Like a Leaf From a Tree: The Gene Patent Ruling
Can companies lay claim to pieces of the human genome? A federal appeals court decision says yes.
Friday's much-anticipated gene-patenting ruling from a federal appeals court reads like a variation on the timeless joke about the legal profession: What do you get when you have three judges writing about the same case? You get four opinions (and a great deal of navel-gazing about the nature of life's building blocks).
So it is with The Association for Molecular Pathology v. US Patent and Trademark Office, a ruling delivered to the world Friday afternoon by the United States Court of Appeals for the Federal Circuit. All three of the judges on the three-judge panel wrote an opinion, the vote was 2-1 protecting most of the existing patents, there were at four (or maybe five or six) different points of law identified, and in the wake of the decision there is about as much clarity on the topic as there was before. Relationship status: "It's Complicated."
Complicated and, for the foreseeable future, in flux. The intersection of law and technology always is a messy, crowded place. Judges are always scrambling to keep up with advances in science; eternally struggling to apply established legal doctrine to emerging new concepts. Think the good folks who drafted the Constitution (and federal patent law) in 1787 reckoned that one day scientists would be splitting human genomes in a quest to help cure cancer? Me neither. Yet here we are.
THE RULING
The majority opinion held that Myriad Genetics, Inc. holds valid "composition" patents on two isolated human genes, BRCA1 and BRCA2, which are linked to a predisposition to ovarian and breast cancer. The ruling restores the status quo ante that existed for more than a decade after the U.S. Patent Office issued the patents to Myriad. And it (mostly) overturns a 2010 federal trial court ruling that had voided the patents and concomitantly thrown this area of law and science (and commerce and medicine) into a tizzy. (Here is the take I wrote in April about that ruling and the oral argument which preceded Friday's announcement).
The central question of the case, then and now, was whether "isolated" human genes are unpatentable "products of nature" or patentable as "markedly different" compositions from their "unisolated" counterparts. After a lengthy dissertation on the science of DNA testing, and after dozens of pages dispatching with the jurisdictional aspects of the case, Judge Alan D. Lourie (who holds a PhD in chemistry) concluded:
In this case, the claimed isolated DNA molecules do not exist as in nature within a physical mixture to be purified. They have to be chemically cleaved from their chemical combination with other genetic materials. In other words, in nature, isolated DNAs are covalently bonded to such other materials. Thus, when cleaved, an isolated DNA molecule is not a purified form of a natural material, but a distinct chemical entity. In fact, some forms of isolated DNA require no purification at all, because DNAs can be chemically synthesized directly as isolated molecules.
Score one for Myriad, and its investors, in their aggressive efforts to preclude others in this field from working on the BRCA1 and BRCA2 genes. However, the Federal Circuit didn't give the patent holder a clean win. The appellate judges agreed with the trial judge that (all but one of) the company's "method" patent claims -- in which the company compared or analyzed BRCA sequences -- were not patentable. They were, instead "abstract mental processes" not covered by federal patent law. One such "method" patent, however, did pass the test: Myriad may continue to hold a patent on what the Court called its "method for screening potential cancer therapeutics via changes in cell growth rates."
Judge Kimberly A. Moore (who holds a degree in electrical engineering) saw things a little differently. She agreed with Judge Lourie that the plaintiffs had standing to fight Myriad's patent in court. And she ultimately agreed that most of Myriad's patents were valid. But her analysis -- both legal and scientific -- differed from that of Judge Lourie. In Judge Moore's view, the different chemical nature of the isolated DNA wasn't the only material factor to be considered in determining the validity of Myriad's patents. She focused instead upon the new "utility" the isolated DNA would have. She wrote:
The shorter isolated DNA sequences have a variety of applications and uses in isolation that are new and distinct as compared to the sequence as it occurs in nature. For example, these sequences can be used as primers in a diagnostic screen-ing process to detect gene mutations. These smaller isolated DNA sequences -- including isolated radiolabeled sequences mirroring those on the chromosome -- can also be used as the basis for probes. Naturally occurring DNA cannot be used to accomplish these same goals. Unlike the isolated DNA, naturally occurring DNA simply does not have the requisite chemical and physical properties needed to perform these functions.
