By Kevin E. Noonan —

In an article in The Cancer Letter entitled "Robert Cook-Deegan's Viewers' Guide To the Super Bowl of Gene Patent Cases," Professor Robert Cook-Deegan (at right) of the Institute for Genome Sciences & Policy and Sanford School of Public Policy, Duke University provides his colleagues in the medical arts with an update on the progress of the Myriad case, specifically the several pending district court actions, now consolidated before Judge Robert Shelby in the District of Utah.  Continuing the pervasive presence of kitsch in everything Myriad (recall Judge Moore's disdain for Acting Solicitor General Katyal's "magic microscope on these grounds), Dr. Cook-Deegan analogizes patent litigation to a "blood sport," complete with analogies between hemorrhage and spilled ink/lost profits.  Dr. Cook-Deegan's focus is on Judge Shelby's recent denial of Myriad's preliminary injunction motion, as well as providing broad hints to the court and defendants regarding other legal avenues for attacking Myriad's patents.  Dr. Cook-Deegan is not a thoughtless partisan in this debate (indeed, he provided an insightful basis for invalidating Myriad's probe-and-primer claims based on traditional patent law concerns with novelty; see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims"), but he has certainly taken a side.

The article starts with Judge Shelby's 106-page ruling; as with most articles on the Judge's decision its length is apparently a relevant supernumerary for the correctness of the Court's conclusion (brevity being the soul of wit but clearly not a hallmark of judicial acumen).  Dr. Cook-Deegan correctly points out that the Court understood that Myriad might in fact suffer irreparable harm to its BRCA gene testing franchise but that this likelihood was trumped by the Court's determination that Myriad was unlikely to prevail on its patent infringement claims.  Dr. Cook-Deegan characterizes the Court's assessment as being that "the claims to DNA molecules — mainly to DNA primers used to amplify the DNA in its tests — are in trouble; and the claims to methods are in very deep trouble."  He cites the Myriad franchise in BRCA gene testing as having generated $2.8 billion in revenues since 1996, and asserts that Myriad's "monopoly" on testing (it always a tell for a writer's opinion on patents to describe them as a monopoly) ended in June 2013 with the Supreme Court's decision in AMP v. Myriad Genetics.

Dr. Cook-Deegan (much like Judge Shelby in his opinion, one of the reasons it is 106 pages long) then follows with a synopsis of the Supreme Court's decision in the Myriad case, recognizing that Justice Thomas's opinion, while more straightforward than most of the Court's pronouncements on patent law did not produce "a map locating [the] Rubicon" between patent ineligible and patent eligible forms of DNA.  (This characterization is somewhat unfair to the Court's opinion; it seems clear that the Court decided that merely being synthetic in nature was not enough, but that the DNA sequence itself could not occur in nature.)  The article sets forth what has transpired since the Supreme Court's decision, specifically Myriad's activity in suing anyone offering a BRCA gene test and there being several potential or actual Myriad targets filing declaratory judgment actions against Myriad for invalidity based on the Supreme Court's decision.  This list includes Ambry Genetics, Gene-by-Gene, Ltd. (this defendant has since settled with Myriad); Quest Diagnostics; GeneDx; InVitae; Counsyl Genetics; and LabCorp.

Dr. Cook-Deegan notes that these lawsuits generally involve Myriad's assertion of several of the hundreds of claims remaining after the ACLU's suit against 7 claims of 15 patents.  The article questions why Myriad would sue in view of its track record before the Federal Circuit (as to some of its method claims) and the Supreme Court, and of course mentions Myriad's profits as a motive (recall that patents are intended to garner money damages upon infringement), and that the $10 million that Myriad purportedly "set aside" for patent litigation represents "one week's profits" from a purported $520 million in revenues (not profits) Myriad made "in its most recent fiscal year."  In fairness to Myriad, Dr. Cook-Deegan also acknowledges that the company thinks it will win, particularly because these lawsuits are more traditional patent infringement actions and very different from the "court of public opinion" that the ACLU manipulated so expertly in the AMP case.  But he also correctly notes that Judge Shelby's ruling on Myriad's preliminary injunction motion has changed the odds against Myriad, returning to the sports theme by drawing an analogy with the Denver Broncos recent unsuccessful experience in the Meadowlands relating to meeting a strong offense with a strong defense.  This section of the article ends by noting that up until now the issue has been one of patent eligibility, and there may be other grounds for attacking Myriad's claims that may be raised in the pending lawsuits.

