By Kevin E. Noonan --
Two academic amici -- Robert Cook-Deegan (at right), Research Professor and Director, Center for Public Genomics at Duke University, and Christopher Holman, Ph.D. (Molecular Biology) (below left), Associate Professor of Law, University of Missouri – Kansas City School of Law -- filed a brief in the AMP v. USPTO (Myriad) appeal that rebuts many of the distorted (albeit emotionally effective) arguments made by plaintiffs and their supporters (specifically, the ACLU and PubPat) against patent-eligibility for human genes. While disavowing any interest in the brief by either party or any other amicus, they state their purpose in filing the brief as:
Our sole interest in this case is maintenance and development of a sensible patent system that accomplishes the constitutional goal of "promot[ing] the Progress of Science and useful Arts," particularly in the area of genetic diagnostic testing, and more generally in biotechnology and life sciences.
While that certainly may have been their intention, in the execution of the brief, this pair of academics debunks most of the public policy rhetoric advanced by the ACLU and PubPat to support their anti-gene patenting agenda.
They begin their argument by pointing out the risks occasioned by plaintiffs' invocation of the "recently re-invigorated patent eligibility doctrine" that they assert "threatens to wreak substantial collateral damage on future innovation in genetic diagnostic testing, personalized medicine, and biotechnology in general." They concede that "plaintiffs have identified numerous potential concerns with gene patents in the context of some types of genetic diagnostic testing." They then state plainly and forthrightly the fundamental flaw in the argument: that "there is insufficient evidence that harms attributable to patents on genes justify broad, subject matter-based invalidation of all patents made of or based on DNA." Calling patent-ineligibility a "blunt doctrinal instrument," the brief notes that "DNA patents have created incentives critical in attracting the substantial investment necessary to fuel the discovery and development of life-saving products produced by the biotechnology industry," the policy point never acknowledged by plaintiffs or their supporters. There are "other tools more appropriate to the task" of regulating the impact of patenting genes on diagnostics and other areas of genetic medicine, and thus the brief argues the District Court's decision should be reversed.
Amici argue that the problem with plaintiffs' zealous attack on gene patents in response to "what they perceive to be a significant public health concern," however justified by "Myriad's patent enforcement and business practices," is that the strategy, and asked-for remedy would invalidate "a host of patents claiming gene-based inventions, often referred to as 'gene patents' and indeed many other technologies based on making and analyzing DNA." It is the broad scope of this remedy that threatens the "substantial negative implications for future developments in genetics and biotechnology." The brief reminds the Court that it has "substantial discretion under applicable Supreme Court precedent to interpret and implement the patent eligibility doctrine in a manner that fosters innovation," with amici citing the U.S. Patent and Trademark Office's Guidelines for implementing the Supreme Court's decision on patent-eligibility of process claims in Bilski v. Kappos (75 Fed. Reg. 43922) for the principle that "issues of claim validity are better addressed using more targeted and well-established doctrines of patent law" (i.e., "compliance with the requirements of §§ 102, 103, and 112" rather than § 101 "except in the most extreme cases").
The argument is supported by a thorough analysis of the facts relating to the effects, good and bad, of gene patents on biotechnology, genetics, and medicine. The brief notes that gene patents have been granted for more than thirty years and form "the core intellectual property platform for companies dedicated to translating the fruits of biomedical research into life-saving therapeutic and diagnostic agents." This has not been the experience in the European Union, the brief notes, and while different countries in Europe permit varying degrees of scope and enforcement of claims to isolated human DNA, the Biotechnology Directive (1998) requires EPC member states to grant patents on human DNA. This includes claims to the BRCA genes at issue in this lawsuit, which were found valid despite being subjected to opposition proceedings in the European Patent Office. Paradoxically in view of the differing histories of gene patents in Europe and the U.S., many of the claims held valid in Europe would be invalid under the District Court's patent-eligibility requirements.
The brief also addresses the idea that gene patent holders enforce (or threaten to enforce) their patents against medical doctors or clinical labs. Citing Professor Holman's study of gene patent litigation (see "Science Article Should Help Allay Gene Patenting Fears"), the brief states the study's conclusion: that litigation based on gene patents has arisen between innovator biotechnology companies and direct competitors in the marketplace for a biologic drug. In this way, the brief notes, gene patents in biotechnology are akin to drug patents in the pharmaceutical industry. This analogy is supported by reports from the Congressional Office of Technology Assessment (OTA) and the Federal Trade Commission that gene patents "have provided the 'fuel' for the 'R&D engine' bringing biologic drugs to patients." The specific example cited in the brief is erythropoietin, which is protected by Amgen "primarily" using its gene patent protection; these claims are "almost identical to some of the composition of matter claims invalidated" by the District Court (and by implication, Amgen would have been unable to bring EPO to market in the absence of these patents).
