Digest Comment: The Future of Gene Patenting after Association for Molecular Pathology v. U.S. Patent and Trademark Office
By Caity Ross - Edited by Abby Lauer
In 2004, Fiona Murray and Kyle Jensen published a prominent article in the journal Science. They reported that the USPTO had issued 4,270 human gene patents for 4,382 distinct human genes. Approximately one-fifth of known human genes were claimed in a U.S. patent.[1] Beyond human genes, there are approximately 20,000 patents covering a wide range of naturally occurring DNA sequences.[2] Gene patents include “[n]ine patents [that] have been applied for on the genes which determine your eyeball, 40 on those for your heart, and no fewer than 152 on a single grain of rice.”
However, scholars and practitioners often question the scope and validity of gene patents on the grounds that genes are so essential to basic research. They claim that it is unethical to grant a private monopoly on genes, which should not be patentable subject matter or controllable by individuals.[3] The USPTO has declined to rule on this issue, treating gene patenting as matter of statutory interpretation.[4] Therefore, attempts to end gene patents generally aim to overturn court precedent or to advocate new legislation.
A recent decision in the ACLU-supported case Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al. will help determine the future of gene patents in the United States. On March 29, 2010, United States District Court Judge Robert W. Sweet granted a summary judgment motion that invalidated patents on two genes. If upheld, this decision essentially eliminates patents covering all naturally occurring genes. For a summation of the opinion, see the Digest's coverage.
Restrictions on Gene Patenting in the United States
Concerns about gene patenting have been voiced for years. In 2007, Congress introduced a bill, the Genomic Research and Accessibility Act (GRAA), that would have radically altered United States patent law, banning patents on the human genome and naturally occurring genes as well as synthetic DNA or RNA molecules.[5] GRAA was largely motivated by a perception that human genes patents threaten to impede biomedical research.[6] In spite of those concerns, GRAA did not garner much support. After its introduction and referral to subcommittees in early 2007 the Act seems to have been abandoned.[7]
Recent NIH-proposed guidelines recommend wide licensing of patented inventions to nonprofit researchers and public health agencies, emphasizing that exclusive licensing agreements have "detrimental short-term and long-term effects on both the quantity and quality of health care."[8] The Secretary’s Advisory Committee on Genetics, Health and Society (SACGHS) for the Department of Health and Human Services (HHS) has produced a report on gene patents.[9] The Committee proposes to exempt healthcare practitioners and researchers from infringement liability for gene patents. The recommendation, in its entirety:[10]
1. Supporting the Creation of Exemptions from Infringement Liability
The Secretary of Health and Human Services should support and work with the Secretary of Commerce to promote the following statutory changes:
A. The creation of an exemption from liability for infringement of patent claims on genes for anyone making, using, ordering, offering for sale, or selling a test developed under the patent for patient care purposes.
B. The creation of an exemption from patent infringement liability for those who use patent-protected genes in the pursuit of research.
With the report facing stiff opposition from the Biotechnology Industry Organization (BIO), legislative action may be a long time coming. Former Indiana Senator Birch Bayh, co-author of the Bayh-Dole Act, appeared in support at the BIO press conference. Bayh maintained that the SACGHS recommendations "would have a disastrous impact on the American economy." Dr. Jim Davis, Executive Vice President, General Counsel and Secretary of Human Genome Sciences, Inc., stated that gene patents are the backbone of biotech innovation. With such vocal dissent it would be disingenuous to suggest that the issue will be resolved legislatively in the near future. It should be no surprise that researchers and opponents have already turned to litigation in an effort to eliminate gene patents.
Does Gene Patenting Prevent Research?
The plaintiffs in the Association for Molecular Pathology case claim that "[a]llowing patents on genetic material imposes real and severe limits on scientific research, learning, and the free flow of information." In its brief, the ACLU argues that "the First Amendment limits the reach of intellectual property laws."[11] This prohibits the researchers from drawing any conclusions on patented BRCA genes, even if they used unpatented methods to study the genes.[12] For example, the ACLU cites Myriad's patent '999, which lays claim to the act of looking at the patented BRCA1 gene. “The claim does not specify or claim any particular method of obtaining or comparing the sequences; it simply covers the act of looking at the two sequences and concluding they are the same or different."[13] Thus, researchers are prevented from conducting even the most basic studies of differences between the normal gene and the cancer-marker.
