The transcript for today’s Supreme Court oral argument in The Association for Molecular Pathology v. Myriad Genetics, Inc., No. 12-398 (2013) has been released, and the importance of the gene patenting debate to personalized medicine was discussed. The Court was well briefed on the issues and questioned the parties and U.S. government regarding why isolated genes should or should not be patent-eligible, the distinctions between DNA probes or primers and claims to full length sequences (isolated genomic DNA and cDNA) and the difficulty in crafting a test that would exclude broadly claimed inventions under Section 101 of the patent act rather than limiting broadly claimed inventions as failing under Section 102 (novelty) and/or Section 103 (obviousness). Continue reading this entry
As reported in my January 24th, 2013 post, the Office for Civil Rights of the U.S. Department of Health and Human Services (HHS) issued an omnibus final rule (the Rule) implementing changes in current regulations under the Health Insurance Portability and Accountability Act of 1996 (HIPAA), pursuant to the Health Information Technology for Economic and Clinical Health Act (HITECH Act). In addition to finalizing proposed regulations set forth in a proposed rule dated July 14, 2010, it also addressed other HIPAA provisions. It also finalized a proposed rule issued in 2009 that implements the HIPAA-related genetic privacy provisions of the Genetic Information Nondiscrimination Act (GINA). Continue reading this entry
The application of medical technology in the pediatric setting must serve the best interest of the child. Genetic testing of children and infants presents unique challenges. In contrast to the testing of adult patients, most children cannot understand the risks and benefits or provide informed consent. The American Academy of Pediatrics (AAP) and the American College of Medical Genetics and Genomics (ACMG) recently issued recommendations regarding genetic testing or screening of infants and children. In Ethical and Policy Issues in Genetic Testing and Screening of Children (“Report”), the AAP and ACMG review the scenarios in which genetic testing or screening of minors may occur and recommend best practices for such testing.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)
On July 20th, 2012, the parties in the Ass’n for Molecular Pathology v. Myriad Genetics, Inc., No. 10-1406 (Fed. Cir. 2011)(also known as the “ACLU gene patenting” case) argued (again) before the Federal Circuit. Recall, the U.S. Supreme Court had asked the court to reconsider its prior ruling as to the patent-eligibility of claims to isolated DNA, in light of its unanimous decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (S. Ct. 2012) (“Mayo”). In Mayo, the U.S. Supreme Court held that that certain diagnostic inventions cannot be patented under 35 USC Secion 101 because they effectively claim a law of nature.Continue reading this entry
The U.S. Patent Office recently announced that it will not be delivering its report on Genetic Testing as required under Section 27 of the America Invents Act (“AIA”) by the June 16, 2012 deadline.Continue reading this entry
A multiplex test that can analyze tumors for over 200 genes is now available from Foundation Medicine Inc., the Wall Street Journal reported today. The test will be used by Novartis, Sanofi SA, Johnson & Johnson and Celgene to analyze patients in early-stage clinical trials of new cancer drugs to identify patients most likely to benefit from the drug and to accelerate the drug approval process. Continue reading this entry
The Canadian Patent Office released today practice guidelines regarding the patent-eligibility of medical diagnostic methods and medical methods. The practice guidance are in effect immediately and until further notice, and in place of any contrary guidance presently in the Canadian Manual of Patent Office Practice (MOPOP, the Canadian equivalent to the US MPEP, setting forth examination criteria for patent applications).
The guidance document indicates that many diagnostic methods can be thought of as comprising two distinct aspects: data acquisition steps and data analysis steps. A claim often contains one or more data acquisition steps, such as a step for determining, measuring, identifying, assaying, etc. which may be implicit or explicit. Diagnostic methods are patentable before the Canadian Patent Office if the claim describing the method satisfies all the requirements of patentability, i.e., novelty, inventive, useful, sufficiently disclosed and unambiguously defined and contains an inventive concept that is statutory.