The brief cites Heller and Eisenberg's "landmark" paper (Heller & Eisenberg, 1998, "Can Patents Deter Innovation? The Anticommons in Biomedical Research," Science 280: 698-701)) warning of a "tragedy of the anticommons" as being a major source of the fear that gene patents would harm medical research. But as all other honest commentators have acknowledged, study after study has shown that the feared tragedy has not arisen, "at least in noncommercial, academic research." In support of this point, the brief cites Professor Holman's study, as well as papers by Walsh et al., "Effects of Research Tool Patents and Licensing on Biomedical Innovation," in Patents in the Knowledge-Based Economy 285-340 (Wesley M. Cohen & Stephen A. Merrill eds., 2003), and could have cited many more, including Walsh et al., 2003, "Science and the Law: Working Through the Patent Problem," Science 299: 1020); Straus, 2002, Genetic Inventions, Intellectual Property Rights and Licensing Practices); Nicol et al., 2003, Patents and Medical Biotechnology: An Empirical Analysis of Issues Facing the Australian Industry, Centre for Law & Genetics, Occasional Paper 6 and Nagaoka, 2006, "An Empirical Analysis of Patenting and Licensing Practice of Research Tools from Three Perspectives," presented in OECD Conference in Research Use of Patented Inventions, Madrid).
Importantly, the brief also addresses the fear of a "patent thicket" in the "gene chip" industry, exemplified by Affymetrix (one of the few biotechnology companies that opposes gene patenting, at least in part due to the feared negative effect gene patents and their "thickets" could have), as discussed in Barton, "Emerging Patent Issues in Genomic Diagnostics," Nature Biotechnology 24: 939 (2006). These feared outcomes have also not manifested themselves, the brief states, again citing Professor Holman's research showing that "hybridization array technology has never been the subject of a patent infringement lawsuit involving a gene patent" (emphasis in original). The brief argues that this may be a consequence of the low probability that a court would enjoin production of a gene chip "serving an important public health function" and that the royalties available to a gene patent holder having rights to a small number of gene sequences on a chip comprising thousands of sequences would be too "modest" to support litigation. "Most concerns about the negative impact of gene patents are based on an assumption that patents are always enforced, but experience with hybridization arrays illustrates that there are practical constraints on injudicious patent enforcement," amici assert. Unstated is that these assumptions are generally made by individuals with little experience in patent litigation or biotechnology.
Turning to genetic diagnostic testing, the brief cites the SACGHS report ("Revised Draft Report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests") for the "potential for a substantial negative impact of gene patents on genetic diagnostic testing" (emphasis in brief) but ultimately concluding that there was "no conclusive evidence" that gene patents have had the purported "net negative impact on the availability of genetic testing services."
The brief cautions against "conflating" two types of restrictions on access to these tests: restrictions on competition from other commercial diagnostic labs and restrictions on the ability of patients to obtain a particular test on a particular (patented) gene. Myriad is cited as an example of this distinction: while its enforcement policies have prevented competing companies from access to the U.S. market (the first type of restriction), "there is no clear evidence that this has resulted in less patients being tested in the US" (the second type of restriction). The brief cites efforts Myriad has made to facilitate reimbursement by insurance companies as well as "promoting awareness of BRCA testing," and the paradox that the SACGHS study discussed whether BRCA testing was being over utilized. This lack of effect of gene patents on genetic testing access was a general finding:
[O]ne surprising finding from the case studies was that the per-unit price of the full-sequence BRCA test, which often is cited as being priced very high, was actually quite comparable to the price of other full-sequence test done by polymerase chain reaction (PCR), at both nonprofit and for-profit testing laboratories.
In practice, Professor Holman's study found that lawsuits involving genetic diagnostic testing patents have been few and have settled "quickly," and no court has been asked to consider the validity of genetic diagnostic method claims, either for invalidity under the substantive patent law sections or patent-ineligibility until the District Court below. As a consequence, the brief argues, affirming the District Court's basis for invalidating gene patents instead of applying "less sweeping patent challenges" would be "premature."
The brief argues extensively that "other doctrines of patentability and claim interpretation" would be better tools to use in limiting any negative effects of gene patents than patent ineligibility. The brief notes that many of the arguments raised below against the Myriad BRCA gene patents (that their existence was "well-known," that isolation of the genes was "inevitable," that BRCA gene genetic testing would have become available "without Myriad's contribution" and that Myriad was not the first to identify the BRCA gene sequence) are matters of substantive patent law, not patent eligibility. The brief argues that using these statutory patentability standards is advantageous (at least in comparison with patent-eligibility) because they can be used to distinguish what is new and non-obvious (and thus deserving patent protection) from what is not (although this analysis avoids the plaintiffs' principal contention that genes fail the threshold requirement of patent eligibility).
