well, they didn't list any other8 funding sources, so I don't know how that was paid9 for.10 Q. But you don't know what was in that11 grant application?12 A. I don't know, specifically, what the13 aims of the experiment were.14 Q. You don't know if the grant indicates15 that 21-day implantation period is supposed to be16 used for this study, right?17 A. No.18 Q. Did the NIH review Exhibit 101819 before its publication?20 A. My experience with the NIH is that21 they don't need to review the application.22 Q. Have you ever seen a NIH funded study23 that you thought used incorrect scientific24 methodology?25 MR. TESCHNER: Objection to the form



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1 of the question.2 A. I think that I have read studies that3 were NIH funded that promoted data that I was4 skeptical about.5 Q. Have you ever seen a NIH funded study6 that used an inappropriate animal model?7 A. Not one that was published. I mean,8 I haven't seen an unpublished one but...9 Q. Have you ever seen an NIH published10 study that you were surprised received funding from11 the NIH?12 A. I mean, I certainly wasn't in the13 room when they were making the decision. I'm always14 surprised when they reject my grants.15 Q. Have you ever received grants from16 the NIH?17 A. Yes.18 Q. In the event when the NIH turned down19 your request for funding, did you agree with the20 decision?21 A. Sometimes.22 Q. How many times have they turned down23 your grant requests?24 A. So that the typical grant strategy is25 one where you're trying to obtain reviews of your

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1 proposal. So you're, essentially, writing the grant2 to get it funded the second time. It's called the3 revision process. So it used to be at previous4 points until say about 2008 that you could resubmit5 the same exact proposal that's edited or improved up6 to three times and now you can only do that -- you7 can only put it one more time. So that was part of8 the grant writing improvement process. So I would9 say that I have gotten grants that were funded at10 the first stroke, meaning, the very first time and11 others I had to write revisions to get them funded.12 I can't give you the number off the top of my head.13 Q. I don't have any further questions14 for you.15 A. Okay.16 MR. TESCHNER: We have a few17 redirect.18 EXAMINATION BY MR. TESCHNER:19 Q. Doctor, you were just answering some20 questions about the various articles that were cited21 attached to your declaration.22 A. Yeah.23 Q. The subject of endocarditis came up24 several times, do you recall that?25 A. Yes.

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1 Q. Is endocarditis something that's2 possible or likely in carotid artery like the one3 studied in the Kaplan article?4 A. No.5 Q. Also, this morning you were asked a6 number of times about the level of information7 provided in Kaplan. Do you recall those questions?8 A. Yes.9 Q. Do you recall also being asked if you10 would have written the disclosure in question11 differently?12 A. "The disclosure," you mean the13 publication?14 Q. The disclosure for that particular15 question, whichever one it was at the time. Were16 you asked if you would have written it differently?17 A. Written the particular. -- I guess I18 don't know --19 Q. If you would have written the section20 that you were discussing of Kaplan differently is my21 question.22 A. Oh, yes.23 Q. And do you recall answering some of24 those questions that you would?25 A. Yes.

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1 Q. And, when you answered those, were2 you talking about a time period of today or 19853 when Dr. Kaplan's paper was published?4 A. I was referring to today.5 Q. Okay. And, based on her article and6 the contemporary articles that you've reviewed,7 would you consider the level of information that was8 provided in the Kaplan article to be appropriate?9 A. Yes.10 Q. And would the omission of some of the11 information that was discussed this morning be a12 reason to doubt what was actually reported in the13 article?14 A. When you say by "omission," you mean15 the fact that they didn't have say absorption16 spectroscopy data or radiography, something like17 that?18 Q. Yes, correct.19 A. No, I don't think that disqualifies20 what was reported.21 Q. Finally, counsel pointed out an error22 in Paragraph 51 of Exhibit 116, which is your23 declaration. If you could -- if you have that in24 front of you.25 A. Okay.



74 (Pages 290 to 293)

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1 Q. And the error was identified with2 respect to the citation of the Levy 1983 article.3 A. Yes.4 Q. And you expressed a belief at that5 point that the statement you made in Paragraph 516 was correct but, obviously, you had pointed to the7 wrong exhibit?8 A. Yes.9 Q. Have you had time since then to look10 further at the other exhibits that were referenced11 in your declaration?12 A. Yes.13 Q. I'm going to show you -- it's got to14 be in the pile somewhere. But this is Exhibit 2003,15 the Shemin article, Shemin 1988; is that correct?16 A. Yes.17 Q. You're familiar with this article?18 A. Yes.19 Q. Is this the exhibit that you meant to20 reference in Paragraph 51 instead of the Levy 198321 article?22 A. Yes.23 Q. And Dr. Schoen is a coauthor of the24 Shemin 1988 article?25 A. Yes.

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1 Q. And does the Shemin article use2 quantitative methods for measuring calcification?3 A. No.4 Q. Okay. That's all I have.5 MR. WEINER: I have a couple of6 questions on recross.7 EXAMINATION BY MR. WEINER:8 Q. Are you saying that in Paragraph 519 you referred to Levy 1983 when you intended to refer10 to Shemin 1988?11 A. So when I said -- I meant to refer to12 Carpentier and Levy in 1982, since Levy was a13 coauthor of Carpentier and then an article that was14 coauthored by Schoen, which that was the trouble15 that I had, and it's the Shemin article in 1988.16 Q. I'm confused by that.17 In Paragraph 51, you said Carpentier 198218 and Levy 1983 provide no quantitative data.19 A. Yes.20 Q. But --21 A. That's -- the text says that. I'm22 telling you it's a typo.23 Q. I just want to make sure --24 A. Yeah.25 Q. So the typo says -- where it says

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1 "Levy 1983," you meant to write Shemin 1988; is that2 what you're saying?3 A. No, what I meant to say was4 Carpentier and Levy 1982.5 Q. So what does that have to do with6 Shemin 1988?7 A. That's the article that's coauthored8 by Schoen.9 Q. But Shemin 1988 is referred to in10 Paragraph 51.11 A. Yes. It is also referred to. I12 understand that. That's why --13 Q. You're saying it should have been14 referred to two times?15 A. No, I'm saying that I meant to refer16 to the Carpentier article and the Shemin article in17 this paragraph. So this is a summary of paragraphs18 from 48, 49 and 50. And so, you know, I was trying19 to summarize that.20 Q. Yes. But, on 49, you also referred21 to Levy 1983 Exhibit 2005.22 Are you saying there is an error in23 Paragraph 49 as well?24 A. No, I meant 48 through. So each one25 has its own contribution to the statements that I

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1 was trying to address in terms of the standards set2 by the PO for Kaplan.3 Q. So are you saying the error in 51 is4 where it says "Levy 1983" that should be crossed out5 and replaced with Shemin 1988?6 A. Well, no. I would say that7 Carpentier 1982 -- you could easily do it by saying8 Carpentier 1982 and then strike "and Levy 1983,"9 both.10 Q. Okay. So you're referring to two11 articles there, but you really meant to refer to12 one?13 A. No, I really meant to refer to the14 Carpentier 1982 and the Shemin 1988.15 You mean in that one sentence or...16 Q. I want you to explain how you correct17 this paragraph to correct for the typographical18 error.19 A. So I'm saying that I would strike the20 word "and Levy 1983." Well, I guess you could keep21 the comma but both. So you would say, Carpentier22 1982 coauthored by the inventor Dr. Levy provides no23 quantitative data, only data that Dr. Schoen admits24 is semi-quantitative.25 Q. So you referred to two articles there



75 (Pages 294 to 296)

294

1 but you really just meant to refer to one; is that2 what you're saying?3 A. In that one sentence?4 Q. Yes.5 A. Yes.6 Q. So why did your counsel on redirect7 ask you about Shemin 1988? That has nothing to do8 with the error that you're saying occurred in9 Paragraph 51, right?10 A. Because I wanted to -- in this11 paragraph -- to refer to these two articles.12 Q. To Carpentier 1982 and Shemin 1988?13 A. Yes.14 Q. So you did refer to Shemin 1988 and15 Carpentier 1982?16 A. Yes.17 Q. That's already there.18 So what does that have to do with the19 supposed error you had in listing Levy 1983 when you20 didn't mean to?21 A. I guess I don't know what you're22 saying. It's a typo. I meant to refer to those two23 articles. I mean, clearly, when I looked at -- when24 I discussed the Levy paper in Paragraph 49, I'm25 discussing calcium levels and quantitative data. So

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1 I didn't mean that one.2 Q. Why did you cite to Exhibit 2000, the3 Schoen declaration of Paragraph 25 there?4 A. I think I was referring to what5 Schoen says semi-quantitative data is. But I have6 to see it to make sure.7 (There is a discussion off the record.)8 A. I probably have it somewhere here.9 Q. I don't have an extra copy.10 A. I probably have one. Here, okay,11 paragraph 25. So it says, "Calcification may also12 be evaluated by radiographic studies using" -- this13 is Paragraph 25 -- "calcification may also be14 evaluated by radiographic studies using X-ray15 densitometry, which is a semi-quantitative method16 that evaluates the density and extent of calcific17 deposits on the tissue."18 Q. Okay. I don't have any further19 questions. Thank you.20 MR. TESCHNER: We're done.21 (Time noted 6:19 p.m.)22232425

296

1 C E R T I F I C A T E23 I, SILVIA P. WAGE, a Notary Public and4 Certified Court Reporter of the State of New Jersey,5 License No. 30X100182700, Certified Realtime6 Reporter and Registered Professional Reporter, do7 hereby certify that prior to the commencement of the8 examination, JONATHAN T. BUTCHER, Ph.D., was duly9 sworn by me to testify the truth, the whole truth10 and nothing but the truth.11 I DO FURTHER CERTIFY that the foregoing is a12 true and accurate transcript of the testimony as13 taken stenographically by and before me at the time,14 place and on the date hereinbefore set forth.15 I DO FURTHER CERTIFY that I am neither a16 relative nor employee nor attorney nor counsel of17 any of the parties to this action, and that I am18 neither a relative nor employee of such attorney or19 counsel, and that I am not financially interested in20 the action.212223

________________________________________24 Notary Public of the State of New Jersey

My Commission expires November 9, 201725 Dated: December 4, 2013



1

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26:4,7,12,16,18,2127:7 29:13,20 30:3,530:20 31:2,19,22,2432:7,12,20 33:2,5,834:2,5 35:8 36:3,2036:22,23,24 37:13,2438:3,6,18,19,2439:15,16 40:10,2441:3,17,17 42:11,1742:19 43:13 46:6,1546:18 52:14,19 53:453:13,22 56:6,8,1256:13 57:6,8,10,1257:17,18 58:1,8,1258:16,20,21 59:9,2159:24 60:2,10,17,2160:22 61:1,24 63:1964:17,24 65:2 68:170:9,14,18,23 71:6,971:15,18 72:22 73:273:7,10,16,21 74:1,674:22 75:2,13,2376:14,16,20 77:480:1 82:18 84:5,1384:20,25 86:1 89:3,489:8,12,18,21 96:1396:21 97:15 98:14,2499:9,17 100:4 105:17111:8,17,23 112:15112:24 113:3,8,21114:3,15,19,21 115:3115:8,11,12,18,21,22116:1,10 117:23118:6,13,16,17,19,21119:25 120:5,6,8,12120:16 122:20,23124:25 125:1 128:16129:12,15 130:13,14130:17 131:4,13135:5,11,16 137:4,7137:9,15 143:16,16146:11,14,18,23147:3,9 149:12150:14,20,23 151:7,9151:25 152:21,24153:3,5,8,14 154:15



6

154:15,20 155:12158:24 160:9 162:1,7162:10,12,17 164:21165:10,21,24 166:4166:15,18,24 167:8167:17 169:11 170:7170:22 171:1,8,11,18171:22 173:19 177:2177:6,9,14,18,20179:14,23 180:12,19180:24 181:18184:10 185:3,6,11,16186:1,11,16,23187:15,21,24 188:6,9188:15,22 189:2,13189:22 190:5 191:2,8191:10 192:24193:11 194:8 195:4,5195:11,12 196:3,19196:21,24 197:25198:3,4,9,16 199:6,8199:10,15,17,23200:2,9,11,12,15201:14 202:10,16,22202:23,25 203:8,17205:25 206:5,9 207:6208:9,17 209:8,11210:1 211:20 212:10212:22,23 213:5214:24 215:1,9216:10 218:2,6,10,22220:11,13,15 221:9221:17,24 222:1,3,21222:22,25 224:14225:11,14 226:2,18227:18,25 228:3,13228:24 229:7,14,18229:21 230:16,23231:8,11,23,25232:13 233:3 234:4,9234:13,18,24 235:2235:14,22 236:2,14236:16,22,24 240:6240:13 243:5,18,22248:17 249:13,20250:3,13 253:9,20

261:21 262:15,18,22263:1,4,7,15 265:7265:15 266:7 267:11272:16,22 273:4,7,12273:17,21 274:1,12274:14,16 276:14277:14 278:8,23281:23 282:11,20284:23 285:2 291:2295:11,13

calcifications233:12calcification-related77:10calcified9:9,16 24:13 30:22

57:5 64:10 145:8,12158:9,13 160:10161:23,24 188:1205:16 206:17,21207:14,18,23 210:8210:10,15 211:4,25212:13,19 216:3,8217:24 219:9 225:17274:7

calcifies98:9 208:23 209:23

225:12calcify33:12,22 37:2,4,10

39:4,14 42:21 56:2199:19,19 132:1,3135:25 145:10 155:4160:18,22 171:4189:25 190:8,10,21194:10 207:11209:12 210:25225:16,18,19 226:24264:22

calcifying56:20calcium23:25 24:7,9,12,15,19

24:21,22 25:1,3,3,625:13,24 61:4 94:6,894:19,24 95:4,10,19

96:1,18 97:19 99:699:21 102:16,23184:24 185:1 232:17232:24 233:13,25235:19 236:4,7,9239:1,3 245:25248:21 249:1,15,17249:21,25 250:12253:16,22 261:25262:10,19,24,25280:3,7,14 281:11294:25

call13:24called1:10 22:9 127:23

139:10 279:7 287:2calves239:25 266:21 272:12canine118:1 125:22 126:6

143:18 193:17,19,21197:6,16 201:23229:25 238:18240:11 259:3,21,25260:12 261:14

capable173:22cardiac43:14,17 258:25 259:8cardiology1:3 8:14 85:3 128:6cardiopulmonary269:5Cardiovascular52:3 251:1care43:8Carolina8:10,12carotid125:22 126:6 172:10

190:16 193:17,19,21197:6,16 201:23288:2

Carpentier

3:9 92:4 105:15,19220:20,22 221:3,12222:7 291:12,13,17292:4,16 293:7,8,14293:21 294:12,15

carried259:13case1:2 6:6 7:10 20:22

37:7 38:14 53:2562:21 67:3,22 86:12104:6 111:3 114:4121:7 127:10 137:19158:5 180:13 206:7206:11,15 209:24273:13 278:11

cases8:22 9:2,8,9,23 53:16

72:18 171:21category145:22cause32:12 162:6,12 171:22

261:20 262:18 265:6265:14

caused114:19 162:17 171:18

216:10 217:16,20218:9,22

causes262:21,22,25causing170:21CDP234:13,16ceased151:18 214:17cell13:19 24:25,25 25:15

25:18 56:18 61:1cells13:20 24:16,20 25:19

29:14 30:17 31:951:18 56:7,19

cellular26:13,14 168:3 234:13



7

certain20:16 24:23 25:7

70:24 99:2 137:16162:8 251:7

certainly16:13 34:7 62:7 63:6

71:2,20,21 78:584:21 97:16 129:16164:8 173:22 178:12182:9,14 213:15215:15 229:19275:24 286:12

Certified1:12,13 296:4,5certify296:7,11,15cetera25:20 30:19 57:14

62:22 71:2 72:18139:5 155:24 164:19208:21 213:14

challenging270:19chance61:12 63:24,25 263:15change100:8 117:8,17 134:6changed26:22changes14:11 230:16 261:5channels24:22chapters15:19characteristic152:25characteristics32:18 57:25 78:18

128:17 129:13152:15,23 203:6

characterize165:4characterized50:15charged

103:19 104:1,8checked183:12chemical21:5 56:10,11,20

137:12 152:15 203:5222:9

chemicals57:25chemistry68:24 69:17Chicago2:11child38:22,25 39:3,5 42:16

42:18 226:15childhood9:4children38:14 226:11,17choice152:16choose195:20chose123:16 195:19 224:22

227:13 239:11,14,16chosen152:13 203:4Christopher124:1circulation128:6circulatory47:24 48:7circumstance169:21circumstances137:16 162:3citation106:23 138:6 290:2citations127:21,25 128:2,4,5cite106:13 130:7 141:6

143:3 156:17 215:8

215:25 274:8,19275:16 276:8,13283:16 295:2

cited18:5 21:8 22:7 106:11

121:12 127:2,4,9202:10 213:20214:22 220:20257:24,25 267:4,7274:23 276:4 278:13283:18 287:20

citing156:22claim17:6 60:9 62:8,13

67:24,25 83:22 84:12264:4

claimed281:3claims17:5 62:10 67:21 84:9clarified78:7clarify27:12 83:14 86:11

88:13clarifying147:10class10:2classifies81:1clean172:14clear81:2 88:25 113:17

192:15 216:20 256:9256:10

clearly99:9 101:8,13 111:16

227:14 294:23Cliff3:19 19:18clinical8:18,19 9:8,20 23:18

23:19 45:15 51:14

70:8 72:15 78:6180:20,22,25 181:1,8181:22 184:8 185:7280:14

clinically34:3 270:11,19 280:8

280:18clinician43:11 80:12clinicians43:7,14 72:15 80:20

185:11close197:23closer16:12 81:17clotting143:7coagulation138:3 140:7coated220:2 237:21coating237:25 238:7,9,16coauthor107:7 290:23 291:13coauthored92:6 105:4,15 291:14

292:7 293:22coauthors108:9coincidently244:1collaborate44:16collagenous176:22 177:22 179:16colleagues45:15 72:17 85:11column28:17 29:1 34:24 84:3