In order to be patentable, the inventive concept of the diagnostic method claim must provide a solution to a technical problem and either have physical existence or manifest a discernible effect or change. If the claim includes at least on step of physically acquiring data from an analyte (such as a substrate, marker, tissue, body, for example) then the inventive concept is statutory. However, where a known analyte had been previously assessed using the same or similar technique to those in the claim, the inventive concept may therefore be limited to the significance, understanding or interpretation of the acquired data. In these situations, the claim is not statutory because the inventive concept is limited ot the interpretation of the acquired data.
The guidance also emphasizes that medical methods are not statutory in Canada, while medical use claims are permitted, as long as do not equate to medical or surgical methods and they satisfy all other requirements of patentability.
For patent-eligibilty, the inventive concept of a medical use claim must provide a solution to a technical problem and have either physical evidence or manifest a discernible effect or change. If a claim to a medical use includes a dosage regime or range for the purpose of defining patentability, the inventive concept does not need to include that dosage regime or range if the use itself meets all the requirements for patentability. In contrast, if the inventive concept requires a dosage regime or range, then the inventive concept is considered to be a methods of medical treatment, and therefore not patent-eligibility.
Similarly, where the inventive concept necessary to support patentability only serves to instruct a medical professional “how” or “when” to treat a patient, rather than “what” to use, this may not be patent-eligible as the claim would encompass a method of medical treatment.
Prometheus’ Claims in Canada
As those in the medical industry reconsider US patent strategies in light of Prometheus and the expected US PTO guidance for examiners for medical diagnostic methods, (see our posts of March 20, 2012 and March 25, 2012), the patenting of similar technologies in other jurisdications is of concern as global patenting strategies adopt to the uncertainty of the application of Prometheus by the US PTO.
Canada’s recent guidance appears to follow the US Supreme Court holding that such claims are not patent-eligible for failing to claim a patent-eligible method.
The “determining” step of the Prometheus claims was stated by the US Supreme Court to add nothing of signficance to the art, and merely told doctors to engage in well-understood, routine, conventional activity previously engaged in by scientists who work in the field. In interpretating the “determining” element under the Canadian guidelines, the inventive concept would be limited to significance, understanding or understanding of the acquired data (as stated by the “wherein” clause of the claim) because the element was previously assessed using the same or equivalent analytical techniques known in the art.
The “wherein” clause would also fail to rescue the claim under the Canadian guidelines as it could be argued to be an expression of the understanding of the discovery of the significance of the acquired data.
Finally, the “administering” step also was admitted to be known to those in the art and could be precluded from the claim in Canada as being directed to claiming a method of medical treatment.
However, if a diagnostic method is tied to the use of a therapeutic and that use would meets all the other requirements of patentability then the claim is more likely to possess the requisite inventive concept. In addition, if the “determining” step of the claim utilizes analytical techniques unknown to the skilled artisan, the claim is more likely patent-eligible.
A copy of the practice guidelines is available here.
The other day I had the opportunity to speak with Colin O’Keefe of LXBN TV on the subject of Mayo Collaborative Services v. Prometheus Laboratories, Inc. In the short interview, I explain the background of the case, offer my thoughts on why Prometheus’ patent wouldn’t have a detrimental impact on medical research and give my thoughts on what this means for the Myriad “gene patenting” case.
On November 24, 2009, President Obama established the Presidential Commission for the Study of Bioethical Issues (Commission) to advise him on bioethical issues generated by novel and emerging research in biomedical and related areas of science and technology. As part of this initiative, the Commission issued a Notice on March 27, 2012 (Federal Register) seeking comments on the ethical issues raised by the ready availability of large-scale human genome sequencing data.
Privacy And Access
Tremendous technological advances have reduced the cost of sequencing to the point where relatively inexpensive, rapid sequencing of whole genomes is not only likely but imminent. The emergence of this new technology raises, for the Commission, issues how this information can and ought to be collected, used, and governed. Of particular initial interest are issues relating to the privacy of and access to this information by patients, researchers, and medical professionals.