As for the contention that Myriad's claims are overbroad, the brief concedes that some of them may be (Kepler et al., "Metastasizing patent claims on BRCA1"; see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims"), but amici argue that proper claim construction is the appropriate tool for preventing these claims from being successfully asserted against activities outside their proper scope. This also applies to the scope of claims to full-length genes (like the invalidated claims to the BRCA genes here) that are unlikely to be infringed by diagnostic sequencing (citing Cook-Deegan et al., "Impact of gene patents and licensing practices on access to genetic testing for inherited susceptibility to cancer: comparing breast and ovarian cancers with colon cancers," Genetics In Medicine 12: S15-S38 (2010)). The brief also cites successful instances of "designing around" gene patents for biologic drugs (Genzyme Corp. v. Transkaryotic Therapies, Inc., 346 F.3d 1094 (Fed. Cir. 2003), Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), Novo Nordisk of North America, Inc. v. Genentech, Inc., 77 F.3d 1364 (Fed. Cir. 1996), Biogen, Inc. v. Berlex Laboratories, Inc., 318 F.3d 1132 (Fed. Cir. 2003), Schering Corp. v. Amgen Inc., 222 F.3d 1347 (Fed. Cir. 2000)) in support of its argument that a finding of patent-ineligibility is not necessary to avoid any disadvantages or threats to innovation produced by gene patents, and cites Regents of University of California v. DakoCytomation (517 F.3d 1364 (Fed. Cir. 2008)) as an example of BRCA testing that could be practiced using reagents (peptide nucleic acids) that would not infringe Myriad's claims. Even the much-argued term "isolated" may not be enough to confer broad scope on gene patent claims to "isolated" nucleic acids, amici argue, since such claims have never been litigated and may well receive a narrower interpretation than commonly imagined (since the more broadly the term is asserted the more vulnerable it becomes to validity challenges).
In sum, "[p]roperly drafted and interpreted, gene patent claims should not have the broad inhibitory effect on access and innovation asserted by the critics. The remedy to unduly broad scope is invalidation based on insufficient enablement or inadequate written description, not a blanket prohibition on the patenting of anything made of or based on DNA."
Finally, the brief argues that insofar as the "current anxiety surrounding gene patents in general, and Myriad's patents in particular, centers around their potential negative impact on genetic diagnostic testing and research," and this anxiety is a consequence of Myriad's business practices (insofar as they may be), there are more appropriate remedies directed specifically at these practices that are better suited to the task than a broad gene patenting ban. One of these is a limitation on infringement liability for individuals using patented genetic technologies for research or genetic testing uses (as suggested by the SACGHS report). The brief also cites the never-enacted Genomic Research and Diagnostic Accessibility Act of 2002, H.R. 3967, 107th Cong. (2002) that would have eliminated liability for such activities, analogous to current patent law provisions (35 U.S.C. § 287(c)) that preclude liability for the practice of patented surgical procedures and other "medical activities." Other possibilities include compulsory licensing, use of "march-in" rights under the Bayh-Dole Act, and practice by state-affiliated institutions protected by sovereign immunity (although the brief characterizes them as "extreme" and "not [apparently] justified at the present time"). Citing restrictions on Myriad's business and enforcement policies abroad, the brief state that a more appropriate remedy may be "awakening US agencies and institutions from their stupor rather than foregoing the patent incentive for all inventions based on DNA."
The brief concludes with a discussion of the potential "unintended consequences" of a broad gene patenting ban on such areas as pharmacogenomics and personalized medicine, calling gene patents "critical to securing the funding necessary to bring these products to market" based on amicus briefs filed in the District Court by BayBio, Genetic Alliance, and the Biotechnology Industry Organization. Also potentially at risk are biologic drugs, the brief argues, in view of the historic role of gene patents in "providing market exclusivity for biologic innovators in the past." The brief also makes the distinction between diagnostic testing based on the BRCA gene patents and other single-gene based tests, and the "next generation of genetic testing technologies" that are likely to involve "a large number of genes" with "more complex patterns of genetic variation" as has been discussed elsewhere (see "Like Peas in a Pod"). Finally, the brief suggests that greater regulation by the FDA could minimize the "harm" caused by gene patents. Any of these alternatives would be preferable to the de facto gene-patenting ban created by the District Court's decision.
For additional information regarding this and other related topics, please see:
• "Amicus Briefs in AMP v. USPTO: Genetic Alliance," November 10, 2010
• "BIO and AUTM File Joint Amicus Brief in AMP v. USPTO," November 9, 2010
• "AIPLA Submits Amicus Brief in AMP v. USPTO," October 3, 2010
• "IPO Files Amicus Brief in AMP v. USPTO," November 2, 2010
• "AMP v. USPTO -- Briefing Update," November 1, 2010
• "DOJ Tries to Be All Things to All Constituencies in Myriad Amicus Brief," October 31, 2010
• "Myriad Files Appeal Brief in AMP v. USPTO," October 28, 2010