Aventis Pharma S.A. v. Amphastar Pharmaceuticals, Inc.

Aventis Pharma S.A. (“Aventis”) (plaintiff) held the ‘618 patent and the reissue patent, ‘713, related to a composition of low molecular weight heparins (“LMWHs”) used to prevent blood clotting and marketed as the drug Lovenox in the U.S. and Clexane in Europe. A patent examiner with the U.S. Patent and Trademark Office (“PTO”) rejected the ‘618 application under 35 U.S.C. §§ 102(b) and 103 for prior art references, including the European Patent ‘144 (“EP ‘144”). The examiner concluded that the ‘618 patent did not claim to demonstrate some “unexpected or unobvious property not demonstrated by the prior art products,” including EP ‘144. Aventis amended its claim to address the anticipation rejection under 35 U.S.C. § 102(b), by highlighting the compositional differences of the ‘618 compound from the EP ‘144 compound, thereby asserting the two were structurally different. Aventis provided a declaration from a non-inventor, Dr. Andre Uzan, to demonstrate that the ‘618 compound’s half-life at 40 mg was longer than the EP ‘144 compound and thus the ‘618 compound achieved the same effect in a lower dose. Aventis also refuted the obviousness rejection under 35 U.S.C. § 103, claiming the properties of the ‘618 compound were not exhibited by the EP ‘144 compound. The patent examiner again rejected the ‘618 application, stating that Aventis had failed to provide evidence that the difference between it and the EP ‘144 was statistically significant. In response, Uzan submitted another declaration showing a statistical analysis between the mean half-life of the ‘618 compound and that of the EP ‘144 compound, but which did not include a dosage for EP ‘144. Uzan asserted the difference between the half-life values of the compounds were statistically significant. The patent examiner then approved the ‘618 application. Seeking to manufacture and market a generic version of Lovenox, Amphastar Pharmaceuticals, Inc. (“Amphastar”) (defendant) was sued by Aventis for infringement of the ‘618 patent in the U.S. District Court for the Central District of California. Amphastar moved for summary judgment, alleging Uzan intentionally failed to disclose the dosage information when comparing the half-lives of the ‘618 compound and the EP ‘144 compound. The district court found evidence of inequitable conduct by Aventis, granted Amphastar’s motion, and held the ‘618 patent unenforceable. Aventis appealed. The court of appeals concluded that the withholding of the EP ‘144 dosage information prevented the examiner from considering information relevant to patentability, but noted that the district court was required to determine whether Aventis intended to deceive the examiner. The appellate court reversed the district court’s grant of summary judgment of unenforceability and remanded for a determination of intent to deceive. On remand, the district court held a bench trial and found an intent to deceive because, but for Uzan’s intentional omissions, there was a high probability that the ‘618 patent would not have issued. Aventis again appealed.