94:13 102:21 119:18119:19 133:16,21,22139:18 143:15146:25 193:18197:15 224:14 233:8



8

234:12 242:11 246:9251:25 260:20261:24

columns195:22combat13:4combination56:17 237:22,24 282:6

282:8come30:8,13 32:23 59:2

127:11,14 151:21183:2 250:8 251:2

comes41:19 44:3 66:19comfortable7:16coming140:12 142:18comma293:21commencement296:7commencing1:19comment54:5comments170:16,17 232:9Commission296:24committees32:4common38:5 213:14 265:2communicate72:17compare10:13 12:19 39:12

55:16 98:1 157:14,16227:24 249:24 279:2

compared37:24 38:23 57:3

58:23 205:21 226:23230:10 250:3

compares227:1comparing45:11 96:12 253:16,22comparison27:9 30:4 33:23 53:1

61:16 62:20 98:4132:14 134:7 157:20158:2,25 159:6,16,19159:22 213:21 250:8250:16

comparisons159:23compatibility238:14,21complete20:20 96:19 220:3

254:11completed252:16completely112:1complex234:14complication216:11complications124:22 184:8component30:19components14:14 143:9 164:16

166:11composite219:17composition147:6comprehensive236:10 282:16,18comprehensively282:10concentration25:24 95:4concentrations94:6 95:20 96:1concept

78:10concern37:13 64:12 184:21concerning134:25 135:3 136:21

180:23 181:2,9 183:8195:3,12 201:14202:16 203:11

concerns89:7conclude188:13concluded133:8 134:15 214:5

235:13conclusion53:2 133:11 151:22

155:18 171:20 187:9214:11

conclusions123:1,3 219:25 227:9condition61:8,14 100:13 145:10

146:1 158:2 191:18199:2 200:5 213:1

conditions38:21 47:19 100:14

130:9 161:5 197:11252:8 279:3

conduct43:3 52:25 62:20

242:25conducted56:9 122:11 151:14

250:16 283:17conducting63:4 70:8 81:20

243:15conduit246:9,13conference15:19conferred70:2configuration35:6 46:22 117:5,15

119:9 120:3 134:3configurations47:2confirm235:25 236:13 278:6

283:7,13confirmed117:7,16 134:5confused31:12 106:15 129:17

168:17 291:16confusing88:14connectin276:5connection22:3 30:6 72:8 85:10

88:8 121:10 201:11251:10

connective168:2consequence217:21consequences13:12 124:23 126:4

224:24consider31:18 33:15 70:7

121:17 144:16181:23 289:7

consideration33:12 127:24 134:22considered24:13 25:6 32:8 40:9

40:15,19 41:6 42:252:13,18 53:3,15,2259:1 78:20 79:1380:19 168:10 221:19

considering84:7,8consistent73:12 156:10 168:25

188:15,22 189:15212:17 215:10

constant117:13 133:4 134:2



9

199:3 200:5constraints33:15consult8:19 121:9 251:10,14contain105:16contained125:2 152:22contains31:1 123:8,18contemporary289:6content102:23 249:1 253:16context35:23,24 83:10 86:22

133:24 206:1 236:3continue195:12 202:8 252:15continues133:21continuing195:6 202:1 272:23contract104:8contracting140:18contracts140:15contrast55:16contribution112:8,21 292:25contributor171:11control97:22 98:5,10,18

109:22 117:21157:11 158:3,4,20,25159:12 221:5 230:8,9281:7

controlled139:21controls61:6,8,20,23 62:1

157:7 158:6 183:22183:25

convenience35:22convenient7:15 50:12,22 126:15conveyed187:1convince44:8convinces43:11convincing43:7copied88:17 156:4,6copies7:7,12,16 90:14copy6:23 7:2 27:24 28:7

88:4 90:7,8 220:24223:18,21 257:10284:18 295:9

cordal244:15core25:15Cornell5:2 12:11corner88:20,21 257:15coronary197:23correct10:6 15:7 20:5 22:5

28:15 29:11 39:2349:7 82:12 101:1118:16,21 132:21133:10 134:14 137:5141:14 174:9 199:6227:5,19 242:9 266:3266:21 289:18 290:6290:15 293:16,17

corrected7:23correctly

27:18 35:8,19 40:1148:18 69:3 96:23111:18 114:22120:17 128:19132:17 134:12136:17 138:4 139:25143:19 176:23186:12 205:18 220:5222:5 280:9 283:10

correlation238:13correspond25:23corresponds280:14counsel2:7,13 6:3 7:2 21:3

22:11 23:2,6,7,10,1328:7 50:20 78:9 83:586:9 88:4 101:24105:22 126:14167:11 223:22289:21 294:6 296:16296:19

counsel's108:20count179:21,23couple17:24 78:16 89:2

241:1 255:23 284:9291:5

course35:24 157:10 158:20

159:7,15,23,24,25173:1,6 183:5 184:4227:16 247:17

court5:24 6:14 19:12 28:2

104:17 254:6 296:4cover67:16 172:10covered219:3crack238:24

crash217:17CRC21:5,11create14:13 110:11crime237:6,7,9,11criteria50:4criticizing107:21 110:8cross196:14crossed293:4cross-plant245:7crystalline236:1,13crystallinity24:4crystals24:3 25:4,14 233:11CT9:21 57:13culture56:18cultured51:17cured252:18currency24:17current261:14currently12:10 15:18curved197:21cusps243:22cut106:9cutoff250:19



10

CV10:4 15:6,10cycle51:13cylinder64:24,25

DD3:1 5:1damage162:4 167:18 169:3,6

169:12,18,23,24171:7

data12:1,4,8 15:24 16:5,8

16:11,15,19 17:550:6 55:3 60:13 91:991:12,12,19 92:1,794:1,8,10,24 95:2,3,895:17 96:1,3,12,1998:6,10,20,21,2399:1,13 100:11,12,24101:1,7,9 102:12,19103:5,7 105:17 107:5107:8,23,25 109:15109:19,21 110:3,15128:10 130:13,14134:16,21,24,25158:3 159:8,14,17,19159:21 179:8 189:16191:24 202:7 212:17227:22 228:11 237:4248:17 260:5,12,16267:11 268:18278:12,25 286:3289:16 291:18293:23,23 294:25295:5

databases251:7,12,14 258:3date17:23 49:2 92:7

296:14Dated296:25

DAVID1:16 2:2day159:8 247:8days95:14 97:25 141:17,25

142:3,6 143:23 144:1145:1 146:7,9 150:4151:14,18 152:7158:6 159:22 160:3,7160:9,11 161:23162:2 173:5,6,10174:20,25 181:22182:12,19 183:18188:15,22 206:14,18206:21 208:10,17209:8,13 210:1,15214:15,17 215:1,12215:14,18 216:1217:23 218:15,18225:20 227:5,6,8,8227:11,12,13,14239:6 241:11 242:22243:1,3,6,12 247:8247:22 252:19 269:3276:15 277:5,6,9,14277:21,24

dealing9:15dealt8:25 9:10 14:11death24:25,25 215:24

241:19deaths241:17 269:9,12debris29:14 31:10December1:18 296:25decide11:4 39:16decides122:9deciding182:16

decision11:1 48:14 180:25

181:1,19 185:14286:13,20

decisions180:20,22,23 181:2,8

181:9Deck3:18 272:6,8,11,16

273:15declaration3:8,8,20 6:17,21 7:8

7:20,23 17:11,14,2117:23 18:1,5,6,1619:23 20:13,14 21:821:15 22:7,8 44:1453:20 63:15 65:10,1465:17,19,23,24 66:968:6 69:7 81:24 82:283:3 88:8 91:3,7,1891:25 92:12 96:599:4 100:23 101:6103:8 104:16 105:2105:24 106:12,25107:10,21 111:5,14116:18,24 117:1128:13 129:3,9130:12 132:2,8136:13,24 141:13148:5 177:1 180:18186:6 191:5,6 205:9205:15 213:20214:22 215:8 221:15231:14 235:13 242:2254:3,8 274:9,24278:13 283:2,5284:10 287:21289:23 290:11 295:3

declarations18:17 20:21decline11:23,25deep168:18deficient109:15,23

define39:16 140:8defined139:16defines29:8 131:15 143:3

255:9defining138:21 142:20definitely16:11 77:14 86:22

105:9 114:8,11,20definition72:14 81:16 141:8,10

142:14degeneration13:3degenerative13:8degradation198:6 234:14degree8:4 68:24 69:16,19,21

70:2 89:20 98:24100:8 114:12,21185:5 222:3

dehydration252:18Delaware1:16deliberations48:21delineate148:4demonstrate51:7 158:23demonstrated134:9 139:22 259:15densitometry57:14 59:5 295:15density295:16department5:2 8:14 70:2dependent67:25



11

depending25:11 32:23 62:8 74:8

115:20 273:12depends16:16,24 26:10,10

47:14 60:8 65:377:20 184:3,13261:22

deposed17:11deposition1:9,11 3:23 4:2 5:16

6:20 17:8,16,19 18:719:17 22:4,11 23:223:15 28:4 34:1365:13 67:8 81:2382:2,14 88:2,2 90:3101:19 220:22 224:5225:22 229:1 237:15240:16 243:22 244:4245:22 248:2 251:17254:2,15 256:17258:5 261:25 262:10262:24 263:1 265:21266:13 267:14 272:6278:3

deposits28:23 29:9,15,15

234:15 236:1,13262:6,19 295:17

derive194:4describe8:2 16:23 23:21 31:21

70:3 71:6 76:9 81:1381:14 89:3,5,1194:23 111:22 112:15147:4,6 169:22214:24 231:10,24271:10,13

described27:5,6 141:13 193:22

197:7,17 250:12259:7

describes95:1 118:15 139:8

237:6describing30:15 31:5 148:3,13

175:8 213:12 263:20description3:6 31:13 75:21 81:17

81:18 89:12,18 172:5177:4 237:11,12

design13:3,14,22 41:18

44:19 80:18 145:21208:20,25 209:1211:6,8

designed45:6 65:4 76:22

152:18 215:13244:14 253:3

designing198:12designs45:11desired197:21Despite68:14 259:5detail60:18 89:6,11 110:10

178:8,14,20 221:16221:19 222:1 234:8234:10,17 235:2,4,5235:10

detailed154:14details29:18 63:13 89:15

103:23 213:21221:24

detect25:13 58:20 120:19,23

165:21 222:22,24274:4

detectable25:10 58:12 154:20

162:15 273:17detected58:8 117:24 118:14,15

118:19,21 143:17146:18 153:4 154:16155:12 166:3,5 189:3248:21

detection212:22determination122:13 236:9determine8:22 43:4 51:10 60:8

120:20 143:6 153:7156:2 163:20 189:17222:19 273:12

determined94:19 109:25 118:2

140:12 216:12 222:3determining61:12 78:20 79:13

135:22develop125:21 200:24developed58:17 217:7 218:20

259:9developing13:18development8:17 12:13 13:9developmental8:15 9:12 13:12develops70:4deviation249:9 269:21deviations269:22device37:8 38:22 47:23

184:10 185:6devices37:14 39:7devitalized29:13 30:17 31:9devoid91:19,24diagnosis

111:18diameter124:21 125:23 189:23

190:6 191:11 197:21died215:20 217:12 241:8

241:10 244:24 245:1255:15,20 269:3,4277:15,22

differ46:17difference61:12 133:7 137:25

192:7 227:2 229:17250:1

differences45:20 131:18different7:11 12:5,6 14:3 24:1

24:5,21 25:10,1926:4 27:1 32:22,2338:15 41:15 50:6,751:15 57:9,13 58:658:22 62:17 65:3,871:1,1 80:8 81:1595:25 98:8,22 100:15102:20 112:1 114:16115:22 125:2,24130:6,6,7,8,9 131:17131:21,22 146:21148:24 149:17 159:5159:17 160:16,25161:7,7,13,14,20171:3,10 178:16,25184:20 190:12192:18,20 195:15,17196:10,10,11,15199:21,24 217:16220:16 227:25228:18 229:19,20232:19 242:6 250:6252:20 256:24 261:1265:9,11 267:21269:9 279:2 283:9

differentiating13:19



12

differently62:11 109:25 151:5

288:11,16,20difficult50:8 80:10 81:12

111:6,20 115:19166:2 270:12 285:3

difficulties236:6digital179:6dimensional56:18dip157:23direct6:16 34:11,21 65:9

66:23 87:24 88:1090:1,17 111:13 132:7133:14,19 220:19223:11 254:13256:15 259:2 278:1278:15 279:24281:10 282:13

directed67:22 127:6Direction4:5directions195:18,20 196:10directly39:11 47:20,23 232:12director81:19disagree35:25 40:14,16,18,21

40:23 52:12 66:17,20282:2

disagreement52:24discipline68:24 69:19,25discloses115:7disclosure288:10,12,14

discovered56:7discovery51:14,16 54:21,23,24

204:3,4,11,13discuss8:21 55:20,22 63:16

195:6 202:21 225:4discussed9:7 29:24 54:21 55:11

78:8 85:19 106:20117:4,5 134:20136:20 167:22289:11 294:24

discusses30:2 76:16 77:2

143:15 236:5 268:4discussing51:6 70:25 141:19

169:20 194:3 199:23232:24 233:2,24234:2 236:4 288:20294:25

discussion6:19 19:8 34:15 48:4

52:20 54:6,6,11,2254:24 55:2,12,13,2055:23 65:12 66:567:7 68:11 71:378:24 90:5 93:14101:21 105:13 106:8117:10 119:3 127:18167:25 169:15192:22 193:3,9,13194:11,14,18,20,24195:2,10,21 196:20196:22,25 197:2198:15,16,20 200:3200:14,21 201:6202:18,22 216:16218:21 223:19 224:1226:10 231:14 232:5232:16,20,21 233:16234:20 239:20242:15 248:5 264:17284:7 295:7

discussions8:19 44:16disease13:3,15 181:13disputes85:5disqualifies289:19disrupted24:24dissertation70:4distal139:1distally138:25 139:9distinction14:5distributed98:7distribution160:24 249:11 269:18divide155:2division1:4 209:21doc8:12,13 9:5,7,16docs32:1Doctor287:19doctoral8:9document3:20 10:12 20:1,8

27:11 195:24,25254:4 279:14 281:19282:4

documents4:10 7:10 17:25 18:3

19:6 27:4 81:13,14dog40:8,17,19,21,23 41:2

41:6 42:1 52:12 53:376:19 130:24 160:8

161:13,15,17,18166:10 212:18214:25 226:15239:12,14,16,17240:11 243:8 245:15258:19 260:8 270:18270:23 277:13

dogs41:23 42:3 50:17 77:3

128:19 129:1,5,13130:18 131:1,10,25136:25 141:17161:10 167:9 188:19189:23 190:6,16191:12 192:6 214:12221:13 225:3,5,7,9226:2,8,23 227:1229:6,23 230:6,11231:9,25 237:20239:5,8 240:6,9,20240:23 241:10,13,19241:20 244:10,23245:1,11,19 246:7,10246:21 247:13248:10 251:24 252:1254:22 255:12,15,19256:2,6 258:16,24259:7,19 261:3,10,13266:7,11,24 267:2,2267:5,9 269:25 270:3270:9,16 271:8,13,17271:23,25 272:2274:11,13,16 276:15276:19,20 277:4,6,13277:15,21,22,23285:2

doing31:24 61:6,20 62:4,9

62:19,23 74:9 112:18151:18 156:14,19183:17 191:3 202:20214:18 217:17273:24

double157:23doubt



13

66:11 208:25 289:12Dr3:8,8 5:8,13 6:2,20 7:7

19:9 21:14 31:551:22 65:10,13,17,2266:1,6,8 68:5 80:2286:19 87:3,20,2589:2,23 91:12 92:6105:7 106:9 107:21108:8,9 109:14 110:4110:15 111:14 112:3112:11 113:5 121:20124:2,9 126:24153:12 214:4 274:19275:5 284:10,11289:3 290:23 293:22293:23

drafts15:3draw123:3 227:8drawbacks259:7drew123:1 214:11dried94:7Drive2:10due255:16 262:5 269:12duly5:4 296:8durability35:17 202:2 257:8durable14:8duration261:17dystrophic29:24

EE2:1,1 3:1,5 5:1 296:1,1earlier

70:25 98:13 156:17162:1,17 167:16215:12,18 269:11,20269:20 279:14

early25:13 51:16 78:17

165:10 188:14,21215:20 216:4,9,13217:7,12 218:1,6,10218:22 242:9,17,20243:18,23 264:22269:9 272:17,22273:6,21 277:10278:16

easier27:21 179:13 255:8easiest27:3 57:10easily162:15 293:7edited287:5editor122:9,9,10 124:1editorial10:20,23,25 11:13

121:24 122:3,5 123:2123:5,7,20 124:5,12

educating41:16educational8:2 78:22 79:14,19effect49:3 157:24 165:5

188:11 201:3,7204:11 206:19 210:9

effective61:16,17 158:23

181:23,24 182:1effectively99:15effects118:6 147:3 149:13,14

149:21 165:15,18173:20 188:9

efficacy

51:7efforts8:16 103:14eight35:3 213:2 244:9,23

244:25 246:7,10eighth245:15eight-month98:2,3,5,9,15,19,23

99:12,16,19 100:7101:11

either9:22 21:6 60:23 71:10

104:24 121:12132:15 146:1 211:23212:7 243:15

elaborate194:25elastic176:21 177:21 179:15elective268:15,17electively245:12eleven144:15eliminate96:19Elmer94:20else's17:2embedded164:20embryo13:11embryonic8:17 12:13emphasizing141:9employ46:23employee296:16,18encompass

125:15encountered79:16 280:8encouraging182:6endocarditis245:2 255:20 262:6,12

262:15,18 263:13,18263:23,24 264:3,7265:1,2,4,5,18287:23 288:1

endothelial56:7endothelium152:6engaged12:10 85:7engineered47:16engineering5:3 8:5,8 12:14,18,20