The precise scope of Myriad’s patents, however, is unclear. A comprehensive search of legal databases conducted in 2007 attempted to identify every lawsuit that has ever been filed alleging infringement of a gene patent.[14] Many of the plaintiffs in the identified cases sued to restrict commercial use rather than to limit the infringer’s research efforts. For instance, Myriad filed suit in the past to enforce its BRCA patents. In a widely publicized case, Myriad sued the University of Pennsylvania for infringing its patents relating to the BRCA breast cancer genes.[15] Although suits filed against universities appear to discourage research, in this case the University was engaged in commercialization of the patented technology.[16] The University conducted BRCA screening for a purported $1900 per test, in direct competition with Myriad. Myriad has been heavily criticized for asserting its patents, but this appears to be the only lawsuit brought by Myriad against a university.[17]
Other examples of litigation include suits brought by patent owners trying to ensure that biomedical research continues without impediment. Specifically, a Ligand Pharmaceuticals Settlement Agreement explicitly granted two non-profit corporations a royalty-free, non-exclusive license for the purposes of basic research. Ligand was only interested in using its patent to block commercial infringement, not research.[18] The parties settled the case, with the defendants agreeing to cease commercial use of the patented technology.[19]
The number of infringement lawsuits being filed by gene patent owners has been declining.[20] However, with increases in personalized medicine, including diagnostic testing, there may be a resurgence of gene patent litigation.[21] Moreover, the number of cases does not accurately quantify the potential suppression of research. In addition to lawsuits, companies can assert patent rights through cease-and-desist letters.[22]
In the original complaint, one of the plaintiff’s major concerns is that Myriad can assert its patent rights at any given moment, so researchers are reluctant to conduct research.[23] The complaint states that there are members of the Association for Molecular Pathology, the American College of Medical Genetics, and the American Society for Clinical Pathology who are “ready, willing, and able to engage in research and clinical practice involving the BRCA1 and BRCA2 genes if the patents are invalidated.”[24] Furthermore, the chilling effect impacts more than direct research on BRCA1 and BRCA2. Since the interaction of genes within the human cell is poorly understood, researchers refrain from studying genes that may interact with the patented genes.[25] Efforts to study how multiple genes can influence diseases are curtailed when some genes must be excluded.[26]
Additionally, gene patents are particularly powerful because they are impossible to design around.[27] Once a gene is patented, all non-licensed research related to that piece of DNA sequence ends.[28] A researcher cannot create an alternative DNA sequence and still obtain meaningful results.
The number of restricted genes continues to increase. Between 1970 and 1979, only 123 DNA-based patents were granted. The number increased to 16,057 between 1990 and 1999. Since 2000, about 3,000 to 4,000 DNA-based patents have been granted each year. In its report, the SACGHS noted that, “the complexity of the patent landscape is worrisome and may become ‘considerably more complex and burdensome over time.’”[29] As more genes are subject to patent protection, research options decrease.
The ACLU asserts that gene patents do not just have the potential to limit research, but that they do in fact limit research. While the number of infringement lawsuits may be declining, there is no evidence that this has encouraged researchers to start studying patented genes.
Case History
On May 12, 2009, the American Civil Liberties Union (ACLU) and the Public Patent Foundation (PUBPAT) filed a lawsuit against the U.S. Patent and Trademark Office (USPTO), Myriad Genetics (Myriad), and the University of Utah Research Foundation (UURF). The suit challenged two patents on the human genes BRCA1 and BRCA2 granted to Myriad and UURF.[30] The complaint charged that the patents covering isolated genes associated with breast and ovarian cancer are unconstitutional and invalid. The plaintiffs argued that patents on genes violate the First Amendment and statutory patent law because genes are "products of nature" and therefore cannot be patented. Because of the complaint’s condemnation of gene patenting in general, the ACLU pointed out that the outcome in this case "could have far reaching effects beyond the patents on the BRCA genes."
