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District court ruling maintains patent protection for Allergan’s Saphris®

The inventors of U.S. Patent No. 5,763,476 (“the ’476 patent”), assigned to Allergan/Forest Laboratories, made a startling discovery during the development of Saphris®. Saphris® contains the active ingredient asenapine, and is indicated for the treatment of schizophrenia and manic and mixed episodes associated with bipolar I disorder. During the development process, the inventors discovered that asenapine administered using either a conventional oral tablet or an IV formulation had the potential to cause serious cardiotoxic side effects in subjects taking the medicine. The inventors solved this problem—which had been completely unknown in the art—using a sublingual formulation, a formulation that dissolves under the tongue that leads to the diffusion of the medicine directly through the oral mucosa and bypasses the digestive system. It was completely unexpected that a sublingual dosage form could solve the cardiotoxicity problem and even today, it is unknown exactly why.

Finnegan represented Allergan/Forest in its Hatch-Waxman litigation in the District of Delaware, filed against generic pharmaceutical defendants that sought to make generic versions of Saphris®. The four defendants that proceeded to trial conceded infringement of certain claims of the ’476 patent. Following a two week trial, the district court held the asserted claims valid, rejecting defendants contentions that they were obvious in view of the prior art and were not enabled or adequately described by the specification. It has been established precedent for decades that the discovery of an unknown problem can itself be patentable, and the district court determined that the inventors discovered an unobvious solution to an unknown problem, namely that oral and IV administered asenapine could cause serious cardiotoxic side effects. The district court further explained “[t]he sublingual solution to the cardiotoxicity problem was not ‘predictable’ or ‘expected’. . . . There were numerous other formulations that could have been experimented with to try to solve the problem, but no reasonable expectation that any of them would have.” The district court further disagreed with defendants’ assertions that there was other motivation to make a sublingual asenapine tablet, stating that “skilled artisans reviewing the publications of the publically reported clinical studies would have understood that orally administered asenapine was safe, bioavailable, and clinically effective even at relatively low doses. . . . There was nothing in the prior art that would have indicated that the oral tablet had problems, such that skilled artisans would have been motivated to invest the resources necessary to completely change the route of administration.” As such, “[t]he court discerns no motivation from the record evidence to use a sublingual formulation—a formulation that had never before been used for an antipsychotic drug.”

The district court ordered the Food and Drug Administration (FDA) not to approve the defendants’ Abbreviated New Drug Application (ANDA) for generic asenapine until after the expiration of the ’476 patent.