The Supreme Court’s ruling that a test correlating drug metabolite levels to proper dosage is unpatentable has left the biotech community reeling with uncertainty about whether companies will be able to patent methods of treatment, particularly those involving biomarkers.

In its March 20 decision in Mayo Collaborative Services v. Prometheus Laboratories Inc., the court unanimously concluded that Prometheus’ test, which determines the proper dosage of a thiopurine drug by administering the drug and measuring the levels of metabolites produced in the patient’s body, is not patentable. The court said the processes covered by two patents do not transform unpatentable natural laws into patent-eligible applications of those laws.

The patent claims “purport to apply natural laws describing the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that the drug dosage will be ineffective or induce harmful side effects,” Justice Stephen Breyer wrote in the opinion for the court. But “the steps in the claimed processes (apart from the natural laws themselves) involve well-understood, routine, conventional activity previously engaged in by researchers in the field.”

“The question before us is whether the claims do significantly more than simply describe these natural relations,” he stated. “To put the matter more precisely, do the patent claims add enough to their statements of the correlations to allow the processes they describe to qualify as patent-eligible processes that apply natural laws? We believe that the answer to this question is no.”

BIO Says Decision Creates “Uncertainty and Confusion For Inventors”

It is not immediately clear what impact the decision will have on the life sciences industry. But the community is worried that the Supreme Court is taking a new approach to patent law by looking at patent claims piecemeal rather than as a whole. Hans Sauer, Biotechnology Industry Organization’s deputy general counsel of intellectual property, said that when one looks at the individual pieces of an invention they can appear to be old and unexceptional while taken together they create something new.

“What do we have to do to make these things patentable?” Sauer said. “We don’t know. The decision creates uncertainty and confusion among inventors.”

Former Solicitor General Seth Waxman, who represented Roche Molecular Diagnostics and other diagnostic manufacturers in an amicus brief in support of Prometheus, said the vast majority of biotech inventions are not implicated by the ruling.

The decision does not speak at all to composition of matter and “doesn’t speak at all to the vast majority of products developed by biotech as a whole,” Waxman, now a partner at WilmerHale, stated. However, he said the decision will have to be reviewed carefully to determine what it means for the field of personalized medicine.

“We will have to evaluate what the Supreme Court has said and what, if anything, it means for investment and development in molecular and other forms of diagnostic tools,” he said.

More immediately, the ruling could have an impact on the American Civil Liberties Union’s challenge of Myriad Genetics Inc.’s BRCA1 and BRCA2 gene patents. The ACLU and the Public Patent Foundation filed a writ of certiorari petition in December asking the court to determine whether human genes are patentable. The court was scheduled to review the petition at a conference in February but took no action on it, leading to speculation that it was awaiting a ruling in the Prometheus case Also see "Supreme Court Abstains From Drugs: Will Not Review J&J Vs. Abbott; Takes No Action On Gene Patents" - Pink Sheet, 21 February, 2012..

“We are pleased by the court’s strong reaffirmation that patents on laws of nature and natural phenomena are invalid because they impede, rather than encourage, innovation,” ACLU attorney Sandra Park said. “Today’s decision bodes well for the ultimate outcome of the Myriad litigation.”

Myriad’s BRACAnalysis test detects mutations in BRCA genes, which are the cause of most cases of hereditary breast and ovarian cancers. The Federal Circuit ruled last year that DNA isolated from the body has a different chemical structure from DNA in the body and can thus be patented.

Court Declines To Say Whether Diagnostics Need Increased Protection

The Supreme Court briefly mentioned medical diagnostics at the end of the ruling but did not say how its decision would apply to this technology.

“Prometheus, supported by several amici, argues that a principle of law denying patent coverage here will interfere significantly with the ability of medical researchers to make valuable discoveries, particularly in the area of diagnostic research,” the opinion states.

“In consequence, we must hesitate before departing from established general legal rules lest a new protective rule that seems to suit the needs of one field produce unforeseen results in another,” the ruling continues. “We need not determine here whether, from a policy perspective, increased protection for discoveries of diagnostic laws of nature is desirable.”

Justice Breyer said Prometheus’ test involves telling doctors to apply the laws of nature when treating their patients. He compared that to trying to patent Einstein’s famous law by claiming a process consisting of simply telling linear accelerator operators to refer to the law to determine how much energy an amount of mass has produced, or vice versa.

The court asserted that “simply appending conventional steps, specified at a high level of generality, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patentable.”

Court Is Concerned About Patents That Tie Up Future Innovation

Thiopurine drugs are used to treat autoimmune diseases, such as Crohn’s disease and ulcerative colitis. One of Prometheus’ patent claims a metabolite level of over 400 indicates toxicity requiring a lower dosage. Mayo developed a test using 450 as the toxicity-risk level number. During oral arguments Mayo’s attorney said Prometheus’ patent preempts the entire field and prevents others like the Mayo Clinic from offering a better metabolite test with a different therapeutic range Also see "Drug Calibration Patents Under Scrutiny As Supreme Court Weighs How To Build On Law Of Nature" - Pink Sheet, 7 December, 2011..

Justice Breyer voiced that concern in his opinion. The steps in Prometheus’ test “add nothing of significance to the natural laws themselves,” he said. “Unlike, say, a typical patent on a new drug or a new way of using an existing drug, the patent claims do not confine their reach to particular applications of those laws.

“The presence here of the basic underlying concern that these patents tie up too much future use of laws of nature simply reinforces our conclusion that the processes described in the patents are not patent eligible, while eliminating any temptation to depart from case law precedent.”

A district court had ruled in favor of Mayo, finding that Prometheus’ patents effectively claim natural laws or natural phenomena – namely the correlations between thiopurine metabolite levels and the toxicity and efficacy of thiopurine drug dosages. The U.S. Court of Appeals for the Federal Circuit reversed, concluding that the steps involved in the process involve the transformation of the human body or of blood taken from the body and thus met its “machine or transformation test” of patentability Also see "Biotech's Patent Suite Catches Sparks From Federal Circuit's Prometheus Decision" - Pink Sheet, 21 September, 2009..

Mayo twice petitioned the Supreme Court for review. The court initially remanded the case for reconsideration in light of its 2010 decision in Bilski v. Kappos, which found that the “machine-or-transformation” test used by the Federal Circuit to determine if an invention is patent-eligible is not the only appropriate test. Under that test a process or method claim must either be tied to a machine or apparatus, or transform an article into a different state to be patentable. The Federal Circuit reaffirmed its decision and Mayo again appealed the finding to the Supreme Court.

BIO and the Pharmaceutical Research and Manufacturers of America had each submitted amicus briefs in support of Prometheus, urging the court not to issue a broad ruling that would prevent patenting of diagnostic and therapeutic methods Also see "Personalized Medicine At Stake In Prometheus Patent Case, BIO Tells Supreme Court" - Pink Sheet, 5 December, 2011.. The government also submitted a brief, asserting that Prometheus’ test is patentable but would be found invalid for obviousness and lack of novelty.

Supreme Court Overturns Drug Calibration Patents, Creating Confusion In Biotech Realm

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