2002 aipla - kass & nitabach, a roadmap for biotechnology patents, by kass et al

* © 2002 Lawrence T. Kass and Michael N. Nitabach. Mr. Kass is a former clerk ofthe Honorable Alvin A. Schall at the United States Court of Appeals for the FederalCircuit. Dr. Nitabach received his Ph.D. in Biology from Columbia University.Currently, they are both associates in the Intellectual Property and Litigation Groupsof Milbank, Tweed, Hadley & McCloy LLP, and are resident in Milbank’s New YorkOffice. Dr. Nitabach is also an associate research scientist in the Department ofBiology at New York University. The authors thank Rochelle K. Seide, Ph.D., ofBaker Botts, LLP, chairperson of the AIPLA biotechnology committee, for reviewingthe text and providing valuable feedback.

AIPLA QUARTERLY JOURNAL

VOLUME 30, NUMBER 2 Page 233 SPRING 2002

A ROADMAP FOR BIOTECHNOLOGY PATENTS? FEDERAL CIRCUIT PRECEDENT AND THE PTO’S NEW

EXAMINATION GUIDELINES

Lawrence T. Kassand

Michael N. Nitabach*

I. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235II. UTILITY, WRITTEN DESCRIPTION, AND OBVIOUSNESS . . . . . . . . . . . 236III. WRITTEN DESCRIPTION AND OBVIOUSNESS AT THE FEDERAL

CIRCUIT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239IV. IMPETUS FOR ATTENTION AT THE PTO . . . . . . . . . . . . . . . . . . . . . . . 244V. WRITTEN DESCRIPTION GUIDELINES . . . . . . . . . . . . . . . . . . . . . . . . . 248VI. UTILITY GUIDELINES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256VII. NIH’S VIEW OF THE NEW GUIDELINES . . . . . . . . . . . . . . . . . . . . . . . 262VIII. FUTURE DIRECTIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264

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1 See Diamond v. Chakrabarty, 447 U.S. 303, 206 U.S.P.Q. (BNA) 193(1980).

2 Utility Examination Guidelines, 66 Fed. Reg. 1092 (Jan. 5,2001)[hereinafter Utility Guidelines]; Guidelines for Examination ofPatent Applications Under the 35 U.S.C. § 112, ¶ 1, “WrittenDescription” Requirement, 66 Fed. Reg. 1099 (Jan. 5, 2001)[hereinafterWritten Description Guidelines]. The statutory basis for the utilityrequirement is 35 U.S.C. § 101, which requires that a patentableinvention be “useful.” 35 U.S.C. § 101 (2000). The statutory basis for thewritten description requirement is 35 U.S.C. § 112, ¶ 1, which requiresthat the patent application contain a written description of theinvention. 35 U.S.C. § 112, ¶ 1 (2000).

I. INTRODUCTION

One of the most valuable assets a pharmaceutical or biotechnologycompany can own is a proprietary position on genetic material that willprovide the foundation for developing commercial biological and chemicalproducts. The appropriate requirements for patenting genetic material area subject of vigorous national and international debate.

In the United States, the basic criteria for patenting advancements ingenetic research have been established by the United States Court ofAppeals for the Federal Circuit, following the United States Supreme Courtdecision in Diamond v. Chakrabarty.1 However, several organizations haveexpressed concerns that unduly broad genetic patents still may be grantedand thereby stifle innovation.

In an attempt to address such concerns and to account for FederalCircuit precedent, the United States Patent and Trademark Office (“PTO”)has recently issued guidelines relating to the U.S. patentability requirementsof “utility” and “written description” (collectively, the “Guidelines”).2 TheseGuidelines address various comments made about an earlier version called

2002 A ROADMAP FOR BIOTECHNOLOGY PATENTS? 235

3 See Utility Guidelines, supra note 2, at 1092.

4 See id.

5 See generally Utility Guidelines, supra note 2; Written DescriptionGuidelines, supra note 2.

6 See Utility Guidelines, supra note 2, at 1098; Written DescriptionGuidelines, supra note 2, at 1104.

7 See Utility Guidelines, supra note 2, at 1097; Written DescriptionGuidelines, supra note 2, at 1104.

8 “Prosecution” before the PTO refers to the administrative procedure forseeking allowance of a patent application.

9 See generally Utility Guidelines, supra note 2, at 1092; WrittenDescription Guidelines, supra note 2, at 1099. The statutory basis of thenon-obviousness requirement is 35 U.S.C. § 103, which forbids theissuance of a patent when the differences between the subject matter of

the Revised Interim Utility Examination Guidelines.3 The Guidelines maybe found in the Federal Register, along with the comments and the PTO’sresponses.4 While the Guidelines themselves are not specifically limited tothe examination of patent applications for biotechnology inventions, manyof the comments and responses do address biotechnology-specific issues.5

The PTO has not officially promulgated the Guidelines throughnotice and comment rulemaking, and thus, the Guidelines do not have theforce of law.6 They do, however, represent the PTO’s current understandingof the statutory requirements of utility and written description.7 As asupplement to Federal Circuit precedent, these sources are helpful tounderstand and to plan the prosecution of biotechnology patent applicationsat the PTO8 and may also be of use in litigating biotechnology patents.

The newly-issued PTO examination Guidelines do not expresslyaddress the patentability requirement of non-obviousness.9 However, non-

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the patent and that of the prior art are such that the subject matter ofthe patent would have been obvious to one of ordinary skill in therelevant art. 35 U.S.C. § 103 (2000).

10 Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1567, 43U.S.P.Q.2d (BNA) 1398, 1405 (Fed. Cir. 1997).

11 35 U.S.C. § 101 (2000).

obviousness is a critical issue in biotechnology, especially considering therecent publication of nearly complete genome nucleotide sequences ofvarious organisms. Such organisms include the fruit fly Drosophilamelanogaster, the nematode worm Caenorhabditis elegans, the flowering plantArabadopsis thaliana and, most notably, Homo sapiens. In addition, the FederalCircuit has noted the intimate relationship between written description andobviousness, having stated in the biotechnology context that “[a] descriptionthat does not render a claimed invention obvious does not sufficientlydescribe that invention for purposes” of the written descriptionrequirement.10 Therefore, as a matter of logic, a disclosure must render aclaimed invention obvious to satisfy the written description requirement.

