Gene Patents and Access to Genetic Diagnostic Tests

by

Harleen Khanijoun

A thesis submitted in conformity with the requirements for the degree of Master of Laws (LL.M.) Graduate Department of Faculty of Law

University of Toronto

© Copyright by Harleen Khanijoun 2012

ii

Gene Patents and Access to Genetic Diagnostic Tests

Harleen Khanijoun

Master of Laws (LL.M.)

Graduate Department of Faculty of Law

University of Toronto

2012

ABSTRACT

The utilitarian theory contemplates rewarding the risks of inventors by providing them with

a defined period of exclusivity to recoup their investment. For inventions requiring further

investment, patents enable the creation of financial relationships between inventors and investors by

providing patent exclusivity during the commercialization process. Innovation, contrasted from

invention and conceptualized as commercialization, however, does not necessarily form the best

means for delivering to the public inventions intended to improve health. Although patent policy

conflates the economic growth and health improvement objectives of innovation, these goals do not

always align. While the exercise of BRCA patents instantiates exclusive practicing of patents that

failed to adequately deliver health technology, the patent system does not need significant change.

Rather, to maintain the expectations of patent holders while balancing the needs of the public,

current practices should continue with the encouragement of the creation of voluntary patent pools.

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TABLE OF CONTENTS

I. Introduction ................................................................................................................................................. 1

II. BRCA Case - Criticisms of Myriad’s Exercise of Patent Rights .......................................................... 5

III. Proposed Measures ..................................................................................................................................... 8 A. Deny Patents .......................................................................................................................................... 8

1. Rise of Gene Patents ........................................................................................................................ 9 2. Patent Ineligible Subject Matter .................................................................................................... 12

a. DNA Unpatentable - Duality of DNA .................................................................................... 13 b. DNA Unpatentable as Chemical Entity .................................................................................. 15 c. Robust Public Domain Justification and Outcome ............................................................... 16

3. Statutory s.101 ................................................................................................................................. 18 a. Utility ............................................................................................................................................ 18 b. Non-obviousness......................................................................................................................... 20

4. Constitutional Grounds ................................................................................................................. 22 B. Modify Patents ..................................................................................................................................... 26

1. Challenging the Exclusion of Genes from Patentability ........................................................... 26 2. Narrow Patents ................................................................................................................................ 27

C. Ex-Post Measures ................................................................................................................................ 31 1. Exemptions ...................................................................................................................................... 31

a. Statutory Exemption ................................................................................................................... 31 b. Common Law Exemption ......................................................................................................... 33

2. Compulsory Licensing .................................................................................................................... 36 a. Modifying the Bayh-Dole Act ................................................................................................... 36 b. Reasonable Royalty ..................................................................................................................... 37 c. Crafting a New Regime .............................................................................................................. 38 d. Incentive to Innovate ................................................................................................................. 41

3. Patent Pools/Patent Clearinghouse ............................................................................................. 43 4. Practical Existing Mitigating Factors ............................................................................................ 49

IV. TRIPS ......................................................................................................................................................... 52

V. Conclusion ................................................................................................................................................. 54

BIBLIOGRAPHY ................................................................................................................................................. 58

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I. Introduction

The economic manifestation of the utilitarian theory of patents dominates patent discourse1

and underscores patent protection systems worldwide.2 In the United States (U.S.), the

constitutional enshrinement of the justification elevates it above alternative theories3 and reflects the

significance placed on the patent system.4 The risky process of innovation, valued for its

“development of new products, processes, and services that improve lives and address unmet

needs” is considered best promoted through the patent system.5 In particular, patent rights are

credited by start-up firms for the patents’ ability to attract funding for development and

commercialization.6 The biotechnology industry, known for its need for significant capital

investment, ranks among the industries advocating for strong intellectual property rights.7 Here,

patent rights serve as tools to further innovation in the commercialization sense rather than

instruments that create incentives for invention.8 Innovation, as contrasted from the narrower

concept of invention, either embraces invention as part of its steps or includes the steps taken after

1 William Fisher, “Theories of Intellectual Property Law” in Stephen Munzer ed, (Cambridge University Press, 2001) at 169. 2 See e.g., Canadian Intellectual Property Office, Industry Canada, A Guide to Patents (Gatineau: Canadian Intellectual Property Office 2011), online: http://www.cipo.ic.gc.ca/eic/site/cipointernet-internetopic.nsf/eng/wr01090.html#sec5. The Canadian Intellectual Property Office indicates that patents fuel progress. It states, “[b]y giving inventors monopolies on their creations for a specific time period, patents protect investments and allow inventors to profit financially from their creativity. This in turn provides an attractive incentive for research and development, ultimately benefiting all Canadians. Without the possibility of patent protection, many people might not take the risk of investing the time or money necessary to create or perfect new products, without which our economy would suffer.” 3 For alternative theories see generally supra note 1. See also Peter S. Menell, “Intellectual Property: General Theories” in The New Palsgrave Encyclopedia of Law and Economics (1998) at 131 - 194. 4 In the United States, a patent grant is grounded in utilitarian theory as explicitly stated in the United States Constitution to “promote the Progress of Science and useful Arts”. See United States Constitution, Article I, Section 8, Clause 8. 5 Federal Trade Commission, The Evolving IP Marketplace: Aligning Patent Notice and Remedies with Competition (Washington, DC: FTC, March 2011) at 1 online: http://www.ftc.gov/os/2011/03/110307patentreport.pdf [hereinafter FTC 2011]. 6 Ibid. 7 Ibid. at 43. 8 Secretary’s Advisory Committee on Genetics, Health, and Society, Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests (April 2010) at 20 online: http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_patents_report_2010.pdf (suggesting that while patents do not serve as incentives to invent, they do serve an important role in stimulating subsequent investment for genetic research) [hereinafter SACGHS Gene Patents]. But see infra note 12 at 366 (stating that “patent laws provide direct incentives to invent, but not generally to innovate” and proposing a commercialization patent scheme to encourage innovation).

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invention of a product towards commercialization.9 In either case, innovation forms a broader

concept that extends towards creating a commercial product.10 This economic manifestation of the

utilitarian theory justifies patent protection because the defined period of exclusivity on the

underlying invention provides the patentee an opportunity to recoup its initial investment through

commercialization.11 For those inventions which require further investment to generate a

commercialized product, patents assure against appropriation of the underlying invention and

subsequently enable investments through the creation of financial relationships between inventors

and investors.12

Patents, then, occupy a central role in the commercialization of inventions, and uncertain

patent rights can deter investors from funding otherwise promising inventions.13 Reflecting the

belief of economic advancement coupled with improved quality of life furthered through

innovation,14 patenting inventions is advanced as a means to foster that innovation. Whereas a

patent provides a negative right, a right to exclude, without requiring an affirmative duty to

9 Ted Sichelman, “Commercializing Patents” (2009-2010) 62 Stan. L. Rev.at 366. See also infra note 174 Progress of Science at 1038 (explaining the Schumpeterian perspective that innovation, rather than invention, forms the relevant economic inquiry). 10 Although often used interchangeably, literature increasingly recognizes a distinction between invention and innovation. See e.g., generally Federal Trade Commission, To Promote Innovation: The Proper Balance of Competition and Patent Law and Policy, (Washington, DC: FTC, Oct 2003) online: http://ftc.gov/os/2003/10/innovationrpt.pdf [hereinafter FTC 2003] that discusses invention and innovation interchangeably and compare with supra note 5 FTC 2011 that distinguishes between the concepts of invention and innovation. 11 Supra note 5 FTC 2011 at 1. 12 Supra note 10 FTC 2003 at 5. See also U.S. Department of Justice and the Federal Trade Commission, Antitrust Enforcement and Intellectual Property Rights: Promoting Innovation and Competition (Washington, DC: FTC DOJ, April 2007) at 1 online: http://www.ftc.gov/reports/innovation/P040101PromotingInnovationandCompetitionrpt0704.pdf [hereinafter FTC DOJ 2007]. 13 Supra note 5 FTC 2011 at 43. 14 Supra note 10 FTC 2003. This policy objective is adopted and institutionalized in countries outside the U.S. as well. See e.g., Minister of Finance, House of Commons, Economic Action Plan; Jobs Growth and Economic Prosperity (Ottawa 2012) (iterating the view that the Government “supports an innovative economy...through...translation of public research knowledge to the private sector”) at 55 and 56. See generally also, Industry Canada, Mobilizing Science and Technology to Canada’s Advantage (Ottawa: Industry Canada, 2007) online: Industry Canada http://www.ic.gc.ca/eic/site/ic1.nsf/eng/h_00231.html [hereinafter Economic Action Plan 2012]. See also generally Networks of Centres of Excellence, Networks of Centres of Excellence Canada Annual Report (Annual Report 2010/2011) online: http://ar-ra.nce-rce.gc.ca/_pdfs/AR_NCE_10-11_eng.pdf (for example, MaRS Innovation facilitates innovation for Toronto’s academic and medical research institutions).

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commercialize,15 innovation contemplates the concept of affirmatively practicing the patent.16

Nonetheless, innovation remains linked to the underlying invention protected by a patent grant17

because the patent system facilitates investment into the commercialization process in order to

transform an invention into innovation.18 Consequently, infringement of patent rights can affect the

larger process of innovation. Attempts to modify the rights of a patent holder, either before or after

a patent is granted, should be carefully analyzed to confront the legitimate expectations of a patent

holder against any competing interests at stake. The suggestions on modifying the patent system

following the exercise of BRCA1 and BRCA2 breast cancer patents (collectively, BRCA) held by

Myriad Genetics, Inc. (Myriad) described below, raises important questions on the implications to

commercialization as a vehicle for delivering innovation to the public.

The case scenario of Myriad Genetics, Inc. (Myriad) aptly demonstrates a limitation in the

belief that the process of innovation, described as commercialization serves as the best conduit for

delivering inventions to the public. It further highlights an inadequacy in innovation policy that

merges improved health care and lives with economic advancement.19 While generally, the two

objectives align well and are promoted simultaneously through innovation, conceptualized as

commercialization, the Myriad controversy instantiates a circumstance where the two purposes

conflict. Myriad patented and attempted to commercialize around the world genetic diagnostic tests

for breast and ovarian cancer.20 These tests detected the risk of breast and ovarian cancer among

15 But see Paris Convention for the Protection of Industrial Property, Mar. 20, 1883, art. 5A (providing for the issuance of a compulsory license in certain instances for failure to work a patent). See also infra note 288 at art 2.1 (incorporating the Paris Convention by reference). 16 Supra note 5 FTC 2011 at 40. 17 Ibid. at 43. 18 Supra note 8 SACGHS Gene Patents at 28. 19 This view of innovation aligning economic growth with improved quality of life, in part through better health, is expressed in Canada as well. See e.g., Industry Canada, Innovation Canada: A Call to Action (Ottawa, October 2011) at E-1 (emphasizing that “innovation is the ultimate source of the long-term competitiveness of businesses and the quality of life of Canadians”). See also supra note 10 FTC 2003, Chapter 1 at 1. 20 See generally E. Richard Gold and Julia Carbone, “Myriad Genetics: In the eye of the policy storm” (April 2010) Genetics in Medicine. 12:4.

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those who carried catalogued mutations of the BRCA1 and BRCA2 genes, collectively called the

BRCA genes. Those with increased risk of breast or ovarian cancer detected through the presence

of these genes could benefit from subsequent clinical interventions. Once patented, Myriad

commercialized the tests in the U.S. and attempted to do the same around the world.21 However,

Myriad’s exercise of its patent rights was strongly criticized for its negative impact on women’s

health.22 Unstated, but implicit, in the criticisms was Myriad’s desire to economically benefit from its

patents at the expense of improved health and lives. This particular controversy culminated into a

lawsuit filed by the American Civil Liberties Union (ACLU) and eventually reached the Supreme

Court of the United States.23 The public debate about gene patents also prompted the formation of

the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) that among other

related topics submitted recommendations on gene patents and licensing practices with respect to

patient access to genetic tests.24 The unadopted recommendations have engendered further

discussion and ongoing relevant cases continue to question gene patents and the ultimate issue of

patient access that can be characterized as a failure of the promise of innovation or

commercialization to deliver inventions that ultimately seek to improve health.

This paper attempts to explain the solutions available for increasing access to patented

inventions that commercialization has not fully delivered. In doing so, Part II of this paper will

detail the specific controversies surrounding the BRCA patents in the U.S. and points, in particular,

21 See ibid. generally for a thorough description of the worldwide controversy generated by Myriad’s exercise of its BRCA patents. 22 Ibid. In Canada, Myriad faced additional barriers to implementing the tests because the business model governing administration of the tests was perceived as competing with Canada’s public health care system and intruding on the domain of physicians’ patient management. 23 Ass'n for Molecular Pathology v. USPTO, Case No. 09-CV-4515 (S.D.N.Y. 2010) [hereinafter Myriad SDNY] online: http://www.pubpat.org/assets/files/brca/brcasjgranted.pdf. See also Ass'n for Molecular Pathology v. USPTO 702 F. Supp. 2d 181 (Fed. Cir. 2011) [hereinafter "Myriad CAFC"] online: http://www.cafc.uscourts.gov/images/stories/opinions-orders/10-1406.pdf. See also Ass’n for Molecular Pathology v. Myriad Genetics (2012) No. 11-725 [hereinafter Myriad SCOTUS]. 24 See supra note 8 SACGHS Gene Patents. Similarly, in Canada, a committee was also formed to evaluate the patenting of genes with a desire to reconcile patents on genetic diagnostic test with the implementation of such tests. The broad recommendations calling for sweeping changes were never implemented in Canada. See generally Canadian Biotechnology Advisory Committee, Biotechnology and the Health of Canadians (Ottawa, December 2004).

5

to the underlying issue of licensing practices that have led to calls to change the patent system. Part

III forms the bulk of this paper and will canvass and analyze proposed solutions in literature to the

problem of patient and research access to foundational gene patents. When detailing the proposed

solutions, this paper will support an approach that encourages prudence and abstains from making

broad policy choices based on particular fact scenarios. Recognizing that national patent policy

must align with international obligations, Part IV will also analyze selected solutions to determine

whether they are in keeping with TRIPS before finally concluding with Part V.

II. BRCA Case - Criticisms of Myriad’s Exercise of Patent Rights

Myriad Genetics (Myriad) formed among the start-up companies that emerged during the

early years of the Human Genome Project.25 The goal of the company was to link potential

therapeutics to genes and offer genetic diagnostic tests to patients to assess their hereditary risk of

certain diseases.26 Although several companies offered predictive testing for diseases ranging from

Alzheimer's to cystic fibrosis,27 Myriad garnered significant international attention when it exclusively

began offering tests to predict genetic risk for breast and ovarian cancer.28 Through a combination

of assigned and owned patents, Myriad obtained exclusive rights over conducting these tests.29 A

subsequent lawsuit filed against Myriad reveals the breadth of criticism directed against Myriad’s

ownership and practice of its patented rights.30

Driving each of these criticisms is the health issue of medical access that can be cast as a

failure of innovation policy to deliver health-improvement inventions to the public through

25 R.M. Cook-Deegan, "Origins of the Human Genome Project." Risk: Health, Science and Environment 5 (Spring 1994) 97-118. 26 Supra note 20 at S42. 27 Supra note 8 SACGHS Gene Patents at A-1 (detailing impact of patents and licensing practices on access to genetic testing for various hereditary diseases such as Alzheimer’s disease, cystic fibrosis, hearing loss, hereditary hemochromatosis, Long QT syndrome, spinocerebellar ataxia, and others). 28 See supra note 23. 29 Supra note 20 at S42. 30 Supra note 23 Myriad SDNY.

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commercialization.31 In advocating for better health care options and patient management affected

by lack of access to these tests, the arguments seek to deny the patents obtained by Myriad because

they are “products of nature, laws of nature and/or natural phenomena, and abstract ideas of basic

human knowledge or thought.”32 Arguments are also made that the patents are “unnecessary to

promote innovation in genetic research” and “violate medical and scientific ethics.”33 Others argue

that the patents are not only unnecessary in promoting innovation, but may actually stifle innovation

while “interfering with patient access to medical testing and treatment.”34 The arguments further

characterize gene patents as common heritage stating that privatizing violates precepts of “common

heritage, public domain, and the public trust doctrine” while creating private rights of “unknown

scope and significance.”35 Gene patents’ potential exploitation of indigenous communities is also

addressed in the arguments as well as the right to informed consent by patients.36

The criticisms directed at Myriad’s use of its patented diagnostic tests focus primarily on lack

of patient access to primary testing. This access is hindered, in part, because of cost and insurance

barriers.37 The quality of the first test is also implicated because of the standardized testing process

occurring in a central lab. Secondary or confirmatory testing is affected because Myriad is the sole

provider of the test limiting the availability of second opinions or a variation in the testing method

and interpretation.38 Essentially, the lack of competition prevents the creation of alternative testing

methods or improved quality of tests. Patenting the gene itself inhibits the ability of researchers to

31 American Civil Liberties Union (ACLU), Legal Challenge to Human Gene Patents (May 2009) online: http://www.aclu.org/files/pdfs/freespeech/brca_qanda.pdf (detailing that gene patents prevent patient access to genetic diagnostic tests, prevent free-flow of information from geneticists to patients, and prevent research access hindering future research and improvements and the progress of science). 32 Supra note 23 Myriad SDNY at 1. 33 Ibid. at 17. 34 Ibid. at 19. 35 Ibid. at 20. 36 Ibid. 37 Ibid. at 14, 16. 38 Ibid. at 12.

