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Supreme Court Sends Myriad Back for a Do-Over

By Mari Serebrov
Washington Editor

WASHINGTON – Leaving a lot of personalized medicine claims in patent limbo, the Supreme Court Monday told an appellate court to reconsider a challenge to Myriad Genetics Inc.'s claims on the BRCA1 and BRCA2 genes, used in diagnostics for breast and ovarian cancer.

In remanding The Association for Molecular Pathology v. Myriad Genetics Inc., the Supreme Court instructed the Court of Appeals for the Federal Circuit to reconsider the case in light of its ruling last week in Prometheus, which involved patent claims on applying a law of nature. (See BioWorld Today, March 21, 2012.)

The remand did not come as a surprise, since the court had done the same thing with Mayo Collaborative Services Inc. v. Prometheus Laboratories Inc. In that case, the Federal Circuit was told to revisit Prometheus, keeping in mind the high court's ruling on business method claims in Bilski v. Kappos.

Like Prometheus, Myriad likely "will find its way back to the Supreme Court," Paul Rivard, a Banner & Witcoff shareholder, told BioWorld Today.

Although the claims involved in Myriad represent only a portion of the intellectual property covering the BRACAnalysis, the Salt Lake City biotech has vowed to "vigorously defend" the patents because of the issues at stake. Myriad's diagnostic is protected by 23 patents and about 500 claims, including 245 composition-of-matter claims and 240 method claims. Even if the courts ultimately overturn the 15 challenged claims, the rest of the patent claims would remain in force.

Some of the challenged claims are method claims, which the Federal Circuit already had ruled invalid. But the core of the case is comprised of composition claims on isolated DNA – something the Federal Circuit agreed does not exist in nature. Those claims are much different from the method patents in Prometheus. "I don't think anyone seriously believes the answer lies in Prometheus," Rivard said.

In its Myriad remand, the Supreme Court gave the Federal Circuit no direction, Rivard noted. Rather, it seemed to be saying, "Give us your thoughts on this."

While bouncing such cases between courts can be a lengthy, expensive exercise that underscores the uncertainty of personalized medicine claims, it can lead to more clarity over time as it gives the judges and justices an opportunity to further explain their thinking.

In Bilski, for instance, the Supreme Court said the so-called "machine-or-transformation" test was not the sole test for determining patentability of claims involving nature or abstract ideas. Under that test, the Federal Circuit had held that a claim was patentable if the invention was tied to a particular machine or apparatus or it transformed a particular article into a different state or thing. (See BioWorld Today, June 29, 2010, and July 6, 2010.)

But after Prometheus bounced back to the Supreme Court, the justices further defined their thinking on the machine-or-transformation test, saying it is only a clue to determining patent eligibility – not a definitive test. However, they offered no new test to take its place.

The machine-or-transformation test shouldn't play into the Federal Circuit's review of Myriad, Courtenay Brinckerhoff, a partner at Foley & Lardner, told BioWorld Today. The claims in Myriad follow the so-called "markedly different" test in that isolated DNA is markedly different from what's found in nature, she said.

EMDAC to Weigh in on CVOTs

What the FDA's Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) discusses at a two-day meeting this week could weigh heavily on the future development of obesity drugs.

The FDA is asking the committee to vote on whether a cardiovascular outcomes trial (CVOT) should be required for obesity drugs that have no theoretic risk or signal of cardiovascular harm. If EMDAC thinks they should be required, the FDA wants to know whether they should be conducted pre- or post-approval, or both, and whether an appropriately sized meta-analysis of Phase II and Phase III major adverse cardiovascular event (MACE) data would suffice.

The committee also will discuss possible CVOT designs and the pros and cons of including subjects at higher risk for cardiovascular events in Phase II and III trials of obesity drugs. Currently, most of the subjects enrolled in such trials have a low short-term MACE risk, so the trials don't reflect real-world risks, the FDA said in briefing documents for the Wednesday meeting.

The FDA issued a guidance in 2008 strongly recommending that sponsors demonstrate diabetes drugs do not result in an unacceptable increase in cardiovascular risk. It outlines several steps sponsors should take in Phase II and III development to assess that risk. The question before EMDAC is basically whether development of obesity drugs should mirror that of diabetes drugs.

While EMDAC's discussion likely will help shape the development path for future weight-loss drugs, Rodman & Renshaw analyst Michael King does not expect it to change the course for a trio of obesity drugs, long past Phase II and Phase III, that are taking a second shot at FDA approval.

"We view this meeting as a way for FDA to get ahead of the next round of drugs, including a number of potential anti-diabetes therapies looking to add an anti-obesity indication," King said.

With a PDUFA date of April 17, Vivus Inc.'s Qnexa (phentermine/topiramate) is the closest obesity drug to approval. While EMDAC voted 20-2 last month to recommend approval of the drug, it urged the FDA to require a large, post-approval CVOT, citing inconclusive data about Qnexa's cardiovascular risk. (See BioWorld Today, Feb. 23, 2012.)

The second drug in the trio, Arena Pharmaceuticals Inc.'s Lorqess (lorcaserin), is set to come before EMDAC May 10, a little more than a month ahead of its PDUFA date. Regardless of this week's discussion, Lorqess could have a tough road to approval because of modest efficacy, valvulopathy concerns, the potential for abuse and mammary and brain cancer risk. It also would be in the shadow of Qnexa, which has demonstrated more efficacy, BMO Capital Markets analyst Jim Birchenough said. (See BioWorld Today, Jan. 12, 2012.)

The final drug, Orexigen Therapeutics Inc.'s Contrave (naltrexone HC1/bupropion HC1), is being prepped for a pre-approval CVOT required by the FDA. With that trial slated to begin in the next quarter, Contrave's road to the market is likely a few years longer than that of Qnexa, putting Contrave at a disadvantage. (See BioWorld Today, Dec. 16, 2011.)

But that could change after this week's EMDAC meeting, Leerink Swann analyst Joshua Schimmer said. If the FDA decided to require pre-approval or two-stage CVOTs of both Qnexa and Contrave, the drugs could come to market at about the same time, he added.

Although several obesity drugs have been developed over the years, orlistat, sold as Xenical by Roche AG and as Alli by GlaxoSmithKline plc, is currently the only obesity drug approved for long-term use in the U.S. All the others have been withdrawn because of cardiovascular-related issues. (See BioWorld Insight, July 26, 2010.)

Dexfenfluramine was removed in 1997 because of valvulopathy, and sibutramine was removed in 2010 due to adverse cardiovascular effects. Cardiovascular risks and events also played into the 2004 withdrawal of ephedrine-containing dietary supplements and the withdrawal in 2000 of phenylpropanolamine-containing weight control products.