Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Justices will consider whether Prometheus’ claims cover laws of nature or applications of laws of nature.

The lawsuit between Prometheus Laboratories and Mayo Clinic, which started in 2004, reached the Supreme Court last December. During oral arguments justices repeatedly asked lawyers for both sides to offer them direction on one key question: When does a claim involving diagnostic and treatment-related chemical observations, among examples of natural phenomena, meet the threshold for patent eligibility?

The justices didn’t get the clear answer they sought. Now it will be up to the nine to answer the question as they decide Prometheus Laboratories, Inc. v. Mayo Collaborative Services et. al. At issue are patents covering the methods of dosage calibration for thiopurine drugs for gastrointestinal and nongastrointestinal autoimmune diseases. The methods were designed to account for the context of a treatment regimen based on the individual patient’s metabolism.

Prometheus sued Mayo in U.S. District Court alleging that an announced (but never marketed) Mayo Medical Laboratories diagnostic test infringed two Prometheus patents by measuring the same metabolites as Prometheus’ test; Mayo’s test used different levels to determine toxicity of the two metabolites. Mayo has countered that Prometheus’ patents include claims based on unpatentable natural phenomena—the correlations between thiopurine drug metabolite levels and efficacy and toxicity—and that the claims wholly preempt use of the natural phenomena.

“Whatever the court comes out with is going to have a pretty profound effect on personalized medicine,” Paul M. Rivard of the law firm Banner and Witcoff, who attended the oral arguments, told GEN. “In the therapeutic area, some of these issues are really front-and-center with this case. That is going to force the court to come up with some sort of decision that sets some guidelines on the types of claims that are going to be permissible.”

What the Justices Questioned

Justice Stephen Breyer sought to pinpoint how far a process could go and yet remain patentable. Could patentability apply to a method for determining when there is too little or too much fertilizer in a field? To Einstein’s E=mc2 equation?

“My question is: What has to be added to a law of nature to make it a patentable process?” Breyer said, best expressing the court’s conundrum in a question directed to Prometheus attorney Richard P. Bress of the law firm Latham & Watkins. “If you put too little in the answer to that question, I believe I can take things like E equals mc-squared and make them patentable. And if you put too much in, you are going to wreck your own case.”

Bress cited the court’s O’Reilly v. Morse decision (1853), where one Morse claim—use of electromagnetic force—was deemed too broad to patent because it could preempt many inventions never even thought of. However, the Morse code dot and dash signs were patentable as applied in the telegraph, since they represented a change in state of physical objects.

Another possible answer: In Diamond v. Diehr (1981), the Supreme Court upheld as patentable the execution of a process controlled by a computer program that applied a math formula that by itself was not patentable. That “machine-or-transformation” test was upheld by the Federal Circuit in In Re: Bilski (2008) but watered down by the high court in Bilski v. Kappos (2010), when it cautioned that the standard should not be the sole test but “a useful and important clue” of patentability; that may explain why Bress didn’t cite the case.

Mayo attorney Stephen M. Shapiro cited In Re: Bilski to argue that a patent cannot be used toward a broad preemption of a physical phenomenon—something Mayo and supporters accuse Prometheus of doing.

“Broad patents on natural biological relationships, which we consider the Prometheus patent to be, basically threaten the advancement of personalized medicine,” Roger D. Klein, M.D., chair of the Professional Relations Committee of the Association for Molecular Pathology, and director, Molecular Oncology Laboratory, Blood Center of Wisconsin, told GEN.

“You essentially give a monopoly over biological relationship, and then nobody else can come in and find out a better way to test for it,” Dr. Klein, who also attended the oral arguments, asserted. “And that stifles the advancement of personalized medicine, and it harms patients because it tends to increase costs and increase prices, and the patients don’t benefit from the efficiencies that would be gained by the introduction of novel methods.”

While Breyer’s basic question remained unanswered, Gerald J. Flattmann Jr., a partner in the intellectual property practice of the law firm Paul Hastings, said the closest anyone came to an answer was U.S. Solicitor General Donald B. Verrilli Jr. He noted that Section 101, which covers patentable subject matter, was an easier standard than Sections 102 and 103, which address whether a claim is novel and nonobvious, thus meriting patent eligibility.