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invent around the patent and develop other tests.39 The lack of access by researchers also implicates

patient health by preventing clinician investigators from reporting results to their patients and

research subjects.40 Patient health is further affected by the limited amount of research that takes

place due to the patenting of the genes which prevents follow-on innovation and improvements.41

Finally, patenting of genetic diagnostic tests has been described as a barrier to patient access because

the multiple tests that proliferate prior to the issuance of the patent are subsequently cleared from

the market upon enforcement of the issued patents.42

Accompanying these arguments is the narrative of the heated gene discovery and patent race

in the early years of BRCA identification and sequencing. The consistency by which this story is

repeated indicates the presence of a suspicion that, even if patentable, others’ work contributed

significantly to the identification of the gene perhaps making Myriad less deserving of its

subsequently obtained patent right.43 After a group of researchers in the 1990s identified the general

location of a gene linked to breast cancer, BRCA1, one of the entrepreneurial minded researchers

started Myriad, gaining funding from private investment to continue with the research.44 After

BRCA1 was sequenced, BRCA2 was identified, and a race ensued to sequence the second gene.

Although overlapping patents were granted to different groups, Myriad eventually obtained exclusive

licensing for the patents it did not own becoming the exclusive holder of the BRCA1 and BRCA2

39 Ashley McHugh, “Invalidating Gene Patents: Association for Molecular Pathology v. US Patent and Trademark Office” (2010 - 2011) 62 Hastings L.J. at 197. 40 Supra note 23 Myriad SDNY at 9 and 10. 41 Although Myriad has stated that it would not prevent researchers from conducting research on its patented genes, anecdotal evidence indicates that at least for some researchers the patents coupled with cease and desist letters sent to certain labs served as sufficient impediments to conduct research. See supra note 20 at S44. 42 See supra note 8 SACGHS Gene Patents at 2, 33, 40, 43, 79, 90, and F-25. See also supra note 39 at 196 (describing the variety of low-cost or, in some instances, free breast cancer screening tests discontinued after Myriad’s assertion of its patent rights). See also supra note 23 Myriad CAFC at 18 (describing the three year time period between the filing and issuance of each of Myriad’s two patents). See also Lori Andrews, “The Gene Patent Dilemma: Balancing Commercial Incentives With Health Needs” (2002) 2 Hous. J. Health L. & Pol’y at 86 (describing this extended time period of a patent application as a submarine patent) [hereinafter Dilemma]. 43 Supra note 20 at 6 (explaining “many researchers and clinical geneticists opposed gene patenting in general and felt a degree of hostility toward Myriad because of the way the scientific race had proceeded”). 44 Bryn Williams-Jones, “History of a Gene Patent: Tracing the Development and Application of Commercial BRCA Testing” (2002) 10 Health L.J. at 131.

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gene patents.45 The potential contribution of others without which sequencing BRCA1 would not

have been possible raises another objection to the patents held and practiced exclusively by Myriad.

III. Proposed Measures

The above description serves to highlight the controversy generated by Myriad’s practice of

its patents. By describing the harm faced by researchers and patients as a result of limited access to

patented genetic diagnostic tests, the attention of many has turned to ways to help increase that

access. The proposed solutions can be divided into three categories. The first set of solutions

contemplates denying the underlying patents to genes and so removing exclusivity in genetic

diagnostic tests. By removing the right to exclude, not only is clinical and research access increased

to tests but the improvement of such tests is also envisioned. The second set of solutions advocates

the issuance of gene patents but focuses on the types of patents issued. For example, this set of

solutions suggests narrowing the scope of such patents to increase the quality of granted patents.

The final set of solutions suggests leaving the patent grant intact, but proposes ex-post solutions to

increase access to patented tests. This set of solutions recommends the creation of narrow

exemptions to the patent right to exclude, the implementation of compulsory licensing

arrangements, or the encouragement of patent pools.46 The following sections will explore these

solutions.

A. Deny Patents

As a solution to increasing access to genetic diagnostic tests, denying patents to the

underlying genes has been suggested. Removing exclusivity to the gene frees access to the derivative

45 Supra note 23 Myriad SDNY. 46 A potential fourth set of solutions suggests allowing the patent but guaranteeing access by publicly funding the test. Although this solution is a possibility in countries whose health-care systems are publicly funded, the private health-care system in the U.S. raises different issues outside the scope of this paper. However, even in countries, such as Canada, where the BRCA tests were funded through public money, problems arose through the business model practiced by Myriad that dictated when and how the tests should be administered. This careful control of the test was perceived as an intrusion into the public health care system of the Canada that fettered patient management of physicians who would otherwise dictate the versions the tests were needed and under what circumstances the tests should be provided. See generally supra note 22.

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genetic diagnostic tests for both research and clinical purposes. This approach has the advantage of

creating a bright line rule about gene patenting and provides unencumbered access to the

foundational tools in a scientific field. However, before exploring the justifications for excluding

genes from patentability, the following sections will first explain how patents on genes came to be

granted.

1. Rise of Gene Patents

Patents are granted to inventions meeting the statutory criteria of novelty, non-obviousness

or inventiveness, and utility.47 Patentability, however, is subject to doctrines that exclude from

patentability “laws of nature, physical phenomena, and abstract ideas.”48 Here, the public domain is

sought to be circumscribed from patentability by removing those discoveries which are

“manifestations of...nature, free to all men and reserved exclusively to none.”49 For instance, in

Funk Brothers Seed Co. v. Kalo Inoculant Co., the Supreme Court found invalid a patent claiming a

specific combination of bacterial strains that in concert expressed unexpected non-inhibitive effects

upon each other.50 Previously, individual strains of bacteria had to be applied separately to certain

seeds to prevent inhibition of bacterial growth. The combination, however, allowed for the same

mix of bacterial strains to be used indiscriminately among crops. The Court found that the mixing

of the strains, though useful, simply expressed properties of bacteria that already existed in nature

without human intervention. Because the combination was a “discovery of some of the handiwork

of nature, the qualities of these bacteria...[were] part of the storehouse of knowledge of all men” and

unpatentable.51 This case contemplated the existence of a robust public domain.

47 35 U.S.C. ss.101-103 (2011). 48 Diamond v. Chakrabarty, 447 U.S. 303 (1980). 49 Funk Bros. Seed Co. v. Kalo Inoculant Col., 333 U.S. 127 (1948) at 130. See also supra note 48 at 309. 50 Supra note 49 Funk Bros. at 127. 51 Ibid.

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Despite these categorical exclusions from patenting, courts have shaped the prohibitions that

allow for patenting in certain circumstances. In particular, although products of nature are excluded

from patentability, the emergence of the natural extracts doctrine has allowed patenting of purified

and isolated natural substances that displayed therapeutic and commercial benefits.52 In Parke-Davis

& Co. v. H.K. Mulford Co., adrenaline, isolated and purified, was found patentable.53 Although found

in nature, when isolated and purified, adrenalin possessed therapeutic and commercial usefulness.54

This view was reinforced in Merck & Co. v. Olin Mathieson Chemical Corp. where a patent on purified

vitamin B12 was held valid because the isolation and purification of the vitamin rendered it useful

therapeutically and commercially.55 While supporting the unpatentability of products of nature in

general, the criteria for what constitutes a product of nature was shaped by characterizing the

isolated and purified form of natural products as something “new...commercially and

therapeutically.”56 Otherwise natural substances could take a new form and be rendered patentable

if their isolated and purified forms offered commercial and therapeutic benefits. Adrenalin and

vitamin B12, when found in the body were naturally occurring; when isolated and purified, they were

non-naturally occurring compounds useful both commercially and therapeutically. By distinguishing

between naturally and non-naturally occurring compounds, these decisions paved the way for

characterizing DNA sequences as chemical compounds that are patentable when isolated from the

human body because of their structural variance in the isolated state.57

52 Allen K. Yu, “Why it Might be Time to Eliminate Genomic Patents, Together with the Natural Extracts Doctrine Supporting Such Patents” (2006-2007) 47 IDEA 659, 678. See also Eileen Kane, “Splitting the Gene: DNA Patents and the Genetic Code” (2003 - 2004) 71 Tenn. L. Rev. at 738 [hereinafter Splitting the Gene]. 53 Parke-Davis & Co. v. H.K. Mulford Co. 189 F. 95 (C.C.S.D.N.Y. 1911). 54 Ibid. at 103. 55 Merck & Co. v. Olin Mathieson Chemical Corp. 253 F.2d at 164. 56 Supra note 53 at 103. 57 See generally supra note 23 (the District Court in Myriad favoured the adoption of a dual definition of DNA that encompassed its functional and informational aspect along with structural aspect. The dual definition allowed for a finding against patentability based on the gene encompassing a law of nature). But see Joshua D. Sarnoff, “Patent Eligible Medical and Biotechnology Inventions After Bilski, Prometheus, and Myriad” (2011) 19 Tex. Intell. Prop. L. J. at 411, 412 (arguing that the district court’s reliance on characterizing DNA as informational was unnecessary to a finding of unpatentability and amounted to an “exceptionalist view of genetic materials based on their informational content.”

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Although not dealing with isolated genes, the Supreme Court considered genetic

intervention in the 1980 Diamond v. Chakrabarty case.58 Here, the Court affirmed that a strain of

bacterium genetically engineered to degrade oil spills was patentable subject matter. The bacterium

was readily distinguishable from the combination of naturally occurring bacteria in Funk Brothers

based on the engineered bacterium’s “markedly different characteristics from any found in nature.”59

In affirming patentability, the Court stated broadly that patentable subject matter “include[s]

anything under the sun that is made by man.”60 The pronouncement reaffirmed the broad subject

matter available for patenting so long as it was “a product of human ingenuity.”61

Soon after Diamond v. Chakrabarty, the Human Genome Project (HGP) was conceived in the

mid 1980s with the goal of sequencing the entire human genome.62 With the launch of the HGP

arose applications for patenting genes.63 By 1992, public-private partnerships formed and start-up

companies emerged with a view towards capitalizing the knowledge being created by the HGP to

develop targeted therapeutics and diagnostic tests.64 Patents on gene fragments known as expressed

sequenced tags (EST) were also controversially sought during this time period, though later the

utility requirements were heightened to make more challenging the issuance of such patents.65

Nevertheless, patents on genes were provided for those that met the criteria promulgated in the

Rather, the court could have “readily reached the same result of unpatentability based on the similarity of the isolated materials and the new functions that they perform as not ‘markedly different characteristics’ and only ‘analogous uses.’” Following the line of Supreme Court precedents would have prompted the same result of unpatentability without the need to characterize genes as something different) [hereinafter Biotechnology Inventions]. 58 Supra note 48 at 309. 59 Ibid. at 309. 60 Ibid. at 309. 61 Ibid. at 309-310. 62 See National Institutes of Health “A Brief History of the Human Genome Project” (2011) online http://www.genome.gov/12011239. Last accessed February 23, 2012. 63 Eric J. Rogers, “Can You Patent Genes? Yes and No” (2011) 93 J. Pat. & Trademark Off. Soc’y at 19. 64 Supra note 25. 65 Arti K. Rai, “Patent Validity Across the Executive Branch: Ex Ante Foundations for Policy Development” (2012) 61 Duke L.J. at 1249 - 1255 (ESTs were gene fragments that “could be used as probes to find the full genes of which they were a part”) [hereinafter Ex Ante Foundations]. See also Rebecca S. Eisenberg, “Technology Transfer and the Genome Project: Problems with Patenting Research Tools” (1994) 5 RISK 163 [hereinafter Technology Transfer].

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USPTO Utility Examination Guidelines.66 Accordingly, applications for isolated genes that disclose

the molecular structure and utility continue to be granted.67 These patents on genes are issued based

on the line of reasoning from prior case law such as Parke-Davis distinguishing naturally occurring

compounds from isolated and purified chemical extracts.68 Thus, when considered a chemical

construct, patenting isolated DNA is a natural extension of prior case law granting patents on

isolated and purified chemicals.69

2. Patent Ineligible Subject Matter

The argument that patenting DNA is a natural extension of patenting chemical compounds

has been challenged in two ways. First, some commentators argue that DNA is inappropriately

characterized as purely a chemical construct; rather, its informational quality should also be

considered.70 Because of its dual informational and chemical quality, DNA should not be subject to

patenting in the same way as other chemicals. However, a second view argues that removing DNA

from patentability by ascribing to it both informational and chemical characteristics amounts to

66 Matthew Poulsen, “Jurisprudential and Economic Justifications for Gene Sequence Patents” (2012) 90 Neb. L. Rev. at 210 (stating these guidelines were also later adopted by the In re Fisher court) [hereinafter Jurisprudential]. See also USPTO, Final Guidelines for Determining Utility of Gene-Related Inventions (2001) http://www.uspto.gov/web/offices/com/sol/notices/utilexmguide.pdf [hereinafter 2001 Utility Guidelines]. See also Science-Metrix, Study on the breadth of human gene patents granted by the CIPO, the EPO, and the USPTO (2005) at 18 online: http://www.science-metrix.com/pdf/SM_2005_009_IC_Breadth_Human_Gene_Patents.pdf. 67 Ibid. Jurisprudential. 68 Kristin Wall, “Patently Obvious: Why the District Court’s Ruling in Association for Molecular Pathology v. USPTO is Incomplete” (2011) 93 J. Pat & Trademark Off. Soc’y at 243. See also “Utility Examination Guidelines” (Jan. 5, 2001) 66 Fed. Reg. 1092 (instructing that "a patent claim directed to an isolated and purified DNA molecule could cover, e.g., a gene excised from a natural chromosome or a synthesized DNA molecule."). 69 See Committee on Intellectual Property Rights in genomic and Protein Research and Innovation, National Research Council, Reaping the Benefits of Genomic and Proteomic Research: Intellectual Property Rights, Innovation, and Public Health, (Washington, DC: The National Academies Press, 2006) Stephen A. Merrill & Anne-Marie Mazza, eds at 76 (stating that the issuance of patents on genes and DNA is “consistent with longstanding practice...of allowing patents to be issued on isolated and purified chemical products that exist in nature only in an impure state, when human intervention has made them available in a new and useful form”) online: http://www.nap.edu/catalog/11487.html [hereinafter NRC]. See also Rebecca S. Eisenberg, “Re-examining the Role of Patents in Appropriating the Value of DNA Sequences” (2000) 49 Emory L.J. (explaining that “patents on DNA sequences seemed analogous to patents on new chemical entities”) at 784 [hereinafter Role of Patents]. 70 Arti K. Rai, “Intellectual Property Rights in Biotechnology: Addressing New Technology” (1999) 34 Wake Forest L. Rev. (“Although DNA is, obviously enough, a chemical compound, it is more fundamentally a carrier of information”) at 836 [hereinafter New Technology]. See also supra note 53 Splitting the Gene at 713 (arguing that any consideration of a gene should incorporate “its duality as chemical and template to properly evaluate its eligibility for patent protection”).

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genetic exceptionalism.71 Instead, DNA should be categorically removed from patentability not

because of its dual quality, but because even as a chemical construct, DNA fails to fulfill the

requirements of patentability.72 Both modes of analysis, however, assert that patenting DNA is not a

logical extension of patenting chemicals.

a. DNA Unpatentable - Duality of DNA

The first line of reasoning attempts to exclude DNA from patentability by emphasizing the

duality of DNA as both a structurally chemical and functionally informational entity.73 While

recognizing that DNA possesses a chemical quality, this mode of reasoning stresses that DNA,

unlike other chemical entities, also possesses informational characteristics. DNA is not only a

chemical entity, but it also directs protein production74 and stores hereditary information that defines

physical traits along with influencing the development of diseases and conditions.75 Unlike other

chemicals found in the body, DNA not only stores information relating to its own biological

function but also stores information relating to the “synthesis of other molecules in the body.”76

DNA, then, is unique as an information carrier and must be treated differently from other chemicals

in the body.77 Because DNA possesses informational characteristics, any theory contemplating

patent protection of a gene must incorporate that “duality as a chemical and template.”78

71 See supra note 58 Biotechnology Inventions and see infra discussion III.A.2.b. 72 Ibid. 73 See supra note 69 Role of Patents at 785 (stating that “DNA sequences are not simply molecules, they are also information” and explaining that because DNA sequences are better characterized as scientific information, claims to DNA discoveries “raise unresolved questions that strain the chemical analogy”). See also supra note 53 Splitting the Gene at 709 (asserting that, “[a]lthough the gene is a chemical compound defined by its constituent elements, a full comprehension of the gene must include its dynamic properties as well”). See also supra note 70 New Technology at 836 (advocating the adoption of a dual definition of DNA by stating “[a]lthough DNA is...a chemical compound, it is more fundamentally a carrier of information”). 74 Alberts B, Johnson A, Lewis J, et al. “The Structure and Function of DNA” in Molecular Biology of the Cell, 4th ed (New York: Garland Science, 2002) online: http://www.ncbi.nlm.nih.gov/books/NBK26821/. 75 Supra note 23 Myriad SDNY at 30. 76 Supra note 69 at 251. 77 Ibid. 78 Supra note 52 Splitting the Gene at 713.