At this point the article veers more closely to advocacy, with Dr. Cook-Deegan making a case for invalidating Myriad's claims to the BRCA2 gene (and any that depend, logically or legally, on Myriad's claim to having invented the isolated form of this gene) based in Section 102(g) of the (1952) Patent Act.  This section can be used to invalidate a claim if the claimed invention was made prior to the patentee's making of the invention by a first inventor who did not "abandon, suppress or conceal" the invention.  This argument involves factual issues from the time during which several laboratories, including those of Mark Skolnick (Myriad's inventor) and Mary-Claire King in Seattle, were trying to identify human genes that were involved with an increased propensity for breast and ovarian cancer.  Dr. Cook-Deegan, citing Kevin Davies's book Breakthrough, concedes that the Skolnick lab "won" the race to isolate the BRCA1 gene.  The situation is different for BRCA2, according to Dr. Cook-Deegan, and he lays out in detail the "case" for third party invention of BRCA2.

According to this article, a British group, led by Michael Stratton, first provided linkage analysis data showing the gene now know as BRCA2 resided on human chromosome 13 in 1994.  As it turned out, Myriad filed its BRCA2 patent application three days before Dr. Stratton announced his team's discovery of BRCA2 in the scientific journal Nature.  In a sentence no doubt intended to illustrate the frenzied nature of the scientific race for BRCA2 (but that also seems to imply Myriad-associated shenanigans), Dr. Cook-Deegan asserts that "[t]he scientific scuttlebutt has long been that Myriad scientists learned of the pending publication and filed just in time.  But was it really in time?"  This quasi-allegation is followed by a timeline of events as follows:

The Stratton group, working with Andrew Futreal of Duke, filed a UK patent application on BRCA2 on November 23, 1995 (UK patent 2,307,477 was published on May 28, 1997).  The Stratton team submitted their BRCA2 paper on December 5.  Stratton's UK patent application was thus filed almost a month before Myriad's US application for BRCA2, and the Myriad/Utah team did not publish on BRCA2 until March 1996, three months after Stratton's team.  The Stratton team also got a US patent (6,045,997).  That patent was allowed to lapse when the first maintenance fee was due, but the US patent and patents in 18 other jurisdictions do establish a presumption of priority from Stratton's UK patent.

The plot spun in the article thickens, Dr. Cook-Deegan stating (correctly) that the U.S. Patent and Trademark Office is precluded from granting patents on the same invention (stated in the article slightly differently, that the Office is "not supposed to grant overlapping claims").  He also notes that the Office did not declare an interference proceeding, the way that priority disputes between separate inventors were resolved under the previous "first to invent" patent regime (that changed with the enactment of the Leahy-Smith America Invents Act).  He then states tantalizingly that "[t]he current litigation could finally bring to light the documents that would establish who knew what when, both who made the discovery and who deserves any patent rights on which mutations and the wild type sequence of BRCA1 and BRCA2."  The reader will be excused if she gets the impression that Dr. Cook-Deegan fervently wishes this eventuality to come to pass (and who he thinks will turn out to be the first inventor).

The article then turns to the question of whether Myriad's primer (and probe) claims satisfy the requirements of 35 U.S.C. § 101.  Much of this section of the article unfortunately relates to the recently issued Guidelines from the U.S. Patent and Trademark Office regarding patent eligibility in view of the Supreme Court's Mayo v. Prometheus and Myriad decisions.  While it is true that Judge Shelby's decision was made in consideration of these Guidelines, they do not have the force of law and represent merely how the Office (for now) is interpreting the Supreme Court's decisions.  They are certainly relevant to how claims in pending applications are being examined; they are of dubious relevance to the legal question of where the Court drew the line with regard to the patent eligibility of DNA primers and probes.