In this article, we discuss the implications of the newly-issuedexamination Guidelines with respect to biotechnology inventions. We alsoaddress the relationship between these Guidelines and the law ofpatentability established by the Federal Circuit.

II. UTILITY, WRITTEN DESCRIPTION, AND OBVIOUSNESS

The statutory basis for utility is 35 U.S.C. § 101, which embodies thepatentability requirement that inventions be “useful.”11 Section 101 states:“Whoever invents or discovers any new and useful process, machine,manufacture, or composition of matter, or any new and useful improvementthereof, may obtain a patent therefor, subject to the conditions and


12 Id.

13 Brooktree Corp. v. Advanced Micro Devices, Inc., 977 F.2d 1555, 1571,24 U.S.P.Q.2d (BNA) 1401, 1412 (Fed. Cir. 1992); see also Juicy Whip, Inc.v. Orange Bang, Inc., 185 F.3d 1364, 1366, 51 U.S.P.Q.2d (BNA) 1700,1702 (Fed. Cir. 1999).

14 In re Ziegler, 992 F.2d 1197, 1200, 26 U.S.P.Q.2d (BNA) 1600, 1603 (Fed.Cir. 1993)(citing Cross v. Iizuka, 753 F.2d 1040, 1044, 224 U.S.P.Q.(BNA) 739, 742 (Fed. Cir. 1985)).

15 35 U.S.C. § 112, ¶ 1 (2000).

16 See Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563, 19 U.S.P.Q.2d(BNA) 1111, 1116 (Fed. Cir. 1991).

requirements of this title.”12 Historically, the Federal Circuit has not foundthe utility requirement to pose a major hurdle to patentability; the FederalCircuit stated that “[t]o violate [section] 101 the claimed device must betotally incapable of achieving a useful result.”13 However, the FederalCircuit has also said that a patentable invention must have a substantial orpractical utility that must be disclosed where such utility would not beobvious.14

The “written description” requirement is imposed by 35 U.S.C. § 112,first paragraph, which states:

The specification shall contain a written description of theinvention, and of the manner and process of making andusing it, in such full, clear, concise, and exact terms as toenable any person skilled in the art to which it pertains, orwith which it is most nearly connected, to make and use thesame[.]15

In 1991, the Federal Circuit’s test for written description became what maybe termed the “possession” test.16 Compliance turned on “[w]hether thedisclosure of the application . . . reasonably conveys to the skilled artisan

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17 Id.

18 35 U.S.C. § 103 (2000).

19 SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1355,55 U.S.P.Q.2d (BNA) 1927, 1930-31 (Fed. Cir. 2000)(citing Graham v.John Deere Co., 383 U.S. 1, 17-18, 118 U.S.P.Q. (BNA) 459, 466-67(1966)).

20 Id.

that the inventor had possession . . . of the later claimed subject matter.”17

The “non-obviousness” requirement derives from 35 U.S.C. § 103, whichstates:

A patent may not be obtained . . . if the differences betweenthe subject matter sought to be patented and the prior art aresuch that the subject matter as a whole would have beenobvious at the time the invention was made to a personhaving ordinary skill in the art to which said subject matterpertains.18

Deciding the issue of obviousness requires an inquiry into the scopeand content of the prior art, the level of ordinary skill in the field of theinvention, the differences between the claimed invention and the prior art,and any objective evidence of non-obviousness, such as long-felt need andcommercial success.19 The Federal Circuit has also required that there be asuggestion or motivation to modify the prior art in such a way as to arriveat the claimed invention; the suggestion or motivation may be derived fromthe prior art reference itself, from the knowledge of one of ordinary skill inthe art, or from the nature of the problem to be solved.20


21 Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 U.S.P.Q.2d (BNA)1016 (Fed. Cir. 1991).

22 Fiers v. Revel, 984 F.2d 1164, 25 U.S.P.Q.2d (BNA) 1601 (Fed. Cir. 1993).

23 In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d (BNA) 1210 (Fed. Cir. 1995).

24 Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 43U.S.P.Q.2d (BNA) 1398 (Fed. Cir. 1997).

25 Amgen, 927 F.2d at 1205, 18 U.S.P.Q.2d (BNA) at 1020.

26 Id. at 1206, 18 U.S.P.Q.2d (BNA) at 1021.

27 Id.

III. WRITTEN DESCRIPTION AND OBVIOUSNESS AT THE FEDERAL CIRCUIT

Recent cases have raised the question of whether the Federal Circuithas imposed new substantive criteria regarding written description forgenetic inventions. Those recent cases include the following: Amgen, Inc. v.Chugai Pharmaceutical Co. (1991),21 Fiers v. Revel (1993),22 In re Deuel (1995),23

and Regents of the University of California v. Eli Lilly & Co. (1997).24

In Amgen, a scientist claimed priority to a purified and isolated genebased on his allegation that he conceived how to identify and isolate thegene before the patentee.25 The Federal Circuit held that the conceivedmethod for identifying and isolating the gene was not conception of the“purified and isolated DNA sequence” that had been claimed by thepatentee.26 Because the patentee was first to actually isolate the gene, he wasdeemed the first to conceive it and was entitled to priority of invention.27

The patentee’s disclosure of the DNA sequence of the isolated gene was

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28 Id.; see, e.g., Fiers v. Revel, 984 F.2d 1164, 1171, 25 U.S.P.Q.2d (BNA)1601, 1606 (Fed. Cir. 1993); Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555,1555, 19 U.S.P.Q.2d (BNA) 1111, 1111 (Fed. Cir. 1991).