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By highlighting the duality of DNA, DNA is sought to be characterized as a law of nature

and, thus, excluded from patentability. A law of nature is explained as something that “defines an

invariant relationship that governs the interaction of two or more physical entities.” It is

“fundamental to the operation of a defined process in the natural world...[whose] operation is

universal, and that universality reveals its history.”79 Because the genetic code is “invariant, has

existed throughout time, and exhibits universality”, the genetic code is arguably a law of nature.80 As

a law of nature, it is precluded from being patentable subject matter because it appropriately resides

in the public domain. Although the DNA as a chemical construct can qualify as patentable subject

matter, its informational characteristics “possess public domain attributes that...frustrate private

appropriation.”81 The dual nature, then, forms the basis for excluding DNA from patentability as a

law of nature.

A variation of this approach subsumes the product of nature doctrine into the law of nature

doctrine to exclude DNA from patentability. Although one approach differentiates between the

product of nature doctrine and the law of nature doctrine by finding the product of nature doctrine

to be an “insufficient analytic tool”82 for DNA’s dual characterization, the district court in Myriad

merged the doctrines into one, ultimately finding DNA unpatentable under the product of nature

doctrine. The district court reasoned that “DNA represents the physical embodiment of biological

information” and a focus on the chemical nature “fails to acknowledge the unique characteristics of

DNA that differentiate it from other chemical compounds.”83 For the district court, the defining

informational character of DNA remains unchanged in its native and isolated form. The isolated

79 Ibid. at 751. 80 Ibid. 81 Ibid at 753. 82 Ibid. at 744. 83 Supra note 23 Myriad SDNY at 28.

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DNA performs the same function, coding for the same protein, as the naturally occurring DNA.84

In Myriad, because the patents-in-suit were not “markedly different” as required by Diamond v.

Chakrabarty, the DNA, even when isolated, remained an unpatentable product of nature.85 Similar to

the above variant, this method also seeks to circumscribe the public domain from encroachment by

the patent system, leaving unpatentable those laws or products of nature that form the foundation

of a multitude of scientific endeavors.

b. DNA Unpatentable as Chemical Entity

Another avenue, while recognizing that DNA may also have an informational character,

chooses to de-emphasize the duality of DNA when conducting the patentability analysis. Rather, this

approach considers DNA ineligible for patenting even when considering only the chemical

composition of DNA. Here, it is argued that the district court in Myriad “may have gone too far in

seeking to justify its decisions on the isolated claims on an exceptionalist view of genetic materials

based on their information content.”86 Rather, the prior line of Supreme Court precedents

necessitates a finding of unpatentability for DNA characterized as a chemical construct. This is

because patentability requires that an invention created from natural products be a “‘new and

different article, having a distinctive name, character or use.’”87 Mere isolation of a product to

increase purity while retaining its natural functions is insufficient for patentability.88 This is

supported by the finding in Diamond v. Chakrabarty that found patentable the genetically engineered

oil-degrading bacterium that possessed “markedly different characteristics from any found in nature”

84 See supra note 69 at 249 (explaining that the isolated DNA and the naturally occurring DNA code for the same proteins that “go on to perform identical tasks”). 85 Supra note 23 Myriad SDNY at 42. 86 Supra note 57 Biotechnology Inventions at 411, 412. See also supra note 39 at 212, 214 (stating that the “district court...incorrectly categorized DNA as information and not as a chemical compound” but arguing that denying gene patents is too broad of a remedy under the purification doctrine). 87 Ibid. at 410. See also supra note 23 Myriad CAFC at 37 and 38. 88 Ibid.

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as well as the potential for significant utility.89 The “markedly different” standard is further

supported by the finding in Funk Brothers that reasoned the prescribed combination of applied

bacteria to encourage their helpful growth on seeds, though useful, already existed in nature to

“serve the ends nature originally provided.”90 Consequently, isolated genetic sequences that retain

their natural functions without any “markedly different characteristics from any found in nature” fail

to be eligible for patenting. According to this view, the dual quality of DNA, though correct,

remains unnecessary in finding DNA sequences unpatentable. The DNA as a chemical entity, when

isolated, retains its natural functions and fails to qualify for patentability.

c. Robust Public Domain Justification and Outcome

Whether characterizing DNA as a dual entity or as a chemical construct, each line of

reasoning seeks to exclude DNA from patentability based on an underlying desire to maintain a

robust public domain.91 So long as an invention meets the statutory criteria of patentability, a patent

is granted. However, to ensure a patent monopoly does not inappropriately remove foundational

discoveries for an entire field, threshold categories have been created to exclude certain subject

matter from patentability. This subject matter includes “laws of nature, physical phenomena, and

abstract ideas.”92 These “exclusions from eligibility...protect the public domain of science, nature,

and ideas.”93 These foundational discoveries are “‘manifestations of...nature, free to all men and

reserved exclusively to none.’”94 Genes, then, are argued to be foundational discoveries that form

89 Supra note 48 at 310. See also supra note 58 at 410 (explaining that in order to be eligible for patenting, the invention must have “markedly different characteristics” from any found in nature). 90 Supra note 49 at 131. 91 Joshua D. Sarnoff, “Patent Eligible Inventions After Bilski: History and Theory” (2012) 63 Hastings L. J. 2at 57 (advocating the existence of categorical exclusions from patentability in order to ensure the existence of a robust public domain) [hereinafter History and Theory]. See also supra note 42 Dilemma at 67 (explaining that “patent laws are designed to assure that the public benefits from a new invention in exchange for the monopoly” and that “laws do not allow patents on products of nature because the public would not gain anything new”). 92 Supra note 48 at 303. 93 Supra note 97 History and Theory at 94. See also supra note 53 Splitting the Gene at 707 (stating that a “public domain is explicitly recognized in patent law by judicial exclusion of the laws of nature, natural phenomena, and abstract ideas from patent protection”). 94 Supra note 48 at 309.

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either a product or a law of nature. Consequently, they are sought to be categorically excluded from

patentability in order to protect a robust public domain.

However, the conclusions of unpatentability above were rejected at the Federal Circuit level

in Myriad.95 In restoring Myriad’s patents on the BRCA genes, a fractured federal court reasoned

that because the isolated DNA molecules do not exist in nature, the patents are not barred under the

products of nature doctrine.96 The Federal Circuit further directly employed the “markedly

different” standard in favour of finding patentability stating that because the claims were found to

cover molecules that were “markedly different” from molecules that exist in nature, the isolated

DNA were patentable. In contrast to the above argument that sought to deny patentability to genes

based on their use or benefit, the court here elevated the importance of chemical structure over

function.97 The court stated the distinction between a product of nature and a human-made

invention giving rise to a “markedly different” standard depended upon a “change in the claimed

composition’s identity compared with what exists in nature.”98 Accordingly, it reasoned, that

“because the claims cover molecules that...have a distinctive chemical identity and nature” from

molecules that exist in nature, the claims were drawn to patentable subject matter.99

In finding the “distinctive chemical identity” the court focused on the structural differences

that necessarily occur between isolated and naturally occurring DNA, explaining that genes, as

chemicals, “are best described in patents by their structures rather than their functions.”100

Emphasizing the smaller length and free-standing characteristic of isolated DNA as compared to the

greater length and integrative nature of native DNA within other cellular components lead the court

95 On appeal, the Federal Circuit on July 29, 2011, reversed the finding of unpatentability of the patents on the genes while affirming the unpatentability of all but one of the method claims. See supra note 23 Myriad CAFC at 8. 96 Ibid. 97 Ibid. at 44 (stating that “it is the distinctive nature of DNA molecules as isolated compositions of matter that determines their patent eligibility rather than their physiological use or benefit”). 98 Ibid. at 41. 99 Ibid. at 41. 100 Ibid. at 45.

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to find that isolated DNA possesses a distinct chemical identity.101 In distinguishing isolated DNA,

the court found that although the isolated DNA was removed from its native environment, that

cleaving of the DNA that broke covalent bonds caused the isolated DNA to be “manipulated

chemically so as to produce a molecule that is markedly different from that which exists in the

body.”102 By focusing on physical differences, the court rejected the line of reasoning that sought to

deny patentability to genes based on the retention of their functional features when isolated. Rather,

the court stressed the importance of the structural differences that resulted during the removal

process that rendered the isolated DNA “markedly different” and chemically distinct from native

DNA.103 The above line of reasoning, then, may remain unavailable in attempting to deny

patentability to genes.

3. Statutory s.101

a. Utility

Alternatively, excluding genes from patentability can rest on statutory s.101 grounds where

the genes are found to lack novelty, utility, or be obvious in light of prior art. Indeed, utility has

already been used to narrow the scope of patents issued. In 2001, utility guidelines were introduced

to limit the patents granted on expressed sequence tags (ESTs).104 By the late 19920s, thousands of

applications were filed on ESTs, gene fragments, of unknown biological function.105 These

controversial patents eventually stopped issuing under the promulgation of new guidelines that

101 Ibid. at 42. 102 Ibid. 103 The Federal Circuit reaffirmed its reasoning and holding regarding patenting genes when the case was returned from the Supreme Court with the direction to be re-decided in accordance with the decision rendered in Mayo Collaborative Services v Prometheus Laboratories, Inc., No. 10-1150 (U.S. Mar. 20, 2012). Because Mayo v Prometheus dealt with process claims, the subject matter of this paper remains unaffected. The Federal Circuit, for this subject matter, followed its prior reasoning to affirm that isolated DNA, as a “discrete portion of native chromosomal DNA” has a “distinct chemical identity as compared to native DNA”). Ass'n for Molecular Pathology v. USPTO, (Fed. Cir. 2012) at 45. 104 Supra note 65 Ex Ante Foundations at 1255. See also supra note 66 2001 Utility Guidelines. 105 Supra note 65 Ex Ante Foundations at 1251.

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required the demonstration of heightened utility.106 In In re Fisher,107 the Federal Circuit endorsed the

2001 Utility Examination Guidelines and affirmed a finding of unpatentability for ESTs because of

their failure to meet the requirement of “specific and substantial use” articulated by the Supreme

Court in Brenner v Manson.108 “Specific utility” requires the availability of a “well-defined and

particular benefit” and “substantial utility” requires the showing of a “significant and presently

available benefit to the public.” Because patent applications claiming ESTs of unknown biological

function failed to show any utility except for vague potential as a research tool to yield the

“structure...[and] function of the underlying gene” the ESTs themselves failed to qualify for

patenting.

Under the above-described standard from the 2001 Utility Guidelines and the utility

standard affirmed in In re Fisher, gene patents meet the requirement of utility. For instance, the

BRCA genes held by Myriad have a “specific use” because of the availability of a “well-defined and

particular benefit” in detecting increased risk of breast and ovarian cancer among those who possess

that gene. With its application of detecting increased risk of breast and ovarian cancer, the genes

also possess “substantial utility.” Thus, gene patents, under the current standard, are unlikely to fail

qualifying for patenting. However, the earlier tightening of the utility standard evidenced by the

2001 Utility Guidelines indicates that utility can once again be heightened to make more difficult the

patenting of genes. For instance, once a gene sequence is patented, the entire range of uses for the

gene is precluded for others except the patent holder.109 Patenting the gene sequences forecloses all

uses of the gene. Consequently, a proposed measure to heighten utility could include the

106 Ibid. at 1255 (explaining further that even if EST applications were approved, they were approved in a limited manner, preventing the claiming of surrounding nucleotide sequences). 107 In re Fisher, 421 F 3d 1365 (Fed Cir 2005). 108 Brenner v Manson, 383 US 519 (1966). See also supra note 91 2001 Utility Guidelines. 109 Sean C. Pippen, “Dollars and Lives: Finding Balance in the Patent ‘Gene Utility’ Doctrine” (2006) 12 BU J Sci & Tech L at 212.

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requirement that genes be limited to the use envisioned or discovered by the patent holder.110 Such

a requirement would free the gene in question for new uses as discovered by others. In the instance

of patents on genes whose use predicts risk for certain diseases, the genes would be available for

new uses. It remains unclear how this solution would allow variations in testing or better access to

testing for patients. However, the possibility exists that utility could be used as a means of limiting

the gene patents granted.

b. Non-obviousness

Similarly, non-obviousness has been raised as a potential ground for challenging gene patent

applications. Under this challenge, patents are denied for inventions that, given the state of the field

of the invention, are obvious to persons of ordinary skill in the art.111 Although the four-part

Graham112 test detailed below arguably renders DNA patents obvious, this line of reasoning was

rejected in two cases decided in relative succession that upheld the patentability of DNA sequences

identified through routine work as long as the structure of the DNA molecule was not predicted

based on the prior art.113 Applying the Graham test in the Myriad scenario, some commentators find

DNA patents to be precluded on obviousness grounds.114 Under the first part of the test, a person

of ordinary skill in the art would have found the invention obvious because the BRCA genes were

located using public information. Indeed, the race to sequence and patent the BRCA genes lends

support to the point that one skilled in the art would have found the process of locating the gene

obvious and would have used publicly available information to do so.115 The Graham test further

110 See ibid. generally. See also infra III.B.2 for greater discussion on narrowing gene patents based on different criteria, including use. 111 Supra note 69 Role of Patents at 795. 112 Graham v. John Deere Co., 383 U.S. 1 (1966). 113 See In re Deuel, 51 F.3d 1552 (Fed. Cir. 1995) and In re Bell, 991 F.2d 781 (Fed. Cir. 1993). See also supra note 69 Role of Patents at 795. 114 Supra note 69 at 252. 115 Ibid. See also supra note 44 at 131. See also supra note 20 at S40 (stating that “[c]ompetition among the seven major research teams working to locate and identify BRCA1 and BRCA2 was vicious”).

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shows that little difference exists between the prior art and present claims.116 In fact, the “gene

sequences claimed in Myriad’s patents [were]...substantially close to the information that was

publicly available at the time the patents were filed.”117 Because the level of skill in the relevant field

of inquiry was high, the discovery was more likely to be obvious. Finally, the secondary

considerations articulated in the Graham test also militate against a finding of non-obviousness for

the BRCA genes because the genes were located using well-known methods and the general location

had been narrowed by another group in the field.118

In addition, the argument against patenting DNA as obvious may be subject to some

challenge. For instance, the Supreme Court’s recent decision in KSR International Co. v. Teleflex, Inc.

reaffirmed the Graham test and held that “the fact that a combination was obvious to try might show

that it was obvious.”119 Although the decision was not related to a biotechnology invention, it has

been used by the Board of Patent Appeals and Interferences to support a rejection of a DNA

molecule as obvious. The decision has been further upheld by the Federal Circuit in In re Kubin.120

Nevertheless, the argument against patenting DNA remains unsure in the face of In re Deuel and In re

Bell that compare the chemical structural version of the derived DNA rather than the known and

routine methods of derivation. Some commentators remain critical of these cases given the

changing nature of genetic technology that makes finding DNA sequences a routine process.121

Although it has previously been acknowledged that the “net result of this jurisprudence has been to

116 Supra note 69 at 253. 117 Ibid. 118 Supra note 20 at S40 (detailing that another “group of US researches lead by Mary Claire King at the University of California at Berkley...provided the first evidence of the potential existence of genes for hereditary forms of breast cancer”). 119 KSR International Co. v Teleflex Inc., 550 U.S. 398 (2007). 120 See supra note 8 SACGHS Gene Patents at 70 for discussion on In re Kubin, No. 2008-1184 (Fed. Cir. Apr. 3, 2009). 121 See generally supra note 69. See also supra note 53 Splitting the Gene at 716 (detailing criticism that “the court has not appreciated the nuances of genetic technology that alter the nature of the [non-obviousness] inquiry”).

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remove the non-obviousness doctrine as a barrier to routine gene patenting,”122 non-obviousness

may very well provide an additional ground for challenging DNA patents.123

4. Constitutional Grounds

Another justification for excluding genes from patentability rests on constitutional grounds.

