Petitioners (The Association for Molecular Pathology et al., represented by the American Civil Liberties Union or ”Petitioner” or “ACLU”) filed their brief with the U.S. Supreme Court yesterday urging the Court to reverse the Federal Circuit’s decision and the USPTO’s decades long practice of granting patents on isolated DNA. Similar to their arguments in all prior briefings, the Petitioners argue that the patents issued to Respondent Myriad Genetics, Inc. et al. (“Myriad”) were erroneously issued because they claims products of nature. Petitioner also applied the Supreme Court’s Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S. Ct. 1289 (2012)(“Mayo”). A copy of the brief is attached [MyriadPetitionersMeritsBrief].Continue reading this entry
As reported in my November 30th, 2012 post, the U.S. Supreme Court granted certiorari to review the issue “are human genes patentable?” The issue arises from the long-running dispute among a consortium of plaintiffs, led by the American Civil Liberties Union (collectively “ACLU”) who sued Myriad Genetics, Inc. and the Directors of the University of of Utah Research Foundation (collectively “Myriad”) challenging the patentability of composition and method claims related to human genetics. The Supreme Court’s opinion has the potential to overrule over 30 years USPTO practice that supported the growth of the U.S. biotechnology industry. Continue reading this entry
Patents protect proprietary information but are of limited duration. After expiration, the patented technology becomes part of the public domain. Trade secrets, in contrast, never expire and therefore are not accessible to the public as long as the information remains secret. Thus, the authors of “The Next Controversy in Genetic Testing: Clinical Data as Trade Secrets?“ argue that trade secret protection of genomic data is inappropriate because it impedes the free flow of information that is necessary to advance personalized medicine.
Myriad’s Proprietary Technology – Patents and Trade Secrets
In positioning their argument, the authors take aim at Myriad Genetics (“Myriad”), the provider of BRCA1/2 diagnostic testing. Through its diagnostic services, Myriad has tested nearly one million patients and compiled genetic data from the tests. In most instances, the authors argue, the test results are simple to interpret — whether or not the patient sample contains the wild type or variant version of the gene. In a minority of cases, however, sequence differences from wild type are difficult to interpret. These are variations of unknown significance (termed “VUS”) and are valuable to those tested and to other researchers who are trying to interpret the unknown variations. This information, which Myriad for the most part has chosen to maintain as a trade secret, creates an economic inequality that, the authors argue, was created through its patent monopoly. While Myriad has access to public databases in interpreting mutations, outsiders do not have access to Myriad’s data and analytic algorithm. Thus, the authors argue, Myriad’s proprietary database gives Myriad an indefinite exclusivity independent of patent protection unless and until others can repeat Myriad’s sequencing and analysis of patient samples.
Comprehensive databases of genetic information such as VUS data exist, but Myriad has not consistently contributed to them. The objectives of these databases and research consortia, the authors state, are to accumulate data and to refine interpretive methods in order to create publicly available information for improving clinical interpretation of genetic testing. The authors acknowledge that as public resources accumulate data, the value of proprietary databases will erode. In the meantime, however, health plans will pay for many genetic tests that cannot be accurately interpreted based on publicly available information. Several options for encouraging the sharing of this information are suggested.
One option is that free access be a prerequisite to publication. Those having access to genetic information should be required to share data and algorithms as a prerequisite to publication of that information. However, only those who choose to publish would be required to share the data.
Another option would require that databases that list mutations or availability of genetic tests (e.g., the NIH’s nascent Genetic Testing Registry) mandate that test providers share sequence data and interpretive algorithms as a condition of listing their tests.
Another option would rely on the power of payors and regulators. Health plan payors currently reimburse bundled genetic tests and interpretive services. Payors, it is argued, could demand the evidence underlying the clinical determinations when interpretations cannot be independently verified. Payors could also refuse payment unless clinically relevant data are shared and subject to independent verification.
The authors alternatively suggest that national authorities that regulate genomic tests mandate public disclosures as a condition of pre-market approval. Yet further, national and international institutions could fund research to re-create the data in proprietary databases by ensuring that results of genetic analysis be incorporated into large databases. Finally, national health systems could craft payment policies to create incentives for disclosure of data needed to interpret genetic tests – e.g., establishing payment codes for public deposit and interpretation of genomic data.
Patents, Trade Secrets and Public Benefit
One of the benefits of patents is their limited duration. After the patents expire, the technology is placed into the public domain in a manner that allows the public to reproduce the technology. Those involved in the debate over patenting genes (brought to the fore by the challenge to Myriad’s BRCA gene and testing patents, see for example, my prior post of September 25, 2012) have cautioned that removing the ability to protect intellectual property with patents could result in companies deciding to protect the information by the use of trade secrets, rather than patents. Thus, as noted by the authors, the public ultimately loses as the technologies may never enter the public domain.
