Kowa Co. Ltd. v. Amneal Pharms. LLC

Because the prior art did not explicitly or inherently disclose the claimed polymorphs, the court found the patent-in-suit valid and infringed.

October 20, 2017

GENERICally Speaking

Case Name: Kowa Co. Ltd. v. Amneal Pharms. LLC, No. 14-CV-2758 (PAC), 2017 U.S. Dist. LEXIS ______ (S.D.N.Y. Sept. 19, 2017) (Crotty, J.)

Drug Product and Patent(s)-in-Suit: Livalo® (pitavastatin); U.S. Patent No. 8,557,993 (“the ’993 patent”)

Nature of the Case and Issue(s) Presented: Livalo is a statin used to treat elevated cholesterol, more specifically, hyperlipidemia or mixed dyslipidemia. Amneal alleged that the claims of the asserted patent were anticipated and obvious; in addition, Apotex argued that its proposed ANDA product would not infringe the asserted claims.

The patent-in-suit claims six polymorphs of pitavastatin calcium, forms A-F, and the amorphous form, a pharmaceutical composition comprising an effective amount of the form, and a pharmaceutically acceptable carrier. The claims include descriptions of x-ray powder diffraction patterns characteristic of the polymorphs. The court found the asserted claims valid and infringed.

Why Kowa Prevailed: Defendants argued that the challenged claims were anticipated by a reference that inherently disclosed Form A of the polymorph. The court found that the reference did not necessarily produce Form A. The court allowed that the reference could produce Form A, but that the reference did not specify how synthesized product should be dried. The court credited plaintiff’s expert that the range of reasonable drying conditions “could be quite broad,” and that the presence or absence of a particular polymorph could depend on the exact drying conditions. The court also discounted the probative value of defendant’s two replications of the purportedly-anticipating reference on the basis that they did not test a reasonable range of drying conditions.

Defendants also argued that the claims were obvious, because by the time prior-art pitavastatin was known (in 2003), it was routine to perform polymorph screens, and that a POSA would have a reasonable expectation of finding the Form A polymorph. The court rejected this argument. It found, and reported that other courts agree, that crystallization and polymorphism are unpredictable. Accordingly, a POSA would not have a reasonable expectation of finding Form A.

In reviewing the objective indicia of non-obviousness, the court found that even if defendants had established a prima facie case of obviousness, three indicia (commercial success, unexpected results, and long-felt need ) would overcome that case. Concerning commercial success, the court found that [“t]he absolute dollars and produced volumes are really quite substantial. “ The court discounted defendants’ argument that the patent product had not been as successful as the patentee planned. The court found that pitavastatin demonstrated unexpectedly superior tolerability and reduced drug-drug interactions. Finally, because pitavastatin works well in patients intolerant of other statins, those patients had a long-felt need, one first satisfied by pitavastatin.

With respect to Apotex’s infringement argument, it centered around how closely the observed x-ray diffraction pattern needed to match the claimed spectrum. The court concluded that the plain and ordinary meaning of two claims did not require an exact match of every single recited peak position and relative intensity. For the remaining asserted claims, the court looked to whether the pattern was “substantially, or approximately, as depicted in Figure 1 of the '993 patent.” Given the conclusion that to show infringement it was necessary find only “some quantity, however miniscule” of the Form A polymorph in the accused products, it found for Kowa.

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