This line of argument attacks genes as patent ineligible subject matter because patenting the genes

would remove foundational discoveries from an entire field and hinder further research.124 This

influential concept was first advanced by Michael Heller and Rebecca Eisenberg to explain that

increasing privatization of upstream biomedical research can result in underutilization of those

privatized resources thereby stifling downstream innovation.125 Inhibiting the advancement of a

field is antithetical to the utilitarian foundations of patent law which is constitutionally enshrined in

the U.S.126 Broadly, this approach views the grant of a time-limited monopoly over intellectual

works as a way to structure incentives for innovation127 making innovation the primary goal for

intellectual property law.128 While ideally, patents should encourage innovation, in some

circumstances, patent grants have been criticized for failing to fulfill their obligation to advance

innovation.129 Arguably, in the instance of genes, patents deter rather than enhance innovation

because they create barriers to downstream research. For example, in order to create multiplex

testing, patents on multiple underlying genes and associations need to be negotiated.130 Even

122 Supra note 53 Splitting the Gene at 716. See also supra note 69 Role of Patents at 795 (stating that this nonobviousness “standard fails to serve this important function [of preventing the issuance of patents] in the context of DNA sequencing”). 123 See generally Joanna Kwan, “A Nail in the Coffin for Gene Patents” (2010) Berkley Tech. L. J. 9. 124 See generally Michael A. Heller and Rebecca S. Eisenberg, “Can Patents Deter Innovation? The Anticommons in Biomedical Research” (May 1998) Science 280:698. 125 Ibid. at 698 (explaining the tragedy of the anticommons as a mirror image of the tragedy of the commons where multiple fragmented patented rights on upstream research products gives too many people “the right to exclude others from a scarce resource and no one has an effective privilege of use”). 126 Supra note 4 (mandating that Congress "promote the progress of science and the useful arts by securing for limited times to inventors the exclusive right to their respective discoveries”). 127 Supra note 1 at 169. 128 Supra note 4. 129 See generally supra note 10 FTC 2003. 130 Supra note 8 SACGHS Gene Patents at 3.

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assuming successful negotiation, the “cumulative cost of multiple licenses could make products

unmarketable.”131 The constitutional justification for removing patents from DNA, then, argues

that because the underlying purpose of patents is to “promote the progress of science and the useful

arts”132, any patents that hinder research are inappropriately granted and should be constitutionally

excluded.

This argument, though advanced in the Myriad case, was dismissed because application of

the doctrine of constitutional avoidance dictated that judgment be reached on other grounds if

possible.133 Although the case was decided on s.101 grounds, this argument continues to be offered

to justify a limitation on gene patents. For example, the SACGHS report found that not only are

patents unnecessary to stimulate genetic research, but “patents can also harm genetic research.”134

The harm occurs when follow-on innovation is discouraged. For example, modern genetic

diagnostic tests are moving towards multiplex testing where rather than testing one gene for one

disease, multiple genetic markers are tested either to detect one condition with multiple genetic

causes or to “simultaneously [test] for multiple conditions that have one or more potential genetic

causes.”135 Thus, with the approach of affordable whole-genome sequencing, a person’s entire

genome can be sequenced to test for genetic disorders.136 However, patents held on multiple genes

diffused over multiple owners and assignees interferes with the use and development of multiplex

131 Ibid. 132 Supra note 4. 133 Memorandum of Law in Support of Defendant United States Patent and Trademark Office’s Motion for Judgment on the Pleadings and in Opposition to Plaintiff’s Motion for Summary Judgment at 4. Ass’n for Molecular Pathology v. U.S. Patent & Trademark Office, No. 09 Civ. 4515 (S.D.N.Y. Dec 23, 2009) [hereinafter USPTO Brief]. 134 Supra note 8 SACGHS Gene Patents at 2. 135 Ibid. at 49. 136 Christopher M. Holman, “Debunking the myth that whole-genome sequencing infringes thousands of gene patents” (2012) Nature Biotechnology 30:3 at 240 (correcting a numerical misinterpretation of a widely cited Jensen and Murray study that 20% of human genes are patented. By conducting a detailed analysis, the author argues that much less than 20% of human genes are patented creating a lesser cause of concern.). See also supra note 8 SACGHS at 51 (acknowledging that “although the Jensen and Murray study cannot be extrapolated to conclude that precisely 20 percent of human genes are ... [patented], the study does suggest that a substantial number of genes are protected by patents”). For the study referenced, see K. Jensen and F. Murray, “Intellectual property landscape of the human genome” (2005) Science 310:239.

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tests in at least two ways. First, in order to commercialize a multiplex test, a multiplex test developer

must identify patents requiring licenses, determine whether licenses are available, and negotiate such

licenses with each individual patent holder.137 Second, as an alternative to negotiating licenses, users

of multiplex tests can decline reporting the patented portions of the test results, thus interfering with

the clinical utility of the test.138 The existence of patents on genes, then, hinders the use and

development of multiplex testing and the advancement of a field. Patents on genes are sought to be

denied on constitutional grounds, then, because of the barriers posed by patents to the progress of

research and innovation.

This argument, implicates both patient access to genetic diagnostic tests as well as barriers to

research erected as a result of patents on genes. First, patient access to genetic tests is hindered

because tests that existed prior to the issuance of the patent are narrowed or cleared from the

market after the issuance of the patent.139 This indicates that not only is the patent unnecessary to

stimulate the development of the test, but that it actually impedes patient access by removing

existing tests from the market.140 Patient access is also affected because of the inability to obtain

second-opinion testing when the patent is practiced exclusively. Indeed, this criticism formed a

strong argument against Myriad’s exclusive practice of its patents. By its exclusive practice, patients

were limited in their options for second opinion or confirmatory testing to those tests authorized by

Myriad that excluded confirmation of certain positive test results and all negative test results.141 This

controlled confirmatory testing forced patients to make major medical decisions regarding surgical

intervention such as mastectomy or oophorectomy with limited information.142 This argument

137 Supra note 8 SACGHS Gene Patents at 51. 138 Ibid. at 50. 139 Ibid. at 2. 140 Ibid. 141 Supra note 23 Myriad SDNY at 69. 142 Supra note 8 SACGHS Gene Patents at 44 (stating also that confirmatory “testing by another laboratory is the laboratory equivalent to the time-honored practice of obtaining a second opinion from a clinician”). See also supra note 39 at 197.

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serves to highlight the tension between improved health and innovation. While patents may very

well have helped bring the original diagnostic test to market thereby transforming an invention to

innovation, the patent did not necessarily result in improved health as envisioned by stated

innovation policies.143

Second, barriers to research and subsequent innovation are imposed when limitations are

placed on research using existing tests. For example, multiplex testing, the testing of one condition

through multiple genetic markers or the detection of multiple conditions through the testing of

several genetic causes, is threatened because its development requires the use of multiple potentially

patented genes. One of the criticisms leveled against Myriad is that the patenting of the underlying

gene prevented the creation of independent alternative ways of testing for BRCA mutations.144 The

SACGHS found that existing patents posed potential barriers to the development of multiplex

testing.145 Relatedly, quality assurance is also implicated in this scenario where second opinions are

limited to the original test from the exclusive provider.146 For example, a study revealed that 10-20%

of high risk patients received false negatives through Myriad’s exclusive testing.147 While limiting the

types of tests available ensured the same quality of tests were supplied across laboratories, these tests

all suffered from a lower quality than what otherwise may have been available through quality

143 See generally supra note 5 (stating that innovation drives economic growth as well as improved quality of life). 144 Supra note 39 at 197 (arguing that “due to the nature of patenting the gene itself, there is no available workaround for researchers to develop improved diagnostic test”). But see Sam Kean “The Human Genome (Patent) Project” (February 4, 2011) Science Vol. 331 at 531 (explaining that some workarounds are available in genetic testing; for example, since many genes are expressed together, searching for products of the related unpatented genes can circumvent the patented gene) [hereinafter HGPP]. But see supra note 8 SACGHS Gene Patents at 15 (cautioning that genetic workarounds can fail to meet clinical standards. Some patients fail to be diagnosed while for others an unpatented substitute of the gene may not be available). 145 Supra note 8 SACGHS Gene Patents at 103 (stating that while “new technologies enable simultaneous evaluation of multiple genes through multiplex testing, parallel sequencing, and whole-genome sequencing, fragmented ownership may create a host of problems such as patent thickets, blocking patents, high transaction costs, royalty stacking, and holdouts.” Stating also that “the evidence indicates that patents have already limited the potential of these [multiplex] tests”). 146 Ibid. at 3. 147 Brenda M. Simon, “Patent Cover-Up” (2010-2011) 47 Hous. L. Rev. at 1309 (explaining the importance of quality assurance in genetic diagnostic testing).

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assurance, verification, and peer assessment.148 Further, given the publishing norms of academic

science as well as the requirement for acceptance among the clinical community, patents on genes

may be wholly unnecessary to the disclosure of research results.149 These criticisms regarding patient

access and barriers to research combine to form the foundation for a constitutional challenge to the

patentability of genes in diagnostic testing. Patents, in this instance, fail to fulfill their role of

increasing innovation; rather, they hinder the innovation of better tests.

B. Modify Patents

1. Challenging the Exclusion of Genes from Patentability

The arguments detailed above advocate denying patents on genes as a solution to the

limitations on patient access to genetic diagnostic tests as well as a solution to removing

impediments to follow-on innovation. While the grounds for denying patents vary from

constitutional arguments to the inability of genes to constitute patentable subject matter, the

solutions themselves require the maintenance of a robust public domain. Keeping patents in the

public domain is viewed as a necessary prerequisite for not only removing barriers to research but

also ensuring patient access to diagnostic tests. However, removing patents on genes altogether has

a wider effect on the biotechnology industry in general. According to some commentators, denying

patents on genes “may retard investment in biotechnology.”150 The resultant “collateral damage to

socially valuable patents underlying therapeutics, and possibly also to future diagnostics” makes a

general rule about DNA patentability too sweeping to justify.151 Because patents in biotechnology

may contemplate innovation as a means of taking an invention through to commercialization rather

148 Ibid. See also supra note 8 SACGHS Gene Patents at A-4 (relaying that a 2006 study found that Myriad’s then-version of its testing “missed up to 12% of large genomic deletions or duplications”). 149 Ibid. 150 Supra note 124 at 32. 151 Robert Cook-Deegan, “The Overstated Case” GeneWatch online: http://www.councilforresponsiblegenetics.org/GeneWatch/GeneWatchPage.aspx?pageId=299. But see supra note 90 at 215 (claiming invalidation of patents on genes is an inadequate response because a monopoly on diagnostic tests can still exist “through other patents on platform technologies or methods of use” and arguing for crafting statutory exemptions in response as a more appropriate remedy).

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than as promoting invention itself, patents take an important role in encouraging research.152

Consequently, excluding genes from patenting can result in an underinvestment in the field of

biotechnology because of the inability of investors to recover costs.

As an alternative to denying patents on genes, modifications to the patents granted have

been suggested. Rather than denying patents and removing the incentives for innovation, narrowing

the patents by certain criteria can ensure that not only are inventive activities appropriately rewarded,

but also that future research is not limited. The suggestion to narrow patents is discussed below.

2. Narrow Patents

Narrowing patents by use forms an alternative to denying patents outright in order to

increase patient access and encourage follow-on innovation. Rather than excluding genes from

patentability, this solution envisions narrowing the patent to the purpose claimed. For instance,

although Myriad practiced its patents over BRCA mutations to provide diagnostic services, its broad

composition patents precluded research into therapeutics for breast and ovarian cancer.153

Composition claims cover “all uses of the molecule including uses outside of diagnostics.”154

However, additional avenues of research could be opened for others by circumscribing the claims to

stated diagnostic uses.155

Patents can also be narrowed to gene variants, known as alleles, rather than the entire range

of mutations of a gene. Because each gene has multiple variations, some of which may be harmful

or affect disease expression, patents can be narrowed by limiting application to the individual

mutations. Thus, rather than granting patents to all unknown and potential variations of a gene, the

152 See supra note 8 SACGHS Gene Patents and surrounding discussion. But see also Tiana Leia Russell, “Unlocking the Genome: The Legal Case Against Genetic Diagnostic Patents” (2012) 16 Marq. Intell. Prop. L. Rev. at 111 (arguing that “patent rights appear largely unnecessary in order to encourage clinicians and scientists to develop new diagnostic methods.” Stating further that once new diagnostic tests are discovered, “the investment to commercially develop these discoveries is minimal”) [hereinafter Unlocking the Genome]. 153 Tina Saladino, “Seeing the Forest Through the Trees: Gene Patents & the Reality of the Commons” (2011) 26 Berkeley Tech. L.J. at 323. 154 Supra note 8 SACGHS Gene Patents at 14. 155 Ibid.

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patent can be limited to specific mutations that are actually found. For example, in Myriad’s case,

restricting the patents to the mutations that are known to confer risk would limit Myriad’s monopoly

to those specific mutations.156 As other risk-increasing mutations were discovered, they could be

patented by those who discovered them. This would force a break in the monopoly held by Myriad

because in order to offer a comprehensive and competitive test, these additional mutations would

have to be licensed by the test-provider.157 Failure to test even one gene among many that could

contribute to a disease would mean the test is an incomplete clinical test.158 In the absence of a

monopoly, additional testing services could be created thereby decreasing cost and increasing access

to patients, and follow-on innovation could continue because others would be free to search for

additional mutations. In Myriad’s case, alternative testing would spur competition, improve the

quality of tests, lower the cost of diagnostic testing, and allow confirmatory testing allowing patients

to make better informed decisions regarding medical intervention.159

However, for many, narrowing the patent claimed provides an inadequate solution to the

problem of research barriers and ultimately patient access. For instance, one commentator argues

that limiting the patent to the specific diagnostic use fails to remedy the problem of monopolistic

diagnostic tests.160 Whereas limiting the patent to a therapeutic or diagnostic use would narrow the

scope of the patent to those prescribed areas, it would not prevent the creation of a monopoly

within those domains. Exclusivity in diagnostic testing could still exist, despite the narrowing of the

patent to use.161 However, limiting patents to the disease-causing alleles may address this issue. If

patenting is limited to the gene variants rather than the application of the gene, then a firm’s

156 Supra note 152 Unlocking the Genome (arguing that the broad patents held by Myriad placed it in a position “to assert a monopoly for mutations they [sic] never discovered or had not yet discovered”). 157 Ibid. 158 Supra note 8 SACGHS Gene Patents at 15 (stating that in order for a “diagnostic test to be useful, it must encompass all (or at least most) of those particular genes associated with a disorder”). See infra III.B.2. for discussion on potential anticommons problem. 159 Supra note 39 at 197. 160 Ibid. at 214. 161 Ibid.

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monopoly over the diagnostic test can be broken. Allowing narrower patents on mutations of genes

prevents the creation of a monopoly because the rights over the various mutations are diffused

among different holders. With no single firm dominating the market, some of the impediments to

research and patient access can be removed.

However, this fragmentation of rights may very well be criticized for its potential role in the

creation of an anticommons. The tragedy of the anticommons contemplates a cluster of upstream

patents that serve as inputs for a downstream product.162 Each of these upstream patents must be

negotiated and the transaction costs of each negotiation, even if incremental, can combine to deter

downstream innovation.163 A 2011 Science article provided anecdotal evidence of a start-up company

that faced barriers in offering multiplex testing because many of the genetic conditions it sought to

test were covered by different patent holders.164 The cost of identifying and investigating the

potentially relevant claims alone exceeded the funding the start-up had available; the addition of

subsequent negotiation costs and licensing fees far exceeded what was available to the company.165

Narrowing the scope of the patents and providing multiple patents, then, can increase the

transaction costs a company must sustain in order to provide a comprehensive genetic test. This

increase of costs can contribute to the creation of the anticommons.

Nonetheless, while excessive fragmentation of patent rights can contribute to an

anticommons, it has been noted that the real culprit is not the number of patents issued but how far

upstream the patents can be classified.166 In this instance, these multiple patents are necessary for

the creation of a comprehensive diagnostic test, but also function as independent, though

incomplete, diagnostic tests themselves. Altogether, they function complementarily in the creation

162 Supra note 124 at 699. 163 Ibid. 164 Supra note 144 HGPP at 530. 165 Ibid. 166 Supra note 66 Jurisprudential at 37.

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of a comprehensive test. Relatedly, it has been noted that even narrowing the patent claims “can

only mitigate, not prevent, the problem of excessive rights proliferation.”167 Negotiating with

diverse holders of patents on multiple genes increases transaction costs and exacerbates the problem

of barriers to research and patient access.

