By Kevin E. Noonan --
With the U.S. Supreme Court set to consider the patent-eligibility of claims to isolated human DNA in AMP v. Myriad Genetics this morning, another aspect of Myriad’s control over BRCA testing technology is being contested. As reported on Friday by Gina Kolata in the New York Times ("DNA Project Aims to Make Public a Company's Data in Cancer Genes"), a group headed by Dr. Robert Nussbaum, Chief of the Division of Genomic Medicine, University of California at San Francisco has started an effort to "recreate" Myriad’s database of mutations (in addition to those disclosed in its patents) that are predictive for increased risk of breast or ovarian cancer.
The genesis of this effort, termed Sharing Clinical Reports, stems from Myriad’s decision in 2004 to keep such information proprietary. Myriad says its decision was based on misuse of the information in its database, which was intended for research use but was being used for patient diagnostics, a particularly sensitive area where such uncertainties can exist. As a consequence of its patents restricting BRCA gene testing, Myriad has developed a proprietary database of such "new" mutations, including ones of "unknown significance" (i.e., that have not been associated with risk prognosis) as well as mutations having predictive capability. (The Times article reports that the frequency of such "unknown significance" mutations was 40% in 1996, 20% in 2004 and 3% today, without attributing these figures.) While there have been more than ten thousand basic research reports published in academic and medical journals since the time Myriad’s patents were granted, it is undoubtedly the case that there are undisclosed mutations known only to Myriad.
As reported in the Times, proponents of the effort are contacting physicians having patients who have received the Myriad test and thus have received a Myriad test report. The requests are initially for the information to be donated, but the effort is sufficiently well funded that offers of thirty-three cents per report are being made. (While that doesn’t sound like much, it might prove expensive if hundreds of thousands or millions of test reports were involved, as the article suggests.) Reflecting the present informal nature of the effort, the article reports that the work of transmitting the patient test results is done by students "who need extra money" and that physicians who provide a minimum of 200 variants are rewarded with an Apple iPad mini. Present funding is provided by Dr. Peter Kolchinsky, managing director of RA Capital Management in Boston (which should raise its own set of motivational questions in Ms. Kolata’s readers).
The article is, de riguer, replete with assertions that genetic researchers are "furious," and that Myriad is preventing second opinion testing (ironically, by the managing director of GeneDX, "a gene testing company working with Dr. Nussbaum"). [H]aving one company control the data for genes is contrary to the way medicine is developing," according to Heidi Rehm, a Harvard geneticist, who is reportedly also working with Dr. Nussbaum. As detailed in the article, Dr. Rehm is apparently referring to "whole genome sequencing," which creates a situation where there are "22,000 genes" and "50 million variants" (which, even if true, is irrelevant to the subject under discussion, the two human BRCA genes and their mutations and variants). And as might have been expected, the group is requesting the National Institutes of Health start a publicly funded database of all variants of all human genes studied.
Nonetheless, the group raises an important issue. As has been reported here previously, one aspect of the gene patenting debate routinely ignored is that the genetic information is not patented. Accordingly, the Sharing Clinical Reports effort is in no sense "illegal" (provided that the provisions of the Health Insurance Portability and Accountability Act, HIPAA, regarding patient confidentiality are not transgressed) nor should it raise patent infringement liability for the group. If Myriad had amassed its database using proprietary means, or if trade secret misappropriation were involved, the company might have a way of preventing any effort to obtain the genetic data produced by such proprietary means.
Here, Myriad elected to enjoy the benefits of patent protection, wherein it could prevent anyone else from making, using, selling, offering to sell or importing its inventions. In return, Myriad was required to disclose those inventions pursuant to the provisions of patent law that require a written description of the invention that enables a person of skill in the art to practice the invention after the patent(s) expire throughout the full scope of the claims, and to disclose the best mode of practicing the invention (the latter requirement having been significantly blunted by the Leahy-Smith America Invents Act). And there is no allegation that Myriad did not properly satisfy these requirements, at least with regard to the mutations it had identified when it filed the applications that were eventually granted as its patents.
These disclosure requirements do not apply with regard to any "new" mutations contained in Myriad’s database, for the simple reason that they were unknown at the time these applications were filed. Indeed, there is no requirement in patent law to supplement a patent specification unless new inventions are claimed. But the advantages Myriad enjoys (and that "infuriate" the geneticists so) were procured based on the exclusivity provided by the patents, and these advantages will persist after the patents expire. These facts raise the question of whether there is any aspect of this situation that would constitute "patent misuse," a concept used as a defense to a charge of patent infringement that involves (relevant to this discussion) extending patent exclusivity after the expiration of the patent term. While the situation typically arises in patent licensing, it is reasonable to ask whether the policy drivers behind the defense have any relevance to the situation here, which can be expected to arise for any genetic diagnostic patents (exclusively or non-exclusively licensed), provided there is no obligation to make public or at least share new genetic information generated during the patent exclusivity period.
The answer is not to ban patents on isolated DNA (which are not infringed by genetic diagnostic methods in any event) or genetic diagnostic methods per se. This is because the policy-based obligation, if any, arises from the patent grant itself and the quid pro quo of disclosure in exchange for such exclusivity. Abolishing the exclusivity would abolish the obligation, and would provide incentives for companies to disclose as little information as possible. Instead of identifying the mutations now sought by Dr. Nussbaum and his colleagues, for example, future (unpatented) genetic diagnostic methods could come merely with the information that a patient has a genetic mutation associated with an increased risk of a particular disease, with statistics on survival and treatment options and their success rates but no information on which mutation(s) were involved. While this outcome would be even more inconsistent with the way genetic diagnostics is and has been developing than Myriad’s behavior bemoaned by Dr. Rehm in the article, what patients and their doctors want most are reliable diagnostic results, and a company offering such advanced diagnostics would be in a position to adopt a "take it or leave it" attitude regarding disclosure. This possibility is even more likely for the majority of diseases that, unlike breast cancer and BRCA are multivariate and less readily reverse engineered.
These considerations are not amenable to judicial intervention (despite rumors that at least one of the legal proponents of the Myriad case is planning to file such a lawsuit). Congress could intervene, but any bill would need to provide the right balance between return on investment (said to be more than $500 million by Myriad) and public access to information during and after the relevant patent term. Any such attempt to legislate will also require less rhetoric and more problem solving than has been evident in the gene patenting debate, which in large part involves physicians demanding the right to freely infringe genetic patents in the name of patient rights. Of course, none of these physicians is proposing to perform these tests for free, and that of course is one of the distinctions between these physicians and the researchers behind the 10,000 scientific research papers on the BRCA genes. Regardless of the outcome of the Myriad case before the Supreme Court (which, no matter how it turns out, will have little to no effect on availability of genetic diagnostic testing for the BRCA genes), addressing the policy considerations involving human genetic diagnostics is something that will remain. While the politics of confrontation generates headlines and contributions to those who paint themselves as patient champions, it has done and will do little to resolve these important issues.