By Donald Zuhn --
In an appeal from a District Court judgment of validity and infringement, the Federal Circuit affirmed the District Court's finding of validity, holding that U.S. Patent No. 5,229,382 (the '382 patent) was not anticipated by Chakrabati et al., 1980, J. Med. Chem. 23:878-84 (Chakrabati) or the patentee's clinical trials, or rendered obvious by the prior art.
Plaintiffs-Appellees Eli Lilly and Co. and Lilly Industries Ltd. (Lilly) own the '382 patent, which relates to olanzapine (sold under the trademark Zyprexa®) and the use of olanzapine to treat schizophrenia. Prior to discovering olanzapine, Lilly had identified a number of drugs in the same family of compounds, including clozapine, flumezapine, ethyl flumezapine, and ethyl olanzapine. Of these prior art compounds, clozapine had been shown to be effective in treating some forms of schizophrenia - but not without potentially fatal side-effects as one percent of patients treated with clozapine would suffer from the blood disorder agranulocytosis.
Until the discovery of olanzapine, the efficacy of clozapine (and other antipsychotics) had been attributed to the presence of an electron-withdrawing group such as a fluorine or chlorine atom. However, while clozapine has a chlorine atom on its benzene ring, olanzapine has a hydrogen atom, which is not an electron-withdrawing group.
Seeking approval to market generic olanzapine, Defendants-Appellants Zenith Goldline Pharmaceuticals, Inc. (now known as IVAX Pharmaceuticals, Inc.), Dr. Reddy's Laboratories, Ltd., and Teva Pharmaceuticals USA, Inc. (IVAX) filed an Abbreviated New Drug Application (ANDA) with the FDA. In response, Lilly filed suit against IVAX, alleging that the filing of the ANDA infringed the '382 patent. Following a bench trial, the District Court determined that the '382 patent was valid and infringed, and found no inequitable conduct. IVAX appealed the District Court's determinations of validity and no inequitable conduct.
With regard to its anticipation defense, IVAX argued that Chakrabati anticipated claim 1 of the '382 patent because that reference identified compounds from the family of compounds - thienobenzodiazepines - to which olanzapine belonged. IVAX cited In re Petering, 301 F.2d 676 (C.C.P.A. 1962) and In re Schaumann, 572 F.2d 312 (C.C.P.A. 1978) in support of this argument.
In distinguishing Petering, the Federal Circuit noted that "in contrast to this case, the prior art in Petering did more than make a broad disclosure. In Petering, the prior art disclosed a limited number of specific preferences from a specifically defined group of [compounds]." With respect to Schaumann, the Court observed that "the prior art patent [in that case] embraced a very limited number of closely related compounds and specifically described the claimed compound." The Court also noted that while "the prior art in both Petering and Schaumann expressly spelled out a definite and limited class of compounds that enabled a person of ordinary skill in the art to at once envisage each member of this limited class . . . , the number of compounds actually disclosed by [Chakrabati] numbers in the millions."
The Federal Circuit further noted that while Chakrabati discloses several preferred compounds, none of these preferred compounds resembles olanzapine. In addition, the Court observed that because Chakrabati "always expressed a preference for halogen-containing compounds (fluorine or chlorine), [and] not hydrogen," one of ordinary skill in the art "would have to depart from the teaching of the article and recombine the components of the specific illustrative compounds with hindsight." The Federal Circuit, therefore, concluded that Chakrabati did not place olanzapine in the public's possession, and thus, the District Court did not err in finding no anticipation.
With regard to IVAX's argument that Lilly's clinical trials of olanzapine constituted a public use, the Federal Circuit cited TP Labs., Inc. v. Prof'l Positioners, Inc., 724 F.2d 965 (Fed. Cir. 1984), as standing for the proposition that "[e]ven a use that occurs in the open may not invoke a bar when undertaken to experiment on or with the claimed invention." The Federal Circuit noted that the instant case satisfied several indicia of experimental use set forth in TP Labs., and therefore concluded that the District Court did not err in finding no public use.
Eli Lilly & Co. v. Zenith Goldline Pharm., Inc. (Fed. Cir. 2006)
Panel: Circuit Judges Rader, Schall, and Gajarsa
Opinion by Circuit Judge Rader
For a discussion of the Federal Circuit's decision on the issue of obviousness, readers are encouraged to turn to Kevin Noonan's article on the Lilly case.