Recognizing that both too broad and too narrow protection contribute to creating

impediments for research implicates two influential economic theories. The first view, the

Schumpeterian perspective advocated by Edmund Kitch calls for broader upstream patent rights to

(1) encourage development by rewarding the prospect owner and (2) to allow coordination of

development efforts.168 This view is contrasted with competition literature that favours competition

over monopoly as a means to encourage innovation.169 While both theories seek to advance

innovation, the exact measure at which each succeeds in doing so is debatable.170 In the context of

gene patents, anecdotal evidence indicates that monopolies may lead to inefficiencies and pose

barriers to further research and development. By contrast, more diffused patent holdings can

dismantle monopolies and encourage a competitive marketplace for testing.171 While diagnosis

forms one-half of the clinical picture, with intervention forming the other half, the individual

diagnostic tests, though incomplete, are downstream products. Although a complete diagnostic test

would be more useful, its creation is not far removed from its component diagnostic tests. Because

167 Arti K. Rai, “Fostering Cumulative Innovation in the Biopharmaceutical Industry: The Role of Patents and Antitrust” (2001) Berkley Tech. L. J. Vol. 16 at 842. 168 Ibid. at 819. See also infra note 174 Progress of Science at 1038. 169 Ibid. at 820 (explaining that patent law theorists, Robert Merges and Richard Nelson, have argued that “swift progress in innovation requires competition”). 170 E. Richard Gold and Matthew Herder, “The Role of Biotechnology Intellectual property Rights in the Bioeconomy of 2030” (OECD International Futures Project on “The Bioeconomy to 2030: Designing a Policy Agenda” December 2007) at 4 (explaining that “overly narrow intellectual property rights...lead to underinvestment in research and development as innovators obtain a return that is less than the social value of any invention created. Overly broad intellectual property rights represent, on the other hand, a social cost by diminishing investment in both the use of an invention and improvements and innovative deployments of it. The ideal intellectual property right scope would vary according to the characteristics of the particular invention involved”). 171 Supra note 151 (explaining that “PGxHealth’s monopoly on testing for long-QT syndrome was broken, when GeneDx secured countervailing exclusive rights to long-QT mutations”).

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the individual tests are not far upstream compared to the comprehensive test, the creation of an

anticommons is arguably unlikely to occur in this instance.

C. Ex-Post Measures

The final set of solutions does not attempt to modify or deny the patent grant. Rather, it

seeks to increase access to the genetic diagnostic test for clinical and research purposes after the

patent is issued. These proposed solutions are discussed below.

1. Exemptions

a. Statutory Exemption

An oft-proposed solution to increase access to genetic diagnostic testing is a broadening of

the research use exemption or experimental use exemption. This exemption, conceived in the early

1800s172 exempted from liability “an experiment with a patented article for the sole purpose of

gratifying a philosophical taste, or curiosity, or...mere amusement.”173 Since then, despite the

theoretical recognition of the existence of the exemption as well as increased calls by commentators

to expand its use, it has rarely been successfully invoked in practice.174 This limited exemption exists

in two forms. First, a statutory experimental use exemption exists to exempt pharmaceuticals and

medical devices from liability for the process of data collection during clinical trials for regulatory

review.175 This statutory exemption is limited to test kit developers because test kits and not

laboratory-developed tests, are subject to regulatory review.176 Further, the statutory exemption only

applies during the regulatory review process. Once approved, the use or marketing of the genetic

172 Whittemore v. Cutter, 29 F. Cas. 1120 (D. Mass. 1813). 173 Michael S. Mireles, “An Examination of Patents, Licensing, Research Tools, and the Tragedy of the Anticommons in Biotechnology Innovation” (2004 - 2005) 38 U. Mich. J. L. Reform at 206 [hereinafter Examination of Patents] cf. Poppenhusen v. Falke, 19 F. Cas. 1048 (C.C.S.D.N.Y. 1861). 174 Rebecca S. Eisenberg, “Patents and the Progress of Science: Exclusive Rights and Experimental Use” (1989) 56 U. Chi. L. Rev. at 1023 at 1023 [hereinafter Progress of Science]. 175 35 U.S.C. s.271(e)(1). See also Miri Yoon, “Gene Patenting Debate: The Meaning of Myriad” (2009 - 2010) 9 J. Marshall Rev. Intell. Prop. L. at 971. 176 Supra note 8 SACGHS Gene Patents at 61 (explaining that because the Food and Drug Administration regulates test kits and not laboratory developed tests, the exemption would only apply to test kits).

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diagnostic test incorporating a patented gene “would no longer be exempt from infringement.”177

Consequently, the statutory exemption, as it currently stands, is too narrow an exemption to provide

any relief for those seeking to expand access to genetic diagnostic tests.

Recognizing the limited applicability of the statutory experimental use exemption has led to

calls for the creation of statutory exemptions specific to genetic tests.178 The SACGHS proposed

two such exemptions. First, the SACGHS supported the creation of an “exemption from liability

for infringement of patent claims on genes...for patient-care purposes.”179 Second, the SACGHS

supported the creation of a similar exemption from patent infringement liability for research

purposes.180 Both of these exemptions seek to narrowly apply to gene diagnostics in order to

increase patient access and remove research barriers; neither seeks to apply to gene patents on

therapeutic applications.181 By exempting infringement liability for patient care purposes, this

recommendation seeks to enable multiple test providers thereby increasing patient access to testing

technologies. The exemption envisions improved testing quality and confirmatory testing through

the restoration of free market conditions.182 This recommendation has been criticized on two

contradictory fronts. First, this recommendation can be criticized for its breadth; by removing

infringement liability, the patent is effectively rendered defunct. With no ability to exclude, free

market conditions are completely restored not for a limited set of circumstances, but for the very

purpose the test was created. Using a more technical approach, however, this recommendation has

also been criticized for its insufficiency. Because patents can be asserted on methods as well as

composition, removing infringement liability for composition patents does not remove infringement

liability for method patents. Because this recommendation allows for the assertion of method

177 Ibid. 178 Ibid. at 4. 179 Ibid. 180 Ibid. 181 Ibid. 182 Ibid.

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patents, “the exemption could have little to no practical effect on increasing patient access to genetic

tests.”183 Assuming, however, that overly broad method patents are not granted, this

recommendation has the advantage of removing significant barriers to patient access. It also has the

advantage of limiting its application to patents on genes for diagnostic rather than therapeutic

purposes.

b. Common Law Exemption

Besides the first statutory form, a second common law experimental use exemption also

exists. This form envisions exempting from infringement liability certain experimental uses because

“it could never have been the intention of the legislature to punish a man, who constructed a

[patented] machine merely for philosophical experiments, or for the purpose of ascertaining the

sufficiency of the machine to produce its described effects.”184 The unavailability of this exemption

in pursuit of any commercial purpose, however, has been confirmed throughout case law.185 Thus,

any company developing a multiplex test or alternative test that uses patented genes would be

commercial in nature and would deny the company protection from the experimental use

exemption.186 Further, even academic institutions seeking to offer laboratory tests for clinical care or

experiments may be excluded from the narrow exemption. In Madey v. Duke University,187

commercial purpose was broadly defined to embrace academic research that advanced an academic

institution’s business interests. The business interest held by the academic institution included

“educating and enlightening students and fully participating in...[research] projects.”188 Thus, even if

the purpose of developing a clinically useful diagnostic test is not to directly generate profits but

rather to improve patient care, the creation of a test relates to the overall business motive of a non-

183 Supra note 39 at 216. 184 Supra note 172 at 1121. 185 See Roche Products v. Bolar Pharmaceutical Co., 733 F.2d. at 858 (Fed. Cir. 1984) (describing the experimental use exemption as “truly narrow” and rejecting its application towards any pursuit motivated by a commercial interest). 186 Supra note 8 SACGHS Gene Patents at 60. 187 Madey v. Duke University., 307 F.3d 1351 (Fed. Cir. 2002). 188 Ibid.

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profit university center. Because the business interest of an academic institution is broadly defined,

the development of a genetic diagnostic test by an academic institution would also likely relate to the

legitimate business of an academic medical center and exclude the academic institution from

protection under the exemption.189

Calls for modified exemptions have, thus, developed. Recognizing the difficulty in applying

an experimental use exemption as it exists, one such proposal suggests implementing a statutory

version of the exemption that distinguishes between experimenting “on” an invention and

experimenting “with” an invention.190 With the understanding that the purpose is to increase

research and patient access, the proposal recommends that experimenting on an invention should

not be considered infringing if the experimentation is done to discern, among other things, the

“validity of the patent and scope of afforded protection” or to discover “novel alternatives,

improvements, or substitutes.”191 Although this exemption is not intended to be “unbounded,”192 it

contemplates allowing clinical laboratories to independently verify test results when a sole provider

exists, thus alleviating the problem of confirmatory testing.

However, this solution has been rejected by the subsequently formed SACGHS as a practical

matter.193 The SACGHS report believes there is little incentive and “many disincentives, for a

laboratory to develop and maintain a test simply to provide second opinions or verification

requests.”194 Further, the SACGHS report questions the ability to provide high quality tests given

the potentially low volume of confirmatory testing requests.195 Finally, if implemented as a

189 Supra note 8 SACGHS Gene Patents at 60. 190 Janice M. Mueller, “No Dilettante Affair: Rethinking the Experimental Use Exemption to Patent Infringement for Biomedical Research Tools” (2001) 76 Wash. L. Rev. at 40. See also NIH, “Report of the National Institutes of Health Working Group on Research Tools” (Washington, DC: NIH). See also supra note 69 NRC at 148 (recommending that “Congress should consider exempting research ‘on’ inventions from patent infringement liability”). 191 Supra note 69 NRC at 148. 192 Ibid. NRC. 193 Supra note 8 SACGHS Gene Patents at 48. 194 Ibid. 195 Ibid.

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common-law form, the experimental use exemption is criticized for the uncertainty it creates for the

patent-holder because the “boundaries of the exclusive right would not be known until the

experimental use exception had been litigated.”196 Consequently, this form of an experimental use

exemption is of questionable meaningful value when seeking to bring diagnostic tests to market

while increasing patient access and follow-on innovation.

An alternative to providing confirmatory testing recommends the implementation of a

quality-assessment exemption. This exemption defines quality assessment to include activities

necessary to “identify and analyze limitations, accuracy, validity, and weaknesses of the patented

invention.”197 In limiting itself to quality assessment, the exemption allows confirmatory testing as a

means of assessing the quality of previous tests but prevents free-riding by not including within the

exemption another avenue of primary testing.198 Because the purpose of the exception is to assess

quality and “not to protect experimentation to create an alternative to the patented invention,”

substitutes for the patented invention are not protected.199 Thus, the research into creating the

alternative patented method would be protected, but the alternative method itself would not be

protected.200 This recommendation could be subjected to some of the same criticisms faced by the

previously discussed experimental use exemption. Limiting the exemption available to confirmatory

testing fails to address the larger-scale problem of patient access in general.201 Additionally, although

confirmatory testing is highly important, limiting laboratories to only confirmatory testing results in

a lower-volume of requests and potentially lower quality of testing.202 However, this exemption also

dismantles research obstacles by exempting previously suppressed research into the validity and

196 Supra note 173 Examination of Patents at 215. 197 Supra note 147 at 1342 (advocating for the creation of a quality assessment exemption). 198 Ibid. at 1343. 199 Ibid. at 1345. 200 Ibid. 201 Supra note 8 SACGHS Gene Patents at 48. 202 Ibid.

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usefulness of testing methods.203 The emphasis of this proposal, then, is on the dissemination of

information rather than the creation of alternatives that could supplant the demand for existing

patented technologies.204

2. Compulsory Licensing

a. Modifying the Bayh-Dole Act

An alternative approach to remedying problems of research and patient access is to permit

the creation of compulsory licensing regimes. One form of compulsory licensing is already

embedded within statute. This form of compulsory licensing is found in the Bayh-Dole Act.205

Because the purpose of the Bayh-Dole Act is to promote the dissemination of federally-funded

research and inventions,206 certain march-in rights are built into the Act to fulfill the stated purpose.

The current march-in rights that compel licensing under the Bayh-Dole Act necessarily apply only to

inventions arising from federally funded research and are limited to certain circumstances.207 Two

instances justify the invocation of compulsory licensing. First, a federal agency may practice its

march-in right if it determines the inventor or assignee is not working towards a “practical

application of the subject invention.”208 Second, an agency may also exercise its march-in right in

order to “alleviate public health or safety needs or requirements for public use specified by Federal

203 Supra note 145 at 1301 (asserting that genetic “testing companies have prevented research and analysis related to their patented genes for susceptibility to cancer and heart conditions, although the validity and usefulness of their testing methods has been called into question”). 204 See generally ibid. 205 Bayh-Dole Act of 1980, 35 U.S.C. ss. 200-12 (2006) ("It is the policy and objective of the Congress to use the patent system to promote the utilization of inventions arising from federally supported research or development."). 206 Ibid. By giving a greater role to university technology transfer offices, the Bayh-Dole Act of 1980 has frequently been credited with helping grow the then-nascent biotechnology industry. See also Kenneth Sutherlin Dueker, “Biobusiness on Campus: Commercialization of University-Developed Biomedical Technologies (1997) at 454 (stating that “[i]n 1970, one-eighth of the patents issued to universities were for biomedical inventions; by 1990, the percentage had doubled.”). But see supra note 168 OECD at 8 (arguing “[w]hile Bayh-Dole is often credited with the rise of the biotechnology industry, this is clearly false”). 207 Arti K. Rai and Rebecca S. Eisenberg, “Bayh-Dole Reform and the Progress of Biomedicine” (2003) 66 Law & Contemp. Probs. at 294 [hereinafter Progress]. 208 35 U.S.C. s.203(1)(a), (b).

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regulations.”209 However, the incorporation of technical administrative proceedings coupled with

multiple rights of appeal make impractical the exercise of a compulsory licensing initiative.210

Moreover, the ability to compel licensing is limited to those inventions arising from the use of

federal funds. As a result, this exemption proves too narrow because of its limited applicability to

federally funded inventions and unwieldy because of its technical requirements. Indeed, the

National Institutes of Health (NIH), though possessing this right, has never exercised it.211

Variations of this compulsory licensing regime have been suggested. One suggestion has

been to fine-tune the Bayh-Dole Act in order to more practically allow the statutory march-in right

to be practiced. Currently, once an agency acts, its decision to compel licensing is suspended during

the entire appeals process.212 This lengthy delay renders inoperative the exercise of its right. While

the propriety of the action may ultimately be upheld, it may fail to fulfill its desired function in a

timely manner, particularly when seeking to attain practical application of the invention in order to

“alleviate public health or safety needs.”213 By affording greater discretion to funding agencies,

compulsory licensing can become a viable option to ensure research or patient access to inventions.

Although this solution seeks a small statutory adjustment to provide greater agency discretion in

compelling licensing, its application is limited to inventions arising from federal funds. Because it

fails to address issues of research or patient access in remaining inventions, other forms of

compulsory licensing may be necessary.

b. Reasonable Royalty

Another example of compulsory licensing draws on a variation of the experimental use

exemption. In this case, after finding infringement, a court can decline to provide injunctive relief in

209 35 U.S.C. s. 203(1)(b)-(c). 210 Supra note 207 Progress at 294. 211 Ibid. However, it is also possible that firms act in the shadow this mandate obviating the need to exercise the right. See infra note III.A.4. Practical Existing Mitigating Factors. 212 Ibid. at 311. 213 Ibid.

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favour of awarding a reasonable royalty. In eBay Inc. v MercExchange, L.L.C., the Supreme Court held

a finding of infringement does not necessitate the issuance of a permanent injunction.214 Declining

to provide injunctive relief for infringement effectively provides a compulsory license, the rate of

which is determined through the calculation of damages. The provision of a compulsory license

here is granted after infringement has occurred rather than prior to an infringing activity and is also

determined in courts rather than through an administrative body.

c. Crafting a New Regime

Finally, the creation of new compulsory licensing statutory regimes have also been suggested.

Compulsory licensing has been proposed as a solution in certain industries where multiple patented

inputs are necessary to create an output.215 It is also considered beneficial where patentees fail to

work the technology in a crowded field, where patentees seek royalties after the creation of a

successful product, and where the new innovation requires a license from the patent owner in order

to be an effective development.216 In the case of multiplex testing, this solution could prove useful

to ensure all relevant patented genes are included in order to provide the test with clinical utility. A

compulsory license could be modeled after the laws of other countries. For example, similar to the

type of licenses granted in France and Belgium, a compulsory license over patents claiming

diagnostic methods could be granted.217 In addition, the “European Union...provides for

compulsory licensing of patented inventions under certain circumstances to prevent the abuses that

can result from the exclusive rights granted under a patent.”218 In the case of Myriad, the perceived

abuses emanating from its exclusive practice of its patents have been carefully detailed in literature

and above. As a result, a compulsory license may alleviate the harms caused by removing the

214 eBay Inc. v. MercExchange L.L.C., 547 U.S. 288, 294 (2006). 215 Carol M. Nielsen and Michael R. Samardzija, “Compulsory Patent Licensing: Is it a Viable in the United States?” (2007) 13 Mich. Telecomm. Tech. L. Rev. at 511 (noting the existence of patent thickets in some industries, where “access to hundreds of patents may be necessary in order to product a single commercial product”). 216 Ibid. at 512. 217 Supra note 39 at 219. 218 Supra note 42 Dilemma at 103.