29 Fiers, 984 F.2d at 1166, 25 U.S.P.Q.2d at 1602.

30 Id. at 1167, 25 U.S.P.Q.2d (BNA) at 1603.

31 Id.

32 Id. at 1169, 25 U.S.P.Q.2d (BNA) at 1605.

33 Id.

34 Id.

sufficient to demonstrate that he had possession of the invention and, byimplication, also satisfied the written description requirement.28

Fiers was an appeal from a three-way interference action in the PTOto resolve conflicting claims to priority of invention between Fiers, Revel,and Sugano.29 Sugano was the first to file a U.S. patent application; hisapplication covered a gene that coded for beta interferon ($-IF).30 Fiersargued that he previously conceived a method for preparing the DNA,which entitled him to claim the DNA itself, per se, without requiring him tospecifically claim the process for preparing it.31 The Federal Circuit rejectedFiers’ position, explaining that “[c]onception of a substance claimed per sewithout reference to a process requires conception of its structure, name,formula, or definitive chemical or physical properties.”32 Fiers could notclaim the substance per se; he was only entitled to a product-by-processclaim limited to the particular method for making it.33 The Federal Circuitfurther explained that conception of the substance per se required the abilityto “describe” the substance itself, with particularity as required by thestatute.34


35 Id.

36 Id. at 1170-71, 25 U.S.P.Q.2d (BNA) at 1606.

37 Id. at 1171, 25 U.S.P.Q.2d (BNA) at 1606.

38 In re Deuel, 51 F.3d 1552, 1553-54, 34 U.S.P.Q.2d (BNA) 1210, 1211 (Fed.Cir. 1995).

39 Id. at 1556, 34 U.S.P.Q.2d at 1213.

The Federal Circuit expanded on this reasoning in rejecting Revel’sargument for priority based upon his previously proposed method forisolating the DNA, as described in a foreign counterpart patent application.35

The Court stated:

An adequate written description of a DNA requires morethan a mere statement that it is part of the invention andreference to a potential method for isolating it; what isrequired is a description of the DNA itself. . . . A barereference to DNA with a statement that it can be obtained byreverse transcription is not a description; it does not indicatethat Revel was in possession of the DNA.36

The Federal Circuit further explained: “If a conception of DNA requires aprecise definition, such as by structure, formula, chemical name, or physicalproperties, as we have held, then a description also requires that degree ofspecificity.”37

In Deuel, a patent applicant appealed from a determination by thePTO Board of Patent Appeals and Interferences (“BPAI”) that claims tocDNA molecules encoding heparin-binding growth factors were invalid forobviousness.38 The PTO rejected the relevant claims over the combinedteachings of two references.39 The first reference taught the partial N-terminal amino acid sequence of several such growth factors, but did notdisclose the polynucleotide sequence of any cDNAs that encode these

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40 Id.

41 Id.

42 Id.

43 Id. at 1558, 34 U.S.P.Q.2d (BNA) at 1215.

44 There are twenty possible amino acids, compared to sixty-four possiblethree-base ordered triplets (“codons”). Consequently, certain aminoacids are encoded by more than one codon. This disparity is the so-called “degeneracy” of the genetic code. Due to degeneracy, a verylarge number of distinct possible cDNA sequences can encode aspecified amino acid sequence (or polypeptide). However, a specifiedcDNA sequence encodes only a single particular amino acid sequence.

45 In re Deuel, 51 F.3d 1552, 1558, 34 U.S.P.Q.2d (BNA) 1210, 1215 (Fed.Cir. 1995).

growth factors.40 The second reference was a manual of techniques thatexplained in general terms how to isolate cDNAs by screening a library ofcDNAs with a radioactive probe.41 The obviousness rejection was based,inter alia, upon the reasoning that a person of ordinary skill in the art couldhave designed a gene probe based upon the N-terminal amino acid sequencedisclosed in the first reference and then obtained cDNAs encoding thegrowth factors using the standard methods taught by the second reference.42

Nevertheless, the Federal Circuit held that the cited combination ofreferences failed to render the claims obvious.43 The Federal Circuitreasoned that the degeneracy44 of the genetic code “precluded contemplationof or focus on the specific cDNA molecules” of the claims, and that “onecould not have conceived the subject matter of [the relevant claims] basedon the teachings in the cited prior art because, until the claimed moleculeswere actually isolated and purified, it would have been highly unlikely forone of ordinary skill in the art to contemplate what was ultimatelyobtained.”45 The Federal Circuit concluded that “[w]hat cannot be


46 Id.

47 In re Bell, 991 F.2d 781, 784, 26 U.S.P.Q.2d (BNA) 1529, 1531 (Fed. Cir.1993).

48 Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566-69,43 U.S.P.Q.2d (BNA) 1398, 1404-05 (Fed. Cir. 1997).

49 Id. at 1568, 43 U.S.P.Q.2d (BNA) at 1405.

50 Id.

contemplated or conceived cannot be obvious.”46 The Federal Circuit reliedupon its earlier holding in In re Bell, which explicitly rejected the propositionthat “the established relationship in the genetic code between a nucleic acidand the protein it encodes also makes a gene prima facie obvious over itscorrespondent [sic] protein.”47

In Lilly, the Federal Circuit affirmed a district court’s judgment ofinvalidity due to inadequate written description where the patentee hadbroadly claimed cDNA that codes for the hormone insulin, while onlydisclosing the relevant cDNA sequence of rat insulin.48 Because the claimswere broadly directed to vertebrate, mammalian, and human cDNA, theFederal Circuit affirmed the finding of inadequate written description.49 TheFederal Circuit stated that a written description of the relevant humancDNA, including its structure, is necessary for a claim that would coverhuman insulin cDNA.50

While the example provides a process for obtaining humaninsulin-encoding cDNA, there is no further information inthe patent pertaining to that cDNA’s relevant structural orphysical characteristics; in other words, it thus does notdescribe human insulin cDNA. Describing a method ofpreparing a cDNA or even describing the protein that thecDNA encodes, as the example does, does not necessarilydescribe the cDNA itself. No sequence information

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51 Id. at 1567, 43 U.S.P.Q.2d (BNA) at 1405.

