Azurity Pharms., Inc. v. Alkem Labs. Ltd.

Case Name: Azurity Pharms., Inc. v. Alkem Labs. Ltd., No. 19-cv-2100, 2023 WL 1927613 (D. Del. Feb. 10, 2023) (Goldberg, J.)

Drug Product and Patents-in-Suit: Epaned® (enalapril maleate); U.S. Patents Nos. 10,786,482 (the ’482 patent) and 10,918,621 (the ’621 patent)

Nature of the Case and Issue(s) Presented: Azurity alleged that Alkem infringed the patents-in-suit when it submitted its ANDA for an enalapril oral liquid. The patents-in-suit claim liquids containing the blood pressure medicine enalapril. Azurity did not invent enalapril; rather, Azurity claimed to have invented a way to mix enalapril with water and prevent the mixture from degrading over a certain period.

The court presided over a three-day bench trial and found that Alkem infringed all of the asserted claims (Alkem conceded infringement of all but two asserted claims) but that Alkem presented clear and convincing evidence that those claims were invalid as obvious and for lack of written description.

Why Alkem Prevailed: Infringement. Alkem disputed infringement of two asserted claims, leveraging two arguments. Neither argument prevailed. First, Alkem argued that its ANDA product formulation includes pH adjusters, added as needed to achieve the target pH range. The patents-in-suit do not claim pH adjusters and, thus, according to Alkem, its ANDA product does not infringe certain asserted claims (“consisting essentially of” claims). Azurity countered with several arguments, and one prevailed: adding pH adjusters does not avoid the “consisting essentially of” limitation because pH adjusters are consumed and are no longer present once the solution is mixed. The court credited expert testimony on this point. Second, Alkem argued that Azurity did not prove that its ANDA product had a buffer in the claimed concentration. Alkem argued, without support, that certain reactions “must affect the buffer concentration in some unknown way.” The court did not accept Alkem’s unsupported argument, noting that Alkem asked to court “to infer it as a matter of logic,” without supporting expert testimony.

Obviousness. The court walked through extensive prior art related to the claimed oral liquid enalapril formulations. Indeed, several oral liquid dosage forms of enalapril existed before Azurity’s inventions, including Azurity’s own “Epaned Kit” product. The court determined that a POSA would have known that stability is critical to developing an oral liquid dosage form, and that pH affects stability. A POSA also would have known to administer enalapril, which converts to enalaprilat in the body, because the body does not absorb enalaprilat. A POSA also would have known that enalapril may convert to enalaprilat in water, even when not in the body. “It was thus known before the present invention that enalapril can degrade in water, a fact relevant to enalapril’s chemical stability.”

Azurity conceded that the claimed ingredients were known—instead, obviousness turned on whether the prior art disclosed liquid enalapril known to be stable for a year or more at a refrigerated temperature. Though the prior art “did not provide a ‘direct road map’ for making enalapril stable,” Alkem’s expert testified that it would be an “easy task.” The prior art indicated that long-term stability was possible, and thus a POSA would have been motivated to make it work. The court determined that Alkem’s expert was “convincing,” and that FDA guidance provided the motivation to accomplish the claimed stability profile. The court ultimately determined that a POSA would achieve the claimed inventions based on “routine application of a well-known problem-solving strategy.” “While Azurity claims it found a ‘specific combination of things’ that avoids ‘all of the different reactions that could potentially happen with’ enalapril in water, the steps Azurity took to achieve that goal were largely to try the obvious combination of ingredients and realize that they worked.”

Written Description. Alkem also prevailed on a lack-of-adequate-written-description argument. The patents’ shared specification does not include an example practicing any asserted claim. Instead, a POSA could prepare the claimed inventions only by combining ingredients from separate places in the specification. Indeed, Azurity’s expert conceded that the specification does not describe a formulation that meets all limitations of any asserted claim. The court ultimately determined that, though a POSA could combine separately described aspects of the invention, “all asserted claims lack written description because the specification describes a large variety of ways to combine ingredients but does not say which combinations that use paraben preservatives are stable.” The specification lacks adequate stability guidance.