69:22England22:20enhanced197:10entails223:10entire143:5 172:2environment56:20 61:9 137:12environmental38:17 263:4environments229:19equal263:13erased89:7error216:21 289:21 290:1

292:22 293:3,18294:8,19

errors7:22



14

especially48:1 155:21 233:11ESQ2:3,3,9,10essentially8:20 13:8 25:1 31:25

42:16 59:3 117:1129:23 256:24 287:1

establish34:5 50:4 57:12 78:18

128:25 228:17231:22 280:12282:18

established101:3 222:8establishes49:2 198:2 202:7establishing235:14,21 236:7estimate16:4et3:9,9,10,10,11,11,12

3:12,13,13,14,14,153:15,16,16,17,17,1825:19 28:4 30:1957:14 62:22 71:272:18 92:25 101:19139:5 155:24 164:19208:21 213:14220:22 224:5 225:22229:1 237:15 240:16244:4 245:22 248:2251:17 254:15256:17 258:5 265:21266:13 267:14 272:6

ethanol132:16 133:4,8 134:15

134:17,22 135:23136:15 145:1,6,20148:16,20,23 149:12150:15,19,24 151:3152:11 153:25 154:3154:18,19,24 155:3,9156:9 157:2,17,19158:9,19,23 161:25

165:17,19 168:18,23168:25 169:2,16170:5 172:3,5,11,14172:18 173:4,9,24174:3,4,8,11,24175:3,17,18,19,22176:2,7 183:9 188:6188:10 198:21 201:3201:7,10,18 202:20203:2,12 204:3,11205:15,21 206:16,19206:20,23 207:19,22208:12,22 209:23210:8,24 211:24214:6 252:14

ethanols252:18ethanol's211:1ethyl117:12 118:3 134:1,9

145:11,14 150:13151:24 152:13 153:4200:6 201:12,13203:3

evaluate40:3 47:15 50:9 73:10

73:21 76:22 77:1097:15 113:20 114:9115:3,11 123:16149:16 170:7 185:23219:16 253:3 256:13

evaluated46:14 62:6 119:5,22

125:24 139:2 177:8177:14 238:18,23295:12,14

evaluates295:16evaluating26:15 36:8 61:24 62:2

63:9 70:11 71:9,1571:18 73:6,16 74:1,675:1,22 76:13 77:380:14 115:15,22124:21 154:12

156:10 196:12 231:6247:13

evaluation57:21 59:24 72:22

114:7 117:7,17 134:5139:20 164:17

event207:15 212:24 286:18events242:17evidence39:17evolution43:24exact37:8,8,9 98:10,20,21

287:5exactly43:22 74:15 113:15

163:18 217:19 223:9252:22 264:5

examination1:10 3:3,3 5:7 28:20

57:11,11,15,16,2058:3,9,9,13,18 119:8120:19 139:5 273:14287:18 291:7 296:8

examinations60:2examine244:15examined5:5 174:12 227:15example28:22 33:25 43:3

47:12,13 56:5 102:15222:2 232:8 233:7234:11 255:11

examples69:20exceeded110:5 189:7excellent110:9 139:22 140:20

141:6 201:22 259:15259:25 260:11,14

261:3 271:2,11,14,25272:3

exception18:24excerpts21:5 117:3excessive24:19excludes175:2,5exclusively163:20excuse83:5 105:22 131:5

149:24 166:8 167:11219:4 231:16

executing70:4exerted205:16 206:16exhaustive122:11exhibit3:6,7,8,8,9,9,10,10,11

3:11,12,12,13,13,143:14,15,15,16,16,173:17,18,18,19,19,213:21,22,23 6:17,2015:11 18:13 19:13,1719:18,21 21:11,12,2127:20,22 28:2,4,1034:12,13,16 51:2365:10,13,16 67:8,1267:17 79:6 87:2588:2,5,20 90:2,3,1090:18,20 91:6,15,1692:21,23,24 93:20101:14,18,19,23,25105:2 106:4,11,17,23113:12 116:13,14,21117:14 119:13126:25 127:12128:17 216:17220:21,22 223:12,25224:5,7 225:21,22228:25 229:1,4



15

237:14,15,18 239:18240:15,16 244:4245:21,22 246:3248:1,2,6 251:16,17251:19 254:2,7,14,15256:16,17,19,22,23257:12,14 258:4,5,7258:14 264:12265:20,21,23 266:12266:13,15 267:13,14267:16 272:5,6,8274:18 276:12,21278:2,3,17 279:5,13279:16,18,19 284:12285:18 289:22 290:7290:14,19 292:21295:2

exhibiting62:25exhibits7:8,13 15:10 18:5,9,10

18:17 19:11,22 20:320:4,21 22:4 65:1865:20 106:24 214:23258:12 264:14290:10

exist73:11 75:4existed29:25existence73:9,16expanding140:18expands140:15expect71:23 127:22 128:18

129:4,8,14 135:14137:8 160:19,21161:16 178:3 188:14188:21 192:14 210:8212:18 218:1

expectation122:4 129:9,21,23

130:1 245:24

expected189:25 190:8,20,23expensive47:4,5 247:20 285:4experience9:6 11:12,14,23 31:22

32:24 41:20 42:645:1,15 55:24 69:170:6,7 71:9,11,14,1771:21,22 72:7 125:11125:12 166:4 239:16242:4 247:1,3 261:13285:20

experienced220:3experiment34:1,4,7 55:1 117:20

130:6 136:7 149:23152:17 156:9 158:2,4159:7,9 161:12 167:9191:3 200:4 207:13208:20,25 209:1211:6,9 215:13 253:2285:13

experimental29:3 35:1 118:1 125:7

143:19 148:2 158:22160:16 191:17221:19 233:11244:14 259:8 277:4277:20 279:3,3

experimentally50:12experimentation136:25 137:3 172:17

214:18experiments32:20 33:8,16 36:20

42:20 46:7 55:2356:9 97:5,8 98:18137:25 140:4 141:20151:13,25 152:18157:8 159:5 160:3176:16 195:5 199:2214:25 225:9 247:16259:3,12,13 266:7

expert6:3,9,13 31:18 86:25

87:17 89:21 122:20124:25

expertise70:3 72:4 80:9 124:15

125:9 242:3expires296:24explain13:7 45:19 70:18 79:2

82:17 83:9 168:5293:16

explant98:15 184:18 206:12

225:17explantation184:6 248:24explanted57:4 215:17 216:2

222:10 249:1explants98:22,23 99:12,17

222:10explosion25:1exposed56:20 132:15exposes156:8exposing32:11exposure198:22expound52:22 197:3expressed290:4expresses119:6 139:3 143:1expressly187:14extend25:18 194:25extended172:9

extending193:13,14extends152:2extensive236:11extent295:16extra90:7 295:9extremely167:2 172:13extrinsic26:18,20 27:6 28:22

29:6,8,19,23 30:5,20eye26:8 57:19

FF296:1fabricating13:16facility45:24 46:4fact51:16 52:16 95:10

107:14 123:2,4 160:2164:2,8 179:8 186:11186:15,22 187:23202:21 204:18 206:2209:12 283:23289:15

factor127:24 128:3 239:17factors78:20 79:1,13fail12:23 273:7failed280:8,19failing104:8fails145:25failure



16

181:22 185:17280:14

fair15:25 78:2fairly20:16 225:18familiar29:12 44:1,2,4 45:12

52:5 59:11 73:1,374:5,25 75:3,1076:12,15,18 77:1,1677:22,25 78:10 79:25110:23,25 111:2121:3,5 124:2,6128:2 170:24 222:13223:9 250:24 290:17

familiarity45:2,4,9 68:14far46:6 48:24 115:21

131:4,13 140:3152:18 154:18 183:3247:18 258:20283:23

fast225:18faster38:19 215:9favor155:16 261:25 262:9

262:24 263:3,11favors263:4FDA48:11,19 49:10,12,16

50:1,3,16 51:6,12181:17 182:10189:20 281:21

feature16:23 23:19 33:14,18

151:23 180:19,25181:18 207:12 227:2228:3 263:4,24 278:8278:23 282:20

features25:9 29:13 78:18

149:22 199:24 202:5213:13 229:20 244:2

feed46:1 224:19feeding224:23feel7:17 10:16 11:22 27:7fellowship8:9felt53:10fewer215:14 276:15 277:5

277:21fibers25:19fibrous29:16 176:22 177:22

179:16field11:6,17 14:6,12 29:24

30:9 31:3 41:1047:11 54:18 55:1572:7 78:13 79:19,2284:22,24 87:1,18125:5 128:6 204:19

fields15:20figure12:15 21:10 23:19

154:6 179:20 245:4246:13 257:9 279:19279:22

figured21:24figures234:22filed27:17final122:12 181:14Finally289:21financial32:25

financially296:19find11:5 25:16 35:9 65:2

78:19 81:12 91:20105:3 114:24 115:5,9115:15 116:12117:21 132:22133:17 137:7 145:21145:24 166:1 167:2178:19,23 183:13185:11 198:13215:15 219:8 242:16244:19 260:17 275:4275:8,10 277:13285:3

finding189:17 193:14 199:22

243:14findings9:21 53:21 54:4,9,14

55:14,16 57:3 132:9132:13 194:25263:21 283:8

fine27:11 92:19 116:20

126:17finished17:11first11:1,2 12:23 13:7 20:3

27:5,11 28:12 29:231:6 34:19,25 36:447:7 55:6 64:5 74:2094:18 115:10 116:17119:19 122:8 127:6133:15,21 137:2,24139:18 143:14146:24 152:9 173:6197:11,15 198:24200:20 202:4 218:15219:6 220:1 242:11242:23 253:11 268:7287:10,10

five29:5 39:4 42:24

208:22 211:23212:13 213:2 230:7241:13,17 261:14

fixation126:2 154:8fixed132:15 137:18 151:15

220:13 229:14244:21 266:4 277:2

floating164:25Floor1:18flow47:18 48:2,10 117:6

117:16 119:8 134:4138:3,25 139:22140:12 141:3 142:18193:24 197:18

flowing185:1flows142:16focus198:9 238:20focused80:11,16 275:6focusing189:6 198:19follow71:3 110:12 151:14

155:20 172:17182:10 189:18 206:8236:25

followed98:16 164:12following117:25 143:18 232:9

241:20follows5:6 87:15 131:8 190:4

193:7follow-on182:6 283:19follow-up9:3 51:3 183:7,19



17

205:3 283:12,21forces8:17foregoing296:11forget269:19forgo47:21form16:9 25:8 26:9 29:21

33:19 37:16 38:1944:13 46:19 55:963:1 64:18 66:1070:20 77:5 82:11,2287:6 94:2 100:17110:6 112:14,16130:19 131:20 151:4154:23 155:10,19159:3,20 164:4175:13 177:11 178:5178:22 179:4 180:8182:3,4 184:12186:17 187:6,17188:24 190:9 194:22195:16 198:18199:18 205:4 210:6211:11 213:8 215:3215:22 221:23227:10 229:16230:25 232:3 235:7237:3 241:22 249:18250:5,14,22 257:1273:9,19 274:2 277:7277:17 281:25282:22 283:25285:25

formation25:14 56:13 165:3

238:24 245:25forming56:9forth296:14forward54:17

found30:21 110:3 117:11

137:25 146:21151:12,23 183:13,15222:9 232:9 249:25251:15 257:23 258:2263:22

four88:17 132:1 189:19

212:12,15,16 217:9221:10 241:16248:14 272:17,22273:4,22

fragment61:1free7:17 18:20 64:11

119:7 139:4 143:2167:3

front7:8 113:8,19 114:1

115:13,18 254:10289:24

full28:19 29:2 34:25

139:18 143:14146:24 197:12198:24 234:11242:12 253:4 262:3269:24

function10:23 14:1 24:5functions24:11fundamentally33:1funded285:22 286:3,5 287:2

287:9,11funding284:11,23 285:8

286:10,19further40:6 60:17 83:10

133:2 142:5,21 143:3147:4,6 156:16

182:13 194:15 195:5214:18 238:12287:13 290:10295:18 296:11,15

Furthermore12:19 96:17

GGA134:8,10,16 143:17

201:23 205:17,18207:22,23 208:13,16209:7,12 210:1,11,14211:21 212:19

Gabbay3:15,15,16 254:14,15

254:17,20 255:11,19256:17,19,20 258:5,7258:8,18,23 259:5,12261:24 262:8,23,25263:11,17,18 264:13

gain13:6 261:18gained14:9 140:9 260:5

261:12 280:12gaining77:24general17:3 27:14 29:18

30:25 37:3 42:1943:7 70:22 76:1,284:22 89:11,18 171:5262:12

generally17:13 23:21 31:3,21

33:4,7,25 38:24 40:940:15,19 41:6 42:245:23 52:13 53:3,8,953:15 54:12 60:1671:5 74:2 84:2,497:8,10 168:10190:15 194:19

generating112:9 141:2 278:25geometry

198:5Georgia8:8GERSTEIN2:9getting14:6 51:22 130:11

139:12give5:23 7:12 32:2 54:16

59:4 70:22 89:17114:5 115:25 123:5130:21 144:4 167:12240:10 287:12

given38:23,25 42:23 167:3gives61:15 81:17,18 187:9giving69:20glutaraldehyde32:12 117:25 124:20

126:2 132:15,16,20133:9 134:23 136:16137:18 144:1 145:8146:10 151:15,19154:8 155:3,4,9157:5 158:8,12 159:1159:11 160:10161:25 165:20166:19,24 167:17169:11,18,20,23174:8 175:6 176:10187:23 188:1 189:4189:10,11 203:17205:21 207:1,3,5,10208:21 209:22210:24,25 211:23,25214:7 219:20,24220:10,13,18 229:14238:3 239:24 240:19244:9,16,18,21254:21,24 255:2,9266:2,4,19 276:25

go12:21 16:2 27:3,4



18

47:20 51:19 65:882:19,23 90:15 93:1697:21 109:7 117:19126:22 136:23163:19 164:18182:11 185:21 208:6215:4,7 223:25 224:2224:23 225:21228:25 237:14239:18 240:15 244:3245:21 248:1 251:16258:4 265:20 266:12267:13 272:5 284:5

goal12:14 14:9goes12:20,20 42:12 94:21

96:15 122:8 147:14176:19 205:12 222:7234:17,20 257:18

going10:1,2 17:10 19:12

21:10 40:1 45:1046:21 48:20 53:1091:2 118:9 136:12142:16 143:13155:15,22 170:12175:14 182:21198:13 223:21249:20 263:9 264:20272:21 283:1 290:13

Golomb3:10 223:15 224:5,7

224:10Gonzalez-Lavin3:10 225:22,24 226:1good5:8 12:8 43:1 193:22

197:7,17 239:9Google127:7 183:12gotten287:9graded252:24graduate

14:16 32:1graft117:9 119:10 120:4

125:24 138:1,22,24139:1 140:14,14,16140:18,23 143:5152:2,5,24 153:4,24158:19 168:13 170:4171:15 172:13,15,23175:25 176:1,1,5,20191:12 200:23 202:6203:6 241:5 246:18

grafts117:12,18,24 119:5,22

124:21 132:20 133:3134:1,7,8 135:8,11135:17,22,24 137:9139:20 141:24 142:2142:6,22 143:17,22143:25 144:6,8,25145:5 146:7,9 147:14147:15,17,19,20,22147:23,24 148:8,10148:11,12,16,19,22148:23 149:5,25150:14 151:7,9,15,18152:10,10,16 153:25154:2,16,19,24 155:2156:9 157:1,5,17,19158:9,11 159:1160:10 161:23,24162:18 165:16,22166:6,19,24 167:18168:18,19,23 169:1,2169:11,16,18,23170:6,15 172:1,3,6,7172:11,15,18,24173:1,2,5,8,9,23174:3,4,7,11,11,13174:14,18,22,23,24175:2,3,5,6,9,22,22176:2,6,10 187:25189:3,23 190:6 199:3200:6 206:19,23207:1,6,11 209:7,8209:12,15 210:1,12

210:15,23 211:21212:12,19 238:17246:7 247:7,8,11,13248:21 276:19

gram227:19 248:22 249:4

249:22,23 280:3,7,14281:17

grams249:5grand8:19 9:25grant284:15,15,16,19,23

285:1,5,11,14 286:23286:24 287:1,8

grants286:14,15 287:9graph61:4 279:25 280:21

281:6graphs70:12 139:2 253:10

280:20 281:12great7:1,14,18 12:18 28:6

67:4greater37:13,23 38:3,6,21

52:22 63:24,25gross57:10,15 58:9,13,18

115:23 273:14grossly25:20,22 26:3group8:20 81:13 84:24

111:7 123:13 145:11210:10 225:8 228:24241:7,16 245:8248:24 249:3 250:15253:17,18 267:4

groups209:21 228:1,9 241:1

242:4,5 249:25 279:2grow

24:3growing38:16 221:7 226:15,15

226:16,17growth25:3guess7:3 16:24 23:19 28:1

34:3 36:4,17 47:1248:15 68:3 74:2377:6,6 138:17 161:2187:7 235:8 273:14288:17 293:20294:21

guessing40:3

Hh2:3 3:5 5:1,1,1half16:13 144:17,19

212:12 255:20halfway28:21 68:16 111:15

233:18 259:11260:21

Hall5:3Han3:11 237:15,17,20

276:18handbook21:5handed278:16handing67:11handling193:23 197:7,17handy67:2happen57:9 129:23,25 149:23

149:24 169:7 191:17192:5,17 193:15



19

194:16 213:14220:16 243:7,9,16244:1

happened43:8 149:17,19 167:6happens31:11 164:24hard39:8 40:14 168:15

238:17 263:8 267:8hardening114:13,18head82:25 132:14,14

208:19 209:16 240:9287:12

heading94:13 139:19healed263:24healthy24:8 184:24heard111:4heart8:17 9:16,17,18 12:13