52 Id. at 1569, 43 U.S.P.Q.2d (BNA) at 1406.

indicating which nucleotides constitute human cDNAappears in the patent, as appears for rat cDNA. . . .Accordingly, the specification does not provide a writtendescription of the invention[.]51

The Federal Circuit explained that, for the same reasons, the specificationalso contained inadequate written description to support genus claimscovering cDNA of vertebrates or mammals, which otherwise could havebeen supported by describing the sequence of a representative number ofcDNAs falling within the scope of the genus, or by describing structuralfeatures common to the genus.52

IV. IMPETUS FOR ATTENTION AT THE PTO

Parallel to the developments at the Federal Circuit, there has beenpublic debate among interested parties about the appropriate patentabilitycriteria for genetic inventions. In general, there has been support for criteriathat would prevent the patenting of broad claims based upon partial DNAsequences and, in particular, those partial sequences for which no specificbiological utility has been demonstrated. In 1991, the American Society of


53 The ASHG represents professionals and students in the field of humangenetics. Members are involved in various areas of genetic researchand related health care services and in the study of the human genome.ASHG’s website is located at http://www.ashg.org.

54 See Letter from Human Genome Committee and Board of Directors,American Society of Human Genetics, to the Editor, 254 SCIENCE 1711-12 (1991)[hereinafter American Society of Human Genetics].

55 ESTs are determined from the products of gene transcription. Duringcellular transcription, gene segments of nuclear DNA are copied intomessenger RNAs (“mRNAs”). Scientists reverse-transcribe the mRNAsto provide complementary DNAs (“cDNAs”), parts of which aresequenced to provide ESTs. Thus, ESTs may complement protein-encoding parts of expressed genes, i.e., “protein-encoding” portions ofthe nuclear DNA.

Human Genetics53 (“ASHG”) published a position paper that expressed thisview.54

The issue of expressed sequence tags (“ESTs”), however, hasengendered some controversy. ESTs are partial cDNA sequences ofexpressed genes.55 Databases of ESTs permit scientists to search anycatalogued species for genes or gene clones having ESTs similar to a gene ofinterest. Such similarity usually corresponds to a similarity in the proteinsencoded by the genes and the functions of those proteins. In addition touses for tagging or probing, scientists can combine information from relatedESTs to catalogue the members of a related gene family.

It has been argued that identification of an EST, without more, lacksutility and provides inadequate written description for a functional gene.The argument that ESTs may not have “utility” arises from the fact thatvarious ESTs may not have any coding function themselves, nor provide aneasy means to determine either the sequence or the function of the fulllength gene from which the ESTs were derived. In fact, the majority of ESTsequences in the public database have no definitively assigned function.

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56 One source of debate was a set of patent applications filed in the nameof Craig Ventner et al. and assigned to the National Institutes of Health(“NIH”). See U.S. Patent Application 07/716,831 (filed June 21, 1991);U.S. Patent Application 07/837,195 (filed Sept. 25, 1992); U.S. PatentApplication 07/952,911 (filed Feb. 12, 1993). These applications werecriticized as lacking utility. In the wake of the criticism, NIHabandoned the applications and expressed its intention of not filingsimilar applications in the future. However, NIH continues to play acentral role in the debate by actively expressing its views about thebroader public policy of patenting genetic inventions.

This is why questions have been raised about whether an EST itself can meetthe “utility” requirement of U.S. patent law.

The argument that identifying an EST may not satisfy the “writtendescription” requirement for a claim to an entire functional gene is based onthe fact that a single EST may correspond to a number of functionallydistinct cDNAs. Thus, a claim to any cDNA that “comprises” the sequenceof a particular EST might read on a multiplicity of structurally andfunctionally distinct cDNA species, none of which have been separatelyidentified and described. Also, a single gene can express multiple cDNAs,and some genes have partial sequences in common with other genes.Consequently, multiple genes will often have some ESTs in common. It istherefore argued that a full written description of a functional gene mustdisclose more than just ESTs.

This argument has been raised in connection with the HumanGenome Project—the most visible genetic endeavor of internationalconcern.56 The ASHG has stated:

An international collaborative venture as bold as the HumanGenome Project should not be jeopardized by the possibilityof irrevocable damage inflicted by EST patents. . . . Let usstrive to ensure that patents are obtainable . . . that [they] willstill allow commercial exploitation of genetic information,


57 See American Society of Human Genetics, supra note 54, at 1711.

58 The Human Genome Organization, HUGO Statement on Patenting ofDNA Sequences: In Particular Response to the European BiotechnologyDirective (April 2000), at http://www.hugo-international.org/hugo/patent2000.html.

59 See also Letter from Herbert Curien, French Minister for Research andTechnology, to Editor, 254 SCIENCE 1 (1991).

60 ASSINSEL, What is ASSINSEL?, at http://www.worldseed.org/what_asse.htm (last modified Apr. 12, 2001).

61 ANNINSEL, Development of New Plant Varieties and Protection ofIntellectual Property (June 1999), at http://www.worldseed.org/IPprotectione.htm (other position papers adopted by ANNINSELmembers can be located at http://www.worldseed.org/positions.html).

but not so early in the process that it will stifle individualscientific endeavor and lead to international chaos.57

Similarly, the Human Genome Organization (“HUGO”) issued a statementexpressing “serious concerns about the negative impact on further progressof genomic research and successful exploitation of its results should broadclaims of the so-called ‘having’ and ‘comprising’ type be issued for ESTs.”58

In addition to human genetics,59 concern about plant genetics hasbeen raised by the International Association of Plant Breeders for theProtection of Plant Varieties (“ASSINEL”), an international organization ofcrop producers.60 ASSINEL has recently issued a statement that partialDNA sequences such as ESTs should not be patentable,61 in contrast togenetic components that are known to express a characteristic or trait (forexample, in crops). This position was based upon a survey in 1998 ofASSINSEL’s members in twenty-nine industrialized and developing

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62 Id.

63 Id.

64 Request for Comments on Interim Guidelines for Examination of PatentApplications Under the 35 U.S.C. § 112, ¶ 1, “Written Description”Requirement, 63 Fed. Reg. 32,639 (June 15, 1998).