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opportunity to exclusively practice its patents. This can increase patient access as well as remove

barriers to research.

Provision of a compulsory license, however, must occur in a way that leaves intact the

incentives to invent. Although the following list of factors proposed by Nielsen and Samardzija is

targeted for non-practicing entities who seek to obtain a royalty from others who have successfully

commercialized a product embedded within a patent thicket, the list of considerations proves a

useful guideline for compulsory licensing.219 The first factor asks whether the requestor is infringing

or likely to infringe220. This factor is easily met since a license would otherwise be unnecessary. The

second factor inquires whether the patent is part of a patent thicket.221 If considered in the context

of multiplex testing, then a patent thicket exists since multiplex testing requires inputs of multiple

patented genes.222 The third factor asking whether the patentee is working the invention poses a

difficulty.223 While in some instances, a patented gene may not be commercialized for diagnostic

purposes, in many other instances, business models exist surrounding genetic diagnostic testing. For

example, Myriad was actively practicing its patents on the BRCA genes and forcing a compulsory

license to a competitor would remove its monopoly. While this is the effect sought by those

criticizing Myriad, compelling a license from a non-practicing entity is easier to justify than

compelling a license from a company actively pursuing a business model with its patents at the

centre.

The fourth factor requires denial of a compulsory license if the patentee has a legitimate

business reason for not practicing the claimed invention.224 In this instance, Myriad was practicing

its invention, and it is difficult to deny the patent based on those grounds. Additionally, providing

219 Supra note 213 at 536. 220 Ibid. 221 Ibid. at 537. 222 See supra note 9 and surrounding discussion. 223 Ibid. 224 Ibid.

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others with a compulsory license would create competitors for the original patentee who had

invested capital in commercializing the claimed invention. This factor would, however, work for

those entities who patented a gene and failed to bring it to market as a diagnostic test. The fifth

factor examines whether reasonable alternatives are unavailable to the patent sought to be

licensed.225 For patents on genes, it has been established that workarounds are difficult.226 Although

unpatented genes can be used as a substitute in those instances where the patented and unpatented

genes are inherited together, use of a proxy can cause errors leaving some patients undiagnosed.

Because in some instances the clinical utility of the test is undermined, this factor favours the grant

of a compulsory license. The sixth factor casts the compulsory license as a remedy of last resort and

inquires into whether negotiations have broken down.

The seventh factor weighs the public interest against the patentee’s right to not license the

invention. In the instance of Myriad, the public interest served by licensing the invention is well

documented. Licensing the invention more liberally would increase patient access to the diagnostic

genetic tests. Additionally, the test quality could increase along with follow-on innovation that

tested for more mutations that increased risk of disease. The final factor seeks to tailor the terms of

the compulsory license. The guidelines indicate that the compulsory license should be non-

exclusive, non-transferable, and revocable. Additionally, the royalty rate should be set as one that

takes into account that the patent licensed is one of many in the patent thicket. This view mirrors

the one proposed by some companies offering multiplex testing. For instance, Navigenics, a

California based company offering multiplex testing has proposed a model that sets the royalty rate

225 Ibid. 226 See supra note 39 and surrounding discussion.

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for the contribution of the licensed gene relative to the overall value of the service. In addition, it

caps the total royalties so they do not exceed 5% of their sales.227

By contextualizing the patent sought to be licensed as one of many for which licenses are

needed, the royalty rate can be managed. Additionally, by ensuring the license is non-exclusive, non-

transferable, and revocable ensures the license is not encumbered by this particular transaction.

Moreover, setting this type of rate limitations can encourage negotiation for a license that is better

suited for the two parties. For example, if a compulsory license offers a lower royalty rate than one

that could potentially be negotiated, the patentee can be urged to engage in negotiations.

Conversely, if the potential licensee is seeking an exclusive or transferable license, those terms can

be negotiated. The threat of a compulsory license with less than ideal terms alone can encourage

negotiation among the involved parties. Indeed, if the scope of the patent is narrowed, as discussed

above, to patent alleles, then a patent thicket is necessarily created in the context of a multiplex test

or even a single diagnostic test. For that purpose, a compulsory license can serve as a useful tool to

ensure that patents are not so exclusively exercised so to exclude follow-on innovation or the

creation of comprehensive tests.

d. Incentive to Innovate

A criticism of this approach is the failure to recognize that the right to exclude and not

practice the patent is itself a valuable and legitimate action of the patent holder. The question then

arises: when is the right to exclude no longer a legitimate action of the patent holder that requires an

intervention such as the grant of a compulsory license? In eroding the patent holder’s right to

exclude, criticisms arise regarding the effect on the incentive to innovate. This view echoes the

227 Brendan Borrell, “Patent disputes could trip up genome wide scans for disease” (March 2010) Nature Medicine 16:3 at 245.

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earlier sentiment justifying the grant of a patent based on the prospect theory.228 If one subscribes

to the prospect theory for patents, then weakening the right to exclude also lessens the incentives to

invest in the invention. This is because uncertain rights fail to appreciate the importance of the

opportunity of monopoly profits that drive firms to innovate in the first place. Here, ex post returns

correlate with “heightened ex ante incentives to innovate.”229

Innovation forms the key justification for the patent regime. Whereas once the justification

of the patent regime was to create incentives to invent, it has since subtly shifted to incorporate the

creation of incentives to innovate.230 In this regard, the justification for patents has expanded from

one that encourages invention to one that encompasses the larger concept of innovation

conceptualized as commercialization. The desire to promote innovation itself stems from the

understanding that innovation enhances economic competitiveness as well as quality of life, in part,

through better health.231 Innovation fulfills this function by taking to the public inventions that may

otherwise fail to be used, and patents promote innovation by structuring incentives through

exclusivity. Patents form the incentives that drive innovation, and innovation is the vehicle of

distribution, making available to the public otherwise ignored inventions and enhancing

competitiveness as well as quality of life.

Patents, practiced exclusively, perversely withdraw from the public the very inventions

sought to be widely distributed. The failure rests in a seemingly benign business model that seeks to

enforce its legitimate right to exclude others from practicing the impugned invention. However,

rather than making the invention widely available, by enforcing its right to exclude, the invention is

withheld from the public. By doing so, the underlying purpose of innovation is also thwarted. In

228 See supra note 166 and surrounding discussion. See also supra note 215 at 517 (contrasting the prospect theory proposed by Edmund Kitch with competition theory as the basis for creating incentives for innovation). 229 Alan Devlin, “The Misunderstood Function of Disclosure in Patent Law” (2009 - 2010) 23 Harv. J. L. & Tech. at 434. 230 See supra note 10 and surrounding discussion. 231 See supra note 5 FTC 2011 and surrounding discussion.

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the instance of Myriad, the exclusive practice of its BRCA patents denied to the public vital

diagnostic tests. The withholding of such tests failed to serve the underlying health improvement

purpose of innovation. In that regard, while the patent served its purpose in promoting invention

and also served its purpose in encouraging commercialization, the business practice relating to the

commercialization failed to fulfill the underlying basis for the patent grant.

The foregoing analysis reveals the assumption that commercialization is the best means of

distributing inventions to the public. The exercise of Myriad’s patent rights illuminates otherwise.

The issue that arises questions how to reconcile the grant of a patent, a right to exclude, with the

desire to broadly disseminate the invention to the public. Because the business practice has been

identified as barrier to widespread dissemination, the solutions naturally point towards modifying the

business practice. Adjustments to the business practice include creating a regime that encourages or

even compels licensing of the patent in certain narrowly defined circumstances. While eventually

the invention will be naturally made available at the expiration of the patent, the (1) the patent term

is arbitrarily set and does not readily correspond to the industry from which it emanates.232 This

means that the patent expires far beyond the rate of potential and actual biotechnological

innovation; and (2) by the end of the patent term, it is unknown what other improvements will be

made available or even would have been available had less restrictive access to the innovation been

provided.233 Consequently, modifying the business practice to encourage access to the patent for

research and health-care purposes accords with the underlying justification for innovation, and by

extension, patents.

3. Patent Pools/Patent Clearinghouse

232 Supra note 170 (explaining that “[i]n general the intellectual property system still imposes a fairly arbitrary level of protection that does not take into account neither the true social value of inventions nor their costs of development”). 233 Ibid. (noting that “we do not know whether, overall, the current patent system overprotects or underprotects patent holders”).

44

Besides exempting certain research uses or compelling a license, another solution suggested

to deal with barriers to patient and research access is pooling or cross-licensing of patents. Whereas

compulsory licenses have terms decided judicially and exemptions define the contours of the right

granted, patent pools possess the advantage of being voluntarily formed and upon mutually decided

terms. Patent pools are arranged by “two or more patent holders assigning or licensing their

individual IP rights to one another or to an administrative entity specifically created for this

purpose.”234 Cross-licensing is a form of patent pooling that refers to a bilateral exchange of

licenses, and patent pooling envisions multiple parties, the creation of a separate entity, or an

otherwise more complex arrangement.235 The creation of a pool benefits the parties of the pool by

allowing them to exchange licenses of mutually infringing, blocking, or complementary patents.236

By pooling their patents together, the parties can avoid infringement of each other’s patents and

practice without the threat of or actual litigation.237 With the patents no longer being exclusively

enforced, the parties can continue to focus on advancing technology and innovation, an underlying

goal of patent law.238

Patent pools have been suggested in the context of genetic research to aggregate patent

rights that otherwise in a divided form erect barriers to research and innovation.239 Patent pool

arrangements involve making available to those interested, including non-members, non-exclusive

licenses at a pre-determined rate.240 These licenses provide access to overlapping or blocking patents

that can otherwise be asserted to prevent future innovation. Additionally, these pools can serve the

goals of innovation because bundling licenses in a pool can lower transaction costs when compared

234 Rebecca Goulding, et al. “Alternative Intellectual Property for Genomics and the Activity of Technology Transfer Offices: Emerging Directions in Research” (2010) 16 B.U. J. Sci. & Tech. L. at 210. 235 Herbert Hovenkamp, et al., IP and Antitrust: An Analysis of Antitrust Principles Applied to Intellectual Property Law (Austin, TX: Wolters Kluwer Law & Business, 2010) at 34-3. 236 Ibid. 237 Ibid. 238 Ibid. 239 Supra note 215 at 518 and 529. 240 Supra note 234 at 210.

45

to licensing each transaction individually.241 Transaction costs are also lowered because greater

efficiency in purchasing a bundled license reduces the potential for royalty stacking that can arise

when a single product infringing multiple patents owes a royalty to each of the different patent

holders.242 The ability to purchase patents individually as well as in pre-determined packages can

ensure that unnecessary patents are not bundled or tied-in with the essential patents.243 The

flexibility afforded and the reduction in transaction costs removes hurdles in gaining access to

necessary patented products.

In the context of gene patents, pooling arrangements can ensure access to patents necessary

for future innovation. For instance, with the arrival of affordable whole genome sequencing,

multiplex testing offers an advancement over the current state of genetic diagnostic testing.244 By

testing for multiple genetic aberrations at once, this technology offers a lower-cost but higher yield

alternative to current services which have more limited testing capability. This advancement in the

field, however, finds itself encumbered with existing patents over single genes.245 These individually

patented single genes contribute to the development of a “patent thicket” that must be negotiated

before multiplex testing employing those genes can legally proceed.246 A patent thicket can be

attributed to the nature of innovation in fields such as genetics that are characterized by incremental

and rapid improvements.247 While individually, the patents can offer single gene testing, the

transaction costs they impose makes difficult the commercialization of multiplex testing. For

instance, one survey has found that a fourth of diagnostic labs stopped offering a genetic diagnostic

test because of patent concerns while half declined to even the pursue the option because of the

241 Supra note 235 at 34-8 (citing the treatise handling Broadcast Music Inc. v. Columbia Broadcasting Sys., 441 U.S. 1 (1979)). 242 Mark A Lemley & Carl Shapiro, “Patent Holdup and Royalty Stacking” (2006 - 2007) 85 Tex. L. Rev. at 1993. 243 Richard J. Gilbert, “Antitrust for Patent Pools: A Century of Policy Evolution” (2004) Stan. Tech. L. Rev. 3 at para 2. 244 See supra note 144 HGPP at 530. See also supra note 134 and surrounding discussion. 245 See generally supra note 144 HGPP. 246 Ibid. 247 See generally Carl Shapiro, “Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard Setting” in 1 Innovation Policy and the Economy (Adam B. Jaffe, et al. eds., 2001).

46

same worries.248 Although multiplex testing has commercially emerged, its legality in terms of patent

infringement remains unclear.249 For others, the potential infringement constitutes too great a risk

to pursue the commercialization of such testing.250

Patent pools offer a solution to the problem of patent thickets. Pooling arrangements

provide the opportunity for otherwise blocking or complementary patents to be licensed together.

Consolidation of relevant patents signals to innovators the availability of needed patents and a

shrinkage in transaction costs. For multiplex gene test developers, a patent pool means rather than

transacting for gene patents individually, a bulk license can be purchased. This also means that

identification costs for patents can be lowered as well as the possibility of a lower royalty for a

consolidated license rather than an individual license. The possibility of grant-back provisions also

helps make patent pools an attractive option to test developers. Grant-back provisions in a patent

pool require that users of the pool to return to the pool any relevant and essential patents generated

from the use of the patents from the pool.251 This fosters innovation by ensuring that those who

benefit from access to the pool’s technology also contribute to it with future technology.252

Although a pooling arrangement cannot offer a complete removal of transaction barriers, it

does offer a reduction in the challenges faced by multiplex test developers. For instance, unless a

test developer is offering whole genome sequencing, the patents needed for multiplex testing will

still have to be identified. Despite the identification costs that persist in a patent pool for multiplex

genetic diagnostic tests, purchasing the licenses for those patents in a bundle rather than individually

248 Supra note 144 HGPP at 530 (describing a 2003 survey by Mildred Cho of Stanford University and stating “one-quarter of diagnostic labs had already stopped providing a test because of patent worries, and half had scrapped plans to develop one”). 249 Ibid. 250 Supra note 144 HGPP. 251 See supra note 12 FTC DOJ 2007(noting that while grant-back provisions prevent free-riding by requiring sharing of essential technology derived from the pool use, the provisions can paradoxically discourage innovation because of diffused responsibility of innovation throughout the pool. Pools, then, can encourage free-riding for those who understand that essential patents derived from the pool will be returned to the pool and shared). See also Mark A. Lemley & Christopher R. Leslie, “Categorical Analysis in Antitrust Jurisprudence” (2008) 93 Iowa L. Rev. at 1243. 252 Supra note 235.

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can reduce overall transaction costs that would accrue when attempting to negotiate multiple

individual licenses.253 Another disadvantage to a pooling arrangement is that the pool can be

improperly used to shield potentially invalid patents.254 Litigation, though expensive, invalidates

improperly granted patents. Pooling, however, provides an avenue for settlement allowing a small

royalty on patents that would otherwise enter the public domain.255 Although not a pooling

example, the Cohen-Boyer patents highlight a historical instance of where cheap and non-exclusive

licensing discouraged litigation. The Cohen-Boyer patents, addressing a method for combining

DNA from different organisms, were made widely available through nonexclusive and low-cost

licensing. Because the patents were “licensed nonexclusively and cheaply,” firms were encouraged

to “take licenses rather than to challenge the patents.”256 This can be described this as imposing a

“modest tax on product development.”257 Similarly, pooling potentially invalid patents can

discourage litigation, and the cost of licensing the patents can be bundled with the larger patents.

Another issue associated with pooling arrangements for gene patents is the cost of updating

a patent pool comprised of incremental innovations.258 For a gene patent pool to remain relevant,

each of the potentially hundreds of patents on alleles will have to be added to the pool when

discovered. If patents are, however, broadly provided, then the broad patents will have to be added

to the pool, but holders of broad patents have less incentive to participate in a pooling arrangement.

This is because a broad patent holder, such as Myriad, can retain a monopoly by offering the most

complete diagnostic test available on the market. If it contributed its broad patents to a patent pool,

then it might be better positioned to offer a multiplex test testing for multiple disorders, but it would

253 Supra note 235 at 34-8. 254 Joanne Clark, et al., “Patent Pools: A Solution to the Problem of Access in Biotechnology Patents?” (Dec 5, 2000) United States Patent and Trademark Office at 10. 255 Ibid. 256 Supra note 207 Progress at 289. 257 Ibid. 258 Scott Iyama, “The USPTO’s Proposal of a Biological Research Tool Patent Pool Doesn’t Hold Water” (2004-2005) 57 Stan. L. Rev. at 1231.

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also lose its monopoly on testing for a specific disorder. Instead, it would become one of many

competitors offering a multiplex test. This decreases incentives for a broad patent holder to

participate in a patent pool.