The article then discusses whether Myriad's primer and probe claims satisfy the written description and enablement requirements of Section 112.  The grounds for this challenge are that Myriad uses primers that flank BRCA gene exons and thus fall outside the scope of the claims reciting primers and probes that are fragments of BRCA cDNA (in view of the fact that these primers and probes are not expressly described in the BRCA gene patent specifications).  This argument seems to conflate whether these primers fall within the scope of Myriad's claims (and thus that construing the claims to so include these sequences may render them invalid for lack of descriptive support) and whether the practice of BRCA gene diagnostic testing by others using these non-exonic primers and probes would infringe Myriad's primer claims insofar as they are properly cabined within the confines of exonic sequences.  But Dr. Cook-Deegan is correct when he states that the validity vel non of these claims may depend on how they are ultimately construed by the District Court.

The article also focuses on claim 6 of U.S. Patent No. 5,747,282 which is not directed to DNA amplification methods and that would doubtless "capture" genomic DNA molecules clearly invalidated by the Supreme Court in Myriad.  These are also the types of molecules Dr. Cook-Deegan and colleagues showed to be invalid under 35 U.S.C. § 102, and the article briefly reviews the scientific basis for this conclusion.

Dr. Cook-Deegan further attempts to implicate the government's rights in the BRCA genes (stemming from National Institute of Health support for the basic genetic research underlying discovery of the BRCA genes).  It is worth noting that the "march-in rights" he cites as part of the Bayh-Dole Act have been available for the entirety of the time Myriad has held and threatened to assert its BRCA gene patents, and that the government has never used these march-in rights under any circumstances (although, famously, the government threatened to do so regarding the availability of the antibiotic Cipro in the wake of the anthrax scare after the terrorist attacks on September 11, 2001).  And it is further worth noting that the government has not acted even in the face of calls by Senators to do so after Myriad filed its lawsuits against BRCA genetic diagnostic test providers in the wake of the Supreme Court's decision invalidating some (but not all) of its claims.  Here, Dr. Cook-Deegan invokes not only Bayh-Dole but the Stevenson-Wydler Act (relating to rights in inventions made in government laboratories), as well as assorted misfeasances by Myriad having to do with reporting and other requirements with regard to whether the government can and should act.  And in this regard Dr. Cook-Deegan cites the knowledge (and possible testimony) of Dr. Andrew Futreal, who the article describes as:

[A] pivotal figure in understanding the discovery process in court proceedings.  He was a coauthor and co-inventor on the Myriad/Utah team that first characterized BRCA1 when he was at NIEHS, and then coauthor and coinventor on the Stratton papers and patents that first reported BRCA2.  . . .  He is thus the only person who was coauthor and coinventor for the first papers and patents for both BRCA1 and BRCA2.

In view of these assertions, it is surprising that the article doesn't supply defendants' counsel with Dr. Futreal's address.

Finally, Dr. Cook-Deegan points his readers (and defendants' counsel) to Myriad's litigation against OncorMed in 1997 over U.S. Patent No. 5,654,155, one of the patents Myriad is now asserting but that it attempted to invalidate in the prior litigation.  Dr. Cook-Deegan presents no information about any relevant evidence from this earlier litigation, but speculates that "[t]he 1997 litigation may have left a paper trail that the discovery process will unearth" because "[c]laims in the OncorMed patents were likely to be revoked or considerably weakened in 1997, and they are no more likely to be robust and enforceable now."

Finally, after noting more putative evidence of Myriad's bad behavior (here, with regard to "hoarding" its BRCA gene mutation database as a trade secret, complete with reference to "tart words" from Judge Shelby in dicta from his preliminary injunction decision), Dr. Cook-Deegan confesses that:

The historian in me wants this to go to court so we can learn what happened two decades ago.  Litigation is very costly, however, and the trial and appeals process is protracted, saps management attention, and poses recurrent decisions about whether and how to proceed further.  Moreover, litigation is a very expensive and not entirely reliable way to document historical events.  No one predicted a safety on the first play from scrimmage in the Super Bowl; any number of outcomes can still emerge from the litigation over BRCA1 and BRCA2.  The business models that emerge, however, are likely to entail more competition than Myriad's unitary genetic testing service that prevailed 1996-2013.

Perhaps.