65 Revised Interim Guidelines for Examination of Patent ApplicationsUnder the 35 U.S.C. § 112, ¶ 1, “Written Description” Requirement,Request for Comments, 64 Fed. Reg. 71,427 (Dec. 21, 1999)[hereinafterRevised Interim Written Description Guidelines].

countries.62 The countries included Argentina, Australia, Austria, Belgium,Brazil, Canada, Chile, Croatia, Czech Republic, Denmark, Finland, France,Germany, Netherlands, India, Ireland, Israel, Italy, Japan, Kenya, Norway,New Zealand, Poland, Slovakia, South Africa, Sweden, Switzerland, theUnited Kingdom, and the United States.63

V. WRITTEN DESCRIPTION GUIDELINES

In response to the evolution in written description criteria occurringat the Federal Circuit, the PTO formulated Interim Written DescriptionGuidelines, which were published along with a request for public commenton June 15, 1998.64 The PTO received a number of comments advocating anexpansion of the PTO’s efforts and urging that the biotechnology-specificguidelines be made generally applicable. The PTO attempted to implementthese suggestions in its Revised Interim Guidelines for Examination ofPatent Applications Under the 35 U.S.C. § 112, ¶ 1, “Written Description”Requirement, issued on December 21, 1999.65 After another round ofcomments were collected, the PTO issued its final Guidelines forExamination of Patent Applications Under the 35 U.S.C. § 112, ¶ 1, “Written


66 See Written Description Guidelines, supra note 2, at 1099.

67 Id. at 1104.

68 Id. at 1105.

69 Id.

70 Id.

71 Id.

72 Id.

Description” Requirement (“Written Description Guidelines”) on January5, 2001.66

Beginning with general principles, the Written DescriptionGuidelines set forth a methodology for determining whether patent claimsare supported by an adequate written description.67 The first steps includereading the specification and construing the claims.68 The claims areaccorded their broadest reasonable interpretation consistent with thespecification, and the weight to be accorded the preamble is evaluated.69

The entire application is considered in determining what the applicant hasdescribed as the “essential features” of the invention.70

The examiner must then consider whether the written description issufficient to inform a person of ordinary skill in the art that the applicantwas in possession of the claimed invention at the time the application wasfiled.71 The examiner has the initial burden of presenting evidence orreasons why the written description is inadequate for such purpose, in lightof a strong presumption of adequacy.72

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73 Id.

74 Id.

75 Id. at 1106.

76 Id.

77 Id.

78 Id.

79 Id.

The written description may indicate possession of the claimedinvention in any number of ways.73 The description may provide details ofan actual reduction to practice, clearly depict the invention in detaileddrawings, or provide identifying characteristics.74 For single embodimentor species claims, the examiner must search the description for identifyingcharacteristics that distinguish the claimed invention from other materials.75

For genus claims, the examiner must look for a representativenumber of species.76 Although individual support for each species coveredby the genus claim is unnecessary, a sufficient variety should be describedwhen there is substantial variation within the genus.77 The descriptionshould provide adequate evidence of the attributes common to members ofthe genus, in view of the species disclosed.78

Throughout the Written Description Guidelines, the most-emphasized point is that the written description must be sufficient to leada skilled artisan to clearly recognize the applicant’s possession of theclaimed invention.79 Any claim that fails to meet this requirement is to be


80 Id.

81 The training materials are not published in the Federal Register, butcurrently may be downloaded from the PTO’s website. See PTO,Revised Interim Written Description Guidelines Training Materials, availableat http://www.uspto.gov/web/offices/pac/writtendesc.pdf.

rejected under section 112, paragraph 1, as lacking support in the writtendescription.80

The PTO seems to have accomplished its goal of generalizing thenew Written Description Guidelines. There are few provisions in the bodyof the Written Description Guidelines that are biotechnology-specific andnone relating to problems raised by partial DNA sequences or ESTs.

While the Written Description Guidelines themselves are couched ingeneral terms that apply to all of the arts, the PTO has providedbiotechnology-specific guidance in its responses to comments, its WrittenDescription Guidelines’ footnotes, and its internal training materials, whichcontain an entire section replete with biotechnology examples.81 In oneinteresting footnote to the Written Description Guidelines, the PTOaddresses a generic claim to any DNA that encodes a particular amino acidsequence:

For example, in the molecular biology arts, if an applicantdisclosed an amino acid sequence, it would be unnecessaryto provide an explicit disclosure of nucleic acid sequencesthat encoded the amino acid sequence. Since the geneticcode is widely known, a disclosure of an amino acidsequence would provide sufficient information that onewould accept that an applicant was in possession of the fullgenus of nucleic acids encoding a given amino acid sequence,but not necessarily any particular species. Cf. In re Bell, 991F.2d 781, 785, 26 U.S.P.Q.2d 1529, 1532 (Fed. Cir. 1993) and In

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82 Written Description Guidelines, supra note 2, at 1111 n.57.

83 See supra Part III.

84 See Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1567,43 U.S.P.Q.2d (BNA) 1398, 1405 (Fed. Cir. 1997).

85 The Federal Circuit has acknowledged in dictum a very narrowcircumstance under which a disclosed amino acid sequence mightrender obvious claims to each of the possible DNA molecules that couldencode that amino acid sequence. In re Deuel, 51 F.3d 1552, 1559, 34U.S.P.Q.2d (BNA) 1210, 1215 (Fed. Cir. 1995). The Federal Circuitasserted that, given “a protein of sufficiently small size and simplicity”,each DNA molecule that encodes that protein might be obvious overthe protein. Id. (citing In re Petering, 301 F.2d 676, 682-83, 133 U.S.P.Q.(BNA) 275, 280-81 (C.C.P.A. 1962)(holding that prior art referencedisclosing limited genus of twenty compounds rendered every specieswithin the genus unpatentable)). Because on average each amino acid

re Baird, 16 F.3d 380, 382, 29 U.S.P.Q.2d 1550, 1552 (Fed. Cir.1994).82

This footnote is interesting when viewed in light of Federal Circuitprecedent embodied in In re Bell, In re Baird, and In re Deuel.83 The FederalCircuit interpreted those cases as indicating that, for a disclosure to satisfythe written description requirement, it must provide enough information tohave also rendered the claim obvious had the disclosure been contained ina prior art reference.84 Under the PTO’s Written Description Guidelines,disclosure of an amino acid sequence satisfies the written descriptionrequirement for a claim to the full genus of nucleic acids encoding the aminoacid. In light of Bell, Baird, and Deuel, this would mean that a prior artreference disclosing an amino acid sequence must necessarily provideenough information to render obvious the same claim to the genus of nucleicacids encoding the amino acid sequence. However, the Federal Circuitstated that this is not the case. In Deuel, the Federal Circuit stated thatdisclosing an amino acid sequence does not render obvious a claim to thegenus of nucleic acids encoding the amino acid sequence.85


of a protein can be encoded by any of three distinct codons, even aprotein consisting of only ten randomly-selected amino acids could beencoded by almost 60,000 distinct DNA sequences, and thus would notlikely be “of sufficiently small size and simplicity” to satisfy the court’sdictum. Id. at 1559, 34 U.S.P.Q.2d (BNA) at 1215.