Despite the issues surrounding the creation of patent pools for genes, pooling arrangements

maintain innovation incentives. By allowing the purchasing of bulk licenses, transaction costs are

reduced removing one barrier to innovation. Although some potentially invalid patents may be

shielded within the pool, avoiding litigation also reduces costs allowing the focus to remain on

innovation. Moreover, invalid patents can be kept out of the pool through oversight by the

Department of Justice and the Federal Trade Commission in ensuring only essential patents enter

the pool.259 Independent experts also evaluate patents to include those essential to the pool and

value them accordingly.260 Finally, authorizing industry experts to evaluate licenses “more nearly

represent[s] a market valuation than a court or legislative determination.”261 In fact, a gene patent

pool is already under formation by MPEG LA.262 MPEG LA, formed in the 1990s, created a pool

as a solution to accessing patents that enabled the adoption of MPEG-2 digital data compression

technology.263 MPEG LA now proposes the creation of a pool for genetic diagnostic testing to

provide access to a catalogue of patent rights. In particular, the pool recognizes its usefulness in the

case of multiplex genetic testing where multiple patent rights distributed across several owners may

be necessary.264 Because the pool remains in formation, its effectiveness remains to be seen.

Nonetheless, commercial movement towards the creation of a patent pool for genetic diagnostic

testing indicates that a patent pool is a viable solution to the problem of further innovation

necessary for patient access to comprehensive test.

259 Supra note 254. 260 Ibid. 261 Supra note 173 at 222. 262 See MPEGLA, “Public Hearing on Genetic Diagnostic Testing” (February 16, 2012) online: http://www.mpegla.com/main/pid/mds/default.aspx. 263 Ibid. at 2. 264 Ibid. at 4.

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4. Practical Existing Mitigating Factors

Existing evidence does not point to an emergence of an anticommons, nor does evidence

suggest an anticommons does not exist.265 Accordingly, for some, inconclusive evidence justifies

declining intervention until more evidence is gathered266 whereas for others the available anecdotal

evidence is sufficient to justify the creation of policy decisions that must be made in the absence of

complete information.267 The lack of evidence regarding the emergence an anticommons has been

attributed to, in part, the formal and informal policies that have allowed the free flow of research

materials and information.268 Realizing the structure and relationship of the public research system

and patenting has prompted some to caution against the implementation of hastened policy

decisions and instead allow the system to continue untouched until more information is revealed.269

In this regard, the solution is simply to allow the continuation of the current system since inherent

within it are practices that serve to encourage research access.270

Although the majority of patents are held privately, the federal government as an entity is the

holder of the “single largest bloc of patents.”271 Consequently, the federal government uses its

power in the market to encourage the sharing of information and resources developed with federal

265 E Richard Gold, et al., “Gene patents - more evidence needed, but policymakers must act” (April 2007) Nature 25:4 at 388. 266 See generally Chester J. Shiu, “Of Mice and Men: Why an Anticommons Has Not Emerged in the Biotechnology Realm” (2008 - 2009) 17 Tex. Intell. Prop. L. J. 413 (explaining that mitigating practical factors exist that have prevented the emergence of an anticommons and commenting that more data should be collected to help make a more informed decision). 267 Supra note 265 at 388 (observing that although evidence supporting the emergence of an anticommons is lacking, without a comparator model, it is unclear whether innovation has comparatively slowed. Although agreeing that more evidence is needed, the report also recommends formulating a policy based on limited evidence). 268 Supra note 266 at 415. 269 See generally ibid. See also Heather Hamme Ramirez, “Defending the Privatization of Research Tools: An Examination of the ‘Tragedy of the Anticommons’ in Biotechnology Research and Development” (2004) 53 Emory L. J. at 362 (firmly believing the potential for an anticommons is remote and arguing that “exceptions to the patent laws for research tools is unwarranted) [hereinafter Ramirez]. 270 Ibid. See also generally supra note 267 Ramirez (arguing that the potential for an anticommons has been “overstated” since information is freely shared and a tragedy is “unlikely to emerge” ). 271 Ibid. at 428.

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funds.272 This includes the “Best Practices” guidelines disseminated by the National Institutes of

Health (NIH) that for public health-oriented technology seeks to “balance the rewards of broad

intellectual property protection afforded to founders of enabling genomic inventions with the

benefits of fostering opportunities for those striving to improve upon those inventions.”273

Whereas the Bayh-Dole Act has been interpreted to encourage patenting where possible,274 the

guidelines in public health instances, encourage patenting only where further development is needed

to bring the invention to practice.275 This seeks to ensure that important technology is not

encumbered upfront.

The guidelines also seek to encourage transfer of inventions and research by instituting a

policy of broad and nonexclusive licensing where possible.276 This also includes encouraging the

adoption of liberal licensing terms by those not funded by the NIH.277 For example, when certain

universities resisted DuPont’s reach-through provisions of an important research technology, NIH

intervened and threatened to boycott the technology unless DuPont removed the burdensome

licensing terms for all universities.278 The reach-through provisions would have provided DuPont a

claim to technologies derived from use of their patented technology.279 Because NIH funded many

of the would-be purchasers of the technology, their market share ensured DuPont removed the

272 Supra note 234 at 217 (observing that the principles supported by NIH “ensure (1) academic freedom and publication; (2) the appropriate implementation of the Bayh-Dole Act; and (3) dissemination of research resources developed with NIH funds, while minimizing administrative impediments to academic research”). 273 Best Practices for the Licensing of Genomic Inventions: Final Notice, 70 Fed. Reg. 18,413-15 (April 11, 2005) [hereinafter NIH Best Practices]. 274 See generally supra note 65 Technology Transfer (discussing the development of federal policy that reflects an “increasingly confident presumption that patenting discoveries made in the course of government-sponsored research is the most effective way to promote technology transfer and commercial development of those discoveries in the private sector”). See also supra note 207 Progress at 303. 275 Supra note 234 (stating “in considering whether to seek patent protection on genomic inventions, institutional officials should consider whether significant further research and development by the private sector is required to bring the invention to practical and commercial application”). 276 Ibid. 277 Supra note 234. 278 Ibid. at 431. 279 Ibid.

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restrictive licensing term and assured widespread dissemination of the foundational research

technology.

Additionally, informal norms exist that encourage sharing materials freely,280 and the

practical reality limits the amount of barriers that can be imposed on what may be otherwise

unauthorized research. For instance, academic institutions often “retain the right to transfer their

rights to other nonprofits for further research.”281 This indicates that materials are encouraged to be

shared freely. Further, a “de facto fair-use” aspect to patent law stems from the “difficulty of

detecting infringement and the immense cost of prosecuting it once discovered.”282 Not only are

the costs of identification and prosecution of small-scale infringements, such as in academic

experimentation, high, but the rewards from a successful lawsuit against an academic institution are

meager.283 Additionally, a lawsuit against an academic scientist, even if successful, threatens to

undermine valuable industry-academic relationships. Because the biotechnology industry is heavily

dependent on the basic research conducted by academic institutions, lawsuits against academic

institutions can not only stir negative publicity but also interrupt licensing relationships.284

Consequently, an informal regime of selective enforcement against academic researchers exists.285

Because the identification and prosecution costs of infringement are high both socially and

financially, restricting experimentation occurring in these institutions remains a practical difficulty.

Thus, it may be unnecessary to implement further policy changes given that at least academic

research access is rarely hampered.286 This approach is particularly attractive because while academic

280 Supra note 269 Ramirez at 362. 281 Supra note 266 at 429. 282 Supra note 229 at 435. 283 Supra note 266 at 432. 284 Ibid. See also supra note 147 at 1340 (explaining that although the extent of barriers imposed on academic research is debatable, patent holders “often engage in ‘rational forbearance’ from suing academic researchers”). 285 Supra note 207 Progress at 296 (iterating that although selective enforcement against academic researchers exists, “it may be foolhardy for nonprofit researchers to rely on the forbearance of patent holders”). 286 Supra note 147 at 1340 (relaying that one study found “only 1% of academic researchers delayed projects more than one month because of patents, and none had ceased their projects”).

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research can continue unfettered, unauthorized experimentation or use on a larger commercial scale

can still be targeted for enforcement.

Although the above discussion indicates that an anticommons may not yet have emerged to

the extent predicted, relying on informal norms and aspirational guidelines may not be a sufficient

solution to ensure relatively free research access. For example, although the NIH guidelines

encourage nonexclusive licensing agreements, the guidelines are not mandatory, and subsequently,

not enforceable. Additionally, although the NIH possesses discretionary authority to restrict

patenting, this authority is limited to “exceptional circumstances.”287 Thus, the NIH could

theoretically restrict patenting when the goals of the Act were better met by allowing free access.

However, the exercise of NIH’s discretionary authority is subject to an “elaborate administrative

procedure” making difficult the practice of this right.288 Similarly difficult is the exercise of the

NIH’s discretionary march-in rights to compel licensing. The assertion of this right can also be

withheld pending the exhaustion of multiple appeals.289 Finally, the success experienced by the

NIH through its guidelines in ensuring relatively unfettered research access may be due to the

endurance of scientific norms that are subject to change over time.290 Reliance on in impractical

discretionary power and aspirational guidelines that depend on scientific norms may not be an

appropriate tool to ensure access for research purposes. Further, unaddressed remains the issue of

patient access to exclusively practiced genetic diagnostic tests.

IV. TRIPS

Because the U.S. is a signatory to the World Trade Organization’s (WTO’s) Agreement on

Trade-related Aspects of Intellectual Property Rights (TRIPS Agreement), it must ensure any course

of action taken accords with the TRIPS Agreement. Accordingly, the solutions proposed above of

287 Supra note 207 progress at 289. 288 Ibid. at 293. 289 Ibid. at 309. 290 Ibid.

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denying patents, narrowing the scope of patents, and licensing agreements must be evaluated to

ensure that they are TRIPS compliant.

One set of solutions advocates denying patents to genes to increase clinical and research

access to genetic diagnostic tests. The TRIPS Agreement is a multilateral treaty requiring signatory

nations to provide a minimum standard of patent protection.291 Accordingly, the TRIPS Agreement

requires that “patents shall be available...in all fields of technology, provided they are new, involve an

inventive step and are capable of industrial application.”292 This technology neutrality principle

indicates that so long as an invention meets the listed criteria, then discrimination against an

invention based on its field of technology, such as a gene, is prohibited. However, flexibilities within

the TRIPS Agreement permit signatories to exclude from patentability diagnostic methods for the

treatment of humans or animals.293 Additionally, inventions can also be excluded from patentability

in order to protect “human, animal, or plant life or health.”294 Consequently, excluding genes from

patentability is likely TRIPS compatible. This view is advanced by the SACGHS in its 2010

report.295

The second set of solutions advocates narrowing the scope of gene patents in order to

increase access to genetic diagnostic tests. Although the TRIPS Agreement requires patenting

inventions subject to some limitations, it allows member countries to determine what constitutes an

invention.296 For instance, India has adopted rigorous criteria for “inventive step” or “obviousness”,

thus limiting the number of patents or the scope of patents that are granted to certain inventions.297

291 Agreement on Trade-Related Aspects of Intellectual Property Rights, Apr. 15, 1994, Marrakesh Agreement Establishing the World Trade Organization, Annex 1C, 1869 U.N.T.S. 299 art 27 [hereinafter TRIPS Agreement]. 292 Ibid. (the term “inventive step” may be replaced by “non-obvious” and the term “capable of industrial application” may be replaced by the term “useful”). 293 Ibid. art 27.3(a). 294 Ibid. art 27.2. 295 Supra note 8 SACGHS Gene Patents at 85. 296 Ibid. at 86. See also Amy Kapczynski, “Harmonization and its Discontents: A Case Study of TRIPS Implementation in India’s Pharmaceutical Sector” (December 2009) Calif. L. Rev. at 1575 and 1589. 297 Ibid.

54

This indicates that this solution could also be consistent with Canada’s obligations to the TRIPS

Agreement.

The final set of solutions advocates intervening after the grant of a patent to encourage

access to the genetic diagnostic test. In this instance, the Doha Declaration of WTO negotiations

insists that the TRIPS “Agreement can and should be interpreted and implemented in a manner

supportive of WTO members’ right to protect public health.”298 The Doha Declaration indicates

that special consideration be provided to the public health needs of a population.299 Accordingly,

the SACGHS report finds that an experimental use exemption would likely be consistent with a

country’s TRIPS obligations.300 Using this logic, any public health intervention that occurs after a

patent is granted is likely permissible.

V. Conclusion

The exclusive licensing practices of Myriad over its BRCA patents have been strongly

criticized for their failure to provide access to patients in need of genetic diagnostic testing as well as

the barriers imposed by the exclusive licensing practices on research and innovation. This case

scenario has been extrapolated to the negative impact of exclusive licensing in genetic diagnostic

testing in general. Solutions aiming to increase access to tests include denying gene patents

altogether, narrowing the scope of gene patents, or managing the patents once granted. The

interaction of these solutions with the expectations of patent holders must be confronted.

Encouraging economic growth and improving quality of life, in part through better health, forms the

basis of U.S. patent and commercialization policy. These aims are sought to be met through the

provision of strong patent rights that drive economic success and better health. However, potential

298 World Trade Organization, “Declaration on the TRIPS Agreement and public health: (November 14, 2001) online: http://www.wto.org/english/thewto_e/minist_e/min01_e/mindecl_trips_e.htm. 299 Ibid. But see supra note 8 SACGHS Gene Patents at 87 (observing that because the Doha Declaration “has confirmed the special treatment to be accorded to patents involving health care, a neutrality requirement no longer makes sense”). 300 The report also suggests alternative grounds for an experimental use exemption. See supra note 8 SACGHS Gene Patents at 88.

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problems arise with the twin goals of economic success and quality of life sought to be achieved

through strong intellectual property rights.

Economic competitiveness is an imperfect proxy for quality of life measured, in part,

through public health. While innovation has the potential to encourage both, it does not necessarily

do so simultaneously. In some instances, innovation, distinguished from the concept of invention,

can encourage economic success at the expense of public health. This is the situation highlighted by

the Myriad case scenario where a company’s economic welfare took precedence over the health of

the members of the nation. Privatization was seen as an efficient vehicle for delivering innovation,

measured through better health, to the masses. However, appropriation of innovation, the BRCA

gene patents, resulted in an imperfect distribution to the public. The suit against Myriad was

prompted because of exclusionary licensing practices that denied to patients access to the clinical

diagnostic test. Others were denied research access to the diagnostic test resulting in an inhibition

of future improvements to the tests.

In other instances, improving public health takes place at the expense of economic success.

This is the scenario sought to be avoided in the proposed solutions. While public health forms an

important goal of innovation, economic success is another objective. Consequently, elevating the

public health goal above the economic success imperative requires making a policy choice regarding

the purpose of innovation. While innovation possesses the capacity to improve public health, its

economic advancement agenda may be marginalized in the process. Seeking to deliver healthcare to

the masses in pursuit of its public health care objective, Canada essentially ignored Myriad’s BRCA

patents. This prompts the question of how meaningful a right to exclude gene patent holders can

expect to possess if a public health mandate can intrude on that right. Denying gene patents,

narrowing the patent right, or subsequently managing the rights afforded by the patent can interfere

with the innovation agenda. Commercialization or innovation is described as an expensive and

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lengthy process requiring commitment of time and funds. Patents, with their ability to exclude

others, prompt that commitment. Disturbing the government granted right to exclude, then,

interferes with the stated agenda. However, a government granted right to exclude is a distortion of

the free market norm in furtherance of an innovation objective. That innovation objective is further

justified by economic advancement and public health. Tempering the granted right to meet the

underlying policy goals of innovation, then, constitutes an acceptable interference.

A policy that recognizes the sometimes divergent goals of improved health and economic

competitiveness can better address these goals of innovation. However, the Myriad case scenario has

captivated the attention of many because of its particular fact situation that created an environment

of hostility to its business practice arising from the exclusivity provided to it through its patent

rights. Crafting a new patent policy directed towards all patents because of a fact situation that may

not recur seems imprudent. Nonetheless, giving appropriate consideration to the options that are

available now that can be a less intrusive way to manage intellectual property once it is granted.

Post-grant solutions, such as compulsory licensing, patent pools, and exemptions can form an

alternative to denying or narrowing patents that increases patient access and distributes inventions as

envisioned by the role of innovation. While these decisions can be made in courts, voluntary

solutions such as patent pools form the least intrusive alternatives. If narrow patents continue to be

granted, then an incentive exists to coordinate and gain access to complementary patent rights that

can improve what a patent holder possesses. Rather than testing for certain limited disease-causing

mutations of a gene, all known mutations can be tested in a single comprehensive and clinically

useful test. Rather than testing for one disease, multiplex testing for multiple conditions can take

place. Combining these different diagnostic tests while permitting research to advance innovation

promotes the ultimate goal of patents. The proposed solutions contemplating the most limited

intrusion on the rights of the patent holder, such as maintaining the status quo until greater imperative

57

exists to intervene, can ensure that the expectation of a patent holder’s right to exclude is met along

with the expectation of the public to receive that innovation.

