Thursday, May 15, 2008

Federal Circuit Affirms Decision Holding Lovenox Patent Unenforceable

Earlier today, the Federal Circuit affirmed a district court decision holding Aventis's patent on Lovenox (enoxaparin) unenforceable. The district court had found that renowned Aventis scientist, Dr. Andre Uzan, committed inequitable conduct during the prosecution of U.S. Patent No. 5,389,618, later reissued as RE38,743. Judge Prost wrote for the Court, joined by Judge Moore. Judge Rader dissented.

Dr. Uzan was not an inventor on the patent. Instead, he assisted in drafting one of the examples (Example 6) in the originally filed application. He also submitted two declarations during the course of the U.S. prosecution. The prosecution revolved around whether the claimed admixture of low molecular weight heparin (LMWH) was novel and/or nonobvious over a similar LMWH mixture disclosed in European Patent 40,144.

Example 6 compares the plasma half life for a composition embodying the invention with the half life of the LMWH composition disclosed in the '144 patent. The district court found that Example 6, coupled with Dr. Uzan's discussions of it in his declarations, overstated the case for the patentability of the claimed invention. The data from the '144 patent were for a 60 mg dose, but Example 6 failed to mention the dose. The example presented 40-mg and 60-mg data for the claimed LMWH. The 40-mg dose had a longer half life than the LMWH of the '144 patent, while the 60-mg dose did not. The district court found that Example 6 presented these data in a manner that highlighted the favorable results for the 40-mg dose, while obscuring the unfavorable results for the 60-mg dose. The district court found that Dr. Uzan's declarations compounded these potentially misleading aspects of Example 6. Thus, the district court found that the patent would never have issued apart from Dr. Uzan's exaggerated efforts to use Example 6 to distinguish the claimed LMWH from the prior art's LMWH.

Inequitable conduct requires an accused infringer to demonstrate that (1) the withheld or erroneous information was material to patentability, and (2) that the lack of candor was borne out of intent to deceive. Upon such a showing, the district court evaluates the equities and determines an appropriate equitable remedy. In a prior decision, the Federal Circuit had already held that Dr. Uzan's (mis)use of Example 6 was material to patentabilty. The case was remanded to determine whether he acted with deceptive intent.

Aventis, however, took a different course in its appeal. It elected to demonstrate that Dr. Uzan's conduct was indeed reasonable, and that the District Court clearly erred in reaching its finding of deceptive intent. The Federal Circuit was unpersuaded. Particularly, the court noted that some of Dr. Uzan's explanations for his conduct did not emerge until mid-way through the litigation.

In a further twist, the majority and the dissent both appear to question the court's prior materiality determination. After all, Aventis surrendered its original patent, deleted Example 6, and was awarded a reissue patent on the claimed LMWH.

Judge Rader's dissent takes a policy-oriented approach to the question of inequitable conduct. In ignoring the particulars of the case, he appears to concede that a mechanical application of the Court's recent jurisprudence may support the result that the majority reaches. Nevertheless, he suggests that equity is not well served when such a disproportionately harsh punishment is visited upon Aventis for conduct that was not even sufficient to affect the validity of the patent. Judge Rader notes that the Court's 1988 Kingsdown decision sought to make inequitable conduct an extraordinary and rare remedy. But the promise of Kingsdown has not lasted.

Barring an en banc reversal, the enoxaparin patent is no longer an impediment to the marketing of generic versions of bioequivalent LMWH. Amphastar, Teva and Momenta/Sandoz are all seeking FDA approval for a generic version of enoxaparin. LMWH is not a typical small-molecule drug, however; it is a complicated admixture of polysaccharides of varying molecular weights. Therefore, demonstrating bioequivalence is not a simple matter. Some have suggested that generic manufacturers may need to conduct limited clinical trials to gain marketing approval. Momenta recently stated that the FDA has decided not to require it to conduct clinical trials to gain approval for its generic enoxaparin.

The whole judgement can be read here.

(Source:Orange book blog)

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