“It only engendered more confusion with some members of the court,” Flattmann said—notably Chief Justice John Roberts and Justice Anthony Kennedy, who questioned if issues of novelty and nonobviousness should instead be addressed through Section 101.

Justices Sonia Sotomayor and Antonin Scalia, however, pursued lines of questioning that asked whether the patent so broadly preempted a physical phenomenon that Mayo and others could not offer a better metabolite test with more accurate numbers. Justice Elena Kagan, however, took an opposite line of questioning, asking whether the Prometheus patents were too broad and if the company wasn’t merely “point(ing) out a set of facts that exist in the world” and “claiming protection for something that anybody can try to make use of in any way.”

Predictions for the Outcome

“Given the tenor of the questions, it’s likely the justices are going to try to pose an answer to Justice Breyer’s question: How much more is needed? It will be interesting to see if they depart from their earlier precedent, which addressed that question in the sense of saying not much more is needed, anything made under the sun by man is patentable; it just has to have some extra step that renders it more than a mere concept or law of nature,” Flattmann told GEN.

“If it does go down that path and tries to enunciate a new standard, it perhaps will be a more restrictive standard than the one that has applied for the last several decades in the biotech area,” Flattmann added.

Flattmann and Lisa A. Haile, Ph.D., a partner at DLA Piper U.S. and co-chair of the firm’s global life science sector group, agreed this was a more difficult case than most to glean what justices are thinking.

Haile told GEN the decision of a three-judge panel of the Federal Circuit in Molecular Pathology v. US Patent and Trademark Office may prove relevant to this case. Myriad Genetics seeks to protect seven patents related to breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) and its method for analyzing sequences of those genes for mutations associated with breast cancer against a legal challenge by several medical associations and individual doctors, assisted by the American Civil Liberties Union and Public Patent Foundation.

The panel upheld Myriad’s gene claims and methods of screening for cancer compounds as patentable but not its claims for mutation analysis, which it dismissed as “abstract mental processes.” Significantly, the panel contrasted those processes with Prometheus’ claims by arguing that: “Myriad’s claims, in contrast, do not include the step of ‘determining’ the sequence of BRCA genes by, e.g., isolating the genes from a blood sample and sequencing them or any other necessarily transformative step.”

“I’m almost wondering if the Supreme Court is going to do something similar here, and just say, ‘This is just way too broad, administering a drug and determining a level where a body’s naturally metabolizing a drug,’” Haile said. “That’s where I think the court may end up: that the claims as written aren’t patentable, but I don’t think they’re going to preclude patentability for this type of personalized medicine.”

Breyer questioned his own dissent in an earlier case, though it’s hard to say if that was just an intellectual exercise or true regret. Breyer, joined by Justices John Paul Stevens and David Souter, dissented from the majority in dismissing LabCorp v. Metabolite. The majority sided with LabCorp that a Metabolite diagnostic test correlating levels of homocysteine with vitamins B6 and B12 represented “an unpatentable natural phenomenon.”

Specifically, Breyer read the amicus brief of Novartis, which argued that Metabolite’s correlation did not preempt a natural law, but was a patent-eligible application of natural law to facilitate a diagnosis and treatment of vitamin B deficiencies. In an unusual instance of self-criticism, Breyer said he didn’t sufficiently explain when patent claims that feature correlations were indeed patentable and when they were not: “And if you look to LabCorp’s dissent to find an answer to that question, you are better than I, because I couldn’t find it.”

Breyer raises a good point for the Supreme Court to consider in deciding Prometheus v. Mayo: Are Prometheus’ dosage calibration methods just a law of nature or an application of that law toward something patentable, here a method? Given the business tilt of the current court, expect the justices to buy the ‘application’ argument.

This sparks another question, though: What makes it an application? The answer will need to expand on, if not re-embrace, the Bilski machine-or-transformation standard the high court watered down just two years ago.

Alex Philippidis is senior news editor at Genetic Engineering & Biotechnology News.

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