Federal Circuit Affirms Decision Holding Lovenox Patent Unenforceable

Aventis Pharma v. Amphastar and Teva, No. 2007-1280 (Fed. Cir. 2008)

          by Robert S. Dailey

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.

In a previous post, we questioned whether the district court, in this instance, applied the correct legal standard for determining deceptive intent.  For example, the district court appeared to employ a burden shift, requiring Dr. Uzan to prove the absence of 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.

For the immediate future, Aventis will continue to market Lovenox without generic competition.  It is unclear when that will change.

RELATED READING:

• Reuters
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Comments

[Sean]

It's funny that Rader has to even characterize the holding as a "mechanical application" of recent decisions, when the principle is one of equity. While there is considerable discretion given to the trial court, the steep burden of showing both prongs clearly and convincingly should nevertheless be adhered to, followed by an equitable determination of whether the conduct merits finding the patent to be unenforceable. If there was any doubt in this case about either prong OR about the remedy, then the patent should not be unenforceable.

Not that anyone is asking, but I personally think that the early indications are that Judge Moore is taking the court in some bad directions with the decisions on which she participates.

[Robert Dailey]

Sean:

Thanks for your comment. The phrase "mechanical application" is my phrase. Judge Rader did not use those words in his dissent.

I tried to interpret what Judge Rader is doing in his dissent. In many dissents, the dissenter picks apart the reasoning used by the majority to arrive at the holding. Judge Rader did not do that in this case. Instead, he seems to take more of a bird's-eye view of how the facts of this case mesh with the policy rationales for having an inequitable conduct doctrine.

The majority took a narrow approach: They looked at the limited question of whether the district court's fact-finding was clearly erroneous. When the question is circumscribed in this manner, it is difficult to impugn the majority's reasoning. In my estimation, Judge Rader seems to be asking a different question: When sitting in equity, need the court take such a circumscribed approach?