Amphastar and Teva Prevail Over Aventis in Generic Lovenox Trial, But Still May Not Receive FDA Approval

Aventis Pharma v. Amphastar Pharms., No. 03-887 (C.D. Cal. 2007)

In a ruling issued last Friday, Judge Mariana R. Pfaelzer of the U.S. District Court for the Central District of California held Aventis’s U.S. Patent No. 5,389,618 and its U.S. Reissue Patent No. 38,743 unenforceable due to inequitable conduct.  The patents cover Lovenox (enoxaparin), a low-molecular weight heparin composition exhibiting anticoagulant properties and indicated for the prevention and treatment of deep vein thrombosis.  The drug was Aventis’s top seller as of Q3 of 2006, and was on pace to gross nearly $2 billion in U.S. sales for the year.  Amphastar and Teva have filed ANDAs for generic Lovenox, and await FDA approval.

In 2005 the district court found the same patents unenforceable on summary judgment.  On appeal last year, the Federal Circuit affirmed the district court on the materiality prong of inequitable conduct, but remanded the case for a full trial on the intent prong.  Friday's ruling follows a five day bench trial on that issue, held in December.

The standard rule on inequitable conduct requires the defendant to prove materiality and deceptive intent independently by clear and convincing evidence judged by the totality of the circumstances.  Several recent Federal Circuit inequitable conduct opinions have come close to articulating what appears to be a burden shifting test for determining deceptive intent.  Last year’s Ferring v. Barr Labs. probably stands as the high-water mark.  Other cases in the same vein include Bruno Independent Living and Frazier.  When the facts of these cases are examined closely, however, it becomes clear that they signal no significant departure from the general rule.

These recent cases all involve (i) highly misleading statements and/or omissions to the PTO, (ii) circumstances which the make the conduct appear particularly egregious, and (iii) plaintiffs who proffer no explanations for their conduct.  The rule could be stated as follows: A plaintiff whose conduct reeks of bad faith cannot avoid inequitable conduct simply by coming to court and remaining silent.  This is not burden shifting, but a gloss on how to apply the totality-of-the-circumstances test with a particular class of defendants.  After all, none the Federal Circuit’s post-Ferring opinions profess to abandon the totality-of-the-circumstances test in favor of a burden-shifting mechanism.  Moreover, the Federal Circuit has consistently held that defendants must prove more than an absence of good faith, and that plaintiffs are under no obligation to prove anything.

But these nuances were lost on the district court when it ruled against Aventis last week.  In its analysis, the court made express use of a burden shifting test for determining inequitable conduct.  The court cited the aforementioned line of cases and took language from Paragon Podiatry (Fed. Cir. 1993), to craft a rule which would allow a defendant to shift its burden of proof simply by showing an unexplained violation of the duty of candor.  But Paragon Podiatry involved a summary judgment motion.  Of course the court used a burden shift in that instance because that is what courts are required to do in ruling on summary judgment motions.  This was a trial, however, not a mere summary judgment hearing.  The regular totality-of-the-circumstances test ought to have been used in this case.  Instead, the court shifted the burden to Aventis and largely forced the Aventis scientist to prove that he had in fact acted in good faith.  Aventis will most likely appeal the decision to the Federal Circuit.

Even though last Friday's ruling is a blow to Aventis, it is far from clear that Aventis will be facing competition from Generic Lovenox anytime soon.  Neither Amphastar nor Teva has received approval from the FDA to market generic Lovenox and some analysts reportedly believe they never will.  Enoxaparin is a complex heterogeneous mixture of polysaccharides that is difficult to characterize and may be impossible for generic companies to replicate.  Indeed, Aventis filed a citizen petition in 2003 urging the FDA not to approve generic versions of Lovenox until enoxaparin is fully characterized or until the generic companies conduct full clinical trials to establish safety and efficacy.  The FDA has not yet ruled on Aventis's petition.

Robert Dailey, Ph.D. is a physical chemist and a third-year law student at the University of North Carolina at Chapel Hill.  Dr. Dailey was a member of the 2006 class of summer associates at McDonnell Boehnen Hulbert & Berghoff.

RELATED READING:

• Feb. 9 Reuters article, with reaction to Friday's district court decision
• Feb. 9 Forbes article, reporting that Momenta Pharmaceuticals may have the best chance of obtaining FDA approval for generic Lovenox
• Feb. 9 Sanofi-Aventis press release