Mutations in the BRCA genes cause most cases of hereditary breast and ovarian cancers. Women with a familial history of breast or ovarian cancer are often encouraged to undergo genetic testing for BRCA gene mutations. Myriad’s BRCA1 and BRCA2 gene patents give the company the exclusive right to perform diagnostic tests and to prevent researchers from studying the genes unless they have permission from Myriad. Myriad controls the market, preventing patients from obtaining a second opinion or alternative testing. These specific concerns as well as objections to gene patenting in general are the driving force behind the lawsuit.
The lawsuit was filed on behalf of researchers, cancer survivors, breast cancer and women's health groups, and scientific associations representing 150,000 geneticists, pathologists, and laboratory professionals. The complaint charged that the patents-in-suit stifle diagnostic testing and research. The ACLU claims that genes are products of nature and cannot be patented. The ACLU also argues that patents on genes may hinder innovation because, under current law, Myriad and UURF would have the right to enforce patent protection against researchers studying or using these genes.
If diagnostic testing is conducted exclusively by one lab, that particular lab’s standards govern the entire process. Rather than running the risk of inaccurate diagnostic tests, the European Patent Office revoked the patent entirely.
The ACLU has chosen the judicial system as a viable way to challenge gene patents. When the ACLU filed its Section 1983 action, the complaint demanded that the BRCA gene patents be declared invalid as unpatentable under 35 USC § 101 "because human genes are products of nature, laws of nature and/or natural phenomena.”
To some commentators’ surprise, the lawsuit continued after Judge Robert W. Sweet reviewed the Motion to Dismiss. Specifically, the defendants argued that there is a specialized regulatory system in place to govern patents and to redress violations of the Patent Act. Further, there is no statutory scheme providing a remedy for persons who complain about the constitutionality of patents issued by the USPTO and/or the policies and practices of the USPTO.[31] The defendants contended that there is no standing to sue and challenge the USPTO or the patents it grants since “it is well established that third parties do not have standing to challenge the USPTO’s issuance of a patent.”[32]
Judge Sweet denied the Motion to Dismiss on November 2, 2009. He found that “[t]he novel circumstances presented by this action against the USPTO, the absence of any remedy provided in the Patent Act, and the important constitutional rights the Plaintiffs seek to vindicate establish subject matter jurisdiction over the Plaintiffs’ claim against the USPTO.”[33] The court further ruled that the plaintiffs have standing to sue the Patent Office for "constitutional violations" despite the lack of statutory remedy.[34]
The specific complaints meet the Iqbal requirements[35] by alleging that the BRCA mutations are not inventions but "exist in nature," and that the correlation between the presence of these mutations and an increased risk of cancer are "nothing more than a naturally-occurring phenomenon" and therefore unpatentable.[36]
Both plaintiffs and defendants filed motions requesting summary judgment. Oral arguments were heard on February 2, 2010.
Patentability of Genes
Judge Sweet held that Myriad's patents claiming "isolated DNA" do not qualify as patentable subject matter under 35 USC § 101. This decision is a striking departure from previous patentability standards.
Over two centuries ago, the framers of the U.S. Constitution codified incentives for technological innovation.[37] The inventor must show that the invention satisfies a number of requirements, including utility, novelty, and nonobviousness.[38] Yet there are limits to what subject matter is considered patentable. For example, products of nature are not patentable.[39] One of the arguments brought forth is that genes are a product of nature, and therefore cannot be patented. "Patenting human genes is like patenting E=mc2, blood, or air,” argued ACLU attorney Chris Hansen. Nevertheless, the scope of patentable subject matter encompasses “anything under the sun that is made by man.”[40]
Following criticism that the USPTO was too liberal in approving gene patents,[41] internal review led to the conclusion that the agency was bound by policy and case law to reject arguments that genes were products of nature and thus unpatentable.[42]
Both plaintiffs and defendants recognized that DNA in the body is a product of nature and not patentable.[43] The patents at issue cover naturally occurring genes, but the defendants claim that the isolation of the BRCA genes makes them patentable.[44] “The novel compositions and methods resulted from the identification and isolation of two genes,” rather than from natural DNA. [45]
The case for patenting modified genes is fairly direct. In 1980, Diamond v. Chakrabarty allowed the patenting of a living organism.[46] The Court determined that a living organism could be viewed as a “manufacture, or [a] composition of matter.”[47] Moreover, congressional intent suggested that patentable subject matter should be broadly construed. Therefore, the Court concluded that a genetically modified organism is patentable subject matter as “a product of human ingenuity.”[48] The Court in Chakrabarty found that the patentability of a living organism depended on whether it was modified by a human.[49] Thus genes are patentable as long as they are modified by a researcher.
