A classic example of product "evergreening" is how AstraZeneca used its experience with its omeprazole franchise (sold for over a decade as Prilosec®) to promote an alternative form of the drug, Nexium® (particularly, the S-omeprazole enantiomer) as "the little purple pill." One reason this strategy deserves admiration is that it is not the type of evergreening that some commentators and politicians have objected to (such as using formulation or other types of patents to continue protection after the composition patent has expired; for the record, there is nothing improper about that type of evergreening, either). But no strategy is perfect, as AstraZeneca found when the Federal Circuit affirmed a District Court judgment of non-infringement in AstraZeneca v. Hanmi.
The claimed invention was directed to the magnesium salts of the esomeprazole isomer sold as Nexium®. AstraZeneca filed suit under 35 U.S.C. § 271(e)(2) after receiving notice that Hanmi had submitted an ANDA for a generic version of the drug comprising the strontium salt of esomeprazole. The claims of the Orange Book listed patents in suit (U.S. Patent Nos. 5,714,504 and 5,877,192) as filed and the specification recited six specific cations as components of the enantiomeric salts of the invention: Na+, Mg2+, Li+, K+, Ca2+, or N+(R)4, where R is an alkyl with one to four carbons (the latter cation is also called generically an ammonium ion). However, the issued claims recited the esomeprazole isomer more generically as an "alkaline" salt, as in Claim 1 of the '504 patent:
A pharmaceutical formulation for oral administration comprising a pure solid state alkaline salt of the (-)-enantiomer of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole and a pharmaceutically acceptable carrier.
The District Court construed this and all the claims at issue to be limited to esomeprazole salts of the six specific cations recited in the specification, and the parties conceded that under this construction Hanmi's strontium salt formulation did not infringe. AstraZeneca appealed, on the basis that these cations were exemplary and that the skilled worker would recognize that the patents were entitled to the broader scope of "alkaline salts" that would encompass Hanmi's strontium salt of esomeprazole.
The Federal Circuit disagreed with AstraZeneca's arguments, in an opinion by Judge Taranto joined by Judges Dyk and Moore. The Court found that while the plain meaning of the term "alkaline salt" would encompass Hanmi's strontium salt, "[b]y conspicuously choosing only certain members of the class, and using the language [in the patent specifications that] it did, AstraZeneca conveyed a clear and definitive meaning that it was disclaiming other members of the class" including Hanmi's strontium salts. The Court cited portions of the specification in support of this construction, for example, "[t]he first sentence of the Detailed Description":
The present invention refers to the new Na+, Mg2+, Li+, K+, Ca2+ or N+(R)4 salts of the single enantiomers of omeprazole, where R is an alkyl with 1-4 carbon atoms, i.e. Na+, Mg2+, Li+, K+, Ca2+ or N+(R)4 salts of (+)-[omeprazole] and (-)-[omeprazole], where R is an alkyl with 1-4 carbon atoms.
This disclosure is specific, not generic according to the Court, and amounts to an express disclaimer of the scope of the claims AstraZeneca sought in litigation against Hanmi.
The Court further held that this disclaimer was not overcome by more generic language in the specification, when taken in context, because there was no evidence that AstraZeneca used the more generic terms in any sense other than joined by express recitation of the six exemplary cations. Neither the prosecution history nor the doctrine of claim differentiation was persuasive to the Court; with regard to the latter of AstraZeneca's asserted grounds of error, the Court stated that "the doctrine of claim differentiation does not . . . override clear statements of scope in the specification" citing Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1302 (Fed. Cir. 1999).
Regarding AstraZeneca's prosecution history arguments, at least a part of the Court's reasoning for its decision is that it perceived from the prosecution history that the focus of what AstraZeneca was trying to protect changed during prosecution. Specifically, the Court noted that AstraZeneca "conducted experiments that led it to conclude that one of the two enantiomers gave particularly good results," i.e., that which of the separated enantiomers (if either) was preferable was only known after the patent application was filed. As a result, AstraZeneca "filed amended claims to focus on that enantiomer" in response to a rejection:
When AstraZeneca filed the application that issued as the '504 patent, the language of the claims aligned perfectly with the written description's clear language about the scope of the "present invention": the broadest of the claims were limited in terms to salts using the six identified cations, combined with either one of the two omeprazole enantiomers. . . . After the Examiner rejected those claims for anticipation and obviousness, . . . AstraZeneca shifted the focus to unexpected benefits achieved by using the (-)-enantiomer rather than the (+)-enantiomer. Whereas the original claims and written description treated the two enantiomers with parity, AstraZeneca now distinguished the prior art by amending the claims to cover only esomeprazole, which it argued "unexpectedly exhibits a different and more advantageous pharmacokinetic profile than the racemic mixture or the (+)-enantiomer of omeprazole. To support that assertion, AstraZeneca submitted clinical studies that, it explained to the Examiner, "involved both the monovalent sodium salt and the divalent magnesium salt of the (-)-enantiomer of omeprazole, thus supporting the full scope of the genus of alkaline salts disclosed in the application and as claimed herein."
(record citations omitted, emphasis in opinion).
The Court did not find the italicized language in the patents' prosecution history to be sufficient to overcome the intrinsic limitations in the language of the specification and broaden the scope to alkaline salts to be greater than the six expressly recited cations (the Court characterizing this as a "substantial expansion" of claim scope).
AstraZeneca AB v. Hanmi USA, Inc. (Fed. Cir. 2013)
Panel: Circuit Judges Dyk, Moore, and Taranto
Opinion by Circuit Judge Taranto