While the authors pose some interesting solutions to gain access to Myriad’s technology, they never consider that if Myriad had chosen to patent the technology, the patents would expire and the technology would eventually become publicly available. Indeed, Myriad’s patents on the BRCA1/2 technology will expire in a few years. In addition, most patent applications are published prior to grant, thereby disclosing the technology 18 months after filing.
Myriad’s patents did not give rise to its expansive database, it was access to patient samples and Myriad’s expertise in analyzing that information and creating value from it. It is well documented that patents do not impede genetic research. In a recent letter to the journal Nature Methods, Jim Greenwood of the Biotechnology Industry Organization, reports that the number of reported patent lawsuits involving gene patents is practically nonexistent. “Gene patents do not hinder academic research” Nature Methods, Vol. 9(11), page 1039. He states:
“A 2008 study identified only six instances in which such patents had been briefly asserted against clinical diagnostic testing, and none against basic research. This finding is consistent with earlier reports by the US National Research Council and Walsh et al., [citation omitted] which found little empirical evidence to support the notion that patents created obstacles to biomedical research… Gene patents, like other patents, are critical to the development of basic research inventions into cures and therapies for patients as well as drought- and pest-resistant crops and renewable sources of energy. Encouraging the notion that scientists today routinely incur legal liability whenever they conduct genetic research may inflame public debate over ‘gene patents’ but it has nothing to do with a realistic appraisal of the role of patents in academic research. The likelihood that a researcher will infringe a technology patent by using a smartphone is much higher than the risk of infringing a ‘gene patent’ by doing benchwork.” (Embedded citations omitted)
The increasing importance of genetic markers and diagnostic tests in the drug approval process and the delivery of health care requires consideration of who will underwrite the necessary research and development, Michael Hopkins and Stuart Hogarth argue in the recent issue of Nature Biotechnology. “Biomarker patents for diagnostics: problem or solution?” Nature Biotechnology, Vol. 30(6): 498-500. Consistent with the biomedical model, many innovators have relied on patents and the temporary monopoly patents provide to recoup the cost of innovation, but the appropriateness of this model is being challenged. Whether are not patents covering diagnostic medical tests support or spurn innovation was considered in the U.S. Supreme Court’s Mayo Collaborative Services v. Prometheus, Inc., decision, (see our March 20th post) and is currently under review by the U.S. Patent and Trademark Office (see our January 25th post). The issue also is central to the ACLU’s challenge to the patenting of isolated DNA now before the Federal Circuit in the Association for Molecular Pathology v. Myriad Genetics et al. or the ”gene patenting case” recently sent back to the Federal Circuit for reconsideration in light of the U.S. Supreme Court’s Mayo decision (see our March 26th post.) Patents for this technology are argued to be unnecessary as the cost of providing the tests are low and could prevent clinical scientists in hospital laboratories from developing and offering their services.
A Missed Opportunity
The co-authors suggest that whatever judgments are made against gene patents, the debate thus far has missed an opportunity to consider the wider issue of diagnostic patents and their role in innovation. The conclusions drawn by the co-authors were informed by a seminar convened in London in 2010 by the Human Genetics Commission, whose membership included hospital staff, diagnostic and pharmaceutical firms, research funders, lawyers and ethicists. The co-authors also note that the context of the debate differs between Europe and the United States. However, several important points are raised by the co-authors that are relevant to the ongoing debate in the United States.
For too long, the co-authors note, the gene-patenting debate has been framed by an innovation model that assumes low regulatory barriers to market entry and an easy path to market and clinical adoption. Recent evidence suggests that low-cost and therefore easy market entry is no longer the norm. Test developers are now being asked to provide more evidence, not less, and more quickly, and conventional business models do not support large-scale trials of the utility of new biomarkers. In addition, as noted in our January 24th post, the U.S. Food and Drug Administration will begin regulating laboratory developed tests offered as companion diagnostics.
The SACGHS Report
The Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) for the U.S. Department of Health and Human Services has often been cited by those who oppose the patenting of this technology. The SACGHS committee concluded that the exclusivity provided by patents or licenses had not been necessary to ensure that tests were developed and made available to patients. What is lost in the discussion but noted by Hopkins and Hogarth is that the evidence informing the SACGHS report and conclusion was mainly limited to tests for the diagnosis of rare genetic disorders. Tests related to, for example, infectious agents and drug metabolism were neglected in the SACGHS analysis. The co-authors report that the approach SACGHS took on framing the issues and evidence split their committee, with dissenters writing that the burden of regulatory compliance and the need for clinical utility were pushing up R & D costs for test development. IP was therefore required to incentivize companies to invest in this technology.