86 See PTO, Revised Interim Written Description Guidelines Training Materials,at 30, available at http://www.uspto.gov/web/offices/pac/writtendesc.pdf.

87 Id. at 32.

One way to reconcile Federal Circuit precedent with the PTO’sposition is to note that the relevant Federal Circuit cases dealt with patentapplications filed early in the history of molecular biology. At that time,cloning a cDNA which encodes a known amino acid sequence was far fromroutine. The PTO’s Written Description Guidelines, on the other hand, areintended to apply to more recently filed applications and those filed in thefuture, when cloning cDNA based upon a partial amino acid sequence isindeed routine. A search of the PTO database reveals a large number ofissued patents that contain generic claims to cDNA molecules limited onlyby the encoded amino acid sequence. It remains to be seen, of course, howthe Federal Circuit will apply its earlier precedent to PTO patentabilitydeterminations that embody the new Written Description Guidelines in thisrespect.

One example in the PTO’s training materials addresses ESTs. In“Example 7: EST,” the PTO indicates that the disclosure of a partial DNAsequence corresponding to an EST is insufficient written description tosupport a claim to “[a]n isolated DNA comprising [the partial sequence].”86

In support of its conclusion, the PTO notes that only a single commonstructural feature—the partial sequence—is shared by members of theclaimed “isolated DNA” genus.87 It further observes that the genus

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88 Id.

89 Id.

90 Id.

91 Id.

92 See id. at 50.

93 Id.

94 Id.

95 Id. at 52.

encompasses genes yet to be discovered.88 Finally, it notes that the partialsequence does not “constitute a substantial portion” of the claimed genus.89

In view of the partial structure, the breadth of the claim (including genes yetto be discovered), and a lack of correlation to genetic function, the PTOconcludes that one skilled in the art would not recognize the applicant tohave been in possession of the genus of DNAs which comprise the partialsequence.90 Consequently, the PTO would reject the claim under 35 U.S.C.§ 112, ¶ 1, as unsupported by sufficient written description.91

Another interesting example in the written description trainingmaterials is “Example 13: Protein Variant.”92 In this example, a protein hasbeen isolated from liver, and its exact amino acid sequence is disclosed inthe specification.93 The specification also states that the invention provides“variants” of the disclosed sequence, “having one or more amino acidsubstitutions, deletions, insertions, and/or additions,” but provides nofurther description of the variants.94 The examiner is instructed in this caseto reject the claim for failure to satisfy the written description requirement“because a representative number of species have not been described.”95


96 See id. at 27-59.

Other specific examples in the training materials are: genes, a DNAfragment encoding a full length open reading frame (ORF, a putativeprotein-coding region), hybridization, a process claim, an allelic variant,bioinformatics, a product by function, antisense, and antibodies.96

While not directly addressed in any of the PTO’s publishedmaterials, a related and important question arises in the context of nearlyidentical or similar genes from closely related strains or species. Theproteins encoded by such genes may differ from one another by as few asone amino acid. If a gene from a particular strain of Escherichia coli (“E.coli”) bacteria encoding protein “X” is isolated, sequenced, and disclosed,should that disclosure be sufficient written description to support a claim toDNA molecules encoding the related protein from all strains of E. coli?From E. coli and other Gram negative bacteria? From all bacteria? If onetakes guidance from the Federal Circuit, it would appear, mutatis mutandis,that there is only support for claims to protein “X” from the particular straindisclosed, as one could not conceive the particular amino acid sequence ofany related protein other than the particular one whose gene was sequencedand disclosed.

On the other hand, if one takes seriously the PTO’s suggestion thata disclosed amino acid sequence satisfies the written descriptionrequirement with regard to a generic claim to any DNA molecule thatencodes that amino acid sequence, then one might argue that it is nearly aspredictable and routine in the art to obtain the analogous gene from aclosely related species as it is to isolate a cDNA corresponding to a particularamino acid sequence. The PTO has not yet directly addressed thisargument, but there is anecdotal information to consider. Specifically, thefile histories of several issued patents reveal that at least some PTOexaminers do not consider published sequences of a protein “X” from onebacterial strain to render obvious claims to protein “X” from another strainof the same bacterial species—so long as they differ by at least a singleamino acid. One could therefore argue that, under Deuel and related FederalCircuit precedent, genus claims to protein “X” in strains other than the

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97 Of course, Deuel and related Federal Circuit precedent have notprevented the PTO from drawing its own conclusions on other relatedissues (e.g., concluding that an amino acid sequence satisfies the writtendescription requirement for a claim to the full genus of nucleic acids).

98 See Request for Comments on Interim Guidelines for Examination ofPatent Applications Under the 35 U.S.C. § 112, ¶ 1, “WrittenDescription” Requirement, 63 Fed. Reg. 32,639, 32,639 (June 15,1998)(“These ‘Written Description Guidelines’ are intended to assistOffice personnel . . . in view of” Lilly, Fiers and Amgen.)