However, Chakrabarty alone does not justify the patenting of a naturally occurring gene. Chakrabarty explained that a claimed product must have “markedly different characteristics” from the natural phenomenon.[50] The rationale for patenting a gene with its sequence unmodified is based on the 1970 In re Bergstrom decision, in which a purified form of a compound was held patentable even though its impure form was known.[51] A compound merely discovered in nature would not be patentable, but the purified compound is patentable subject matter.[52] Moreover, patentability is not destroyed even if the pure form of the compound has the same function as the natural compound.[53] An isolated and identified gene would thus be patentable without its functional sequence being modified. The conclusion that an isolated and purified gene is patentable was accepted by the Federal Circuit.[54] In granting summary judgment, Judge Sweets disagreed with the USPTO and moved away from Federal Circuit precedent.
Summary Judgment Decision
The decision divided the patent claims into two groups: patents claiming gene sequences that had been isolated from DNA and patents claiming methods for analyzing genes in order to identify breast or ovarian cancer markers. Judge Sweets rejected both under Section 101 of the Patent Act.
Isolated Genes
Judge Sweet held that isolated genes are insufficiently different from naturally occurring DNA and thus are ineligible for patent protection. The court emphasized the separation between patentable subject matter and other sections of the Patent Act.[55] In Chakrabarty, the court specifically stated that “the laws of nature, physical phenomena, and abstract ideas have been held not patentable.”[56]
Myriad asserted that the isolated genes were not simply products of nature, arguing that the genes were “substantially separated from other cellular components which naturally accompany a native human sequence [such as] human genome sequences and proteins.”[57]
The court concluded that “purification of a product of nature, without more, cannot transform it into patentable subject matter. Rather, the purified product must possess ‘markedly different characteristics.’”[58] The question is whether the BRCA genes meet this standard.
In the decision, the court found that Myriad’s isolated genes failed the test and were nothing more than products of nature. Judge Sweet determined that “DNA represents the physical embodiment of biological information;” it does not operate simply as a chemical. Thus, the isolated BRCA genes fail to demonstrate markedly different characteristics from BRCA genes in the human body.
The court’s focus on genes as something more than merely chemicals is a substantial departure from precedent.[59] With this decision, genes now fall outside of the Bergstrom holding. This demolishes the foundation of gene patenting. Any purified or isolated version of a naturally occurring gene would fail the test for patentability.
Methods for Gene Analysis
In the second part of its analysis, the court applied the “machine or transformation” test from the Federal Circuit’s decision in In re Bilski to the method claims. In applying this test, Judge Sweet held that the patent claims were not linked to any machine, nor was there any tangible transformation. Comparisons between DNA sequences were abstract mental processes and, therefore, unpatentable subject matter.[60] In spite of the physical transformations required to isolate DNA, Judge Sweet determined that the claims would “would still fail the ‘machine or transformation’ test” for subject matter patentability under Bilski.[61]
The summary judgment decision invalidated claims for both isolated genes and methods for gene analysis, leaving gene patenting in a very precarious position in the New York District Court.
Implications of the Decision
The immediate effect of the decision should not be overstated. Myriad will certainly appeal the summary judgment to the Federal Circuit. Judge Sweet’s decision will only apply to the patents at issue in the present case and will not be binding on any other court. However, the decision does present an excellent test case for the Federal Circuit and perhaps the Supreme Court to address gene patentability.
