Sanofi-Aventis SA lost a U.S. patent challenge brought by generic drugmakers Amphastar Pharmaceuticals and Teva Pharmaceutical Industries Ltd. over Sanofi’s blockbuster anticoagulant drug, Lovenox. Lovenox is Sanofi’s best-selling drug, with sales over $2.79 billion in 2005 — even more than Plavix. Lovenox is an injectable drug used in protecting patients against deep vein thrombosis or blood clots that usually develop in the legs. If the clots break free, they can wind up in the lungs causing potentially fatal consequences.
In June 2005, District Court had granted Amphastar and Teva a motion for summary judgment that invalidated Sanofi-Aventis’ US Pat. No. 5,389,618 for Lovenox based on inequitable conduct concerns. In April 2006, a federal appeals court reversed the decision and sent the case back to the trial court. The major issue was whether Sanofi tried to mislead to the U.S. Patent and Trademark Office. The District Court retried the case in December. Amphastar Pharmaceuticals and Teva Pharmaceuticals were seeking approval from the FDA for purportedly generic versions of Lovenox® and were challenging the ‘618 listed in the Orange Book for Lovenox®.
Although the patent covering the Lovenox main ingredient (enoxaparin sodium) does not expire until February 14, 2012, a ruling by the U.S. District Court for the Central District of California has found inequitable conduct by Sanofi when it initially filed the patent. In the decision by Judge Mariana Pfaelzer, the court ruled that there was sufficient evidence that Aventis had withheld material information during prosecution of the ‘618 patent and its replacement, Reissue Pat. No. RE38,743.
The central issue involves Aventis’ representations that Example 6 in the patent “clearly demonstrated” a significantly longer plasma half-life for the low molecular weight heparin (LMWH) compound. At no time did Aventis or its employee, Dr. Andre Uzan, disclose at what dosage the half-life comparisons in Example 6 were made. It was later discovered that the Example compared a 60 mg dose versus a 40 mg dose of the earlier product.
The case for deceptive intent hinged on the credibility and scientific rationale of the testimony of Dr. Uzan. The burden of affirmatively proving intent to deceive fell on Amphastar and Teva and the Court found clear and convincing evidence of intent to deceive in finding that (1) the applicant knew the information; (2) the applicant knew or should have known the materiality of the information; and (3) the applicant did not provide a credible explanation for the withholding. In fact, the Court opined that “Dr. Uzan’s explanation suffers from a total absence of indicia of credibility.” Ouch.
The Court ruled that but for Dr. Uzan’s intentional omissions, there was a high probability that the ‘618 patent would not have issued and the ‘618 patent must therefore be found unenforceable due to inequitable conduct.
If the ruling stands, Sanofi could see 60% of its Lovenox sales at risk to generic competition five years before the patent would have expired. However, the Food and Drug Administration hasn’t approved any generic versions yet. Also, some believe that Sanofi may avoid an immediate generic entry because Lovenox’s complex formula makes it difficult for other companies to copy. Generic-drug makers must prove their products are bioequivalent to brand-name drugs — meaning it must have the same strength and reach the desired target in the same way as a brand-name drug.
See the entire ruling here: teva-v-sanofi.pdf