99 Utility Examination Guidelines, 60 Fed. Reg. 36,263 (July 14, 1995).

100 “The Revised Interim Guidelines [for written description] are not theappropriate vehicle to fully address the patentability of ESTs. In viewof comments and testimony with respect to ESTs and the enablementand utility requirements, the PTO is revising the Utility Guidelines aspresented at 60 Fed. Reg. 36,263 (July 14, 1995).” Revised InterimWritten Description Guidelines, supra note 65, at 71,427.

particular strain from which the protein “X” gene was cloned and sequencedmust be rejected for failure to satisfy the written description requirement.97

VI. UTILITY GUIDELINES

The comments to the Interim Written Description Guidelines,published on June 15, 1998,98 also suggested to the PTO that its UtilityExamination Guidelines99 needed revision or clarification.100 Somecomments suggested that the utility of an EST is not established when itscorresponding gene is unknown, and the sole disclosed use of the EST is toidentify other genetic material of unknown utility and function (i.e., function


101 See Revised Interim Written Description Guidelines, supra note 65, at71,433.

102 Revised Utility Examination Guidelines: Request for Comments, 64 Fed.Reg. 71,440, 71,440-41 (Dec. 21, 1999).

103 Id. at 71,440.

104 Utility Guidelines, supra note 2, at 1092.

105 Id. at 1094.

106 Id. at 1093.

107 See id. at 1098.

as a “probe”).101 Even if an EST is sufficiently described as a DNA sequence,it might not be useful for specific mapping of a gene or tissue typing.According to the PTO, the general concern was that patents would begranted for “nonspecific and nonsubstantial utilities, contrary to establishedcase law.”102

On December 21, 1999, the PTO issued Revised Utility ExaminationGuidelines with a Request for Comments.103 After these comments werecollected, the PTO issued its final Utility Examination Guidelines.104

According to the Utility Examination Guidelines, if an invention has a well-established utility that would be known to one of ordinary skill in the art, anexaminer should not issue a rejection for lack of utility.105 A rejection also isinappropriate if the applicant asserts that an invention has a specificpractical purpose—a “specific and substantial” utility—that would becredible to a person of ordinary skill in the art.106 Credibility in such acircumstance is assessed in view of the disclosure along with any otherevidence of record, such as test data, statements of experts, patents, orprinted publications.107

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108 See id. at 1093.

109 See id. at 1095.

110 See id. at 1097.

111 Id.

112 See id. at 1098.

113 Id. at 1097.

114 PTO, Revised Interim Utility Guidelines Training Materials, available athttp://www.uspto.gov/web/offices/pac/utility/utilityguide.pdf.

Absent a well-established utility or credible assertion of “specific andsubstantial” utility, the examiner is to reject the claim(s) for lack of utilityunder 35 U.S.C. § 101.108 The examiner is also instructed to impose arejection under 35 U.S.C. § 112, ¶ 1, for lack of written description of how touse the invention for any such utility.109

This shifts to the applicant the burden of coming forward withevidence to overcome the rejection.110 The applicant may meet its burden byexplicitly identifying a “specific and substantial” utility and providingevidence that a person of ordinary skill in the art would have recognizedthat such utility was well established at the time of filing.111 Appropriateevidence of utility again includes test data, statements of experts, etc.112 Theexaminer is then required to verify an adequate nexus between theevidentiary showing and the application as filed.113

Like the Written Description Guidelines, the Utility Guidelines arecouched in general terms, but the PTO has similarly provided trainingmaterials with a number of biotechnology examples.114 “Example 9: DNAFragments” refers to a patent application that discloses fragmentary DNA


115 Id. at 50-53.

116 See id. at 50.

117 See id. at 50-53.

118 Id. at 52-53.

119 Id. at 50.

120 See id. at 51.

121 See id.

122 See id. at 51-52. The elements of “specific, substantial and credible”utility in the first step are clearly stated in “Example 10: DNA Fragmentencoding a Full Open Reading Frame (DRF)” as follows: “In order todetermine whether the claimed invention has a well-established utilitythe examiner must determine that the invention has a specific,substantial and credible utility that would have been readily apparentto one of skill in the art.” See id. at 55. Similarly, the definition sectionin the training materials states: “‘Well established utility’ does not

sequences of a gene and how to use the sequences to probe for the gene.115

The gene can be used to make proteins, possibly for further study.116

Although some of the fragment sequences are long enough to encodefunctional proteins, no specific examples are disclosed.117 In view of thisdisclosure, the PTO would find a lack of utility in a claim covering “[a]cDNA consisting of the [fragment sequence].”118

Patentable utility can be established by satisfying one of twoinquiries.119 First, the PTO inquires whether there is a “well-establishedutility,” i.e., one that is well-known in the art, or immediately apparentupon reading the specification.120 Second, the PTO inquires whether theapplicant has asserted a “specific and substantial” utility.121 In practice,however, both inquiries require the examiner to find a utility that is specific,substantial, and credible.122

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encompass any ‘throw away’ utility that one can dream up for aninvention [i.e., insubstantial utility] or a nonspecific utility that wouldapply to virtually every member of a general class of materials, such asproteins or DNA.” See id. at 7.

123 Id. at 51.

124 Id. at 51-52.

125 Id. at 53.

126 See id. at 52.

According to the PTO, the asserted utility of the DNA fragment asa probe is not “specific” because that asserted utility would apply to thegeneral class of all cDNAs and does not distinguish the claimed cDNA fromany other.123 The utility for making a protein is not deemed “substantial”because the protein is considered useful only for identifying and studyingthe protein’s own properties or mechanisms, which “does not define a ‘realworld’ context of use.”124

The PTO therefore concludes from the first inquiry that there is no“well-established utility” for the sequence and concludes from the secondinquiry that there is no asserted “specific and substantial” utility.125 Thus,the DNA sequence does not satisfy either inquiry for the sole reason that thePTO considers the utility of the sequence to be insubstantial andnonspecific.126

Because the two inquiries for establishing utility each requirespecific, substantial, and credible utility, it is useful to consider when thetwo inquiries will differ in result. It appears that this will occur in twosituations. The first situation is when the specific and substantial utility isreadily apparent to one of skill in the art, but is not asserted, i.e., it would be“well-established” (first inquiry), but not asserted to be “specific andsubstantial” (second inquiry). The second situation is when the specific andsubstantial utility is asserted, but is not readily apparent to one of skill in the


art, i.e., it would be “specific and substantial” (second inquiry), but not“well-established” (first inquiry).