Judge Sweet’s ruling has an effect beyond its legal decision. As mentioned above, attempts to restrict gene patenting through the legislature have been unsuccessful. Thus, any court moving on this issue can expect media attention. The simplicity of this fact is evidenced by the articles that shortly followed the summary judgment decision. “Judge Invalidates Human Gene Patent,” “Judge Nullifies Gene Patents,” and “The End of Gene Patenting?” are just a few of the articles and blog postings published in the wake of the decision.
Additionally, the plaintiffs chose an excellent case from a policy perspective. Many women are at risk for breast and ovarian cancer and see genetic testing as one of the few preventative measures available. The plaintiffs are universities, professional organizations and cancer patients who could not afford to pay Myriad’s monopoly price on diagnostics: quintessentially sympathetic figures. The failure of the courts to protect the interests of sympathetic plaintiffs may spur popular support for legislative reform.
This decision may shift the biotechnology industry away from gene isolation. Bryan Roberts, a prominent Silicon Valley venture capitalist, stated that “[t]he government is going to become the funder for content discovery because it’s going to be very hard to justify it outside of academia.” However, the decision could also spur the development of synthetic genes for testing and shift the focus away from naturally occurring genes.
A federal court decision that invalidates specific gene patents on Section 101 grounds calls into question all gene patents. If DNA is a product of nature and an isolated gene does not possess markedly different characteristics, then the isolated gene is not patentable. Even if the Federal Circuit overturns the decision, the outcome of the case has placed gene patents under far more public scrutiny than in the past.
[1] Kyle Jensen & Fiona Murray, Intellectual Property Landscape of the Human Genome, 310 Sci. 239, 239 (2005).
[2] Andrew W. Torrance, After the Gene Rush, BIO-IT World, Nov. 2002, at 80.
[3] USPTO Utility Examination Guidelines, 66 Fed. Reg. 1092, 1093 (Jan. 5, 2001).
[4] See id. at 1093–94.
[5] H.R. 977, 110th Cong. (2007). “Notwithstanding any other provision of law, no patent may be obtained for a nucleotide sequence, or its functions or correlations, or the naturally occurring products it specifies.” Id.
[6] H.R. 977, 110th Cong. (2007); see Christopher M. Holman, The Impact of Human Gene Patents on Innovation and Access: A Survey of Human Gene Patent Litigation, 76 U. Mo.-Kan. City L. Rev. 295 (2007).
[7] Issues regarding the patentability of biological molecules are not mentioned in the latest efforts to reform the Patent Act. S. 515, 111th Cong. (2009); H.R. 1260, 111th Cong. (2009).
[8] David Malakoff, NIH Roils Academe with Advice on Licensing DNA Patents, 303 Science 1757, 1758 (2004) (quoting NIH draft guidelines).
[9] Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests, draft report, available at http://oba.od.nih.gov/oba/SACGHS/SACGHS%20Patents%20Report%20Approved%202-5-20010.pdf.
[10] Id. at 99.
[11] Pls.’ Mem. of Law in Supp. of Mot. for Summ. J. at 32, Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., No. 62 (S.D.N.Y. Jan. 20, 2010) (1:09-cv-04515-RWS).
[12] Id.
[13] Pls.’ Mem. of Law in Supp. of Mot. for Summ. J. at 4, Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., No. 62 (S.D.N.Y. Jan. 20, 2010) (1:09-cv-04515-RWS).
[14] Christopher M. Holman, Learning from Litigation: What Can Lawsuits Teach Us about the Role of Human Gene Patents in Research and Innovation, 18-WTR Kan. J.L. & Pub 215, 217 (2009).
[15] Myriad Genetics, Inc. v. Univ. of Pa., 2:98-cv-0829-S (D. Utah Nov. 19, 1998).
[16] Supra note 22 at 260.
[17] Id.
[18] Ligand Pharms., Inc., Quarterly Report, Settlement Agreement, License and Mutual General Release (Form 10-Q), at B-14 (Mar. 31, 1997).
[19] Id. at B-6.
[20] Supra note 22 at 219.
[21] See id. at 263.