13:15,17,20 14:2,443:2 48:12 49:1264:21 80:3 110:23111:7,21 113:18,20113:22 114:25128:17,23,24 129:15130:7,14 131:3,12186:3 203:10 220:4245:7 248:9 261:4265:14 270:4 275:11275:15,18,24 276:10282:10

heavily216:2,8 217:24help11:21 50:5 267:23helpful12:5 62:7 63:6helps60:7 116:13

hereinbefore296:14heterograft241:4,5Hi5:9high241:19 242:8,12

243:21higher25:23 42:17 163:4

249:6,11 263:15highest163:6highly121:11histological25:16 57:11,20 58:3,8

59:23 60:2,15 72:21115:2 117:7,17 119:7134:5 139:5 149:10152:15,23 153:13164:17 172:4 203:5222:9 250:17

histologically147:13 166:12,14

170:4 172:7 174:18histologist114:6histology114:5 116:11 164:6,7

164:22,23 165:2166:4 281:24 282:9

histopathologic118:3 147:1 150:18

173:17histopathological146:19,23 149:22

153:7 178:1,3,14,20187:20 223:8

histopathologically149:16 162:15historical128:10history44:18

Hoffman191:7,25 192:2 215:25

216:20,21,25 217:3,9honestly205:5hope34:4 110:23 111:7,21

114:25 203:10275:11,15,18,24276:10

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40:2 42:22 50:1051:8 57:4 68:2 84:14126:7 180:23 181:2,4181:6,9,15,15 185:15222:11 261:7,16

humans38:14 42:14 43:19

56:25 78:5 83:2087:10 182:15,18226:19

hundred147:21,23,24,25 163:5

163:8,8,9 210:5213:4 249:22

hydroxy24:4

hyperplasia168:4hypothesis9:11 96:20 136:24hypothesize136:2,14hypothetical79:21 85:4 208:24

IIchikawa3:13 245:22 246:4,6ICP282:9id138:7idea45:11 96:25 150:25

156:6 194:2 203:16245:20 280:16

ideal233:8,21Ideally100:10identical256:23 257:3,5identification6:22 19:19 28:5 34:14

65:15 67:9 88:3 90:4101:20 220:23 224:6225:23 229:2 237:16240:17 244:5 245:23248:3 251:18 254:4254:16 256:18 258:6265:22 266:14267:15 272:7 278:4

identified116:2 206:2 290:1identify12:22 25:5 75:14,20

76:7 77:12 78:4113:2,7 114:17115:17 191:16265:12

identifying26:12 33:13 173:23



20

207:13Illinois2:11image60:23images234:23imagine33:14 40:4 43:8,23

44:8 47:9 58:14111:7,21,24 121:11153:21 226:14281:21

immature35:7 36:2,11,16,19

39:22 40:3immediate241:17immobile63:16,21 64:3,8,12,14

189:22 190:6 191:11192:5

impact8:6 10:17 55:22

127:24 128:3 202:21impacts52:22 193:16 247:24implant33:3 37:2,7 38:2 39:3

40:2 41:18 42:14,1497:24 166:10 182:18206:12 208:6 210:23225:15 270:19

implantable89:9implantation32:13 36:9 48:6 50:10

51:8 56:24 83:2084:6 87:9 99:2117:25 130:6 131:22137:5,7,10,25 141:14143:18,22 152:7154:13 160:7 181:6181:15 198:13 206:3214:8 215:2,14 227:5243:1 245:9 246:9

247:5 248:14 249:4251:22 252:25267:25 268:1,13,24270:11 272:18,23285:15

implanted9:17,23 31:19 32:8

36:25 37:14,24 38:738:22 39:7 46:10,2146:25 47:23 48:2,781:21 99:23 113:25126:7 128:24 129:1129:13,15 130:15,17131:1,3,10,12,24135:18,19,25 141:25142:3,6 143:22,25144:25 146:9 162:11167:9 173:9 184:9185:6 186:4 192:5208:2 212:12 216:1221:6 229:10 237:21238:15 239:24240:20 244:9 246:7248:10 251:23254:21 256:13258:25 261:21266:19,21 267:20272:12 274:15276:19 280:15

implanting43:15 80:14 182:14

268:3implants80:4 99:10 117:23

141:17 142:9 162:4167:19 177:3,8,14186:16,23 187:16,24212:23 214:12217:10 221:9 238:25244:24 252:6 266:2266:20 268:12276:14

implied187:3,8implies263:3

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24:11 33:17 55:8,1155:19 61:20,23 62:162:5,21,24 63:2,4181:7 196:18 202:6204:3,12 228:2,13282:20

Importantly118:1improved287:5improvement287:8inappropriate286:6incidence242:8,12 243:21include15:23 16:5,8,10 25:18

27:1 60:17 72:1478:21 79:14 203:8227:21 257:6

included141:10 154:7 173:3

194:20 213:22248:16 251:14

includes46:4 104:21 120:4

181:4 194:5 198:21201:18 202:19 234:7234:10,22 236:15,20258:15 281:18,23

including18:8 131:25 176:20

236:10 237:24incompatible177:5 187:21inconsistent122:2 228:12incorporate179:8

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108:7 111:18 285:23incorrectly110:14increase38:17increased170:21 171:7independent67:25INDEX4:2indicate20:8 228:8 249:12,14

250:20indicated187:11 275:17 276:9

279:13 281:11indicates249:17 250:11 285:1

285:14indicating165:12 174:2individuals112:9induced14:10 262:15inevitably14:14 24:2infected264:23,24infection162:3,6,8,11,14

216:10 217:14 218:3218:13 259:6 261:4261:20,22,24 262:9262:13,14,18,21,22262:23,25 263:6,18264:2,9 265:3 269:5277:18

infections



21

218:5,9 255:16263:20 264:5 265:6265:10,11,14

infer210:19infiltration168:3inflammation170:25influence205:16 206:17inform128:18 129:4,14

178:25information10:11,17 11:8 13:6,14

43:10,12 55:19 59:460:7 61:4 77:25 94:3100:5,20 103:24106:10,19 112:10115:8 116:1,10 117:4120:11 123:17125:14 129:12,24130:21,25 131:2,10131:11,15 132:4,5134:18 135:24138:16 140:9 141:2,4141:11 144:5 146:6151:12 155:21 160:5172:16 176:12 178:4178:24 182:5 187:1,8187:9 189:24 190:7190:19,24,25 191:19191:22 194:15197:24,25 201:6207:4 209:2 210:18213:7,16 214:13221:21 230:22236:16,20 237:1241:24 242:1 250:9250:10 257:8 261:18267:23 274:5,5280:11 281:19 283:6284:20 288:6 289:7289:11

informative

52:18 53:22 54:5informed78:15informs180:20,25 181:19

243:7infringement103:19 104:1initial194:5 261:15innovations79:17insertion261:17insertions261:15inside24:15 25:15insight192:8inspecting147:9inspection250:17inspire283:6inspired283:21,24instance25:12 43:24 46:3,4

47:15,16 73:12,1784:23 170:13,14181:16 215:18,24269:15

institute110:24 111:1,8,21,25

114:25 153:22203:10 275:12,15,18275:24 276:10

institution223:10instruct108:25 109:2instructing108:14,16intact

152:5 176:22integrate11:8 50:5,5intend107:12intended20:20 46:22 181:5,14

291:9intending35:22 277:5intention20:23intentionally107:9Inter3:18,19 19:17 79:7

254:3interact25:19interactions85:11Interactive250:25interest46:10 80:13,20interested26:12 60:20,25 74:8

74:10 75:11 85:1105:6,7,8 191:2227:16 253:15,21296:19

interior68:2 84:14internal176:21 177:21 179:15

198:7internally31:11interposed171:15interpret10:13 129:22 149:6,7

175:7 176:15 211:19211:22 212:1 214:14252:13 264:6 271:16271:18

interpretation143:4 171:25 192:16

202:4,17interrupt51:1 126:16interval230:10,13intervene8:23,23interventions9:3intracardiac270:11intrinsic27:6 29:23 30:3 31:2introduction83:25invalidate103:15invention80:6 82:4 84:1,4,17

276:3 281:3inventor79:15 92:6 293:22investigate35:5 36:1 97:24

238:13investigated200:23investigator54:19investigators260:22,25invitro47:17involve9:5 51:17 57:21 221:8

238:2,5involved9:8 51:15 72:2,3 112:1

112:7,9 145:4 168:11involves13:16involving70:8in-depth



22

ion95:4ions23:25 24:8,9,13,19,22

25:24IPR2013-000411:2ironic100:23 103:11 107:22

107:24,24issue67:22 84:9iterating44:1Ithaca5:3

JJ5:[email protected]:13JENNIFER2:10Jersey1:15,18 2:4 296:4,24job1:25 10:25 11:4

123:16joint8:13Jonathan1:9 3:2 5:12 296:8Jones3:17 267:14,17,19

268:12 270:3,15271:1,7,22,24

journal10:18 52:2,5,17 53:23

120:25 121:3,5,13,15122:8 127:25 128:6204:16 232:20250:24 251:4

journals10:19 128:1journal's

128:3Jude1:3 3:18,19,22 6:3,7

19:17 85:6 103:13,18104:1,7 111:3 121:6127:11 254:2 278:4279:5 281:18 282:19282:24

judgment10:15 11:9jugular246:14,18 251:23

268:11junction63:20 64:7,14juvenile39:12,18 42:13,15,17

48:11 49:11 50:2189:21 191:9 270:5270:10,15,18

juveniles39:10

KKaplan3:23 53:21 54:8 66:1,6

80:22 81:17,19 86:1987:3,20 88:2 89:2,23111:14 112:3,11,17119:13 120:11126:25 127:2,11,15132:10,14,19 133:3,7134:14 135:10 138:7138:9 139:8,20140:19 141:6,13,24142:2,5,9,21 143:15147:18,20 148:2,9,10150:13,22 151:2,6,18152:3 153:3,12154:15 156:20,23158:22 161:9,22162:20 163:9 165:1165:19 166:17169:17,22 173:22174:3,13 177:7,13178:10,11 179:22

180:11 183:8 186:11186:15,22 187:14,23188:5,10,19 189:2192:21,23 193:8,10195:2,22 196:2203:20 204:2,20,21205:22 206:4,22,25207:17 209:4,6,18,20209:21,22 210:17211:19,22 212:10213:23 214:5,11,17214:21 221:22,25222:24 223:2,4,6,8235:1 237:8 274:19275:5,9 276:12 283:6283:14,17,18,21,24284:3,4,12,14 288:3288:7,20 289:8 293:2

Kaplan's3:8 65:10,13,17,22

66:9 68:6 87:25100:25 113:6 118:9121:20 182:25203:11 284:11 289:3

keep6:24 19:22 22:1 44:1

66:25 67:2 116:20223:13,14 261:14293:20

keeping81:10KEIR2:3kept45:24 117:12 134:1

277:23Kier22:18Kim3:11 229:1,3,6 232:9

234:7,10,20,21235:10,13,16,17,19235:21 236:15,20,23236:25

kind12:9 58:19 60:5 71:22

88:17 145:4 157:23192:10 213:21229:10 232:19249:12

kinds110:[email protected]:6knew17:10 112:24 124:19

124:20 198:12217:16

know8:22 9:4,8,21,21 11:16

11:21 15:13,20 17:2418:1,3,18,24 21:9,2322:8 25:18 26:2527:4,5 29:7,18 30:2,330:18 31:9 36:5,8,1837:7 38:9,10,20 39:839:11,25 41:22 42:542:7 43:9,22 44:3,1745:3,3,5,10,13,2547:1 48:18 49:1550:1,5,16 53:15,1754:4,17,25 60:23,2461:2,5 62:9,20,2263:7,22 64:6,23 65:465:6 66:1,12,16 70:270:14,25,25 71:372:15,21,23 73:8,973:15 74:3,9,12,1374:16,20 75:6,6,1375:25 76:1 78:1,2,3,678:15 79:5 80:9,1080:18,20 82:16 85:285:16 86:1,18,2389:6,15 93:1,3,8 98:698:16 99:21 100:8101:6 103:22 104:5104:13 105:5 107:16111:16,25 112:18,19112:22 115:10,20,21115:23 118:23121:20,23 122:10,19122:21,22,24,24



23

123:11,14,15,19124:9 125:3,4,6126:6,9 127:5 128:4128:10 141:10142:17 144:2 145:2145:13 149:8 150:2,8153:20 155:7,8,21,24156:8 158:5,7,10,12158:15 160:23163:16 164:5,6,11,15164:23 166:7 168:12169:5 170:10,11,11171:19,21,23,24173:12 179:6,18,19180:3,4,11 181:12,14181:16 182:7 184:19184:21,21 185:13,13185:13 187:7 189:1,6190:13 192:19193:15 194:3 195:13195:19 196:5,7,12,16196:16,17 198:11204:4,10,22 205:2,5208:12 209:10210:16,17 211:5,6,8211:12 212:5 213:2213:11 215:16 216:9219:22 223:1 224:20224:24 225:4,5,10,16226:25 227:2,13229:18 235:8,9236:21 237:5 240:9242:1 243:2,6,15246:25 247:1,15250:19 252:22,23256:7 257:11 259:1260:13 262:11,13,20264:4,11 267:3,4268:5,9 269:23270:24 274:4 275:7275:23,23,25 276:4279:10 280:24281:18 282:24283:23 284:2,22285:1,6,8,10,12,14288:18 292:18

294:21knowing73:11 189:20 263:8knowledge14:9 122:1 182:24knowledgeable122:23known10:14 32:15 69:8,10

131:25 162:9 261:25262:9,24 264:22

knows87:2,19 163:9Kossa222:13,16Kossa's222:4Kreptz22:23KRUMHOLZ1:17 2:2

Llab31:24 70:10 81:19

113:7 114:5,12 115:2211:15

laboratory113:19 114:1 271:2lack151:8,24 283:5lacked100:24lacking107:23 109:15,19lacks107:5,7,25 221:16,18lamina176:21 177:21 179:16language173:24 196:24 200:18

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45:16 46:1,17,2047:20,22 49:6 51:13

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197:15left-hand89:1 94:13 246:9

251:25legal78:15 85:5,5,9 86:14

103:22 204:5,6legends104:9length26:5 179:11 197:20LERNER1:16 2:2lesion

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lesions29:6 31:3,7 262:5,20let's19:2 27:11 31:14

51:19 71:13 83:191:14,15 93:20 94:1295:6 96:4 100:9101:16 110:21116:12,20 138:12,13147:12 155:2 197:13208:21 218:23219:23 223:25225:21 226:9 228:25237:14 239:18240:15 241:3 244:3245:21 248:1 251:16253:5 258:4 260:18265:20 266:12,22272:5 278:1 284:5

level24:4 26:13,16,17 34:6

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levels24:21 115:22,24

196:14 294:25Levy3:7,9,12,21 27:22 28:4

28:12 31:5 67:8,1268:20 90:3,22 91:991:15 92:4,7,10,2392:25 93:3,22 96:8101:17,19 102:2103:4 104:21,23105:7,16,19,20



24

106:17,22 107:4,7,10107:15 108:9 110:4110:15 156:3,4,7239:19 290:2,20291:9,12,12,18 292:1292:4,21 293:4,8,20293:22 294:19,24

Levy's107:22 109:14 110:9License296:5lies81:16life51:13 270:6,10,16likelihood38:6,9likes237:22likewise26:15 48:5 95:19limitation179:24limitations179:21 236:6limited157:22 195:18,21,25

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4:16,16,16,16,21,214:21,21 16:2 35:1759:3 64:23 84:3113:17 168:11172:10 268:7 280:1,2

lines29:5 35:3,15 255:23link196:14Linx280:23,24list18:8,20 19:11,22 20:3

20:14,19,20 21:20105:2 128:15 285:7

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42:13 54:15 76:16,1877:2 80:1 155:14251:8

litigation6:[email protected]:6LITTENBERG1:16 2:2little18:25 28:20 31:16

37:19 50:21 53:1988:13 96:15 118:10278:21

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184:4 189:14,17

230:17,19 243:4252:23 256:8,11261:14

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141:16 154:12 195:7240:24 241:14242:25 245:10277:11

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17:4,5 19:1 21:5,626:16 27:10 28:1739:15 42:25 47:857:23 60:7 62:1163:8,18 70:23 82:1982:24 83:1 90:991:14 92:11 93:1094:12 95:6 96:4100:3 101:16 103:6105:1,11 112:3113:12 124:7,13,19124:22,24 125:8127:6,8,17 138:20140:11 143:4 156:21163:19 164:13 166:9170:8 177:16,17,17183:16 184:6 192:19205:6 213:19 216:15217:18 221:18 240:7246:8 247:7 251:24253:9 254:25 255:4,5258:3 260:18 263:19265:8 266:8,11 267:1268:6,14,22 269:13269:18 277:13279:16 290:9

looked56:6 106:11 107:2

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looking25:12,14,21 26:13

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looks19:25 21:19 90:6 98:3

132:25 170:15 241:1252:17 253:2 257:6257:10 269:10 274:6280:11,22 281:15283:17

lot21:25 39:8 58:24 64:9

65:8 82:16 85:2389:6,6,7 132:3149:17,20 161:19,20169:6 171:2 176:12186:18 195:17 196:9196:10,15 197:24198:2,2,7 217:16221:21,24 228:18237:1 240:8

lots12:6 32:21 41:12 50:6

58:5 59:2 65:3 125:7125:12 146:20155:14 171:3 220:16249:19

loud5:23low58:16 139:22 201:22

250:2,11,20lower58:20 88:20 98:23

163:4 257:15Lu3:14 251:17,20,22



25

lumens234:15lunch126:19,21lung277:18

Mmagnitude250:16,19 253:16magnitudes227:25 249:20,21main12:12maintain24:23 152:23 177:21maintained152:14 179:15 203:4maintains199:1major24:16 81:20making14:8 17:4 51:11 53:1

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male224:15 230:8malformation12:25mandating75:15 192:8mark18:12,20 19:13marked6:21 19:16,18 28:3,5

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278:4market43:19MARSHALL2:9massive241:10Masters8:6material9:10 14:8 22:7 46:25

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249:8mean11:15 12:6 16:17

17:10 18:9 21:7 22:623:18 24:15,18,2026:24,25 29:23 30:2231:10 33:6 36:2438:12 39:24 41:8,19

