Eisai filed patent infringement suits in the US District Court for the Southern District of New York against Teva Pharmaceutical Industries and Dr Reddy's Laboratories in November 2003.
The suits were Eisai's response to the two generic drugs companies' applications for abbreviated new drug applications (ANDAs) to manufacture generic versions of Aciphex prior to the patent's expiration date.
Both Teva and Dr Reddy's argued that Eisai's patent was unenforceable for inequitable conduct, but Teva went further in asserting that the patent was invalid for obviousness.
In October 2006, Judge Gerard Lynch granted partial summary judgment to Eisai, upholding the validity of the Aciphex composition of matter patent. In May 2007, he also determined that the patent was enforceable. Teva and Dr Reddy's subsequently appealed to the CAFC.
Eisai's US patent 5,045,552 claims rabeprazole and its salts, the active ingredient in Aciphex.
Teva argued that a combination of three prior art references proved the patent was obvious, most significantly Takeda Pharmaceutical Company's European patent 174,726, which covers the ulcer treatment compound lansoprazole.
Teva targeted lansoprazole, which is nearly identical to rabeprazole, as the so-called lead compound for rabeprazole, arguing that the patent was obvious over lansoprazole.
A lead compound is one that serves as the starting point for chemical modification to a pharmaceutical invention.
Teva argued that it would have been obvious to someone of ordinary skill in the art to choose lansoprazole as a lead compound, since it contains a fluorinated substituent that increases lipophilicity, or the ability of a compound to cross lipid membranes.
However, since rabeprazole does not include this substituent, the Court said that Teva's argument was illogical. In his opinion, CAFC judge Randall Rader, joined by judges Richard Linn and Sharon Prost, said that there was "no discernible reason for a skilled artisan to begin with lansoprazole only to drop the very feature, the fluorinated substituent, that gave this advantageous property".
The Court also rejected Teva's argument that other compounds may have served as lead compounds, noting: "The district court did not rigidly limit Teva's obviousness arguments by forcing Teva to select a single lead compound. Rather Teva alone selected lansoprazole as the anchor for its obviousness theory, not the district court."
For this reason, the Court said: "Teva cannot create a genuine issue of material fact on obviousness through an unsupported assertion that compounds other than lansoprazole might have served as lead compounds", since "post-KSR, a prima facie case of obviousness for a chemical compound still, in general, begins with the reasoned identification of a lead compound."
The April 2007 Supreme Court decision in KSR v Teleflex mandated an "expansive and flexible approach" to determining obviousness.
"We are pleased with the court of appeals' decision to uphold the district court's favourable ruling to prevent the sale of Teva's and Dr Reddy's generic products before the expiration of the rabeprazole sodium composition of matter patent," said Hajime Shimizu, chairman and CEO of Eisai Corporation of North America and Eisai Inc.
A spokesperson for Teva told Managing IP that the company had no comment on the decision.
Bruce Wexler of Paul Hastings, who represented Eisai in the case, said that the ruling bodes well for chemical compound patents post-KSR. "I think it negates any argument that KSR would have a negative effect on the strength of chemical compound patents," he said.
The decision also invalidates Mylan Laboratories' ANDA application for Aciphex, since the company agreed to be bound by the results of the case.
Aciphex has annual sales of about $1.2 billion.
