Invoking the First Amendment, a collective of breast cancer and women's health groups, individual breast cancer patients, and scientific associations representing approximately 150,000 researchers this week challenged the legality and validity of Myriad Genetics' patents for BRCA1 and BRCA2 gene mutations.
The lawsuit, filed in the New York Southern District Court by the American Civil Liberties Union and the Public Patent Foundation at Benjamin N. Cardozo School of Law, will take on the US Patent and Trademark Office, Myriad Genetics, and the University of Utah Research Foundation.
In addition to several individual women patients and researchers, plaintiffs in the case include: the Association for Molecular Pathology; the American College of Medical Genetics; the American Society for Clinical Pathology; the College of American Pathologists; Breast Cancer Action; and the Boston Women's Health Book Collective.
According to the ACLU, this is the first time a group has challenged the patentability of genes in the US.
The plaintiffs are challenging the legality and constitutionality of four categories of claims in seven US patents, arguing that gene patents are illegal under patent law because genes are "products of nature." US patent law (35 U.S.C. 101) restricts patenting of "products of nature" and "physical phenomena."
Furthermore, the lawsuit claims that patenting genetic sequences hinders the free flow of information and therefore infringes the First Amendment protecting free speech. "Genes are informational. [By] allowing a company to have a patent on the actual sequence you are restricting the free flow of information," Tania Simoncelli, ACLU's science advisor, told Pharmacogenomics Reporter this week.
Moreover, the ACLU specifically decided to take on the USPTO in this lawsuit, because they believe the US government's issuance of "thousands of patents covering human genes" is illegal. According to ACLU's estimates, as much as 20 percent of all human genes are currently patented, including genes associated with Alzheimer's disease, muscular dystrophy, colon cancer, and asthma.
"What Myriad has patented is the association between mutations [conferring] an increased risk of breast or ovarian cancer," Simoncelli said. In doing so, Myriad has patented "an idea, a scientific fact, or a piece of knowledge," she said. "That's a violation of the First Amendment because [it's as if] the government has issued a patent on thought or knowledge."
Myriad's holds the exclusive rights to perform diagnostic tests on the BRCA1 and BRCA2 genes and the company also holds the rights to future mutations discovered on the BRCA2 gene. University of Utah is either full or partial owner of the BRCA patents at issue in the lawsuit.
According to the lawsuit, Myriad's "monopolistic control" over its BRCA genes hampers clinical diagnosis, serves as a disincentive for research, and allows the company to charge upwards of $3,000 for testing that many women cannot afford. As a result of these practices, "patients whose tests come back with inconclusive results do not have the option to seek additional testing elsewhere," the ACLU charges.
Meanwhile, ongoing research by the HHS Secretary's Advisory Committee on Genetics, Health, and Society and Duke University's Center for Genome Ethics has identified cases where patenting has had a negative impact on research. However, according to a draft report released earlier this year, the HHS committee did not find that gene patenting caused "widespread overpricing" of tests or that it systematically impeded patient access. At the same time, SACGHS found that patenting is not necessary as an incentive for genetic research or test development.
Although this is the first time Myriad's BRCA patents have come under fire in the US, the company's patenting and exclusive licensing practices have been challenged in courts around the world, including Europe, Australia, and Canada.
[ pagebreak ]
The European Patent Office last November ended a eight-year tussle between Myriad and a number of European research groups in deciding to maintain in an amended form Myriad's patent, EP 699754, covering a "method for diagnosing a predisposition for breast and ovarian cancer" [see PGx Reporter 12-03-2008].
In the US, the ACLU sees its lawsuit as not just challenging Myriad's patents but "the whole notion of gene patenting." The suit "could have far reaching effects beyond the patents on the BRCA genes," the ACLU said in a statement.
In a statement to Pharmacogenomics Reporter this week, Myriad said it plans to "vigorously defend" its IP in the US, but noted that it has not yet been served with the lawsuit.
The ACLU's claim that Myriad's BRCA patents are illegal is based on a 1980 US Supreme Court ruling in Diamond v. Chakrabarty that "a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter."
However, since Diamond v. Chakrabarty, companies have been awarded patents on DNA products when they have been isolated, purified, or modified to produce a unique form not found in nature.
The USPTO has determined that nucleic acid molecules are patentable, and has issued patents on whole genes for which the function is known and for DNA fragments. The USPTO has also developed guidelines for patenting DNA fragments of unknown function.
ACLU's lawsuit comes nearly a decade after the first BRCA patents were awarded by the USPTO. Of the patents ACLU is challenging, five were filed in June 1995, and three other patents relevant to the case were filed in 1996, 1997, and 1998.