42:5 43:21 44:1547:25 49:5 52:1753:4,5,7 56:23 57:1560:8 62:12,19 63:264:15,19 65:1,766:11,19 71:12 72:973:4 74:2,7 75:376:21 93:9 97:18,2098:20 99:7,20 100:1101:5 105:20 106:19109:21 110:25111:24 122:4 124:17124:17 128:21 129:6131:22 137:11142:12,24 144:24153:2,6 157:25 160:4160:15 161:3 162:23162:25 163:11165:12,17 169:6170:1,24 171:1 173:2173:10 179:18180:22 181:2,8,11,13181:24 184:13,16185:23 186:8 187:5,7187:8,9 188:12,25189:1,1,16 190:11,14190:22 191:14,16,24192:11,14 193:12,16194:2 195:6,25196:14 200:16,20201:17 203:16204:19 206:7,9,10,18208:3,9 209:14 210:2210:21 211:12,22213:9 217:15 226:13226:14 227:4,7230:19 231:2,2 235:8235:9 241:20,23,25242:14 243:6 244:2249:9 250:6 252:12252:13 257:20261:11 262:25 263:5265:8,9,10 268:3,18269:17,22 271:16275:19 283:15 286:7286:12 288:12

289:14 293:15294:20,23 295:1

meaning29:13 41:14 71:1 98:8

100:8 129:9,24 156:8157:10 182:1 183:9183:25 271:19287:10

meaningful77:24meanings26:22means53:15 70:15,18 82:18

86:1,15 99:22 104:6104:14 140:15142:14,19 148:10149:21 163:14 168:5174:23 175:22 177:2204:4,22 206:11225:1 226:16 252:12269:19

meant18:22 27:2 53:7 86:5

86:10 99:24 111:22128:23 139:7 206:6235:25 236:12290:19 291:11 292:1292:3,15,24 293:11293:13 294:1,22

measure50:9 118:16measured57:7 58:22 118:13

120:12measurement59:6 232:17,24 233:3

233:14,24 234:3measurements102:20 221:25 227:18

240:13measuring291:2mechanical8:5,8,16 9:24 69:22mechanically



26

14:8mechanisms13:2 31:23media154:9 194:7Medical1:3 3:22 6:3,7 8:10

85:6 121:6 127:11278:4

Medical's279:6medicine68:25 69:17medium136:15 158:24meet22:10 110:4meeting23:6,7,13meetings32:4member121:24 122:5membranous234:16memory267:3mention28:2 120:16,21 179:22

192:23 193:10194:18 195:4,10196:7 199:8,9 217:6223:4,6 265:3

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196:20 200:2 223:8244:17

mentions152:4MENTLIK1:17 2:2mentor32:1merits233:2 234:2met

22:14,16,23 23:1,1466:3

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140:10 285:24methods25:10 56:3 57:13 59:1

62:2 67:23 73:1574:5,9,21 75:1,7,2276:8,10,13 84:9118:22 136:3 138:1138:12 149:15 153:7179:7 219:15 238:12255:1 273:11 274:4282:9 291:2

mice96:18,20,21,25 97:7

97:13,14 99:21,23Michael2:3,9 5:13Michigan1:7 3:19 5:14 85:7

108:10 254:3Michigan's103:15microenvironment13:10micrograms94:7 95:11,20 96:2

155:17microscope57:24

microscopic57:21 234:23middle28:21 138:22midsection168:13,14 170:19mild168:3milligram94:7 95:11,20 96:2

102:16milligrams227:18 248:22 249:4,5

249:22,23 280:3,7,13281:16

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minus249:4,5,7 269:17minute8:1 31:15 139:24minutes167:12minutia70:24mischaracterizes153:16 194:23misread91:23missed

195:8 273:25missing83:13 109:20 223:20

257:11,13mistake111:8misunderstanding83:6misunderstood86:10mitral216:5 217:8 218:20

220:8 267:25 268:19268:24 270:9

mix9:25mixed7:5mobile63:16,20 64:1,5,14mode234:12model32:19 33:1,13 35:5

36:1,11 40:4,9,16,1740:20,24 41:2,4,7,1342:2,13,21 45:2246:21,24 47:4,20,2148:15,23,25 49:4,650:11,19 52:13,1453:4,11 56:12,14,1856:22 57:3 76:1977:3,22,24 78:194:20 97:4 100:2,2,3100:6,7 118:1 143:19157:21 160:8,8181:13 182:9 215:1222:8,10 225:11,12225:14 226:10230:23 239:9,17241:21 242:6 247:2250:21 258:21,24259:16,19,22,25271:2,8,11,14,17,23271:25 272:1,3 277:5277:20 283:9 286:6



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models32:22 39:13,18,19

45:16,17,21 50:851:15 53:12 57:270:11 77:9,13 78:3100:4 131:18,22132:3 181:5 230:24241:25 260:6 261:19279:3

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244:10 246:10248:10 251:23 252:1276:20

month240:24 241:14,18

255:16months43:1 132:1,21 245:12

245:12,19 247:6248:14 255:21 256:3256:6,12 259:14268:13,19,21 269:1,4269:11,16,17,21,22269:23

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103:10 109:14,16184:5 273:11 274:4

mural29:15Muratov3:14 248:2,7,9muscular176:21 177:22 179:[email protected]:12

NN2:1 3:1 5:1,1naked26:7 57:19name5:10,12 22:21 75:21

75:25 76:4named15:7 28:13 34:19natural9:17,24 185:12nature30:15 37:17 52:24

56:2,14 167:4near193:17 235:1,5,9necessarily26:1 70:3 71:25 74:7

77:19 114:18 124:24132:5

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173:19 188:8 296:15296:18

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167:6 183:6 185:16new1:15,15,18 2:4 5:3

10:16 12:18 13:1635:6 43:18 44:6,7,1144:18,22 47:16 54:755:15,15 59:2 73:18159:7 257:8,9 296:4296:24

NIH284:11,15,16 285:5,18

285:20,22 286:3,5,9286:11,16,18

nine144:13,15 145:22

211:3,21 212:6,8,12212:15,16

nitric56:10nodule25:17noninvasively185:24non-ethanol214:18norm193:25 197:19normal24:8 45:25 168:2

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67:17 75:7 90:11106:18 112:8 127:21127:25 128:1,5 144:6151:3 158:7 159:12160:17,18 166:25



28

209:15,20 210:8212:24,25 216:17252:19 255:7 269:8276:21 284:15287:12 288:6

numbers21:23 62:21 88:15

207:4,13,14,17209:18 211:9 249:12250:2,7,11,20

numerical25:7 207:20,21 213:7

237:12

OO5:1oath5:20object25:8 108:2,12,23

182:3 279:12 281:25objection26:9 29:21 33:19

37:16 44:13,24 46:1955:9 63:1 64:1866:10 70:20 77:582:11,22 84:18 87:694:2 100:17 101:2103:20 104:3,11110:6 112:14,16120:13 130:19131:20 151:4 153:15154:23 155:10,19159:3,20 164:4175:13 176:14177:11 178:5,22179:4 180:2,8 182:4184:12 185:8,19,21186:17,24 187:6,17188:24 190:9 194:22195:16 198:18199:18 203:24 205:4210:6 211:11,17213:8 215:3,22221:23 227:10,23

229:16 230:25 232:3235:7,18 236:18237:3 241:22 249:18250:5,14,22 257:1273:9,19 274:2 277:7277:17 278:14279:23 280:4,10,17281:9,13,20 282:12282:22 283:25285:25

objective154:5 244:14 274:22objectives125:21observable25:20,23 26:3,7,8

58:18 146:11observation173:6 214:17 273:18

273:25observations135:3,6,7 203:11

215:12 269:15 273:6observe135:10 263:6 273:3observed39:6 62:25 150:14

153:1,2 163:15167:17 179:14180:13 186:16,23187:15 207:6 209:8211:20 212:10,10,15213:23 221:17

observing137:4obtain189:15 286:25obtained197:20 233:9obtaining12:7obviously290:6occasion23:1occasionally

28:23 233:9occur28:24 29:15 38:24

63:20 64:7,17,25,25129:10 130:17 131:3131:12 184:9

occurred202:23 203:15 231:9

231:11 294:8occurrence171:7occurring38:20 63:24,25 65:3

213:13 215:9 261:7occurs39:16 230:17 265:3October27:15 32:9,16 48:25

58:23,25 59:18,2169:11 178:19

offer54:16offered44:12offering192:8offers141:2 191:9Office1:1 104:17offices1:16official6:24oh15:25 23:12 43:10

62:14 97:2 109:8119:15 129:20133:12 139:15 169:2194:13 204:1,10216:23,24 217:12220:25 257:16263:12 265:16268:17 288:22

Okamura3:12 240:16,18,18

242:19,25 243:17277:12

okay6:18 7:1,4,12 16:14

18:4,11,14 19:4,9,2019:21,25 20:18 21:1921:25 22:10 23:2427:21 28:12,25 31:1434:23 35:18,19 36:1236:14 37:21 40:650:24 51:19,24 53:1753:19 65:11 66:22,2566:25 67:14 68:5,874:18 79:24 83:184:8 86:19 88:10,1888:22 89:10 90:1,1990:24 91:1,5,6,8,1492:17 93:3,21 96:4101:25 103:25 104:7104:15 109:13110:21 116:20,22118:7,11 119:21120:6,15,24 124:2,5126:20,24 128:14132:7,24 136:12137:8,17 139:6,12,17140:8,22 141:5,21147:18 156:13 169:2174:23 183:17187:12 193:2 197:13199:5,25 200:14,22201:5 205:8,11,13208:8 213:18 215:5218:21 219:7 220:19221:1 223:24 224:4225:21 228:25 229:4230:4 231:13 232:16232:23 234:7 237:18239:18,21 240:15242:14 244:3 246:3248:1,6 251:16,19253:11,23 254:6,20255:5 256:10 257:17257:22 258:4 259:4259:17,21 260:18,19261:8 262:5 264:19



29

265:18 267:10 270:2270:14 276:7 278:11282:7 283:3 284:5,22287:15 289:5,25291:4 293:10 295:10295:18

old96:13 97:23 98:9,15

98:19,22,23 99:12,1799:19 100:2,6,7101:11 224:15 226:6226:8 229:22 230:6231:9 259:14

older30:14 33:8 37:4 38:7

98:24 230:11 270:22omission100:25 289:10,14once11:3,4,7 17:22 43:9

151:12,23 175:18252:21,22

ones11:16 19:1,16 20:11

20:15,24 54:9 58:672:16 107:2 145:3196:17 211:25 265:9273:3

one's207:16one-year253:7open46:2 166:8,9 261:4operation217:21 241:8 269:4operations9:9 259:8 261:5operative217:21opinion32:7 36:10,21 41:1,8

41:10,11 42:9 43:1754:16 63:3 80:481:16 82:3,9 86:15110:1 156:24 167:2

187:3 214:4opposed37:14 38:7opposition79:5,7optimal45:13 200:24optimized125:22optimizing200:17Oral1:10order49:12 55:10 89:17

98:7 110:12 157:16225:20

ordinary68:18,23 69:9,13

70:14,17 71:8,2372:20,25 73:8,13,1473:24 74:4,20,2475:19 76:6,11,17,2577:8,11 78:11,2179:14,21,22,24 80:580:19,23 81:3,6,2282:3,9 83:16 85:8,1685:20,25 86:5,17,2087:4,8,21 89:23123:8,20,24 156:25204:9 283:7 284:3

organization84:23organized7:11organizing32:4organs85:3oriented28:23 29:8original152:6Ortho35:13orthotopic

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104:3,11 185:8,19203:24 278:15279:13,23 281:9282:12

outward152:2overgrowth29:16 170:25owe108:8 109:9owner1:7 2:13 21:9 81:18

100:24 129:8,22274:24

Owner's78:16 79:4,7 192:13

257:25oxide56:10

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233:21 296:3page3:2,6 4:6,6,6,6,11,11

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papers32:2 41:12 60:20 65:2



30

179:10 215:8,15249:19 257:2 275:14

paperwork284:16par128:4paraformaldehyde164:19paragraph28:19,21 29:2 31:6,8

34:25 35:4 40:7,7,853:20 63:15 68:9,1391:4,8,8,22 96:5,7,17100:22 101:6,13102:25 105:18,23106:14,16,20 110:17111:6,10,13,15116:13 117:4 118:8119:25 128:13 132:8132:9,12,24 133:2,15133:21,25 134:20,23136:4,12 137:21138:23 139:19 140:3140:22 141:12,19143:14,15 146:25147:5,8,12 148:18150:1 152:8 160:5168:22 170:5 172:1,2173:17 174:1,17175:12,17,18,20,25176:13,19,25 180:18186:8,9,10 191:4197:5,12 198:24205:9 215:25 216:25219:14 221:15231:13,17,18,21232:2,5 234:12235:12,25 236:5238:11 241:15242:12,23 243:20269:25 271:4 283:2,4289:22 290:5,20291:8,17 292:10,17292:23 293:17 294:9294:11,24 295:3,11295:13

paragraphs66:15 78:17 106:21

109:14 117:1 292:17parenthesis29:8parenthetical264:21part8:15 18:10 22:19 35:5

35:15,21 55:1 58:364:21 65:23 82:2591:21 94:18 118:19120:7,15 132:13137:2 146:12 159:24173:1,5 180:19200:16 205:12217:20 220:5 249:10255:22 275:15 287:7

Partes3:18,20 19:18 79:8

254:3participate32:3participated8:18particular10:1,2,18 11:13 13:17

15:19 17:5 25:1128:16 29:23 30:231:13,16 34:21 41:1845:5 52:25 54:1466:14 68:7 76:2378:1,12 80:11 88:2394:5 112:20,21116:12 120:22123:23 132:12134:23 137:12,13141:10 145:9 168:11169:20 182:23 199:7200:10,18 220:17224:13,25 226:4234:6 247:23 263:14264:18 279:15284:14 288:14,17

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particulars254:24parties296:17partner22:19parts64:15passed252:6 253:1pasture46:3patch220:7patent1:1,1,2,7 2:13 3:7 6:10

21:9 62:10 66:2467:8,13,16,19 68:1968:20 69:14,25 78:1679:4,7 80:24 81:7,1883:11,12,17,19,2384:1,3 86:6 87:5,2289:24 100:24 103:16103:19 104:1,2,10,17123:10,21,25 129:8129:22 139:7 142:10147:13,15,19,21,23147:24,25 148:8,9,10148:22 156:3,4,7168:18 170:4 172:1,7173:8 174:4,8,13,18174:23 175:2,3,5,5175:21,22 183:4192:13 204:5 257:25274:24 281:3 283:16

patentcy138:1,21,21,21,23

139:22 140:5,8,11,11140:20,23 141:3,6143:10 163:7 174:14

patentness139:16patents68:14patent's27:17

pathogenic13:11pathologic149:10 269:15pathological147:4 263:21pathway30:3pathways9:13 27:7patient8:24 37:23,25 38:1

43:15 80:10 126:8184:9 185:7,15

patients9:1,9 10:2 37:12,14,15

44:12 180:23 181:3,4181:10,11 182:10186:2

patient's9:20,24pattern39:6Paul21:15pay104:9PCA253:17peculiarities242:2pediatric8:14,25 13:18 37:14

37:18,23 38:1peer10:24 52:8,17 53:23

72:3,5,19 122:2,8,13125:8 146:2 180:17213:16 251:4

peers11:6,8,9 123:15,15pending219:5Pennsylvania1:15PEO



31

238:15people26:23 39:13,17 52:21

54:17 58:6 61:3 71:272:1 84:24,25 86:23112:19 123:4,8,13124:19,20,22 140:10153:18 161:20270:17

percent12:17,20,21 117:12

118:5 132:16 133:4134:1,8 136:14139:23,24 140:20142:10,22 143:17147:2,17,21,23,24,25149:12 150:6,9,19152:8 163:3,5,8,8,9163:12,14,23 164:3165:13 173:13,19,23174:6,15,22,24 188:5188:8 199:4 200:6201:10 208:18 210:5211:2 213:4 268:25

percentage119:6 139:4 143:1,6

209:11 210:14 255:4255:6

perfect232:8perfectly213:3perform72:21 73:4 80:21

115:11 153:19 220:6225:9 247:18 285:4

performance50:4,6,9 80:14 117:8

117:18 130:5,23134:6,22 152:1,19157:16 197:2,3198:20 219:16 246:1256:13

performed59:23 117:22 136:7

161:12 170:18 184:7

203:10 221:4 224:10225:7 241:21 258:15261:16 283:13,19

performing71:12,15 72:11performs47:18 128:24perfused245:8pericardial65:6 268:10 269:6

273:3pericardium244:16 255:1perigraft119:10 167:23 168:1,9

168:12period12:16 38:23,25 68:17

128:7 160:22 174:20215:17 216:13 217:7230:17,19 242:9,17243:23 269:20 270:5270:10,16 285:15289:2

periods159:2 277:8Perkin94:20permanent137:24permit50:17 108:25person37:18,18 68:22 69:8

70:13,17 71:8 72:2072:25 73:8,14,2474:4,16,19,24 75:1976:6,11,17,25 77:877:11 78:11,12 79:2079:21,24 80:5 85:585:16,19,25 86:5,1787:1,3,18,20 156:25283:7 284:3

personally113:7

persons77:7pertaining68:19 69:14,25 80:6

80:23 81:4,7 82:483:17 86:6 87:4,2189:24 123:10,12,21123:24

Petition79:7Petitioner1:4 2:7phase25:11phenomena118:2 150:12 171:6phonetic22:23PHOSITA69:10phosphate23:25 24:7,13 25:3,24

222:20 232:17233:14 236:7,9

phosphates24:9phosphorus232:24 233:25 235:20

236:4photographs178:4 234:22 237:9photo-oxidated253:17phrase40:15physical152:14 201:22 203:5Ph.D1:10 3:2 8:7 31:25

