On Tuesday, the Court of Appeals for the Federal Circuit reversed (pdf) a district court trial verdict that held the asserted claims of Aventis's (NYSE:SNY) patent on Altace not invalid, finding instead that the claimed invention would have been obvious. The patent in suit was U.S. Patent No. 5,061,722, which covers ramipril, the active ingredient in Altace. Aventis owns the '722 patent and King Pharmaceuticals (KG) markets Altace under an exclusive license.
Ramipril is a stereoisomer belonging to a family of compounds that includes 25 stereoisomers. Additionally, ramipril is one of a family of drugs known as Angiotensin-Converting Enzyme inhibitors, or "ACE inhibitors," which are useful for treating high blood pressure. The prior art asserted by Lupin included structurally similar ACE inhibitors, including enalapril, as well as publications describing how to separate stereoisomers from each other.
The Supreme Court's recent decision in KSR v. Teleflex appears to have been a key to the Federal Circuit's decision on Tuesday:
The district court held that Lupin failed to meet its burden of proof by clear and convincing evidence that a person of ordinary skill in the art would have been motivated to purify 5(NYSE:S) ramipril into a composition substantially free of other isomers. The district court saw this as a close case based principally on the absence of a clear and convincing showing of motivation. Since the date of that decision, however, the Supreme Court decided KSR Int'l Co. v. Teleflex Inc. . . . . Requiring an explicit teaching to purify the 5(S) stereoisomer from a mixture in which it is the active ingredient is precisely the sort of rigid application of the TSM test that was criticized in KSR.
Another interesting aspect of Tuesday's decision is that just six days ago, in Forest Labs v. Ivax Pharms., the Federal Circuit upheld the validity of another patent on a stereoisomer pharmaceutical compound: Lexapro (escitalopram). On Tuesday, the Federal Circuit held that ramipril is prima facie obvious (based, in part, on its structural similarity to prior art compounds), and that Aventis and King "failed to show unexpected results that would tend to rebut a prima facie case of obviousness." In contrast, according to Tuesday's opinion, in the Lexapro case "prima facie obviousness of a claim to a particular stereoisomer over a racemic mixture was rebutted where the particular stereoisomer showed unexpected benefits, and evidence indicated that the isomers would have been difficult for a person of ordinary skill in the art to separate."
Given the amount of revenue at stake (about $700 million in annual U.S. sales), I would expect Aventis and King to file a petition for rehearing or rehearing en banc with the Federal Circuit.