The following contribution to our gene patenting symposium comes from Robert Cook-Deegan, Research Professor, Institute for Genome Sciences & Policy and Sanford School of Public Policy, Duke University.
Association for Molecular Pathology v. Myriad Genetics is not your usual patent lawsuit. I come to it not as a lawyer or legal scholar, but as a molecular biologist and physician who happens to study how patent rights affect research and health care. It seems worth commenting on several distinctive features of this case.
The question facing the Supreme Court is peculiarly “human.”
The only question to be addressed by the Supreme Court is “Are human genes patentable?” It is a deceptively simple question. This frame is puzzling to a molecular biologist. DNA is the universal storage and transmission medium for all genetic information. It is also a physical chemical found in every living thing. And it is a polymer that can be engineered, manipulated, and altered to deliberately encode information that will change biological function when put into cells – clearly inventive activities. But in the diagnostic context, any change in DNA sequence would be an error, so that patented molecules are useful only if they have the exact same sequence as found in cells of the person from whom they were taken. Is that an invention? And is it only an invention if the DNA is “human?” Surely not. The BRCA genes that are patented in “isolated” form are found in many other organisms, and are involved in fundamental processes of homologous recombination and double-stranded DNA repair (at least – and who knows what else?). So what will it mean for the Supreme Court to rule on human genes? The degree to which this case affects agricultural biotechnology, environmental biotechnology, greentech, the use of organisms to produce alternative fuels, and other applications will turn on what work the word “human” does in the Supreme Court’s analysis.
Standing to sue did not get addressed.
A decision on standing to sue would have been quite significant. If it had turned on that aspect of this case, the Supreme Court might have broadened the narrow determinations of standing favored by the U.S. Court of Appeals for the Federal Circuit. The Supreme Court did not have to confront this aspect of the case, however, since the Federal Circuit determined that one plaintiff had standing. The usual litigants in patent lawsuits are competitor firms contending in a market. In that case, both litigants generally want to have patent rights, but are fighting over who prevails. This case, however, was brought by two public interest organizations (the American Civil Liberties Union and Public Patent Foundation), and the purpose was to change the law, not dominate a market. The initial plaintiffs included women who wanted to get tested for their risk of inheriting mutations predisposing them to breast and ovarian cancer, their physicians, the laboratories that would do such testing, and organizations representing those constituencies. The Federal Circuit held that only one plaintiff had standing: Harry Ostrer, who runs a university lab that does genetic testing, and who had previously received an enforcement letter from Myriad. In that sense, he is a traditional patent plaintiff. If the question had come down to disagreement about standing to sue between the Supreme Court and Federal Circuit, this case would have had even wider implications. It is clear that the patent rights in this case have affected who can get tested, how testing is conducted in the United States, and who owns and controls the information that results from genetic tests. Those aspects that might have affected standing to sue did not get fully argued, however, because one plaintiff was enough to get to the merits.
Regardless of outcome, it will be hard to interpret the scope of Supreme Court precedent. This is a case only about Section 101 patentable subject matter. There was no Markman (evidentiary) hearing to interpret the claims, and no trial to scrutinize contradictory factual assertions between the litigants. It is clearly a hard and juicy case. All four judges involved (U.S. District Court Judge Robert Sweet and Federal Circuit Judges Lourie, Moore, and Bryson) have all written at great length. The audience for their prose was the Supreme Court. This case was deliberately selected to address the single hottest controversy in patenting and DNA diagnostics – BRCA mutation testing – and it touches on concerns of highly activated breast cancer and women’s health constituencies as much or more than the usual suspects in patent law (companies, patent lawyers, technology licensing offices). The politics are complex, emotions run high, and yet the outcome is likely to remain murky. Affirming the Federal Circuit’s decision would still leave many of the broadest genetic diagnostics claims –method claims – vulnerable under Mayo Collaborative Services v Prometheus Laboratories, although just how vulnerable is going to take a while to work out through patent examiner determinations, re-examination of existing patents, and court challenges. Reversing the Federal Circuit would clearly leave several thousand patents claiming isolated DNA vulnerable, but very few patents have only such claims, and even Myriad would be left with many narrower claims on particular deleterious mutations and specific methods that would probably pass muster under Mayo. This case has already eliminated the broadest method claims that are nearly impossible to work around for DNA diagnostics. Affirming would leave the lines where the Federal Circuit drew them; reversing would further narrow patent eligibility. But there is very little case law to interpret Sections 102, 103, or 112 or utility under Section 101, and this case will not help. And if the criteria for interpreting Section 101 patentable subject matter are as vague for composition claims on DNA as method claims are post-Mayo v. Prometheus, then the zone of uncertainty will be even larger.
We will probably not learn what “isolated” means from this case. Two of the judges, Sweet and Bryson, argue that the word “isolated” in the claims is semantic legerdemain whose purpose is to convert something found in nature (a DNA molecule containing a particular sequence of nucleotides) into patentable subject matter, but in fact the claimed DNA molecules are not “markedly different” from those found in nature, the criterion for patent eligibility from the Court’s decision in Diamond v. Chakrabarty. They don’t buy this “lawyer’s trick.” Judges Lourie and Moore, however, argue that the inventors did just the sort of thing that patent law should reward. DNA does not read out its sequence. Clever people had to clone and sequence the relevant genes, find some deleterious mutations, and describe DNA molecules that can produce diagnostically useful information. Those people had to “isolate” the molecules, and should be able to patent their discovery to reward such activity.
Myriad now reads its claims rather narrowly, so as not to be infringed by whole-genome sequence analysis. Every method of sequencing now and forever, however, will entail isolating DNA molecules with claimed sequences that would appear to be covered by four of the nine composition of matter claims still in dispute (two each for BRCA1/2). If “isolated” is so broad that it means “of course we had to isolate it to determine its sequence,” then such claims are vulnerable to challenge as invalid under Sections 102 and 103 (novelty and obviousness); if it is narrower than that, referring (as Myriad argues) only to determining sequences of one or a few genes, there is still a looming question. How targeted is the claim? Can you include BRCA1/2 in a twenty-gene panel? A hundred? All exons? This matters in the practical world of gene testing, because firms like Ambry Genetics have introduced tests for inherited risk of breast and ovarian cancer that cover over a dozen genes. To date they have left off BRCA1/2, but including them would add very little extra cost. The real-world impact is that doctors and patients right now order two independent tests that cost thousands of dollars each to generate information that would be available more quickly and just as accurately from a single test. It makes no sense clinically, and it is wasteful. It is clear that the litigants disagree on how broad the claims are, but a general rule based on Section 101 patent eligibility is unlikely to resolve this question, yet it is crucial to the competitive dynamics of the BRCA testing market, and DNA diagnostics more generally.