296:8picked122:25picture16:24 178:7 237:10pictures237:6

pig57:2,3pile290:14place11:3 12:24 50:22 55:6

55:7 63:23 122:8132:22 296:14

placed141:17 220:7places18:25 109:16 132:2plan7:12 261:13please5:11 87:13 108:18

190:2 195:8plural145:4plurals207:2plus249:3,5,7 269:17pneumothorax217:13PO221:20 257:24 293:2point17:12,18 25:5 46:13

58:17 66:12,15 78:692:3 98:13 99:3113:9 117:20 125:7136:6 157:9,14 159:8163:22 164:22 195:9203:7 208:7 219:10226:11 233:15242:10 246:23 253:3253:7 256:12 275:15290:5

pointed120:7 289:21 290:6pointing120:15 199:16points39:19 41:15 94:8

100:11,12,20 174:10



32

174:12 184:6 208:11208:14 246:1 247:24252:20 287:4

polymer219:2 238:16polymers238:15polyurethane219:3,12,17 220:2

237:21,25 238:8populate13:21populations13:19porcine65:7 272:21 273:1,2,6

273:16,20porous219:17 220:1portion64:1,3,6,8 118:12,18

197:5 198:14 260:24position37:8 42:15 177:1

228:12 268:25possess11:19 193:22 197:17

197:22possessed197:7possibility137:3 170:24 243:10

243:11possible17:15 73:9 120:22

125:25 144:12145:19,20 149:18161:19 165:12166:23 167:5,16177:19 181:16 185:5204:24 212:5 261:15288:2

possibly282:17post8:9,11,13 9:5,7,16

32:1 252:10postoperative217:7post-ethanol252:8post-operative216:13potential163:22 170:10potentially77:13 201:24potentiate36:22,23potentiates35:7 36:3PO's22:8practical69:1 70:5,7pre252:10preclotting193:24 197:18predicting192:4predictive130:16 190:25preferable42:20 261:10preferred33:5,6 136:15premature269:12prematurely277:16,22preparation83:19 124:20 125:22

126:5 154:10 194:4prepare14:19 17:7 18:7 22:11

23:2,7,14prepared17:14 19:22 20:19

60:2 71:18 139:20preparing17:19 22:3 23:11

65:23 84:20 88:8presence60:21 62:16 155:11

170:21 177:5 180:20180:24 181:7,17187:21 188:25 189:6206:3 228:3,7,14,17231:23 235:14,22236:1,14,16,21,24237:1,5 253:20263:13 278:8,24282:21

present16:21,22 24:8,10

48:20 57:18 60:22,2361:3 100:21 120:5,9120:21 152:7 160:6163:15 166:11177:18,20 184:24198:2 222:20 228:10228:21 234:9 273:8274:1

presentations9:20 32:3presented54:25 176:17 179:9

183:3presenting54:7presents10:12preservation152:1 154:6 198:1,6

198:20,25 201:17244:18

preserve109:1 198:5preserved119:10 120:4 137:9

152:5,6,9,10 153:24153:24 154:3 156:8158:8 176:5,6,9,20187:20 193:22 197:6197:16 244:16

prestigious123:4

Presumably245:24presume179:18 211:12 247:23pretreated203:18 205:17 214:7

219:20 220:10 238:3239:24 240:19 244:9254:21 266:2,19

pretty64:11 180:6 250:2

251:11prevented56:8preventing191:2prevents188:6previous148:13 159:9 175:14

175:16,17 209:14287:3

previously6:21 19:16 28:3,5

65:14 67:9,12 88:3101:20,22 220:23224:6 225:23 229:2237:16 240:17 244:5245:23 248:3 251:18254:16 256:18 258:6265:22 266:14267:15 272:7

pre-ethanol252:7primarily105:24primary125:9,18 180:19,25

181:18 265:16 278:7278:23

prior6:6 51:11 78:22 79:16

121:6,21,24 194:23215:24 296:7

privilege109:1



33

probably21:4 27:3 47:17 76:4

78:25 112:12 117:2144:17 149:19155:20,22 160:24178:7 249:6 295:8,10

problem32:9 106:13 203:18

243:24problems78:22 79:15,17 89:7

185:7 226:18 242:20269:5

procedure12:17 44:7,12 115:3

194:6 255:10procedures102:22 103:1 226:12proceedings6:11process10:24 12:14 15:13

23:5,18,25 24:1625:11,13 26:21 32:638:20 41:16 42:2443:13 44:2,19 47:351:16 56:6 58:1,265:23 72:3,6 80:12164:7,10,11,17 166:3166:8,12 185:14200:16 201:23207:15 220:15229:18 231:11,25287:3,8

processed166:14 220:17 252:13processes13:5,8 14:10 26:24processing125:25 164:22 201:17

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28:17 30:14 31:1534:22 52:9 54:1255:21 63:9 72:1990:22 93:22 102:6104:22 121:9,15,18121:21,25 124:10127:22 156:5 178:9213:22 251:5,9,13256:25 258:10275:22 276:13285:19 288:13

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30:9,11,14 55:1876:12 144:22 274:19278:13

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32:2 72:16 156:16published15:14 28:14 52:2,16

53:23 102:6 120:24145:25 179:10203:21 286:7,9 289:3

publishing54:19pull223:21pulmonary238:19 241:5,16pulsatility138:2,10 139:10,14

140:6,14,24 142:17pulse138:24 139:9puppies226:4,8,22,23 227:1pure233:10purpose51:5 59:12 125:18

180:16 191:20,23236:12

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19:6 31:14 37:943:23 45:6 66:2167:2 90:24 133:24137:14 145:22171:15 242:21 287:7

puzzled53:19 192:10 278:22p.m126:21 127:19 167:15

214:2 254:1 284:8295:21

Q



34

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RR2:1,9 5:1 296:1rabbit221:7

rabbits46:5 221:4rad136:17radiographic295:12,14radiography272:17,21 273:14,18

273:21 289:16raise87:7ramifications111:17ran195:22 196:3range25:7 227:14ranges227:6ranked128:1rapid226:24rapidity78:23 79:17rapidly226:18rarely11:18 164:7rat224:18rate33:11 98:14 163:7

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234:6 235:20 236:4,9ration233:21

ratios236:7rats46:5 97:2,3,20 98:19

98:19 99:6,23,24101:11 224:11,17225:10,13 266:3,5,20

reach50:21 155:18reaction119:10reactivation9:12 13:9read35:8,19 40:10 69:3

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118:7 119:11,12,16119:22,25 125:20136:1 139:17 143:14147:16 148:1 152:9152:16 153:23176:12,16 186:25204:21 256:11



35

readout140:17reads35:4 94:18 220:4realize113:5realized17:23really11:21 16:24 19:1 33:1

48:13,18 103:23125:5 148:10 153:13184:13 206:8 276:6293:11,13 294:1

realm243:10Realtime1:13 296:5reason20:25 81:11 210:23

289:12reasonable115:2 213:3reasons202:9,10 239:15recall18:2 20:11 63:17

93:15 156:22 213:9276:11 287:24 288:7288:9,23

received241:4,5 257:18 286:10

286:15recess51:21 90:16 126:21

127:19 167:15 214:2254:1 284:8

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65:16 67:15 88:590:20 101:25 115:12221:1 224:7 229:4237:18 246:3 248:6251:19 254:7,17258:8 265:23 266:15267:16 272:8 279:5

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45:16 59:5 123:2134:20 174:19 187:2197:5 200:4 201:10201:10 213:1 284:11291:9 292:9,11,14,20293:25

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34:18,24 36:6,15,1837:17 68:5 69:1079:10 88:16 92:1493:4 99:8 101:4,14103:4 106:15,17111:14 115:1 116:14116:17 129:18132:25 134:24136:20 138:7 140:2140:24 142:8 147:16148:12,15,19 149:5163:18 168:14,22,25169:5,15 172:4,5,17172:25 173:4 174:5174:21 192:12,21193:8 197:4 199:20200:19 201:19205:11,20,25 206:2232:1 234:13 249:2257:12 260:8,12262:11 264:5,8265:18 269:24 289:4293:10 295:4

refers

23:22 29:20 30:1246:9 68:17 71:674:11 85:20 89:4,1296:8,8,11 97:13105:18 106:3 117:1130:1 132:9 138:14140:19 141:16 143:7143:22 147:13,20148:9 150:3,5 168:9168:12,18 172:1,2,10173:8,11,13 174:3176:1,5 192:13224:18 229:25251:25 262:15 264:2267:24,25 268:8,14274:6 280:25 281:2284:14

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204:3regardless39:20regenerative13:15REGENTS1:6region30:25 31:1 167:23

168:9 170:8,16,22,23171:11 173:12 179:1263:14

regions65:3 168:7 170:10

178:24Registered1:13 296:6regular65:7regulating24:21



36

regurgitation216:5,7 217:8 218:20reject11:11 155:15 286:14relate54:15 59:8 84:9 135:7

200:15related29:14 31:10 58:3 70:9

169:9 243:18 258:11277:19

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68:24 69:19,24 96:12116:25 275:4

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221:20relied153:18,20rely114:6relying103:14remain132:20 133:4 134:2remainder145:9remained117:13 152:5 176:22

200:5remaining241:17 242:21 256:2

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remove185:25removed113:25removing126:1render10:15repeat9:3 55:3,5 155:23

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reported53:21 94:8 95:11

102:13 125:18 133:3143:11 148:8 151:10160:1,2 161:9 162:14162:20 172:20174:13 178:21 183:8186:11 187:23,25189:2 196:3 204:15207:25 209:4,6,17212:23 218:11240:22 255:19258:11,23 260:15278:12 283:14289:12,20

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228:11 237:4 257:5271:7,22,24 273:16

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71:18 72:10,12,15102:16 122:14132:19 141:24 142:2142:5,9,21 147:18165:2 178:2,15 183:7209:20,21,22 213:6214:5 217:9 221:3224:10 226:1 227:17229:6,22 230:5 237:1237:20 239:23 240:2240:19 242:7,19244:8 246:6 248:9,20250:3 251:22 252:5253:8 254:20 255:11256:1 258:11 266:1266:18 267:19 270:3271:1 272:11,16276:14

represent15:20 261:2represented157:14reputable204:15

request4:10 11:24 286:19requests286:23require46:1 48:11 193:23

197:18 242:3required11:10 48:25 63:7

126:2 178:17 182:13requirement43:7 49:3,24 129:16

129:18,19 192:9251:7

requirements128:25 129:3 130:22

131:15 182:10191:10,15 192:11

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189:21 236:9 281:21282:2

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researcher51:10 78:12 111:21

114:25 115:6,6283:20

researchers41:9 47:15 80:13



37

203:11 222:22 227:7232:12 238:23248:16 275:17278:24

resembles193:24 197:19resist198:5resistant68:2 84:5,13,20resources32:25 33:21 41:21

157:22 247:19respect36:6 116:10 156:20

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responses161:21 238:18responsibilities10:8,10responsive87:12rest31:10 95:6 188:4

272:23restate130:13 146:8 165:7

177:12 230:21259:24

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149:11 150:18173:18 188:7 238:25247:8

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11:17,18,24 14:22

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reviewer10:5,9,10,20 122:16

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38

230:24 231:5,9,15232:18,25 233:25234:1,1,9,11,18,24235:6 236:4,17 237:2237:21 238:1,21,25239:2,3,6,25 240:13240:20,24 241:5,15244:10,21,24 245:13245:16 246:8 247:6247:13 248:11,17,22250:4 251:24 253:1,9254:22 255:3,13,17256:3,20 258:12,16259:22 260:8,12261:11 263:18 267:8267:11,20 268:2,8,9268:14 269:7,14271:2,11 272:2,13,18272:20 274:1,19275:2,18 276:10,15277:1,2,3,6,16,22278:9 280:3 281:7283:24 284:12285:16 294:9

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189:13runs156:9

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218:18 245:12248:13 256:2

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155:12,17 160:18212:24,25

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92:8 108:9 266:13,16266:18,23 267:10274:25 275:7 290:23291:14 292:8 293:23295:3,5

Schoen's22:8Scholar127:8 183:12Schryer3:16 265:21,24 266:1

266:6science70:9,10 180:9 204:6,7scientific10:5 32:4,5 51:14 52:8

52:17 54:12 55:1861:7,21 62:4,13,2363:4 76:12,18 77:277:24 79:25 81:20110:8,10 112:8 127:3127:22 132:6 144:22



39

156:14,15 157:18178:9 204:16 285:23

scientifically191:18,20,23 192:3scientist43:12scientists85:1 275:11scope44:25 84:7 103:21

104:4,12 185:9,20203:25 278:15279:13,24 281:10282:13

score138:11,15 163:11

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55:7 67:6 90:25 91:392:22 133:22 146:25147:5 197:11 203:3205:12 287:2

secrete24:22section52:20 54:6,7,11,22,24

55:2,21,23 57:23119:4 168:10 192:22192:24 193:9,11,13194:12,15,25 195:10198:17 201:6 219:9231:14,15 232:6,16232:20 233:16242:15 248:25288:19

sections25:16 222:5

see10:3 21:11 26:6,13,14

26:17 29:9 30:1135:12,13,18 47:1755:6,8 57:17,1960:13 61:16 63:13,1363:14 65:18 78:1986:11 89:2 91:2093:17 94:3,9,22 95:895:17,22 99:9 100:10100:13 101:8 102:10102:12 107:6 109:20109:22 110:19114:13 116:12 118:7133:23 138:6,12,13140:12 146:6 147:12151:10 152:18155:14 164:23,24166:10 175:19 184:4184:6 185:25 187:1187:19 197:24,25203:7 213:3,16,20218:23 219:14,23226:9 233:18 240:4240:11 241:3 242:22243:5 244:17 245:3,4246:12 247:10,18248:12 250:18251:12 252:4 253:5,5253:10,12 255:3,25257:10,20 260:21261:23 263:19266:22 267:1,21268:3 271:9 273:13278:1,12 279:19,25279:25 282:4,5,14295:6

seeing94:15 99:3seeks14:12seen49:1 61:3 97:12 118:2

127:2 149:2,4 150:12150:15 213:5 234:15250:4 284:16 285:22

286:5,8,9select11:13 247:2selected123:14 239:8SEM116:11 117:8,18 134:6semi-quantitative91:13 92:8 228:19

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181:12 203:1 213:3sensitive96:21 100:8sentence35:4,14,15,16,22 36:7

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separately105:18 140:24series20:4,5 56:9 61:3

137:24 252:17259:13

serious184:18 243:24serve6:3 10:4,19,20 25:2served6:9,13serves158:1

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sets98:6,11 159:8 221:20seven35:3 132:21 213:2

218:14,18 256:12severe216:5 217:8 218:20shape45:5 197:21shaped233:10shapes32:23share55:20 226:15shared41:10,10sheep43:8 48:12,14,19 49:4

49:6,11 50:2,11128:17,24 129:15130:3,8,13,15 131:3131:13,25 161:20181:13 189:21 191:9240:2 243:8 258:15258:18,24 259:12,14259:18 260:14 261:1261:2,9,13 267:20,22268:23 269:3,4,14,15269:16 271:1,7,10,17271:22,24

Shemin3:21 34:13,18 35:25

36:15,18 39:21 40:741:5,23 51:23 52:252:12 54:1 91:23191:7,24 192:2290:15,15,24 291:1291:10,15 292:1,6,9



40

292:16 293:5,14294:7,12,14

Shore3:13 244:4,6,8short12:16 21:20 106:10

137:24 180:6 230:10Shorthand1:12short-term117:20show16:20,22 34:2 165:2

178:7 181:22 215:25228:22,23 290:13

showed169:3showing60:24 98:23 234:23shown147:14 172:8 223:17

227:19 279:22280:20

shows202:1 228:20shunt238:19shutdown284:21side8:18 72:15 89:1

140:13 223:14side-by-side159:6,16,18,21,23signaling9:12 13:9 24:16,17significant32:8 33:21 54:20

132:9,13 179:20203:18

significantly98:8signs34:2 113:20 114:2

234:23silicone

219:17 220:1SILVIA1:12 296:3similar39:19 84:16 99:11

142:17 210:9 221:19226:10 261:6 280:7281:16 283:17

similarities222:9similarity226:16similarly117:22simple141:3,3simply118:18 140:11 180:12

180:13 277:6simulated47:18single125:4 249:10sit106:25site25:2 162:9sites131:22sitting115:13situation58:15 129:11 249:23situations58:7,11 130:10 160:17six35:15 208:21,22

211:23 212:3,7 213:2234:22 244:25 247:6256:6 259:14 268:13268:19

six-centimeter171:15six-hour137:24 139:21 140:4six-month

226:6,8size189:1sized197:20sizes24:5 32:23 270:9skeptical286:4skill11:17,19 68:18,23

69:9,13 70:14,1771:8,23 72:20,2573:9,13,14,24 74:474:20,24 75:19 76:676:11,17,25 77:8,1178:11,21 79:14,21,2279:25 80:5,19,2381:3,7,22 82:3,983:16 85:9,16,2086:1,6,17,20 87:4,987:21 89:23 123:8,20123:24 156:25 242:3283:7 284:3

skilled72:1skills11:23skin46:10 190:18sleeve64:13,21sleeves64:9Slow194:1small41:14 45:17,22,23

46:3,7,11,24 47:6,2149:4 77:22,23 97:4124:21 125:4,23164:1 165:2,6,9184:20 185:5 189:23190:6 191:11 192:5200:17,24 202:6270:5,9

smaller26:3 270:21smooth172:9smoothness193:25 197:19solicit11:5solution152:14 203:4solutions78:23 79:16somebody11:18 13:21 16:21

17:4 42:6 43:2573:13 78:19 80:1981:22 87:8 111:25112:12 122:2 124:15125:3 183:7

sooner34:8 43:1sophistication79:18sorry20:21 35:10 90:6 92:2

97:2 119:12,17136:10 141:21 146:8177:9 193:4 223:20224:2 231:18,19257:16 259:24 271:6276:22

sort9:25 11:3 26:5 30:25

31:12 43:6 53:6 84:7159:17 163:24 204:8250:9

sound249:16sounds53:16 156:9sources285:8South1:17 2:4,10 8:10,12SO3238:16



41

space72:14 195:19,23,25

196:4special53:16species35:7 36:3 37:5,10 38:5

38:8 39:7 42:15161:7 270:13

specific74:10 75:7,17 82:14

132:22 187:2,10,13264:8

specifically30:16 74:25 96:8

106:3 148:4 165:14166:21 246:2 263:17264:2 281:14 285:12

specimen161:13,14,17,18

280:19specimens62:6,25 280:8spectroscopy57:14 94:20 289:16speculate50:18 82:20 89:14,19

