By Brian Craig, J.D.
The U.S. Court of Appeals for the Federal Circuit has concluded that patent claims for the opioid dependence drug Zubsolv are nonobvious and valid. In reversing the decision by the federal district court in Delaware, the Federal Circuit found that the defending generic drug manufacturer failed to prove obviousness by clear and convincing evidence. The Federal Circuit held that unobvious improvement in properties or use is highly relevant to patentability of a new product.The appeals court concluded that the novelformulation combining buprenorphine with the opioid antagonist naloxone in substitution therapy enables reduced dosage and enhanced efficacy in substitution therapy products, deterring abuse (Orexo AB v. Actavis Elizabeth LLC, September 10, 2018, Newman, P.).
Orexo AB and Orexo US Inc. ("Orexo") own U.S. Patent No. 8,940,330 ("the ’330 Patent"). The ’330 Patent, entitled "Abuse-Resistant Pharmaceutical Composition for the Treatment of Opioid Dependence," claims a product having the brand name Zubsolv, approved by the FDA for treatment of opioid dependence. The federal district court in Delaware held the asserted ’330 Patent claims invalid, ruling that a skilled artisan would obviously have selected these components from the prior art and reformulated them as in the ’330 Patent. The district court concluded that generic drug maker Actavis Elizabeth LLC ("Actavis"), which filed an Abbreviated New Drug Application ("ANDA") for a generic counterpart of Zubsol, met its burden of proving by clear and convincing evidence, that certain claims of the ’330 Patent are obvious. Orexo appealed the district court decision.
The ’330 Patent. The Federal Circuit first reviewed the claims for the ’330 Patent. ’330 Patent specification explains that opioid based pharmaceutical products intended for the relief of pain have become a source of addiction, dependency, and abuse. Treatment for opioid addiction includes a protocol called "substitution therapy." The ’330 Patent combines buprenorphine with the opioid antagonist naloxone in substitution therapy. Actavis does not dispute the improvement, or its value in treatment of addiction. Rather, Actavis argues that this formulation is obvious based on a combination of references, and that improved function and use are irrelevant if the product is obvious.
Prior art. The Federal Circuit then reviewed the prior art for the ’330 Patent. The buprenorphine and naloxone combination in the 4:1 ratio has been used for substitution therapy at least since 2002. U.S. Patent No. 8,475,832 ("the ’832 Patent") describes an orally dissolvable film that cannot be easily removed once placed inside the mouth. The film contains the buprenorphine/naloxone combination in the 4:1 ratio, and is described as bioequivalent to Suboxone sublingual tablets. Orexo attributes the improvements achieved by the Zubsolv product to the microparticles of buprenorphine adhered to the surface of citric acid carrier particles.
Obviousness. The sole issue before the appeals court was whether the district court properly concluded that the generic drug manufacturer showed by clear and convincing evidence that the patent claims are obvious. To invalidate a patent on the ground of obviousness, the challenger has the burden of proving that the subject matter as a whole would have been obvious to a person of ordinary skill in the field of the invention. 35 U.S.C. § 103(a). A party seeking to invalidate a patent on obviousness grounds must demonstrate by clear and convincing evidence that a person of ordinary skill would have selected and combined and modified the subject matter of the references in the manner of the claimed invention, with a reasonable expectation of success.
Here, the district court found that a person of ordinary skill in the art would not have excluded citric acid. The district court found that the ’832 Patent shows that the use of citric acid with an interactive mixture would also improve bioavailability. The Federal Circuit found, however, that the record does not contain clear and convincing evidence of a teaching or suggestion to use citric acid particles as a carrier for this opioid product in substitution therapy, or that the actual beneficial results would be obtained. The district court also erred in discounting the enhanced bioavailability in the ’330 Patent’s formulation as a difference in degree, not a difference in kind. Furthermore, the district court discounted Orexo’s evidence that Zubsolv is less susceptible to abuse than Suboxone. The FDA deemed the product worthy of approval for the efficacy that was established in the clinical trials. It was established that this novel formulation enables reduced dosage and enhanced efficacy in substitution therapy products, deterring abuse. Based on the record as a whole, the Federal Circuit concluded that Actavis failed to establish obviousness by clear and convincing evidence. Therefore, the Federal Circuit reversed the district court decision and remanded to the case to the district court.
This case is No. 2017-1333.
Attorneys: Errol Taylor (Milbank, Tweed, Hadley & McCloy LLP) for Orexo AB and Orexo US Inc. George C. Lombardi (Winston & Strawn LLP) for Actavis Elizabeth LLC.
Companies: Orexo AB; Orexo US Inc.; Actavis Elizabeth LLC
MainStory: TopStory Patent FedCirNews
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