The Utility Guidelines suggest that the PTO does not intend to grantpatents “too early” in the gene-based discovery pipeline. The first personto clone a fragment of a gene or cDNA must “assert” a utility thatdemonstrates an understanding of the specific role of the gene or encodedprotein in cellular or organismic function. Otherwise, the absence of a “well-established” utility will prevent the person from obtaining patent claimscovering DNA or protein molecules “comprising” that polynucleotide orpolypeptide fragment. Thus, under the PTO’s understanding of the“specific and substantial utility” requirement, patent claims will only begranted to the first person who demonstrates some understanding of thefunction of the gene or encoded protein. It remains to be seen to what extentthe PTO will consider DNA and amino acid sequence homology tosequences of known function as evidence of specific and substantial utilityand what degree of homology might be required.

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127 The PTO made the comments to the new guidelines available for publicinspection at the PTO by April 19, 2000. In addition to hard copycomments available at Suite 918, Crystal Park 2, 2121 Crystal Drive,Arlington, Virginia, comments provided in machine readable formatare currently available through the PTO’s website available athttp://www.uspto.gov/web/offices/com/speeches/00-25.htm. Inaddition to NIH, comments were submitted by, inter alia, the AmericanIntellectual Property Law Association and the Biotechnology IndustryOrganization. See PTO, Public Comments on the United States Patent andTrademark Office "Revised Interim Utility Examination Guidelines,” availableat http://www.uspto.gov/web/offices/com/sol/comments/utilguide/index.html; PTO, Public Comments on the United States Patent andTrademark Office "Revised Interim Guidelines for Examination of PatentApplications Under the 35 U.S.C. § 112, ¶ 1 ‘Written Description’Requirement," available at http://www.uspto.gov/web/offices/comsol/comments/utilitywd/index.html.

128 See Letter from Harold E. Varmus, Director of the National Institutes ofHealth, and Francis S. Collins, Director of the National Human GenomeResearch Institute, to The Honorable Q. Todd Dickinson, Commissionerof the PTO (Dec. 21, 1999)(on file with authors)[hereinafter Varmus &Collins]; Letter from Jack Spiegel, Director of the Division ofTechnology Transfer & Development, Office of Technology Transfer,National Institutes of Health, to The Honorable Q. Todd Dickinson,Commissioner of the PTO (Dec. 21, 1999)(on file withauthors)[hereinafter Spiegel].

129 See Varmus & Collins, supra note 128; Spiegel, supra note 128.

VII. NIH’S VIEW OF THE NEW GUIDELINES127

Prior to submitting comments, the National Institutes of Health(NIH) sent two letters to the PTO.128 In the letters, NIH strongly supportedthe requirement that a claimed invention possess a specific, substantial, andcredible utility.129 NIH expressed concern, however, that an examiner mightfind a bold assertion of theoretical function sufficient to meet the utility





133 See Letter from The Honorable Q. Todd Dickinson, Commissioner ofthe PTO, to Harold E. Varmus, Director of the National Institutes ofHealth, and Francis Collins, Director of the National Human GenomeResearch Institute (Jan. 7, 2000)(on file with authors). By January 7,2000, Dr. Harold E. Varmus had left the NIH. He is currently thePresident and Chief Executive Officer of the Memorial Sloan-KetteringCancer Center in New York City.

134 See id.

135 See id.

requirement.130 Such a bold assertion could be made, it suggested, regardingan encoded protein that theoretically might be expected, based uponhomology, to be useful as a kinase, helicase, zinc finger, or other knownfunctional class of protein.131 NIH also expressed concern that the PTO’swillingness to grant open-ended “comprising claims” for partial sequencesmight result in overly broad patents unsupported by sufficient disclosure.132

The Commissioner of the PTO responded to NIH by emphasizingthat patent applications would be examined on a case-by-case basis usinggeneral principles.133 The Commissioner acknowledged, however, that aprotein’s mere membership in a family might not warrant an inference ofutility, for example, if individual members require specific activation.134 Inparticular, a failure to describe how to activate the protein could lead toutility or enablement problems, depending on the facts.135 With regard to“comprising claims,” the Commissioner assured NIH that the PTO would

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136 See id.

137 Brooktree Corp. v. Advanced Micro Devices, Inc., 977 F.2d 1555, 1571,24 U.S.P.Q.2d (BNA) 1401, 1412 (Fed. Cir. 1992)

138 In a recent decision, the Federal Circuit, while considering the question“interesting,” declined to address whether a patent specification’sdisclosure of a sequence of 191 amino acids was sufficient to enable aclaim covering all possible DNA sequences that encode that amino acidsequence. See Bio-Technology Gen. Corp. v. Genentech, Inc., 267 F.3d1325, 1333, 60 U.S.P.Q.2d 1430, 1436 (Fed. Cir. 2001).

follow the recent cases of the Federal Circuit, such as Lilly, which set forthcriteria for the written description requirement, as described above.136

VIII. FUTURE DIRECTIONS

It remains to be seen how the Federal Circuit will respond torejections of claims to biotechnology inventions for lack of utility under 35U.S.C. § 101. In particular, it is an open question whether a partial DNAsequence such as an EST, which an applicant asserts to have utility as a tagfor an expressed gene of unknown function, is “totally incapable ofachieving a useful result.”137

It also remains to be seen how the Federal Circuit will view thecontrast between its own precedent and the PTO’s plan to allow genericclaims to any DNA molecules that encode a disclosed amino acidsequence.138 It will be of great interest to see how the Federal Circuitincorporates the dramatic advances in the ease with which cDNAs can becloned into future obviousness and written description decisions. As thePTO has recognized, it is now technically quite routine to clone cDNAs thatencode particular known protein sequences. It is not clear to what extent thePTO recognizes that it has become nearly as routine to clone cDNAs thatencode a homologous protein from a number of different species or strains.


For example, today it would be trivial to clone a human insulin cDNA if onepossessed a rat insulin cDNA.

Although the new Guidelines raise some substantial new questions,they represent a rational approach to addressing industry concerns. TheGuidelines will be helpful in navigating the prosecution of biotechnologypatents and promise to provide some food for thought or argument inlitigation, perhaps even before the Federal Circuit.

2002 aipla - kass & nitabach, a roadmap for biotechnology patents, by kass et al

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