112:18 185:10227:15 267:3

speculating70:19 112:5speculation44:23speed208:4spend23:10 47:3 77:23

278:25spent23:5split155:8spot255:8squeezing140:16

St1:3 3:18,19,22 6:3,7

19:17 85:6 103:13,18103:25 104:7 111:3121:6 127:10 254:2278:4 279:5 281:18282:19,24

stability117:5,15 119:9 120:3

134:3stabilization197:10,10 199:1stabilized199:2 200:5stable132:21 152:6 160:7

176:23 177:21179:15

stage224:18stain57:24 222:21,24 223:3stained222:4staining58:2 222:14,16stains223:4,6stalls46:1stamp257:14stand85:20standard54:1,3 70:6 85:5 97:3

110:4,5,11 192:14249:9 269:21,22

standards109:24 221:20 293:1stands14:12 253:18stars18:25start71:13 91:15 93:20,25

119:21started198:11,12 260:25starting88:23 89:1 208:6starts28:19 35:16 61:1

68:14 133:25state1:15 5:10 91:9 111:16

136:13 141:12145:25 151:2 165:14166:21 177:7,13180:19 187:10,14188:5 191:7 221:16296:4,24

stated53:21 91:18 110:14

111:6 173:14 176:25180:12 187:4

statement36:4 40:13,17,19,23

44:20 52:12,18 53:262:15,18 69:5 83:1983:25 86:16 107:13107:15 110:17 116:8128:12,22 129:2130:11 143:21 149:1177:2 199:5,7 200:10244:13 262:1 290:5

statements60:14 107:10 108:8

130:23 292:25states1:1 40:8 68:17,22

91:25 102:22 132:13134:3 139:20 143:16177:16 205:15 220:1222:2 224:15 240:23259:5,12 261:24280:6 282:5,8 283:5

statistical62:20,22 98:2,4

160:24,24 207:12,15236:10 250:1

statistically

281:15statistics98:7 269:13stem13:19stenographically296:13step11:3 19:3 181:14

197:13 198:21,22232:4 252:14

steps125:25 252:20stint65:4stinted64:11Stipulations4:15stitched65:6stop48:1storage117:9,14,19 133:5,8,9

134:2,7,9,10,15,16134:17 135:1,4,23136:3,16,21 138:1152:13 154:9 155:9158:24 194:6 198:21199:12 201:11,18203:4,12

store126:4stored117:24 118:3,5 132:20

133:4 134:8 135:12135:20 143:17 144:1145:1,5,7,11,14146:7,10 147:2,17148:16,19,23 149:11150:5,9,13,19,23151:3,19 152:10153:4,25 154:3,19,24157:1,5,17,19 158:11158:19 159:1,11



42

160:10 165:17,18,20165:22 166:19167:17 168:18,23169:16,18 170:5172:3,5,11,14 173:9173:14,18,23 174:2,3174:8,24 175:3,6,9175:22 176:2,6,10187:24 188:1,8 189:3189:10 199:3 200:6205:17,21,22 206:20206:23 207:1,6,10,18207:22,23 209:7,12210:1,11,14 211:21212:19 214:19

straight173:7strange210:23strategies12:22 13:4,15,24strategy125:22 154:10 244:18

286:24stresses220:3stressors38:17strike4:20 87:11 293:8,19stroke287:10structural119:9 120:3 147:6structure117:6,15 134:4 152:5

160:6 176:5,6,20187:20

structures198:7students14:16 32:1studied9:10 20:9,13 45:14

266:10,11 288:3studies

39:9,11,22 40:25 41:346:6,18 47:7 50:759:12,20 61:7,2162:4,23 73:1,6 97:14118:4 132:6 139:22146:19,23 147:1149:10 150:18154:13 157:4,12,17157:22 159:13160:17 173:17 183:6183:6,19,23 195:12198:13 202:8 203:10203:14 204:19,23,25205:3 215:16 224:14240:8 258:15 268:17269:11 270:4 271:2274:9,14,16 283:13284:24 285:2 286:2295:12,14

study16:25 20:24 31:23

39:13 41:22,24 53:154:14 59:9 62:1363:9 84:25 97:12,16112:20,20 115:10125:18 130:2,3145:22 153:13155:23 156:1,14157:10 159:15162:13 173:1 182:6184:4 189:14,14,19193:15 212:18 213:6214:11 219:16224:25 225:4,19226:25 236:10,12238:2,5,20 239:9243:15 244:14,24245:5,10 247:17,20247:24 250:7 267:1,2267:9 268:15 271:8274:12 280:12281:24 283:17,18,19283:21 285:4,16,22286:5,10

studying20:25 77:23 80:21

subcutaneous46:7 97:4 221:8 266:2

266:20subcutaneously221:6subject11:14 35:7 36:2,16

42:22 125:5,6,9136:15 287:23

subjected198:23submission51:11submit14:25 122:15submitted20:22 121:14 122:7

251:3subsequent150:1 151:9,13,25

152:17subset85:1 158:13 209:22,23subsets82:15substitute56:24suffer218:9suffered245:2sufficient10:17 109:24 155:13

164:20 180:15,16282:18

suggested109:18suggestion195:4,11suitability35:5 36:1,6,8 39:25

40:5 50:10suitable11:4 32:19,22 33:8

76:19 77:3 84:6230:23 250:21 270:4

sum154:9,11 176:16 194:3

202:19summarize292:19summary254:7 292:17superior259:19,22supplemental179:7,10 213:15support4:2 17:6 41:22 103:14supported285:4supports60:13suppose161:19supposed114:12 285:15 294:19sure18:1 27:10 48:13

49:16,21 53:7 67:272:13 82:6 89:1692:15 93:9 109:10,13113:11,16 148:6163:1,17 167:14168:4 182:22 214:1221:5 226:25 230:2248:12 252:17,20253:6,25 254:19275:13 282:16291:23 295:6

surface28:23 29:8,14 31:4,7

56:7 117:6,16 119:6119:7,9 120:2 134:4138:14 139:3,4142:25 143:1,5,8162:23 163:24164:13,16,25 165:13166:2 167:3,4 193:24197:19 234:16238:24 263:14

surfaces



43

172:13,15,23 175:25176:1,2

surface-adhered164:9surgeon43:15,18 44:2,8 70:11

80:3,9surgeons8:21 44:16,21 45:1

80:8,12,16surgery52:3 218:15 241:20

245:13,16 251:1surgical9:3 44:7,11 120:25surmise149:23surprised41:5 286:10,14surprising114:24 115:5surrogate181:6survival277:8survive164:10,11,22 166:2

277:6survived239:6 240:24 241:2,13

241:18 242:20 245:1245:11,15 268:25277:23

surviving269:14,16survivors261:14suture162:3 167:18 168:7

169:3,6,9,12,17,23169:24 170:12 171:2171:3,6,10,16 172:10193:23

sutures170:22,23 171:21suturing

171:13,18 197:8,17switch44:9sworn5:5 104:16 296:9system25:1 47:24 48:7 56:12

56:13,15,16 192:18238:19

systemic265:11

TT1:9 3:2,5 5:1,1,1 296:1

296:1,8table95:7,16,22 96:11,12

97:21 98:1,11 99:899:11,14,18 100:5102:16 141:21,22143:11 147:22174:14 253:11 257:8268:4

Tables227:19take11:1 19:2 34:4 35:24

51:3,20 83:1 92:1193:7 94:12 95:6 96:4101:16 105:1,10113:12 116:23126:18 132:5 164:14166:12 192:25195:18 197:13 206:6213:18,19,24 218:24232:4 244:11 246:15252:2 253:23 276:16279:15

taken1:11 5:16 17:16 51:21

90:16 94:24 102:20126:21 127:19134:21 149:19167:15 214:2 215:20254:1 284:8 296:13

takes55:13 127:24 208:6Talbot5:12talk30:17 71:4 193:16

196:6,15 198:25talked45:7 101:10 276:24talking51:25 53:12 63:10

64:20 81:9 83:2388:25 101:7 104:22104:23,25 116:18126:24 138:17158:18,19,21 161:6162:23 165:12173:13 194:11201:16 204:5,6209:17 233:13235:19 289:2

talks138:20tamponade269:6target197:23teach54:9 123:13teachable110:13teaches10:16teaching124:16 182:23team32:24 111:15 112:7,12

112:24 113:2 153:10153:21

team's125:21Tech8:8technical236:6 270:12technically

270:18technique26:11,14 73:6,10,18

74:13,17 76:1 80:17201:18

techniques26:8 73:19,20,25

74:17 76:4 202:19283:8

technologies59:2technology14:15 79:18 280:23,24tell48:21,22 60:10,11

99:15 114:2,19124:11 153:13171:17 201:2 217:18246:1 258:20 273:5

telling45:14 270:17,24

291:22tells191:1TEM116:12 117:8,18 134:6ten34:1,4 39:4 241:2tend32:12 33:12 37:10

226:17,23 262:18tendency36:24 42:17 138:3

140:6 259:6ten-year34:7term23:22 27:2 29:10,19

29:23 30:6,8,2531:16 62:11 78:1580:15 85:8,9,1086:15 117:22 129:8129:22 139:15141:14,16 144:21152:22 154:12190:22 195:7 204:5,6



44

213:6 217:18 224:25243:1 245:10

terminal268:15,17terms9:12 26:22,24 29:25

39:25 40:5 53:570:24 78:21 86:14104:6 112:19 117:3138:1 192:16 209:11293:1

Teschner2:3 3:3 15:12,15 18:15

18:19 20:17 22:13,1525:8 26:9 28:9 29:2133:19 37:16 44:13,2446:19 50:20,25 51:455:9 63:1 64:1866:10 67:5 70:2077:5 82:11,22 83:5,984:18 87:6 90:1392:2 93:7,15 94:2100:17 101:2,24103:20 104:3,11105:10,22 106:2,5,7108:1,4,11,16,22109:2,7 110:6 112:14112:16 116:23120:13 126:14,19130:19 131:5,20136:8,11 138:18151:4 153:15 154:23155:10,19 159:3,20164:4 167:11 175:13176:14 177:11 178:5178:22 179:4 180:2,8182:3 184:12 185:8185:19 186:17,24187:6,17 188:24190:1,9 192:25 194:1194:22 195:16198:18 199:18203:24 205:4 210:6211:11,17 213:8214:1 215:3,22216:19 217:2 218:24

219:4 221:23 227:10227:23 229:16230:25 231:16,19232:3 235:7,18236:18 237:3 241:22244:11 246:15249:18 250:5,14,22252:2 253:25 257:1266:8 273:9,19 274:2276:16 277:7,17278:14 279:12,23280:4,10,17 281:4,9281:13,20,25 282:12282:22 283:25285:25 287:16,18295:20

test47:1,17 98:4 117:19

136:24 140:25 152:1155:23 156:8 160:18161:4 185:16 191:8215:1 224:10 231:2,4252:15,16 277:5

tested48:6 56:4,11,22 97:1

179:23 184:1,2188:16,17,17,19,23205:22 217:10 219:2227:3 230:11 239:5240:23 244:23 245:6248:14 252:6,9255:15 268:13277:10,22

testified5:5 278:7testify296:9testifying5:19testimony81:24 82:2,7 85:21

89:17,22 103:14104:16,18,20,21105:8 112:4 113:6,16114:24 115:5 116:6120:17 123:3 194:23

296:12testing33:5 43:2 47:22 48:12

48:19 49:11 50:2,1751:5,11 53:13 55:24139:10,14,21 140:3145:9 156:16 181:20181:21 182:13,19183:9 217:17 221:9221:12 225:3,6 226:1229:6,10,22 230:5231:8 237:20 239:9239:23 240:3,6,19241:21 244:8 245:19246:6,22 247:22253:1,9,14 254:20255:13 256:6 258:18258:19,21 259:16260:8 261:2 266:1,18266:24 267:19272:11 276:14

testing's244:20tests62:22 138:10 221:3,8

224:21 239:2 243:1257:10

text51:25 61:5 116:25

173:12 180:7 202:11240:10 256:24 257:4260:21 268:7 280:6281:14 282:5 291:21

textual237:13TFS138:11 139:23 142:21

143:10thank28:9 90:19 101:24

106:2,7 231:19 248:4295:19

thickness197:22thin57:22 172:9

thing26:25 51:9 60:11

61:11 79:1 95:23125:4 180:6 183:2217:4 228:13 236:21264:25

things13:5,23 18:2,23,23

22:7 27:1,1 29:2445:8 55:15 56:1763:8 65:8 82:8 120:4120:20,20 125:7146:21 149:17,18153:8 154:7 169:6170:12 171:2 192:20196:11,15,16 198:22199:21 202:19 215:7217:16 263:12

think6:18 12:4,7 15:8,9,11

16:7,9,19,20 17:2218:15,19 19:5 21:1723:5 26:22 27:5,1627:18,19 29:1,2231:16 34:5 35:1636:21 37:1,6 40:141:2,19 42:8,12,2347:10 48:22 51:1352:11 53:2,6 54:2,555:10,19 63:4,6,2367:25 69:19,24 70:2371:25 72:1 73:1074:3,7,12 75:9,11,2476:9 78:2,17 80:2581:19 82:23 83:6,1283:24 84:22 86:9,1386:19,21,22 87:889:5 92:25 93:1199:14 101:5,7 103:3106:20 107:19,24108:8 109:18 110:9112:7,17 115:1 116:9116:9 123:23 125:1126:17 128:9 129:20129:25 131:14,15,16133:13 136:2 137:19



45

138:11 141:1 142:13147:10 148:9,12,15148:22,25 149:20153:18 154:10159:10,12 160:23,25162:6,11,19,20164:21 165:19168:13 169:19 175:8178:8,13,23 179:22180:14 181:4,5182:13 189:5,16,17191:19 192:2,7194:24 195:21,22,24196:2,5,8 197:1198:15 203:14204:10,12,24 208:5211:7 212:14 213:14213:18 216:14,22217:2,3 218:8,23223:17 224:22 226:7227:15,15,24 228:8229:17 230:12,13231:1 234:5 236:20237:4 239:8,11 243:3243:6 245:5 247:21247:24 248:23249:23 250:10253:13,15,21 256:8256:12 257:2,18258:2 260:15 261:11262:14,19 263:2,12268:16,20 270:17271:24 273:11 274:3276:2 282:19 283:15284:20 286:2 289:19295:4

thinking36:7 107:20 129:21third1:17 13:13 35:17Thoracic52:3 251:1thought49:18 174:19 180:14

209:14 216:24 228:2236:23 285:23

three12:11 56:17 128:16

130:8 132:1 143:18151:13 179:11 180:7180:9 188:1 206:3208:2,8 210:7 217:22218:16 239:5 242:21252:19 255:20263:22 268:13,20269:11,21 277:25282:9 287:6

three-dimensional64:24three-quarters102:24three-week98:1,3,18,22 99:19

117:25 159:11,21189:16 224:15

three-year8:9threshold189:8 250:19thrombogenicity201:23thrombosis239:10 241:11 242:8

242:13 243:18,21259:6

thrombotic29:15thrombus119:7 139:4 143:2,6,7

162:3,16,19,21163:15,24 164:1,6,9164:20 165:3,7,9,25166:2,5,20 167:1,4216:10 238:24

thrombus-free119:5 138:14 139:3

142:25 162:23throw192:17thrust13:1,7,13thrusts

12:12,12time10:15 12:16,17 15:9

17:12 19:3 22:2023:4,9,10 27:3 33:2138:23,25 39:9,1940:24 41:7,11,1544:10 62:10 89:893:7 97:15 98:1399:2,3,10 100:20105:1,10 106:10116:23 126:15 128:7131:25 137:6,13151:2 155:13 157:10157:13 158:20 159:1159:7,8,15,23,24,25160:22 164:8 173:1,5174:10,12,19 178:12178:18 179:20 184:3184:5 192:25 196:14197:14 203:20206:11,12 208:2,5,11208:14 213:12 215:9215:17,21 218:24227:5,8,16 230:10,12230:17,20 232:4236:8 244:11 245:25246:15,24 247:5,16247:17 252:2,20,20253:3,7 256:12 274:1275:19,21 276:3,6,16278:25 284:3 287:2,7287:10 288:15 289:2290:9 295:21 296:13

timeframe27:12,14,17 33:23

42:23 215:17timeline215:10times30:1 89:2 100:15

103:10 127:4 130:2150:22 179:11247:19 252:9 286:22287:6,24 288:6292:14

timing38:11,13 48:24tissue9:13 12:15 23:17,23

24:1,6,8,12,14,1925:6,21,25 26:16,1729:16 30:23 31:1,431:12,19 32:8,11,1333:3 37:2 56:19 57:657:16,23 58:4 60:2460:25 61:24 63:16,2164:1,4,14 71:1072:22 89:4,18 94:6,795:13 98:17 99:22113:2,7,24 115:13,17119:10 131:24132:15 135:5 136:16137:18 149:16,18151:16 167:19 168:2168:10 170:9 177:20179:15 184:19,25185:25 190:15196:14 198:6,7,23199:13 203:12,18205:17,21 206:12,13214:7,19 222:5,20238:3 244:9 250:6252:13 262:1,10,24266:3,4 274:13,15280:7 283:9 295:17

tissues9:6 12:19,23 36:25

37:24 38:7 39:1446:9,13 89:12 156:1159:11 164:7 189:25190:8,10,12,14,20205:22 221:6

title21:20 70:1today5:15,20 17:8,20 49:3

49:23 58:23 213:15289:2,4

told53:10 204:25 205:1

283:22



46

tolerate261:4top67:16 82:25 102:8

128:5 167:23 240:9268:22 279:20 280:1280:2 287:12

total62:5 154:9,11 176:17

194:3 202:19 207:21209:20 214:14

touches125:14tough44:8tower2:11track19:22 22:1Trademark1:1 6:10transcript1:9 6:25 87:25 88:7,16