[22] Complaint at ¶ 49, Association for Molecular Pathology, No. 09 Civ. 4515, (S.D.N.Y. Mar. 29, 2010).
[23] Id. at ¶ 97–98.
[24] Compl. supra note 31 at ¶ 7–10.
[25] Id.
[26] Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., No. 09 Civ. 4515, slip op. at 74–75 (S.D.N.Y. Mar. 29, 2010).
[27] Laurie L. Hill, The Race to Patent the Genome: Free Riders, Hold Ups, and the Future of Medical Breakthroughs, 11 Tex. Intell. Prop. L.J. 221, 257 (2003).
[28] See Ying Pan, A Post-KSR Consideration of Gene Patents: The “Obvious To Try” Standard Limits the Patentability of Genes, 11 93 Marq. L. Rev. 285, 295 (2009).
[29] SACGHS supra note 12 at 1 (quoting NRC). (2006). Reaping the Benefits of Genomic and Proteomic Research: Intellectual Property Rights, Innovation, and Public Health. Washington, DC: National Academies Press.
[30] The patents named in the suit include: patent 5,747,282 (the "'282 patent"), 5,837,492 (the "'492 patent"); patent 5,693,473 (the "'473 patent"), patent 5,709,999 (the "'999 patent"), patent 5,710,001 (the "'001 patent"), patent 5,753,441 (the "'441 patent"), patent 6,033,857 (the "'857 patent"). See supra note 21 at 33.
[31] See Block v. Cmty. Nutrition Inst., 467 U.S. 340, 349 (1984)
[32] Mot. to Dismiss, Nov. 02, 2009 at 45.
[33] Id. at 46.
[34] Id. at 46.
[35] Id. at 82.
[36] Supra note 31at ¶ 34, 46, 51, 55–60.
[37] The Constitution gives Congress the power to "promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries." U.S. Const. art. I, 8, cl. 8.
[38] See 35 U.S.C. §100-05 (2000).
[39] Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980) (citing Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948)).
[40] Id. (quoting S. Rep. No. 82-1979, at 5 (1952); H.R. Rep. No. 82-1923, at 6 (1952)).
[41] Jonathan Kahn, What's the Use? Law and Authority in Patenting Human Genetic Material, 14 Stan. L. & Pol'y Rev. 417, 420–21 (2003).
[42] Id. at 439.
[43] John M. Conley & Roberte Makowski, Back to the Future: Rethinking the Product of Nature Doctrine as a Barrier to Biotechnology Patents, Part I, 85 J. Pat. & Trademark Off. Soc'y 301, 305 (2003); Memorandum of Law (1) In Further Support of Plaintiffs’ Motion for Summary Judgment Against All Defendants and (2) In Opposition to The Myriad Defendants’ Motion for Summary Judgment and (3) In Opposition to Defendant United States Patent and Trademark Office’s Motion for Judgment on the Pleadings at 4, Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., No. 219 (S.D.N.Y. Jan. 20, 2010) (1:09-cv-04515-RWS).
[44] Myriad Defs’ Mem. of Law (1) In Supp. of Their Mot. for Summ. J. and (2) In Opp’n to Pls’ Mot. for Summ. J. at 7, Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., No. 153 (S.D.N.Y. Jan. 20, 2010) (1:09-cv-04515-RWS).
[45] Id. at 8.
[46] Supra note 71 at 309.
[47] Id. at 308.
[48] Id. at 309.
[49] Id. at 316–18.
[50] Id. at 309–310.
[51] In re Bergstrom, 427 F.2d 1394, 1401-02 (C.C.P.A. 1970).
[52] Id. at 1401.
[53] Id. at 1402.
[54] See Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed. Cir. 1991) (holding that "[a] gene is a chemical compound, albeit a complex one").
[55] See supra note 35 at 115.
[56] Chakrabarty, 447 U.S. at 309.
[57] Supra note 35 at 92.
[58] Id. at 110–121.
[59] See Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206 (Fed. Cir. 1991) (holding that "[a] gene is a chemical compound, albeit a complex one").
[60] Supra note 35 at 4.
[61] Id. at 147.
Caity Ross is a first-year student at Harvard Law School.