Mayo v. Prometheus Labs: Should Medical Research Be Patentable?

David Yin

The affordable sequencing of the human genome introduced the tantalizing prospect of personalized medicine, where medical decisions could be made not merely with respect to knowledge about a disease, but tailored to an individual’s unique physiology. Treatments might therefore be chosen that were more effective, and less deleterious. Genomics is only part of the personalized medicine dream; as important are proteomics (which measures an individual’s levels of protein expression) and metabolomics (which can measure one’s profile of small-molecule metabolites, produced after the body metabolizes a larger molecule). One particular application of metabolomics is at issue in Mayo v. Prometheus Labs.

Prometheus Labs developed a test to aid in the treatment of immune-mediated gastrointestinal disorders. This test measured the metabolite levels of thiopurine, which can be used to treat disorders such as Crohn’s disease. Then based on the results of the test, the physician could alter the dosage of thiopurine. If the level of a certain thiopurine metabolite was lower than 230 picomoles per 8×108 red blood cells, the dosage of thiopurine should be increased to achieve a therapeutic effect. If the level exceeded 400 picomoles, the dosage should be reduced to avoid toxicity. Several years after Prometheus Labs introduced their test in 1994, Mayo Clinic introduced a cheaper, competing test which was alike in essentially every way except it called for an upper bound of 450 picomoles to inform the maximum tolerable dosage, and advised the lower bound should be 235 picomoles. Prometheus sued for patent infringement.

250px-Heinrich_fueger_1817_prometheus_brings_fire_to_mankindAfter the District Court rejected Prometheus’ claim, and the Federal Circuit reversed the District Court’s ruling (twice, the second time to reconsider in light of Bilski), this case is now before the Supreme Court on the question of whether 35 U.S.C. §101 invalidates Prometheus’ patent. There are four basic provisions an invention must meet to be patentable. §101 provides that: “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.” Under §101, things naturally occurring in nature, and scientific principles with only trivial implementations, cannot be patented. The Court wrote in Chakrabarty that“[A] new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter. Likewise, Einstein could not patent his celebrated law that E=mc2; nor could Newton have patented the law of gravity. Such discoveries are ‘manifestations of… nature, free to all men and reserved exclusively to none.’”

§102 requires that the invention be novel–it cannot have been known by others before, e.g. “prior art”; and §103 requires that the invention be “non-obvious”: it cannot have been obvious to a person having ordinary skill in the art. Finally §112 sets documentation rules. Judging from the oral argument, the battle will come down to whether §101 should function as a high bar that screens out many patent applications on natural phenomena or correlations (as Mayo wishes), or whether §101 should only operate as a “coarse filter” to define merely whether there was a “process”, and then having the patentability of Prometheus’ invention come down to whether it was novel, §102, and non-obvious, §103, with those two sections serving as the main bulwarks (as advocated by Prometheus, and the Solicitor General). That is, according to the respondent, §101 would tell you whether something is patent-eligible, and §102 and §103 determine whether it is patentable.

This case has drawn interest from an eclectic group of amici, including the Cato Institute, the American Medical Association, and even the ACLU. I tend to agree with those amici that the Prometheus patent should be invalidated, both for legal reasons and policy purposes. It’s worth thinking about what exactly Prometheus has invented. Prometheus did not invent the therapeutic drug, thiopurine, or the idea that thiopurine could be used to combat gastrointestinal disease. Prometheus assembled a kit for measuring metabolite levels, but it did not invent either the field of metabolomics, the idea that looking at metabolite levels was useful, or even the specific technical process needed to measure the specific metabolite of thiopurine in question. Prometheus purchased a patent on the 230-400 picomole range being correlated with therapeutic benefit/lack of toxicity. And Prometheus packaged all three of these together into a kit, and called it an invention. Prometheus’ infringement claim is that Mayo’s test also uses a metabolite range to determine the proper dosage of thiopurine–not on the thiopurine drug, or the test of metabolite levels. The petitioners and ACLU argue, persuasively, that Prometheus’ claim touches on the very thinking of medical practitioners: as soon as a physician alters dosage based on metabolite levels, she is violating Prometheus’ patent. This prospect should be absurd not only because it is obvious that certain correlations must inform medical decisions (and physicians have used the results of various blood tests to alter treatments), but because a correlation is precisely a natural phenomenon of the type that scientists and medical researchers have always observed and acted on in predictable ways. Prometheus could patent a drug, and a new test, but not simply knowledge of a scientific correlation.

From a policy point of view, allowing these patents in medical research does little to spur innovation, and much to impede it. Again, this medical correlation does not create a new therapy, or a new technique. Indeed, it creates negligible added incentives even for clinical research. Prometheus’ brief argues that the doctors who originally observed the metabolite correlation and obtained the patent that Prometheus later purchased had unknown motives–perhaps they would not have initiated the research without the prospect of financial gain. I hardly think that physicians at academic medical centers are there to get rich off a clinical correlation-turned-patent. The motives of doctors at research hospitals are to publish, obtain tenure and promotions, achieve fame and accolades, attract more patients, and build a lasting legacy. Doctors, after all, performed clinical research before the 1980s, before publicly-funded research institutions could even apply for patents. Certainly physicians discovered that high glucose indicated a need for insulin in diabetics, and high liver toxicity probably indicated a need to stop administering chemotherapy. Those correlations were discovered without patent protection, and it is highly doubtful that had patents been given the state of medicine would be better for it. Finally, Prometheus’ patent would seek to preclude perhaps important new discoveries on what are safe and effective dosages of thiopurine based on metabolite levels, as Mayo’s test introduces. We should not be stuck with Prometheus’ correlations, immune from further scientific review, simply because of patent protection.

Prometheus Labs’ patent ought to be invalidated. As the respondent’s namesake recognized, knowledge of a natural phenomenon should be disseminated for the progress of mankind, not hoarded only for those with olympian wealth.

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