Mayo v. Prometheus and Diagnostic Patents: What Does the Supreme Court Decision Really Mean?
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I finally had a chance to read the Supreme Court's recent decision in the Mayo v. Prometheus Labs case, which invalided two patents claiming methods for analyzing blood test results to determine correct drug doses. The decision is likely to have substantial impacts on the drug, diagnostic, and biotech industries because it calls into question the validity of a huge amount of intellectual property that those industries rely upon.

My take is that the Court got this one right as a matter of patent law - though it's a closer call than many intellectual property skeptics have claimed. Here, I should note that some colleagues and I contributed to an amicus curiae brief to the Court urging the justices to find the patents invalid. Even so, the decision raises several new questions about scientific innovation. And it may be worth reconsidering the structure of our patent laws or finding another way to incentivize the very important research work that could become less common in the absence of market exclusivity for these kinds of discoveries.

So, what's the case all about?

Prometheus Laboratories held exclusive licenses to the patents at issue, which described a way for physicians to titrate an appropriate dose of thiopurine drugs in the treatment of autoimmune conditions such as Crohn's disease and ulcerative colitis. It has been known for many years that patients vary widely in the way they metabolize these drugs, severely complicating their dosing. Too low a dose, and the drug is ineffective. Too high a dose could lead to toxicity problems. The challenge is finding the sweet spot.

Scientists had already known that certain metabolites of the drugs could be used to guide dosing, but they did not know exactly what range was optimal. And that led to a lot of guesswork in thiopurine prescribing. Enter Ernest Seidman and Yves Theoret, researchers at the Sainte Justine Hospital in Montreal. In the mid-1990s, after a huge amount of investigation and testing, they discovered the appropriate range for two particular metabolites and created a relatively precise test keyed to that discovery.

The problem, though, was that their patented test wasn't a new "invention," as that term is usually understood, but simply a stepwise process that relied on knowing the correct metabolite range: (1) administer the drug to the patient; (2) measure the resulting metabolite levels in the patient's blood; and (3) titrate the drug dosage up or down until the metabolites fall into the appropriate range.

In 2004, the Mayo Clinic and its laboratory, Mayo Collaborative Services, argued that patents on that kind of test method should be invalid because the correlations between the metabolite levels and the appropriate doses were a "naturally occurring phenomenon," which is not patentable subject matter under Section 101 of the US Patent Act. The federal trial court agreed, and so did the Supreme Court by a unanimous vote.

In between, the U.S. Court of Appeals for the Federal Circuit -- a special court created by Congress specifically to hear and develop expertise on a limited area of jurisdiction, including intellectual property law -- concluded that the patents were valid because the administration and measurement steps involved a "transformation" sufficient to "confine the patent monopoly within rather definite bounds." Therefore, the fact that the patented test relied on measuring a natural phenomenon was not sufficient to render it invalid. The patents did not monopolize the correlations; they merely applied those correlations in a specific process.

For the Supreme Court, however, the transformation was not sufficient because the patented process still relied upon a fairly abstract idea: Physicians should give patients a drug and then consider test results when making additional treatment decisions. And, "[b]ecause methods for making such determinations were well known in the art, this step simply tells doctors to engage in well-understood, routine, conventional activity ..." The only thing that was new was knowledge of the appropriate metabolite range, a natural phenomenon.

Just as important, the Court was concerned that affirming the patent could inhibit future use of the correlations in scientific research and patient treatment by "improperly tying up the use of laws of nature and the like." And it's worth noting that the patents could have been enforced even if the physician chose not to alter the patient's dose "in the light of the inference he draws using the correlations." Monopolizing a natural phenomenon becomes a genuine threat, according to the Court, "when a patented process is no more than a general instruction to 'apply the natural law'."

The Court also rejected the argument offered in an amicus brief by the Patent and Trademark Office and U.S. Department of Justice that the transformative steps ought to render the correlations patentable subject matter, but that the patent should fail for other reasons. To secure a patent, inventions must be (1) novel, (2) not an obvious extension of existing inventions or concepts, and (3) useful. The PTO/DOJ brief conceded that Prometheus patents should be invalidated because the test method was either not novel or because it was obvious or both, but argued the minimally transformative nature of the test should otherwise be sufficient to secure a patent.

Justice Steven Breyer's opinion for the Court rejected that argument out of hand, suggesting it would render the "law of nature" preclusion "a dead letter". Furthermore, the Court argued, neither the novelty nor obviousness elements of the Patent Act are well suited to address such a fundamental question. So, shifting the inquiry to novelty and non-obviousness would create significant legal uncertainty in a field of law that is already rife with nuance. Thus, the Court addressed the question of patentable subject matter head on.

In short, patents may rely on a law of nature or other natural phenomenon only if they incorporate other sufficiently transformative steps that are genuinely new or inventive. (That seems, incongruously, to bring novelty and non-obviousness into the underlying patentable subject matter question. But I'll leave it to the patent experts to fight about that.) The decision in this case would not necessarily affect a different diagnostic test that did incorporate genuinely novel steps or processes. But the patents here were invalid because the claimed transformative steps involved things that physicians routinely do already.

That's the good news. The bad news is that much of what medical science is likely to learn from its study of the human body - particularly the human genome and proteome - will almost by necessity involve the discovery and application of natural phenomena and processes. Unless the application of those discoveries in the field of medicine leads to entirely new "inventions," no patent protection will be available to help researchers recoup their significant R&D expenses. That, in and of itself, could eventually prove to be as big a disincentive to innovation as affirming the patents would have been.

The Court's unwillingness to grapple with this question is understandable. After all, it is a court's job to interpret the laws as they are, not as a judge may wish them to be. And under the existing statute and case law, the Prometheus tests are simply not patentable.

What bugs me about Justice Breyer's opinion, though, is that it functionally pretends the problem does not exist. He writes, "[a] patent upon a narrow law of nature may not inhibit future research as seriously as would a patent upon [a much broader phenomenon, such as] Einstein's law of relativity, but the creative value of the discovery is also considerably smaller."

I agree with the Court that allowing patents on natural phenomena with little new "inventiveness" would significantly stifle future research. But to dismiss the added value of Seidman's and Theoret's efforts with a simple wave of the hand is appalling. In truth, their discovery is of tremendous scientific, medical, and financial value, and its importance should not be underestimated. What's more, the quest to continue funding for such research into basic biological mechanisms in the future will be severely undercut by the Court's decision. It is unfortunate that the Court took the matter so lightly.

That said, I'd like to repeat my belief that the Court arrived at the correct decision here. But it does raise some very important questions about how our society will finance the future research that Justice Breyer felt so compelled to protect. And we'll need to begin answering those questions if we hope to benefit from the vast potential that medical science could deliver.


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