According to Simoncelli, the ACLU decided to challenge the BRCA patents at this time because recent scientific advancements in gene sequencing have advanced researchers' knowledge of gene associations and have caused a dramatic growth in the number of marketed genetic tests. Thus, it is critical, now more than ever, to ensure that patents do not hinder scientific research and patient access to tests, she noted.
According to Myriad, the fact that the USPTO has granted gene patents following Diamond v. Chakrabarty is a point in its favor.
"The USPTO has granted tens of thousands of genetic and genetic related patents, which cover a large number of life-saving pharmaceutical and diagnostic products," Richard Marsh, Myriad's general counsel, told Pharmacogenomics Reporter. If served, "Myriad strongly believes that its patents are valid and enforceable and will be upheld by the courts."
Lessons From Abroad
The protracted battle between Myriad and European researchers ended last year when the EPO amended a patent covering BRCA1 mutations to specifically cover frame-shift mutations, but not missense mutations. The amended patent does not "contain claims directed to the BRCA1 gene itself or to mutated forms thereof," and cannot be further contested at the European level, according to the EPO.
The amended patent decision was a bittersweet victory for laboratories in Europe, since frame-shift mutations account for approximately 60 percent of pathogenic mutations in the BRCA1 gene.
According to Gert Matthijs, head of the molecular diagnostic laboratory at the University of Leuven Hospital in Belgium, the EPO's decision could make it more difficult for labs to determine when they are infringing Myriad's patents. Matthijs is a member of the European Society of Human Genetics, a group that has encouraged the EPO to limit granting broad patents.
[ pagebreak ]
According to ACLU's Simoncelli, although many of the arguments in the US lawsuit overlap with the case in Europe, there are slightly different issues at stake because European law precludes patent holders from exercising patents when their IP is being used for research.
In comparison, in the US, patent holders have "the exclusive right to prevent anybody from even looking at the gene in research," Simoncelli said. "Most patent holders have been allowing research, but just that fact that they have the right to restrict research we find extremely problematic because it does have a chilling impact on research."
If anything, she said, the fact that Myriad's patent practices for BRCA mutations have been challenged in Europe and around the world shows that the international scientific community supports the notion that "this kind of patent protection goes too far.
"If there is anything to learn, it's that there is a consistency here," Simoncelli said.
Impact of Gene Patenting
Current research on the effect of gene patenting on research and patient access has reached varying conclusions.
Certainly, some researchers who have joined the ACLU lawsuit maintain that BRCA patents have discouraged and even thwarted their research. A survey of owners of genetic testing patents about their licensing activities, by Schissel et al., reported in 1999 that exclusive licenses of patents are in fact permitting the monopolization of clinical testing services.
Facing Our Risk of Cancer Empowered, a group that represents hereditary breast and ovarian cancer patients, noted in a statement that "on a regular basis" the group "receives calls from people who do not have access to genetic testing due to the prohibitive cost of testing." Although FORCE is not a plaintiff in the case, the group supports the ACLU's effort to increase patient access to genetic testing through the lawsuit.
The HHS Secretary's Advisory Committee on Genetics Health and Society is currently considering whether there should be federal efforts to promote broad gene licensing to ensure patient access to tests. "Evolving intellectual property law and practice has both enabled and limited the patenting of matter and methods directly relevant to genetic tests," SACGHS acknowledges in a draft report on gene patenting issued earlier this year.
In order to craft the draft report, SACGHS worked with Duke University's Center for Genome Ethics to review case studies on the effects of gene patenting on patient access to tests, the price of tests, and research innovations.
Although the committee identified several cases where research was adversely impacted as a result of gene patenting, the overall research did not suggest that gene patenting and exclusive licensing caused "widespread overpricing" of tests or that patient access was impeded by such practices.
At the same time, the committee noted that patents may be only a "minor stimulus" incentivizing genetic test development. Unpatented discoveries were "routinely developed into clinical genetic tests," which suggests that "patents are not needed for development of tests," the committee states in the draft report.
[ pagebreak ]
However, with the US Food and Drug Administration seeking to exert regulatory oversight over certain, more complex laboratory-developed tests, companies may need to seek patent protection for genetic discoveries to offset the increasing cost of bringing a test to market.
If regulatory oversight of genetic testing evolves to require "some type of costly independent review before marketing, patent protection may be needed for companies" to feel the risk and expense is worthwhile, according to the committee.
Ultimately, SACGHS suggested that in order to optimize patient access for genetic tests, "stakeholders should work together to develop a code of conduct to encourage broad access to such technologies."
Also, the committee suggested a more open environment with regard to gene patents. The FDA and the Centers for Medicare and Medicaid Services could require genetic testmakers to display on product labels or websites any issued gene patents covering their tests.
SACGHS' public consultation draft report are the committee's preliminary findings. The committee has not yet decided which policy options to support and recommend to the HHS Secretary with regard to gene patenting. SACGHS is accepting public comments on the draft report until May 15.