Aventis Pharma S.A. v. Hospira, Inc.

Case Name: Aventis Pharma S.A. v. Hospira, Inc., 675 F.3d 1324 (Fed.Cir. Apr. 9, 2012) (Circuit Judges Linn, Dyk, and Prost presiding; Opinion by Prost) (Appeal from D. Del., Sleet, C.J.) (Because the district court's claim construction was adopted and Sanofi did not address key obviousness findings by the district court in its appellate brief, obviousness finding was affirmed; lack of credibility of inventor testimony leads to affirmance of inequitable conduct.).

Drug Product and Patent(s)-in-Suit: Taxotere^® (docetaxel); U.S. Pat. Nos. 5,750,561 ("the '561 patent"); 5,714,512 ("the '512 patent").

Nature of the Case and Issue(s) Presented: The patents-in-suit relate to the administration of the chemotherapy cancer drug docetaxel. Docetaxel is a successor to the cancer drug Taxol^®(paclitaxel). The now-expired U.S. Patent No. 4,814,470 ("the '470 patent") covered the docetaxel composition. Docetaxel and paclitaxel are administered intravenously by slowly delivering the drug in a diluted aqueous solution called a "perfusion." The APIs, however, tend to precipitate out of solution, and so in order to avoid this unwanted effect, the drugs are mixed with additives like surfactants and ethanol. In the prior art, the surfactant Cremophor was used, but it was known to trigger serious allergic reactions, including anaphylactic shock. The patents-in-suit disclose the use of surfactants other than Cremophor with docetaxel and decreasing the amount of ethanol to reduce alcohol intoxication and anaphylactic effects in patients. Plaintiffs ("Sanofi") filed suit against Defendants ("Apotex") for infringement of the '561 and '512 patents. After a bench trial, the district court found that claim 5 of the '561 patent and claim 7 of the '512 patent were invalid for obviousness, that claim 7 of the '512 patent was not infringed, and that both patents-in-suit were unenforceable for inequitable conduct. Sanofi appealed, and the Federal Circuit affirmed.

Why Apotex Prevailed: At oral argument, Sanofi's counsel confirmed that under the district court's construction of the term "perfusion," claim 5 of the '561 patent was obvious. Sanofi therefore challenged the district court's claim construction, arguing that "perfusion" should be construed narrowly and defined to be "effective for treatment, safe, and stable (i.e., not precipitate) for at least eight hours." The Federal Circuit rejected this construction on the grounds that neither the "claims, the specification, nor the prosecution history suggest that the claimed perfusion must satisfy certain safety or efficacy standards." While the eight-hour limit was referenced in the specification and some of the examples in the patent, "these general descriptions of the characteristics of embodiments do not suffice to limit the claims." Because the Court affirmed the district court's construction of "perfusion," it also affirmed the district court's judgment that claim 5 of the '561 patent was invalid as obvious.

Claim 7 of the '512 patent claims a "composition," which the parties agreed can be either a stock solution or a perfusion. With respect to stock solutions, the parties agreed that the phrase "essentially free or free of ethanol" in claim 7 means "no more than 5% ethanol by volume." The district court found that claim 7 was obvious in light of the prior art '470 patent. Because Sanofi did not address the district court's obviousness finding with respect to stock solutions in its opening brief, the Federal Circuit affirmed, holding that Sanofi waived its argument thereby rendering the district court's finding of obviousness unchallenged.

The issue of inequitable conduct concerned the inventor's withholding of two prior art references, "Vidal" and "GV", from the Patent Office. The district court found that the Vidal and GV references were material to patentability and that inventor Fabre withheld them with an intent to deceive the Patent Office. Sanofi argues that (i) inventor Fabre explained why he did not disclose the references, thus, the court's finding that he acted with the intent to deceive was not the single most reasonable inference that could be drawn from the evidence; and (ii) Vidaland GV were not material to patentability because they were duplicative of references that were before the Patent Office. Concerning materiality, the Federal Circuit found that the GV and Vidal references were necessarily material and passed the "but-for" test stated in the Therasense case. Moving to intent, inventor Fabre testified that he did not cite Vidal because the experiments he and his co-inventors performed with doxcetaxel resulted in perfusions that did not demonstrate eight hours of stability, i.e., failed experiments that he felt did not need to bedisclosed to the Patent Office. The Federal Circuit, like the district court, did not find this explanation credible. Fabre testified that he learned of replacing Cremophor with another surfactant from the Vidal reference and that the disclosure of the Vidal reference was "one of the main factors that shaped [his] thinking." Further, the inventors cited references to the Patent Office that illustrated the problem in the art concerning anaphylactic reactions associated with Cremophor, but did not cite the Vidal reference, which revealed the solution to this problem. The same conclusions were reached with regard to the GV reference, which specifically disclosed a better solubility profile using an excipient system that included a surfactant other than Cremophor. Given this testimony, and the findings of the district court that Fabre was not a credible witness, the Federal Circuit affirmed.