Monday, July 25, 2011

Guest Column: Patenting Genes and the Future of Personalized Medicine

By Ashwin Mudaliar, Stanford University

Patents pertaining to the use and appropriation of biological information have been in the news prominently over the last year. The majority of attention has been paid to the case of Association for Molecular Pathology v. U.S. Patent and Trademark Office, which challenges the legality of Myriad Genetics' patent of the breast cancer genes BRCA1 and BRCA2, and more broadly, the patentability of human genes in the United States. However, Prometheus Laboratories Inc. v. Mayo Collaborative Services, which considers the patentability of medical methods, may have just as broad an impact over the greater landscape of biotechnology intellectual property.

The Patent Act of 1952 specifies four categories upon which an invention can be judged patentable: proper subject matter, novelty, non-obviousness and utility. It further specifies that a patentable invention be any “process, machine, manufacture, composition of matter, or improvement thereof.” If a prospective invention does not meet all four of these categories, it is not considered germane in view of the law and is thus not eligible for patent protections, as determined by the United States Patent and Trademark Office (USPTO). Laws of nature, physical phenomena, and abstract ideas are explicitly barred from patentability on the basis of not being proper subject matter.

Method patents, which are patents on processes of performing a set of steps (methods) to obtain certain results, have traditionally been awarded as long as a substantive transformation through the method was demonstrated and if the method in question was tied to a specific apparatus. However, the scope of method patents was brought into question in the case of Bilski v. Kappos (In re Bilski), which stems directly from USPTO’s rejection of Bernard Bilski and Rand Warsaw's patent application for a method of hedging commodities risk, whose claims fell under the unofficial category of business method claims. The examiner at the USPTO rejected the claims of the application because the method was not tied to a specific apparatus and that it "merely manipulate[d]" abstract concepts to solve a mathematic question without a substantive transformation. In further appeals through the legal system, the United States Court of Appeals for the Federal Circuit, which is tasked with handling all patent related matters, affirmed the initial rejections of the Bilski patent and went further by significantly modifying the standards for resolving whether any invention is statutory subject matter under the Patent Act through its promulgation of a new test, termed the machine-or-transformation test, to determine patent eligibility for any process claim. This test aims to determine if a claimed process or method is tied to a specific apparatus and/or if the same claim transforms a specific article into a different state. If either stipulation is met, then the claim is deemed statutory assuming it meets the other categories of patentability (novelty, usefulness, etc.). The plaintiffs appealed to the Supreme Court to reconsider this decision, which obliged by granting certiorari to hear the case.

In Prometheus v. Mayo, Prometheus Laboratories, a diagnostics and therapeutics company from San Diego, Calif., sued Mayo Medical Laboratories for patent infringement on two methods for determining the optimal drug therapy for a gastrointestinal autoimmune disease when Mayo Medical announced that it would sell its own diagnostic test based on similar methods. The original patent specified a method for measuring the metabolites 6-methyl-mercaptopurine (6-MMP) and 6-thioguanine (6-TG) following the administration of a thiopurine drug for autoimmune diseases. Based on the level of both, drug dosage would be altered for maximal efficacy and minimal toxicity. In March of 2008, a district court in California invalidated two patents held by Prometheus on the grounds that the methods were not patentable subject matter. However, in September of 2009, the United States Court of Appeals for the Federal Circuit overturned this ruling and claimed that the methods described in the patents satisfied the machine-or-transformation test, and more specifically that the administration and determination steps in the original claim brought about sufficient transformation. The lawyers for Mayo Medical argue that observed correlations between blood test results and health are simply “basic, natural biological relationships,” and thus non-patentable, but the Federal Court ruled that any kind of treatment that alters the body in a therapeutic manner could be patentable.

The court argued that the claims in the plaintiff’s patent did not simply cover natural correlations (metabolite levels) or data-gathering (measurement) because the, “asserted claims are in effect claims to methods of treatment, which are always transformative when a defined group of drugs is administered to the body to ameliorate the effects of an undesired condition (emphasis added).” The court also ruled that measurement that goes beyond “mere inspection” is transformative. Mayo Medical Laboratories quickly filed an appeal to the Supreme Court.

On June 28, 2010, the Supreme Court issued its ruling on the In re Bilski appeal, which affirmed the Federal Circuit’s ruling that Bilski process was not patentable subject matter. However, the Court also ruled that the machine-or-transformation test was not the exclusive test to evaluate method patents but rather just a “useful and important tool” amongst others. It did not offer further or more specific guidance. The Supreme Court then vacated the initial federal circuit court decision in Prometheus and ordered that this court reconsider its decision in light of the new ruling on Bilski. In its reconsideration of Prometheus on Dec. 17, 2010, the federal circuit court reconfirmed that method claimed by Prometheus constituted patentable subject matter and stated that the Bilski decision “did not undermine [its] preemption analysis of Prometheus’s claims.” As such, its ruling was substantively unchanged. Mayo Medical appealed again to the Supreme Court on May 17, and was granted a writ of certiorari on June 20 for consideration. A definitive ruling is expected next summer.

The issues at stake in Prometheus case are very important to the future of commercial diagnostic tests and, more broadly, the commercialization of personalized medicine. Very often, diagnostic methods similar to those described in the Prometheus patents are used to deliver safer and more effective treatments to patients who might otherwise react adversely to a therapeutic intervention. If the Supreme Court were to side with the defendants and invalidate the Prometheus patents in a broad decision, it could potentially call into the question the validity of a number of previously issued diagnostic patents that companies rely on to protect their investments. Considering that many of these sorts of diagnostic tests are created by smaller biotech companies, invalidation of the “method of medical treatment” system could hinder innovation and prevent early-stage biotechs from attracting investments. This is especially critical as we enter an age of increasingly personalized medicine, where therapeutic regimes will be closely tailored to the specific physiological states of individual patients. Without adequate protection for the research and development of such diagnostic methods, we could see a marked reduction in the number of private companies and research institutions that engage in the type of research that leads to these interventions as well as the quality of that research. Given these considerations, the Supreme Court’s ruling next year will have an enormous impact on the future of life sciences and medical technology.

CHI-Advancing California biomedical research and innovation

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