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Supreme Court Hears Arguments in Mayo-Prometheus Case

By Matt Jones

NEW YORK (GenomeWeb News) – In a case that could impact patent laws that are particularly relevant to the personalized medicine sector, the US Supreme Court yesterday heard oral arguments in a lawsuit between Mayo Collaborative Services and Prometheus Laboratories.

The Mayo v. Prometheus case involves alleged infringement of a medical test that Mayo had licensed from Prometheus and later offered on its own, but the core of the decision likely will focus on the patentability of natural phenomena under existing laws. The test at the center of the case measures metabolite levels and the efficacy and toxicity of thiopurine drugs, which are purine antimetabolite treatments used to treat autoimmune diseases.

The patents at issue are US Patent Nos. 6,355,623 and 6,680,302, which involve the correlation between thiopurine drug-related metabolite levels and efficacy and toxicity. Prometheus holds exclusive licenses to the patents.

Mayo and Prometheus had a licensing arrangement enabling Mayo to use the intellectual property, and Prometheus sued when Mayo began offering its own test based on statistical observations about this particular chemical-reaction relationship.

In 2008, a federal district court found that Prometheus' method claims were not patentable subject matter under 35 U.S.C. Section 101.

Last year, the Supreme Court sent the case back to the US Court of Appeals for the Federal Circuit for fresh consideration in light of the Bilski v Kappos decision, which established that business methods can be patented even if they do not meet the "machine or transformation" test, a determination of patentability based on whether a technology is tied to a particular apparatus or if it transforms an article into a different state.

The appeals court reversed the district court's ruling late last year, siding in favor of Prometheus, on the basis that the company's testing methods were patentable under the machine-or-transformation test.

Paul Rivard, a shareholder at intellectual property law firm Banner and Witcoff who attended Wednesday's arguments, told GenomeWeb Daily News yesterday that the outcome of the case could have implications on both the personalized medicine and tailored therapeutics industries and research areas.

"This patent in particular is addressing personalized medicine, where you're looking at how an individual responds to a drug and how metabolites are produced in the body, and how that can be used to adjust dosing. So that's the immediate spectrum of what they are addressing," he said.

"[The ruling] is going to have implications on therapeutic treatment claims, where it can be argued that you are administering a drug to somebody for a particular effect, but once you put the drug in that person's body whatever happens is just the action of nature ... and whether you're identifying something that happens in the body versus causing it to happen or having actually created that result," Rivard explained.

Mayo is asking the Supreme Court to consider whether Section 101 is satisfied by a claim that covers observed correlations between blood test results and patient health, even though such a patent could preempt natural phenomena, because it involves a "transformation" of body chemistry.

The case now before the highest court hangs on interpretations of these patent laws regarding natural phenomena, business methods, and abstract ideas, and the discussion among the justices on Wednesday was strewn with hypothetical proposals as they tried to pin down the nature of the dispute over the technology.

In its brief, Mayo argued that Prometheus' patents "purport to monopolize the field of blood testing for thiopurine metabolites," and keeps physicians from providing a full range of information about metabolite levels and health for any range of immune diseases. Mayo said that precedents have established that such claims are not supported under Section 101, stating that a patent may not "preempt the laws of nature, physical phenomena, and abstract ideas," which are "free to all men and reserved exclusively to none."

It added, "Under this settled principle, Prometheus' claims are invalid. Prometheus' patents recite a natural phenomenon — the biological correlation between metabolite levels and health — without describing what is to be done with that phenomenon beyond," Mayo argued.

The real-world, practical effect of Prometheus' "open-ended" claims on that correlation, Mayo stated, is to wholly pre-empt the use of this natural correlation of metabolite levels and the drug with regard to any autoimmune disease.

In its brief, Prometheus disputed Mayo's position, saying that its patents do not merely recite natural phenomena, that its claims are preemptive only in the narrow sense that all inventions are, and more broadly that a ruling for Mayo would disrupt the settled expectations about patent law and would hinder innovation.

"And there certainly is no reason," Prometheus continued, "at the dawn of the 21st century, for this court to adopt special rules that would render personalized medicine inventions, or other processes designed to produce useful information, uniquely unpatentable under Section 101."

At the Supreme Court hearing yesterday, Mayo's attorney Stephen Shapiro said that the trouble with the Prometheus patent is "its broad preemption of a physical phenomenon, which prevents others like Mayo Clinic from offering a better metabolite test with more accurate numbers. And this is a huge practical problem for patients."

In support of Mayo's case, a group of biomedical associations led by the American College of Medical Genetics and including the Association for Molecular Pathology, the College of American Pathologists, the American Medical Association, and others, filed an amicus brief arguing that healthcare policy is best served when there are established limits on the patentability of subject matter, including claims to observations about subject matter.

The ACMG-led group said that the patents at issue in this case do not cover innovative drugs or new diagnostic tools. "Instead, these patents grant exclusive rights over the mere observation of natural, statistical correlations between certain metabolite levels in the body, as measured by well-known means, and the potential toxicity and effectiveness of well-known drugs. If these patents remain in force, any physician who measures those metabolite levels and knows about the observed correlations will unavoidably become an infringer. Thus, these patents convert routine, sound medical practice into prohibited infringement."

Siding with Prometheus, the Biotechnology Industry Organization said that excluding this type of patent from eligibility under Section 101 could "do tremendous damage to innovation, affecting entire sectors of the economy."

BIO cited the Bilski v. Kappos decision, stating that the Supreme Court recognized the danger inherent in "adopting categorical rules that might have wide-ranging and unforeseen impacts."

"That danger is present in this case," BIO said in its brief filed with the court. "Announcing a broad rule of ineligibility concerning diagnostic and therapeutic methods that exploit knowledge gained from the study of biological systems would threaten harm to the biotechnology industry, and devastation to the nascent field of 'personalized medicine,' which promises substantial benefits to patients through its capacity to match focused and appropriate treatments and improved diagnostic methods."

During the yesterday's oral arguments, the justices struggled to get to the heart of the argument about natural phenomena, novelty, and the implications of transformation based on measurements by proposing a number of hypothetical analogies.

"So I have a great idea. You take wood, you put it on a grate, you light it, and you get heat," Chief Justice John Roberts proposed. "So I can get a patent for that?"

Justice Samuel Alito tried to pin down how the term "natural phenomenon" is applied under the law. "Suppose someone discovers the level at which a human pollutant that is present in the atmosphere or in the air or the water has an adverse effect on human health. Is that not a natural phenomenon?"

"The justices certainly raised a lot of hypotheticals — as you would expect and as they do in any case, but especially with this — trying to figure out where you draw the line between an abstract idea and a process that is eligible for patenting," Rivard said.

He told GWDN that the case here hinged on the "wherein" clauses in the patents, in this case meaning that in instances wherein a metabolite reading is at one level the drug dosage should be increased or decreased when they are at another level.

Rivard could not say, based on the justices' broad and hypothetical lines of inquiry, whether their questions suggested that they are leaning toward either side of the argument.

"The justices did seem to recognize the need to walk a fine line here and not require too much in a claim where it is going to be easily avoided ... [or] where claims are going to have to be very specific before they could survive this type of challenge," he said. "At the same time they also seemed to recognize that claims that really don't do anything more than preempt the entire law of nature and physical phenomenon that was discovered, that those are problematic as well because they would inhibit all types of research in that area."

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