Sanofi-Aventis and Bristol-Myers Squibb Victorious Over Apotex in Plavix Case

Following a month-long trial held in January and February of this year, last week, a federal district court upheld the validity, and enforceability of Sanofi's (SNY) U.S. Patent No. 4,847,265, which covers the active ingredient in Plavix. In addition, the court permanently enjoined Canadian generic drug maker Apotex from engaging in any activity that would infringe the '265 patent, and stated that damages would be set through future proceedings. If the ruling is upheld on appeal, BMY and Sanofi can avoid generic competition for Plavix until November 2011.

Apotex had stipulated to infringement since its product also contains the patented clopidogrel bisulfate [CBS] compound. Apotex asserted several bases for finding the patent invalid. Its inherent anticipation and obviousness arguments seemed to present the strongest challenges to validity.

Apotex argued that a prior Aventis patent had inherently anticipated CBS. The earlier patent disclosed a broad genus of thienopyridines which included CBS in addition to millions of other compounds. Apotex argued that the court should see this as a type of Petering anticipation, where the patentee’s stated preferences can limit a broad disclosure to an effective disclosure of a very small subgenus of compounds. The court rejected this argument, though.

The Petering rule appears to require precise, unambiguous statements that single out the narrow subgenus from the broad disclosure. In this instance, the court found that the alleged statements lacked precision and could reasonably have pointed to other subclasses as well. Thus, the prior disclosure of the broad genus failed to inherently disclose CBS.

The obviousness issue here has some striking similarities to the issue that the Federal Circuit considered in the recent Pfizer v. Apotex case, concerning amlodipine besylate, the active ingredient in Norvasc. In Pfizer, the CAFC had invalidated a patent because the besylate salt would have been obvious to one of skill in the art based on (1), the instability of the maleate salt, (2), the knowledge of skilled practitioners, and (3), the teachings of the prior art.

In this case, the prior art revealed the hydrochloride salt of the racemate of CBS. Apotex argued that this disclosure should render the bisulfate salt of the enantiomer [CBS] obvious.

The court rejected this argument for the following reasons:

First, the court held that Apotex failed to show that a person of ordinary skill in the art would have reasonably expected that one enantiomer of the racemate would possess all of the racemate’s therapeutic activity and none of its toxicity.

Second, distinguishing this case from Pfizer, the court found that Apotex could point to nothing that would disclose the highly favorable properties of the bisulfate salt. (In fact, one reference appeared to teach away from using sulfuric acid salts.)

The case should present the CAFC with some interesting questions on appeal (Apotex has vowed to immediately appeal the decision). The case will provide a welcome opportunity for the court to refine its post-KSR obviousness jurisprudence, and give district courts additional guidance on the breadth of its recent Pfizer (PFE) holding.

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