Lilly Prevails Over IVAX, Teva, and Dr. Reddy's in Zyprexa Appeal

Eli Lilly & Co. et al. v. Zenith Goldline Pharms. et al., Nos. 05-1396, -1429, and -1430 (Fed. Cir. 2006)

          by Robert S. Dailey

Yesterday the Federal Circuit affirmed Eli Lilly’s April 2005 district court victory in its dispute with ANDA filers Zenith Goldline (now IVAX), Teva, and Dr. Reddy’s over generic Zyprexa.  The patent-in-suit, U.S. Patent No. 5,229,382, claims the the active ingredient in Zyprexa, olanzapine, and its use to treat schizophrenia.

Lilly developed olanzapine in the early 1990s.  The drug proved to be a safe alternative to clozapine and other thienobenzodiazepines that Lilly had previously developed.  The opinion, written by Judge Rader for a unanimous panel, addresses inherent anticipation, obviousness, experimental use negation, and inequitable conduct.

I. Inherent anticipation

The defendants had argued that olanzapine was inherently anticipated by a 1980 journal article that identified compounds in the same family.  The defendants argued that disclosure of a set of structurally similar compounds is sufficient for inherent anticipation, even when the prior art discloses no genus containing the patented compound.  They cited In re Petering, 301 F.2d 676 (CCPA 1962), and In re Schaumann, 572 F.2d 312 (CCPA 1987), to support their argument.  The Federal Circuit distinguished these cases, however.

Petering had addressed a situation where the prior art had not merely disclosed a broad disclosure of a genus, but had actually disclosed a set of compounds such that they formed a class containing only twenty compounds.  In Schaumann, the prior art disclosed compounds that differed only by a single variable, such that only a limited number of compounds was encompassed by the implied class.  In contrast, the 1980 journal article disclosed a wide-ranging series of clozapine-like compounds.  Any genus implied by the class would have included millions of compounds.  And the article gave no indication that the substituents could be interchanged.  Although the journal article did disclose the ethyl homolog of olanzapine, the discussion indicated that the homolog was excluded from the class of preferred compounds.

The defendants’ basic proposition appears to remain intact: that inherent anticipation does not require express disclosure of a genus containing the compound.  Disclosure of structurally similar compounds may be sufficient to anticipate if (i) the disclosure implies a sufficiently limited genus containing the patented compound; and (ii) the disclosure does not exclude the patented compound from membership in a preferred class.

II. Obviousness

The defendants made several obviousness arguments.  The court held that the prior art references generally taught away from modifying the disclosed compounds to reach olanzapine.  Prior to Lilly’s development of olanzapine, those of skill in the art believed that the therapeutic effect of clozapine-like compounds depended on the presence of an electron-withdrawing group at the 7-position of the benzene ring.  (Olanzapine has a hydrogen at this position.)  Even though one reference disclosed the ethyl homolog of olanzapine, the court held that one of skill in the art would have modified the ethyl homolog by adding an electron-withdrawing group at the 7-position rather than replacing the ethyl with methyl.

III. Other arguments

The defendants had also asserted that Lilly had used olanzapine in public in violation of the public use bar.  The court held that Lilly’s clinical trials were not public, and would have been protected as an experimental use (even if they had been conducted in public).

The defendants had also made three different inequitable conduct arguments.  The court held that none of the conduct cited by defendants was material to patentability.

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:

• More at Patent Docs: Dec. 28 post by Kevin Noonan; Dec. 29 post by Don Zuhn