Who Will Pay for Personalized Medicine?
The co-authors also argue that extensive evidence is necessary for a biomarker’s acceptance by drug regulators and health care providers. Such evidence includes, for example, that the biomarker accurately and reliably identifies the target population. If the biomarker is tied to a drug under development by a pharmaceutical company, the drug company has the economic incentive to fund the necessary research. IP can serve additional strategic roles – stakeholders such as diagnostic developers, pharmaceutical companies and regulators are increasingly eager to control who provides diagnostic tests in the future, because safe, speedy and effective prescription of drugs will depend on reliable diagnostics. However, if the test is not tied to the company’s drug, incentives to fund the development of the diagnostic are less obvious. Hopkins and Hogarth cite the case of Roche’s AmpliChip CYP450 as an example of a test that has been approved by the FDA but not widely adopted because follow-up studies to establish its clinical utility were not completed. Although Roche shepherded the test through the FDA, it did not invest in the necessary clinical studies demanded for wide-spread adoption of the technology. The co-authors note that Roche holds no patents or exclusive licenses on the genes encoding CYP450 and that therefore any investment it makes in building the clinical evidence would also benefit rival companies who have entered the CYP450 market or are preparing to do so.
No Easy Answers
Hopkins and Hogarth provide no simple solution to the question of what should be done to ensure that well-validated diagnostics are made available to patients. They encourage continued public debate by all stakeholders to address the contentious issues that surround funding of research and development to generate evidence on the safe and effective use of diagnostics with clinical utility. In concluding this informative report, the co-authors argue that one point is clear: supporting innovation in the diagnostics sector while ensuring patient access to valuable new tests will require different strategies for different circumstances. Even previously controversial options, such at patented diagnostics and exclusive licenses that restrict market entrants, may have a part to play.
For those of you closely following Assn. Molec. Path. et al. v. USPTO et al., otherwise known as the Myriad “gene patenting” case, you already know that both sides petitioned the Federal Circuit for a rehearing by the three-judge panel (not en banc), albeit for different reasons. Specifically, on August 25, 2011, on behalf of Plaintiffs/Appellees, the ACLU filed a Petition for Panel Rehearing on the merits, while Myriad/Appellant filed its own Petition for Panel Rehearing on the standing issue four days later. Both parties filed petitions in response to the precedential decision by the Federal Circuit on July 29, 2011. The latest update is that yesterday, September 13, 2011, the Federal Circuit denied ACLU’s petition, although we still await word on Myriad’s petition.
On August 25, 2011, on behalf of Plaintiffs, the ACLU filed a Petition for Panel Rehearing with the Federal Circuit in Assn. Molec. Path. et al. v. USPTO et al., known as the Myriad “gene patenting” case. Four days later, on August 29, 2011, Myriad likewise filed its own Petition for Panel Rehearing. Both parties filed their Petitions in response to a precedential decision by the Federal Circuit a month earlier. In that decision, a three-judge panel held, among other things, that all “isolated DNA” claims at issue are patent-eligible, contrary to Plaintiffs’ position. All three judges wrote detailed opinions, with Judge Lourie writing the majority opinion, Judge Moore concurring-in-part, and Judge Bryson concurring-in-part but dissenting-in-part regarding claims encompassing isolated genomic DNA. For background details of the case, see August 9 post, July 31 post and July 29 post. (Many thanks to Kevin Noonan at Patent Docs for first providing the Petitions.)
ACLU/Plaintiffs Petition for Panel Rehearing
In their recent petition, Plaintiffs ask the same three judges rehear the case again. Notably, they do not ask for a rehearing en banc, which would entail reconsideration by all active Federal Circuit judges.
Subject Matter Patent-Eligibility of Isolated DNA and Diagnostic Methods Addressed Head-on
On Friday, July 29, 2011, in one of the most controversial and publicized biotech patent cases in recent years, the Federal Circuit decided the “ACLU/Myriad” gene patenting case, formally known as Assn. Molec. Path. et al. v. USPTO et al. In a majority opinion by Judge Lourie, the court addressed the case on the merits, after finding that at least one plaintiff had standing to sue. The court held all “isolated DNA” claims at issue patent-eligible, but held as patent-ineligible diagnostic method claims that in effect recited only “comparing” or “analyzing” DNA sequences. While this ruling could ultimately be subject to en banc review before all judges at the Federal Circuit and/or find its way to the Supreme Court, this decision now and its impact will undoubtedly be of great interest to everyone working in the biotechnology and diagnostic medicine fields.