The Commission is particularly interested in comments informing policies, practices, research, and perspective on issues of privacy and data access as they relate to the integration of large scale human genome sequencing into research and clinical care. Of additional interest are models and mechanisms for protecting privacy in both genetic/genomic databases of sensitive information and the sharing and management of information and access to large-scale human genomic data.
To Submit Comments
Individuals, groups, and organizations interested in commenting may submit comments by email to firstname.lastname@example.org or by mail to the following address:
Public Commentary, The Presidential Commission for the Study of Bioethical Issues, 1425 New York Ave. NW., Suite C-100, Washington, DC 20005.
To assure consideration, comments must be received by May 25, 2012.
For additional insight into the Commission’s thinking on the issues concerning genetic testing, see the Commission’s blog.
The Guardian reports that Mayo Clinic (“Mayo”) has announced that it is starting a pilot study to provide whole genome sequencing to patients. As reported, Mayo will launch the pilot study in early 2012 as part of an ambitious move towards an era of proactive genomics. Recall, Mayo Clinic is a named party in the legal challenge to Prometheus Laboratories’ patents on medical diagnostic methods. This challenge is currently awaiting resolution by the U.S. Supreme Court (see our December 7th post).
The Personalized Medicine Coalition recently published the third edition of its state of the industry report, The Case for Personalized Medicine (“Report”). While the Coalition acknowledges greater adoption of the principles of personalized medicine by the health care industry and the public; technical, legal, regulatory and payor issues are highlighted for improvement to recognize the industry’s full potential and benefits. This post summarizes the Coalition’s view of the state of the industry and the issues identified as critical to the ongoing development and adoption of personalized medicine.
As most in the patent community know, last Friday, September 16, 2011, President Obama signed into law the long-awaited patent reform bill, known as the Leahy-Smith America Invents Act (“AIA”). There are many moving parts to this complicated piece of legislation—many consider it to implement the most sweeping changes to U.S. patent law since enactment of the 1952 Patent Act.
An international intellectual property association filed an amicus curie brief urging the U.S Supreme Court to dismiss the dispute and issue presented in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 131 S.Ct. 3027 (2011), arguing that the district court and Federal Circuit lacked subject matter jurisdiction. The amici argued that for reasons that are not clear, the district court and the Federal Circuit unapplied, misapplied, or simply overlooked Congress’ legislative efforts to achieve a globally-desired limitation of exclusive patent rights.
Yesterday, September 8, 2011, the Senate passed by a vote of 89-9 the House version of the patent reform bill H.R. 1249, also known as the Leahy-Smith America Invents Act, without amendment. Consequently, after many years of discussion, debate and hand-wringing, significant patent reform is imminent. In fact, at this point, the legislation only requires action by President Obama, who has already promised to sign the bill.
Most provisions in the bill impact U.S. patent practice generally, including moving towards a first-to-file system, expanding prior user rights as a defense to infringement, eliminating interference proceedings, and creating new USPTO proceedings for post-grant review. One aspect of the bill, however, in a section entitled “Study on Genetic Testing,” impacts the personalized medicine industry in particular. See previous discussion on this provision on our June 26 post and August 3 post.
On July 27, 2011, the United States District Court for the District of Columbia in Sherley v. Sebelius (Civ. No. 1:09-cv-1575) held that the National Institutes for Health Guidelines for Human Stem Cell Research (“Guidelines”) are neither invalid for violating the Dickey-Wicker Amendment (“Dickey Amendment”) nor the Administrative Procedures Act (“APA”). In reaching this holding, the Court opined that the language of the Dickey Amendment does not prohibit the funding of research involving human embryonic stem cells within the limitations imposed by the Guidelines, but does prohibit NIH funding of research in which an embryo is subject to risk of injury or death in that research, for example, research regarding preimplantation genetic diagnosis. Researchers involved in prenatal genetic testing should therefore be mindful of this opinion and its explicit exclusion of the use of federal monies.