Hedging her bet, Judge Moore also wrote:
If I were deciding this case on a blank canvas, I might conclude that an isolated DNA sequence that includes most or all of a gene is not patentable subject matter... This case, however, comes to us with a substantial historical background.
... I believe we must be particularly wary of expanding the judicial exception to patentable subject matter where both settled expectations and extensive property rights are involved. Combined with my belief that we should defer to Congress, these settled expectations tip the scale in favor of patentability. Congress has, for centuries, authorized an expansive scope of patentable subject matter. Likewise, the United States Patent Office has allowed patents on isolated DNA sequences for decades, and, more generally, has allowed patents on purified natural products for centuries. There are now thousands of patents with claims to isolated DNA, and some unknown (but certainly large) number of patents to purified natural products or fragments thereof.
In other words, whatever ambiguity that exists in federal patent law on human genome patenting ought to be resolved in the first place by legislators. Good luck with that, Judge Moore! It was left to the third judge on the Federal Circuit panel, Judge William C. Bryson, to dissent. First, he was blunt: "In its simplest form," he wrote, the question in this case is whether an individual can obtain patent right to a human gene. From a common sense point of view, most observers would answer, 'Of course not. Patents are for inventions. A human gene is not an invention.'"
Next, Judge Bryson went to the core of the matter. He compared human genes to minerals. He compared them with marble and a baseball bat. And then, memorably, he compared genes to a more familar symbol of nature. He wrote:
In that respect, extracting a gene is akin to snapping a leaf from a tree. Like a gene, a leaf has a natural start-ing and stopping point. It buds during spring from the same place that it breaks off and falls during autumn. Yet prematurely plucking the leaf would not turn it into a human-made invention. That would remain true if there were minor differences between the plucked leaf and the fallen autumn leaf, unless those differences imparted "markedly different characteristics" to the plucked leaf.
THE ROAD AHEAD
Gary Cohen (no relation), Vice President of Bioethics, Law & Policy at Foundation Medicine, has been closely watching all the gene patenting cases (there are others) wend their way through the federal courts. He sees in the Molecular Pathology ruling a sign of the chaos to come in this area of law and technology. On Sunday, he noted as particularly prescient this passage from Judge Bryson's dissent:
Broad claims to genetic material present a significant obstacle to the next generation of innovation in genetic medicine -- multiplex tests and whole-genome sequencing. New technologies are being developed to sequence many genes or even an entire human genome rapidly, but firms developing those technologies are encountering a thicket of patents.
In Cohen's view, this policy question raised in the dissent is a powerful one that must be addressed both in the near and long-terms. "With more than 1,500 people dying from cancer each day in the United States -- and some 20,000 per day worldwide -- waiting for the full Federal Circuit or the Supreme Court to bring clarity to the issue of patentability... is not a real or satisfactory solution," he told me Sunday. Here's his bright idea to help solve the problem:
A path forward would involve a solution that respects patent rights and the system that grants them but yet enables commercialization of affordably-priced multigenic diagnostic tests that physicians are seeking and will continue to seek with rapidly increasing frequency in order to make the best possible diagnoses and treatment plans for their patients. One such potential solution would involve the creation of an independent, non-profit body that would serve as a clearinghouse or pool for human gene patents. Rights holders could license their patents (royalty-free) to the patent pool, which could, in turn, sublicense those rights - for royalties to be passed back to the licensors - to entities wishing to utilize the various IP aggregated in the pool.
The clearinghouse, one-stop-shopping nature of the pool would greatly reduce the uncertainty, administrative expense, and burden of having to seek out hundreds of rights holders - which would currently have to be done without any reliable roadmap for who owns what. Royalty disbursements could be set at a given percentage of net sales of the test and would be divided according to an intelligent algorithm for the relative contribution of the various IP to the value of the test. There is precedent for a similar concept with Navigenics, which, as an individual actor, sets forth on its web site a formula for how much it is willing to pay for any one gene among the thousands it sequences with its customers.
Its going to take at least a few more years for the Supreme Court to resolve this case -- and it will take longer still for the courts to resolve the new cases cropping up in this area. The law always lags behind new science. In this case, the lag is costing lives. Maybe when Congress comes back to work following the debt-deficit debacle it can spend a little time helping to sort out this mess. Then again, likely not.