58

BIBLIOGRAPHY

Statutes

1. 35 U.S.C. ss.101-103 (2011). 2. 35 U.S.C. s.203(1)(a), (b). 3. 35 U.S.C. s. 203(1)(b)-(c). 4. 35 U.S.C. s.271(e)(1). 5. Patent Act, R.S.C. 1985, c P-4. 6. Article I, Section 8, Clause 8 of the U.S. Constitution. 7. Bayh-Dole Act of 1980, 35 U.S.C. ss. 200-12 (2006).

Treaties and International Documents

8. Agreement on Trade-Related Aspects of Intellectual Property Rights, Apr. 15, 1994,

Marrakesh Agreement Establishing the World Trade Organization, Annex 1C, 1869 U.N.T.S. 299 art 27.

9. E. Richard Gold and Matthew Herder, “The Role of Biotechnology Intellectual

property Rights in the Bioeconomy of 2030” (OECD International Futures Project on “The Bioeconomy to 2030: Designing a Policy Agenda” December 2007).

10. Paris Convention for the Protection of Industrial Property, Mar. 20, 1883, art. 5A. 11. World Trade Organization, “Declaration on the TRIPS Agreement and public health:

(November 14, 2001) online: http://www.wto.org/english/thewto_e/minist_e/min01_e/mindecl_trips_e.htm.

Government and Industry Documents

United States

12. Committee on Intellectual Property Rights in genomic and Protein Research and

Innovation, National Research Council, Reaping the Benefits of Genomic and Proteomic Research: Intellectual Property Rights, Innovation, and Public Health, (Washington, DC: The National Academies Press, 2006) Stephen A. Merrill & Anne-Marie Mazza, eds. online: http://www.nap.edu/catalog/11487.html.

13. Federal Trade Commission, To Promote Innovation: The Proper Balance of Competition Law and

Patent Law and Policy (Washington, DC: FTC, 2003).

59

14. Federal Trade Commission, The Evolving IP Marketplace: Aligning Patent Notice and Remedies with Competition (Washington, DC: FTC, March 2011) online: http://www.ftc.gov/os/2011/03/110307patentreport.pdf.

15. MPEGLA, Public Hearing on Genetic Diagnostic Testing (February 16, 2012) online:

http://www.mpegla.com/main/pid/mds/default.aspx. 16. National Institutes of Health “A Brief History of the Human Genome Project” (2011)

online http://www.genome.gov/12011239. 17. National Institutes of Health, “Best Practices for the Licensing of Genomic Inventions:

Final Notice” (April 11, 2005) 70 Fed. Reg. 18,413-15. 18. National Institutes of Health, “Report of the National Institutes of Health Working

Group on Research Tools” (Washington, DC: NIH). 19. Secretary’s Advisory Committee on Genetics, Health, and Society, Gene Patents and

Licensing Practices and Their Impact on Patient Access to Genetic Tests (April 2010) at 20 online: http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_patents_report_2010.pdf.

20. U.S. Dep’t of Justice & Fed. Trade Comm’n, “Antitrust Enforcement and Intellectual

Property Rights: Promoting Innovation and Competition” (Washington, DC: FTC DOJ, April 2007) online: http://www.justice.gov/atr/public/hearings/ip/222655.pdf.

21. USPTO, Final Guidelines for Determining Utility of Gene-Related Inventions (2001)

http://www.uspto.gov/web/offices/com/sol/notices/utilexmguide.pdf. 22. USPTO “Utility Examination Guidelines” (Jan. 5, 2001) 66 Fed. Reg. 1092.

Canada

23. Canadian Biotechnology Advisory Committee, Biotechnology and the Health of Canadians

(Ottawa: CBAC, December 2004). 24. Canadian Intellectual Property Office (CIPO), Industry Canada, A Guide to Patents

(Gatineau: Canadian Intellectual Property Office, 2011), online: http://www.cipo.ic.gc.ca/eic/site/cipointernet-internetopic.nsf/eng/wr01090.html#sec5.

25. Industry Canada, Innovation Canada: A Call to Action (Ottawa: Industry Canada, October

2011). 26. Industry Canada, Mobilizing Science and Technology to Canada’s Advantage (Ottawa: Industry

Canada, 2007) online: Industry Canada http://www.ic.gc.ca/eic/site/ic1.nsf/eng/h_00231.html.

27. Minister of Finance, House of Commons, Economic Action Plan; Jobs Growth and Economic

Prosperity (Ottawa: Minister of Finance, 2012).

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28. Networks of Centres of Excellence, Networks of Centres of Excellence Canada Annual Report

(Annual Report 2010/2011) online: http://ar-ra.nce-rce.gc.ca/_pdfs/AR_NCE_10-11_eng.pdf.

29. Science-Metrix, Study on the breadth of human gene patents granted by the CIPO, the EPO, and the

USPTO (July 2005) online: http://www.science-metrix.com/pdf/SM_2005_009_IC_Breadth_Human_Gene_Patents.pdf.

Cases and Associated Documents

30. American Civil Liberties Union (ACLU), Legal Challenge to Human Gene Patents (May 2009) online: http://www.aclu.org/files/pdfs/freespeech/brca_qanda.pdf.

31. Ass'n for Molecular Pathology v. USPTO, Case No. 09-CV-4515 (S.D.N.Y. 2010) online:

http://www.pubpat.org/assets/files/brca/brcasjgranted.pdf. 32. Ass'n for Molecular Pathology v. USPTO, 702 F. Supp. 2d 181 (Fed. Cir. 2011) online:

http://www.cafc.uscourts.gov/images/stories/opinions-orders/10-1406.pdf. 33. Ass’n for Molecular Pathology v. Myriad Genetics (2012) No. 11-725.

34. Ass'n for Molecular Pathology v. USPTO, (Fed. Cir. 2012). 35. Broadcast Music Inc. v. Columbia Broadcasting Sys., 441 U.S. 1 (1979).

36. Brenner v Manson, 383 US 519 (1966). 37. Diamond v. Chakrabarty, 447 U.S. 303 (1980). 38. eBay Inc. v. MercExchange L.L.C., 547 U.S. 288, 294 (2006). 39. Funk Bros. Seed Co. v. Kalo Inoculant Col., 333 U.S. 127 (1948) at 130. 40. Graham v. John Deere Co., 383 U.S. 1 (1966). 41. In re Bell, 991 F.2d 781 (Fed. Cir. 1993). 42. In re Deuel, 51 F.3d 1552 (Fed. Cir. 1995).

43. In re Fisher, 421 F 3d 1365 (Fed Cir 2005). 44. In re Kubin, No. 2008-1184 (Fed. Cir. Apr. 3, 2009). 45. KSR International Co. v Teleflex Inc., 550 U.S. 398 (2007). 46. Madey v. Duke University., 307 F.3d 1351 (Fed. Cir. 2002).

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47. Mayo Collaborative Services v Prometheus Laboratories, Inc., No. 10-1150 (U.S. Mar. 20, 2012). 48. Memorandum of Law in Support of Defendant United States Patent and Trademark

Office’s Motion for Judgment on the Pleadings and in Opposition to Plaintiff’s Motion for Summary Judgment at 4. Ass’n for Molecular Pathology v. U.S. Patent & Trademark Office, No. 09 Civ. 4515 (S.D.N.Y. Dec 23, 2009).

49. Merck & Co. v. Olin Mathieson Chemical Corp. 253 F.2d at 164. 50. Parke-Davis & Co. v. H.K. Mulford Co. 189 F. 95 (C.C.S.D.N.Y. 1911). 51. Poppenhusen v. Falke, 19 F. Cas. 1048 (C.C.S.D.N.Y. 1861). 52. Roche Products v. Bolar Pharmaceutical Co., 733 F.2d. at 858 (Fed. Cir. 1984). 53. Whittemore v. Cutter, 29 F. Cas. 1120 (D. Mass. 1813).

Articles Legal and Policy

54. Alan Devlin, “The Misunderstood Function of Disclosure in Patent Law” (2009 - 2010)

23 Harv. J. L. & Tech. 401. 55. Alberts B, Johnson A, Lewis J, et al. “The Structure and Function of DNA “ in Molecular

Biology of the Cell, 4th ed (New York: Garland Science, 2002) online: http://www.ncbi.nlm.nih.gov/books/NBK26821/.

56. Allen K. Yu, “Why it Might be Time to Eliminate Genomic Patents, Together with the

Natural Extracts Doctrine Supporting Such Patents” (2006-2007) 47 IDEA 659. 57. Amy Kapczynski, “Harmonization and its Discontents: A Case Study of TRIPS

Implementation in India’s Pharmaceutical Sector” (December 2009) Calif. L. Rev.1571. 58. Arti K. Rai and Rebecca S. Eisenberg, “Bayh-Dole Reform and the Progress of

Biomedicine” (2003) 66 Law & Contemp. Probs. 289. 59. Arti K. Rai, “Fostering Cumulative Innovation in the Biopharmaceutical Industry: The

Role of Patents and Antitrust” (2001) Berkley Tech. L. J. Vol. 16 at 842. 60. Arti K. Rai, “Intellectual Property Rights in Biotechnology: Addressing New Technology”

(1999) 34 Wake Forest L. Rev. 836. 61. Arti K. Rai, “Patent Validity Across the Executive Branch: Ex Ante Foundations for

Policy Development” (2012) 61 Duke L.J. 1249. 62. Ashley McHugh, “Invalidating Gene Patents: Association for Molecular Pathology v. US

Patent and Trademark Office” (2010 - 2011) 62 Hastings L.J. 197.

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63. Brenda M. Simon, “Patent Cover-Up” (2010-2011) 47 Hous. L. Rev. 1309. 64. Brendan Borrell, “Patent disputes could trip up genome wide scans for disease” (March

2010) Nature Medicine 16:3 245. 65. Bryn Williams-Jones, “History of a Gene Patent: Tracing the Development and

Application of Commercial BRCA Testing” (2002) 10 Health L.J. 131. 66. Carl Shapiro, “Navigating the Patent Thicket: Cross Licenses, Patent Pools, and Standard

Setting” in 1 Innovation Policy and the Economy (Adam B. Jaffe, et al. eds., 2001). 67. Carol M. Nielsen and Michael R. Samardzija, “Compulsory Patent Licensing: Is it a Viable

in the United States?” (2007) 13 Mich. Telecomm. Tech. L. Rev. 511. 68. Chester J. Shiu, “Of Mice and Men: Why an Anticommons Has Not Emerged in the

Biotechnology Realm” (2008 - 2009) 17 Tex. Intell. Prop. L. J. 413. 69. Christopher M. Holman, “Debunking the myth that whole-genome sequencing infringes

thousands of gene patents” (2012) Nature Biotechnology 30:3 240. 70. Eileen Kane, “Splitting the Gene: DNA Patents and the Genetic Code” (2003 - 2004) 71

Tenn. L. Rev. at 738. 71. E Richard Gold, et al., “Gene patents - more evidence needed, but policymakers must

act” (April 2007) Nature 25:4 388. 72. E. Richard Gold and Julia Carbone, “Myriad Genetics: In the eye of the policy storm”

(April 2010) Genetics in Medicine. 12:4. 73. Eric J. Rogers, “Can You Patent Genes? Yes and No” (2011) 93 J. Pat. & Trademark Off.

Soc’y 19. 74. Heather Hamme Ramirez, “Defending the Privatization of Research Tools: An

Examination of the ‘Tragedy of the Anticommons’ in Biotechnology Research and Development” (2004) 53 Emory L. J. 362.

75. Herbert Hovenkamp, et al., IP and Antitrust: An Analysis of Antitrust Principles Applied to

Intellectual Property Law (Austin, TX: Wolters Kluwer Law & Business, 2010) 34-3. 76. Janice M. Mueller, “No Dilettante Affair: Rethinking the Experimental Use Exemption to

Patent Infringement for Biomedical Research Tools” (2001) 76 Wash. L. Rev. 40. 77. Joanna Kwan, “A Nail in the Coffin for Gene Patents” (2010) Berkley Tech. L. J. 9. 78. Joanne Clark, et al., “Patent Pools: A Solution to the Problem of Access in Biotechnology

Patents?” (Dec 5, 2000) United States Patent and Trademark Office at 10.

63

79. Joshua D. Sarnoff, “Patent Eligible Inventions After Bilski: History and Theory” (2012) 63 Hastings L. J. 57.

80. Joshua D. Sarnoff, “Patent Eligible Medical and Biotechnology Inventions After Bilski,

Prometheus, and Myriad” (2011) 19 Tex. Intell. Prop. L. J. 411. 81. Kenneth Sutherlin Dueker, “Biobusiness on Campus: Commercialization of University-

Developed Biomedical Technologies (1997) 454. 82. K. Jensen and F. Murray, “Intellectual property landscape of the human genome” (2005)

Science 310:239. 83. Kristin Wall, “Patently Obvious: Why the District Court’s Ruling in Association for

Molecular Pathology v. USPTO is Incomplete” (2011) 93 J. Pat & Trademark Off. Soc’y 243. 84. Lori Andrews, “The Gene Patent Dilemma: Balancing Commercial Incentives With

Health Needs” (2002) 2 Hous. J. Health L. & Pol’y at 86. 85. Mark A Lemley & Carl Shapiro, “Patent Holdup and Royalty Stacking” (2006 - 2007) 85

Tex. L. Rev. at 1993. 86. Mark A. Lemley & Christopher R. Leslie, “Categorical Analysis in Antitrust

Jurisprudence” (2008) 93 Iowa L. Rev. 1243. 87. Matthew Poulsen, “Jurisprudential and Economic Justifications for Gene Sequence

Patents” (2012) 90 Neb. L. Rev. 210. 88. Michael A. Heller and Rebecca S. Eisenberg, “Can Patents Deter Innovation? The

Anticommons in Biomedical Research” (May 1998) Science 280:698. 89. Michael S. Mireles, “An Examination of Patents, Licensing, Research Tools, and the

Tragedy of the Anticommons in Biotechnology Innovation” (2004 - 2005) 38 U. Mich. J. L. Reform 206.

90. Miri Yoon, “Gene Patenting Debate: The Meaning of Myriad” (2009 - 2010) 9 J. Marshall

Rev. Intell. Prop. L. 971.

91. Peter S. Menell, Intellectual Property: General Theories, in The New Palsgrave Encyclopedia of Law and Economics (1998).

92. Ted Sichelman, “Commercializing Patents” (2009-2010) 62 Stan. L. Rev. 366. 93. R.M. Cook-Deegan, "Origins of the Human Genome Project." Risk: Health, Science and

Environment 5 (Spring 1994) 97-118. 94. Rebecca S. Eisenberg, “Re-examining the Role of Patents in Appropriating the Value of

DNA Sequences” (2000) 49 Emory L.J. 784.

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95. Rebecca S. Eisenberg, “Patents and the Progress of Science: Exclusive Rights and Experimental Use” (1989) 56 U. Chi. L. Rev. at 1023 at 1023.

96. Rebecca S. Eisenberg, “Technology Transfer and the Genome Project: Problems with

Patenting Research Tools” (1994) 5 RISK 163. 97. Rebecca Goulding, et al. “Alternative Intellectual Property for Genomics and the Activity

of Technology Transfer Offices: Emerging Directions in Research” (2010) 16 B.U. J. Sci. & Tech. L. 210.

98. Richard J. Gilbert, “Antitrust for Patent Pools: A Century of Policy Evolution” (2004)

Stan. Tech. L. Rev. 3. 99. Robert Cook-Deegan, “The Overstated Case” GeneWatch online:

http://www.councilforresponsiblegenetics.org/GeneWatch/GeneWatchPage.aspx?pageId=299.

100. R.M. Cook-Deegan, "Origins of the Human Genome Project." Risk: Health, Science and

Environment 5 (Spring 1994): 97-118. 101. Sam Kean “The Human Genome (Patent) Project” (February 4, 2011) Science Vol. 331:

531. 102. Scott Iyama, “The USPTO’s Proposal of a Biological Research Tool Patent Pool Doesn’t

Hold Water” (2004-2005) 57 Stan. L. Rev. 1231.

103. Sean C. Pippen, “Dollars and Lives: Finding Balance in the Patent ‘Gene Utility’ Doctrine” (2006) 12 BU J Sci & Tech L at 212.

104. Tiana Leia Russell, “Unlocking the Genome: The Legal Case Against Genetic Diagnostic

Patents” (2012) 16 Marq. Intell. Prop. L. Rev. 111. 105. Tina Saladino, “Seeing the Forest Through the Trees: Gene Patents & the Reality of the

Commons” (2011) 26 Berkeley Tech. L.J. 301. 106. William Fisher, “Theories of Intellectual Property Law” in Stephen Munzer ed,

(Cambridge University Press, 2001) 169.