113:11 296:12transecting139:1trauma217:20treated136:16 173:4 189:12

211:25 219:22,24220:18 221:6 255:2

treatment61:10,10,13,13,16

155:13,15 180:23181:2,9,21,23 182:2184:1,5 214:7 238:6238:8,10 252:8 255:9

treatments84:10 117:21trend184:6triage11:3 122:11,12trial1:1 43:4 104:18

tricuspid267:24 268:19 270:9tried148:4 151:25 253:6tries55:14Trifecta3:22 278:3 279:6

280:23 281:7trouble291:14true270:6 296:12truly91:19truth296:9,9,10try12:12 13:3,7,23,24

24:23 43:13 46:2555:16 185:18,23,25208:19 284:18

trying16:17,20,21,23,25

21:9 23:19 35:942:23 48:15 49:1855:13 60:9,10,1161:17 62:8,13,17,1877:21 92:9 93:5107:18 123:13133:17,19 141:9158:23 181:15186:19 189:20192:15 202:12209:16 219:8 228:8230:18 231:2,4,10,22231:24 233:6 245:4246:12 249:24260:16 279:2 286:25292:18 293:1

TSF138:14 162:22 163:11turned157:9 286:18,22two21:20 56:17 80:7

93:17 104:24 106:21117:13 133:5 134:2134:17,25 135:3,12135:23 136:3,21144:11 145:18,20,22150:22 154:19,25155:1,17 159:5 161:4161:6,7 167:12179:11 184:17192:20 195:22 199:3199:12 200:5 208:22209:21 211:3,21,25212:3,6,7,7 244:2,23245:1,16 249:25250:8 255:19,20261:17 267:21269:22 279:25280:20,21 281:12292:14 293:10,25294:11,22

two-page19:25two-thirds28:18 193:18two-year-old230:7type78:22 79:15 161:20

162:8 179:2 183:14188:25 213:21 236:1236:13 264:9

types45:20 59:20 80:8

189:24 190:8,14,20200:22 265:6,11,13267:21

typical47:6,11 232:20 286:24typically80:5 122:15 180:9typo291:22,25 294:22typographical216:21 293:17

U

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46:16 49:25 59:7,1365:21 67:18 85:1890:23 91:17 96:6102:4,18 110:14133:23 138:8 141:15142:23 146:16 154:1158:14 168:20173:25 183:21188:20 203:19210:13 225:25229:24 233:23234:19 241:9 242:24244:7 246:17 252:11268:9 269:2 278:19

ultimate78:5ultimately185:24ultrasound9:21unambiguous149:4unclear199:25 233:5undeniable186:10,14,21 187:22undergone268:23undergraduate8:4underneath127:9 131:23understand5:19,22 7:6 8:16 10:12

10:13 12:5,13 13:242:24 43:13 47:148:17 68:18 78:1379:20 81:8,11 82:683:15,21 85:4,8,1786:14 89:16 97:7,2099:24 103:13,18,23104:15 120:17



47

125:17 148:6 156:25161:2 163:17 170:11181:25 186:19202:13 230:19 281:2292:12

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30:12 32:6 37:2238:4 49:10,24 50:350:11 70:22 75:12122:1 129:7 130:22151:11,17 160:4239:13 251:6 262:14263:10

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124:22unfortunately43:6uniform50:4uniformed50:9unimpeded142:18UNITED1:1university1:7 5:2,14 8:5,7,10

85:7 103:15 108:10unknown159:11 166:25unnecessarily108:5unpublished286:8unreliable129:24unsuccessful284:20untoward118:6 147:3 149:13,13

149:21 165:5,14,18173:20 188:9

untreated248:20unusual114:14 115:9 243:14un-implanted95:13 97:22 98:5,10

98:12,17 102:19135:8,11 199:13

upper88:20use7:16 26:14 29:9 30:6

33:22 35:6 36:242:20 43:18 44:5,1144:22 46:4 47:1750:17 58:6 59:14,1961:10,17 68:2 73:2175:15,16 84:14 85:1099:16 104:17 116:13140:10 144:23 147:5153:9 157:19 161:20179:3 182:9 183:22184:5 189:21 190:22192:14 200:17,25201:8,9 202:6,11203:12 204:3,9208:20 214:8 222:22222:23,24 227:7228:23 246:21 251:8251:11 258:18 259:7260:25 266:7 267:2,4267:9 270:18,22271:19,20 291:1

useful40:9,15,17,20,24 41:2

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58:24 97:22 100:2157:24 274:22

utilized33:1 39:19 41:13

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utilizing238:7

Vv1:5vague53:5vaguely110:25vales222:10valid59:1validity222:8value41:16 162:22 197:3

200:11 249:10values139:23 162:25valve3:22 8:17 9:22,24,24

12:13 13:2,15,17,2014:2 35:1,6 36:2,938:2 39:3,4 40:243:2,4,18,22,24,2544:2,4,6,11,18,18,1944:22 45:5,12 47:1647:18 48:1 50:656:19,22,23 57:464:11,19,21 80:18113:18,20,23 128:23128:24 130:7 162:9

166:8 181:13 182:7182:23 183:20185:17 186:4 217:9220:4,8,18 226:20,21230:16 231:3,5,7241:4 243:5,8 245:6248:9 254:21 256:14262:6,12,16,25263:14 267:25 268:1268:5,10,10 277:18278:3 279:6 281:7

valves9:10,16,17,18 14:4

43:10,15 45:8 48:1249:12,13 56:8,2464:9 65:6 80:4,14,21128:17 129:15130:15 131:3,12149:24 155:22,23156:1 162:19 182:21185:12,12 189:19191:9 215:16,16,20216:1,2,8 217:24219:2,9,12 229:10230:1,3 237:21238:17 239:24240:20 258:22,25259:16 261:2,6,21262:1,10 263:22,25264:22,24 265:3,6,14266:19,20 267:20268:4,20,24 269:6,20270:4 272:12,21273:1,2,6,16,21280:15,23 282:11

valvular270:12,19,20variables61:14variation161:16variety12:5 24:10 57:12

120:19,20 125:13131:24

various



48

57:24 287:20vascular124:21 125:23 132:20

189:23 190:6 191:11238:17 246:7

vegetations29:16vein201:25 246:14,19

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98:12versus26:3,25 29:23,25

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vessels114:14 118:3 128:18

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204:2 214:10,16226:11 262:17 264:1

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274:5visually272:25 273:23vital282:10vivarium45:24vivo84:5 117:20 126:4

136:25 137:4,7,24140:4 219:16 238:18261:12

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223:23 245:18 253:4256:5,8

waited247:12 253:6 256:11waiting44:22walk46:2

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36:5 43:3,18 46:2350:19,25 51:10 60:1362:20 66:16 72:1375:16 76:2 82:685:22 89:14,16 90:1391:3 100:3,10 106:9108:19 126:16 148:6155:20 182:8,8,18,22185:10 213:16,24247:18 270:18273:13 291:23293:16

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227:24 294:10wasn't21:1 35:22 48:20

73:22 76:23 81:298:17 111:25 129:10159:15 236:3 273:22277:5 286:12

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28:18 31:5 57:1066:1 77:7 81:14,1593:16 102:25 115:23126:3,3,3 129:21140:17 144:21148:23 149:8,25154:8 161:17 163:17163:21 179:19 180:5193:18 194:6 196:13204:20 210:2 211:13211:18,19,24 212:4257:18

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143:18,21 151:13188:2 206:3 208:2,8221:10 272:17,22,25273:4,22,23

weight123:5Weill5:3Weiner2:9 3:3 5:7,13 6:23 7:2

18:12 20:18 28:1,750:24 51:2,19 67:1083:14 87:11 90:12106:1,3,6 108:14,24126:17,20,22 127:20167:14 193:5 213:24214:3 219:7 231:18253:23 254:5 284:5291:5,7

weren't20:12 59:3 146:12

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223:21 224:2we're17:19 132:23 158:18

158:19 161:6 162:23165:12 173:12223:20 295:20

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49

104:22 288:15wide120:19,20 227:14widely50:13wildly211:5Willis2:11withstand220:3witness3:2 4:5 6:4,10,14,24

15:16 19:5 22:2183:6,8,11 105:25108:5,15,25 109:8136:10 199:19 215:5216:23 246:17

word119:20 120:6,8 175:10

175:19 179:20,23192:14 196:21 201:9208:20 240:11 263:3263:3 271:18 279:8293:20

words35:18 114:23 148:24

149:20 187:11,13255:8

work6:7 7:7 9:14 14:20

30:6 31:25 32:344:15 70:8 72:6,8111:3 121:6,10151:18 156:17,23182:23 183:5,7 195:7202:1 232:13 242:4251:10 257:5 258:11

worked45:2 113:22 242:5workers79:19working45:4 70:10 77:15

127:10works

12:17 43:10 47:1154:15

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48:2 50:22 53:2577:6,7 104:13 114:9114:18,20 124:24137:8,17 151:1152:25 157:18 160:9160:19,19,21 165:7178:3,19 179:13180:12 186:2 189:14190:22 212:13,18243:9,13,14,25262:21 264:9 270:22

wrapped139:15write5:24 14:25 72:15

163:9,22 179:5211:15,18 213:11287:11 292:1

writing72:9,12 178:6 179:3

275:19,21 287:1,8written14:19,22 55:3 61:5

151:5 288:10,16,17288:19

wrong27:8 89:15 129:25

290:7wrote17:21 81:4 107:20

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201:24Xylene164:18X-ray59:11,20 73:1,5,15,25

233:9 281:24 282:9295:14

X-rays59:8 73:11

Yyada193:25,25,25yeah7:11 11:25 15:12,17

15:17,17,21 17:3,318:18 19:10 20:10,2321:13,16,22 22:2,622:25,25 24:15 27:2129:7 30:24 34:6,1035:13 36:17 39:2443:16 44:15 45:2249:22 51:4,8 53:9,1453:24 57:17,22 58:1458:19 59:10,10 62:1463:11,12 64:22 65:2572:13 74:2 76:178:20 82:23 83:2492:20,24 93:11,13,2494:9,11 95:5 99:1100:16 101:15102:11 103:22106:19 107:2 114:23115:19 119:2 124:23136:6 141:8 144:20144:23 152:12163:18 168:6 180:11185:1 186:9 187:8194:17 201:21 209:5209:9 211:7 212:16216:6 218:17 225:8231:1,20 233:17,17233:20 236:23241:12 245:6 249:3254:9 256:8 258:2260:4 265:19 267:9

269:8 274:3 277:25287:22 291:24

year101:17 246:11 247:12

252:6 253:1,3,4,6years26:23 32:1 34:1,5 39:4

42:25 43:4,10,2044:21 69:1 70:5117:13 133:5 134:2134:17,25 135:4,12135:23 136:21 199:3199:13 200:6 245:16261:17

York1:15 5:4young36:12,16,19 37:3 38:5

96:13,21 97:23 99:10100:2,5 221:4 224:11224:17,22,23 225:10225:13 246:7,10,21251:23,25 261:1266:3,4 272:12

younger33:4,7 37:9

ZZarins124:1,3,9zero200:8 208:6zeros207:16zones65:1

00155:4 211:1 222:40.65143:17070902:4

11



50

12:21 84:3 95:797:22 99:8 100:5172:8 222:4 240:24241:11 249:3 253:11255:16 268:4,25269:4,16

1.244:31.7269:171:25126:211:26127:191:29127:191023:8 68:9,13 88:24

128:13 142:2 143:3163:19 208:17 216:1217:23 255:15 257:9279:16,16,18,19

10:2251:2110:3251:21100139:23,24 140:20

142:10,22 147:19163:12,14 164:3174:15

100020:310013:7 66:24 67:8,121009117:141013:1210103:8 65:10,13,16 68:13101321:12101421:121016

3:8 6:17,20 91:6101715:11,15,161018116:14,15 118:25

119:1,14,15 126:25127:12 274:18276:12 284:12285:18

10193:9 27:22 28:2,4,10

214:2310203:9 220:21,2210213:10 223:12,16 224:3

224:5,710233:10 214:23 223:25

225:21,2210243:11 228:25 229:1,410253:11 237:14,15,18

276:2210263:12 92:24 101:18,19

101:23,25 239:1810273:12 240:15,16 277:1210283:13 244:3,410303:13 214:23 245:21,22

246:310313:14 248:1,2,610323:14 251:16,17,1910333:15 254:14,15 256:23

258:12 264:12,15,1610343:15 256:16,17,19,22

257:12,16,17 258:121035

3:16 258:4,5,7,1410363:16 265:20,21,2310373:17 266:12,13,1510383:17 267:13,14,1610393:18 272:5,6,810703:18 19:14,17,21

92:18,2110713:19 254:2,7114:22 141:24 143:22,25

144:6,8,25 146:7,9155:2 207:21 210:22241:8

11:2590:1611:3390:16112141:17 142:6 151:14

152:7 157:15 159:7159:22 160:3,7 173:5173:10 174:20,25208:12 214:14

112-day142:9 147:24 157:1,4

157:12,17 158:20159:13 174:14 177:3177:8,14

1152234:121153234:211154233:7 234:21116289:22117227:5,8,131223:8 113:17 227:6

230:6 279:2012:30126:1512:36126:21123224:131332:1 53:20 65:19

256:3133244:251495:14 97:25 127:4,14

128:4 183:15 205:6239:6 277:8

141242:21 243:1 277:2414594:12,1614895:814853-72025:416-year230:61743:10,19 44:21174227:618216:1 217:23 245:12

245:19 269:4180240:23 242:191803-1980511:25182247:8183242:22 243:1184242:7,10,11 243:21188102:8,2119



51

190102:15196247:819763:12 240:17,1819823:9,15,17,18 92:4

102:6 105:15,19,21220:20,23 239:19254:14,16,18,20267:14,17,19 268:12272:7,9 291:12,17292:4 293:7,8,14,22294:12,15

19833:12,13,15,21 90:3,22

91:9,15 92:5,10,2392:25 93:2,22 96:8101:7,19 102:3,9103:4 104:21 105:19106:17,22 107:4,7,11107:15 244:4,6256:17,20 290:2,20291:9,18 292:1,21293:4,8,20 294:19

19843:16 258:5,819853:17 116:16 127:22

128:3,8 178:13266:14,16,18,23267:10 289:2

19863:11,16 223:15 224:8

229:1,3,6 232:10265:22,24

19873:10 224:519883:10,21 34:13,19

40:20 41:1 91:23191:7 225:23 290:15290:24 291:10,15292:1,6,9 293:5,14294:7,12,14

19913:9 27:22 28:4,1419933:11 27:15 32:9,16

48:25 58:23,25 59:1859:21 69:11 178:19191:7 215:25 237:16237:17

19973:13 245:23 246:41998225:241999280:12

221:18 141:22 143:11

147:22 155:4 172:8174:14 210:24,25222:4 227:19

2.5269:222:22167:152:27167:152043:4,20 44:21 50:7

211:1 214:21 269:3281:16

20-year43:3200020:5 295:220033:21 34:12,13,16

51:23 290:142004216:15,1820053:21 90:2,3,12,18,20

91:15,16 92:23 93:2096:9 101:14 106:4292:21

2007

3:22 278:2,3 279:52008287:420103:14 248:3,720123:14 251:17,20,2220131:19 3:23 87:25 88:2,5

113:12 296:252017296:242195:14 97:25 141:17,25

142:9 143:23 144:1145:1 146:7,9 150:4151:18 158:6 160:9160:11 161:23 162:2173:6 174:14,20,24181:22 182:12,19183:18 188:15,22206:14,18,21 208:10208:17 209:8,13210:1,15 214:17,23215:1,12,14,18 227:8227:11,12 241:4,7243:3,6,12 247:22255:12,15 276:15277:5,6,21

21-day141:20 147:22 154:16

159:6 166:6 173:2212:18 214:12285:15

2151253:1022111:6,11 211:22203:92243:102253:10 246:82293:11

2367:24 83:22 84:12

191:42332:102373:1124277:82403:122443:132453:132483:142584:3 139:24 276:22

295:3,11,132513:142543:15,192563:152583:162666:15 215:25 216:20

216:252645251:242653:162663:172673:172763:15 237:62723:18277267:24278



52

3:22279267:25283:9 214:23282268:6285268:14286268:232873:3289269:2429241:11297272:15,16,19,20298272:21

3395:13,16 97:24 128:15

141:20,21,25 143:21155:7 222:4 227:19245:12,18 247:8249:4 256:2 257:8

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241:330X100182700296:53045:33188:11,2031/Line88:24

3122:123288:11,21321222:2324248:25343:21 267:735117:2,2 205:9 268:2536117:4 132:8,9,12,24

133:237113:12,14,17 136:13

137:21 140:3,22257:20,21

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99:11,14 155:7197:21 231:13,17249:3 269:3 296:25

4.2269:174:49254:140214:2341176:25 277:14411248:18,25412

254:25416255:12418255:23 264:18,21419264:2143180:1844231:18,21 232:2,5

235:12449259:345111:13451263:21454260:18,20 261:24

262:3 264:246186:6,947117:2 283:2474-95602:1248221:15 241:8 292:18

292:244996:5,7,17 101:6,13

106:3,16,20 109:17109:18 119:12,17138:20,23 139:8292:18,20,23 294:24

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5,746,7751:25.2

248:22 249:5,75/2913:35:08254:15015:17 117:12 118:5

132:16 133:4 134:1136:14 139:24 147:2147:17 149:11 150:6150:9,19 152:8173:13,18,23 174:6174:22,24 188:5,8199:4 200:6 201:10292:18

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53

56-day147:23 151:7 186:16

186:23 187:15

663:8 79:10,12 155:3,4,6

256:2 269:16.1249:86:01284:86:06284:86:19295:2160's43:256001:17 2:460394:2060606-63572:1163002:1164268:25653:8 117:24 134:8657257:19673:7

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98.0162:249912:17,2099.0162:2499.5162:24 163:3