Firvanq® (vancomycin)
Case Name: Azurity Pharms., Inc. v. Alkem Labs. Ltd., No. 2023-1977, 2025 WL 1036994 (Fed. Cir. Apr. 8, 2025) (Circuit Judges Moore, Chen, and Murphy presiding; Opinion by Murphy, D.J.) (Appeal from D. Del., Goldberg, J.)
Drug Product and Patent(s)-in-Suit: Firvanq® (vancomycin); U.S. Patent No. 10,959,948 (“the ’948 patent”)
Nature of the Case and Issue(s) Presented: The ’948 patent claims non-sterile drinkable liquid formulations of vancomycin, an antibiotic used to treat Clostridium difficile infection. These formulations are particularly useful for treating pediatric and geriatric populations due to a low choking risk and no need for sterilization. The application for the ’948 patent, the ’400 application, was allowed without rejection. But the ’400 application was a continuation of the ’059 application, which had been rejected several times by the examiner over a prior art reference known as Palepu. Palepu disclosed the IV administration of liquid vancomycin to treat Clostridium difficile with “a polar solvent including propylene glycol.”
The district court determined that during the prosecution of the ’059 application, where Azurity made amendments and arguments distinguishing Palepu, Azurity “clearly and unmistakably” disclaimed propylene glycol from the invention claimed in the ’948 patent. Further, Alkem’s ANDA product undisputedly contains propylene glycol. Therefore, Alkem’s ANDA product could not infringe the ’948 patent because the asserted claims used the closed “consisting of” transition. Azurity appealed and the Federal Circuit affirmed.
Why Alkem Prevailed: The Federal Circuit began its opinion with some additional prosecution history context. The earliest claims filed in the ’059 application used the open-ended transition “comprising” to specify the formulation ingredients. Those claims were rejected over, in part, Palepu. Azurity proposed several draft amendments and new claims, among them some that included the negative limitations: “wherein the oral liquid solution does not comprise a propylene glycol,” “wherein the liquid solution does not comprise a suspending agent,” and “wherein the liquid solution does not comprise a propylene glycol.” Azurity’s formal amendments not only included the negative limitation regarding propylene glycol, but also the even more limiting “consisting of” transition. In addition, Azurity submitted a declaration by its Executive Vice President and Chief Scientific Officer in support of those amendments. In continued prosecution, Azurity argued that “[t]he absence of propylene glycol and polyethylene glycol in the claimed invention, in part, distinguish it from [Palepu],” and further stated that “the compositions of Palepu do not fall within the scope of the claimed invention. The claimed invention does not include the polar solvents or lactic acid of Palepu.” The examiner allowed the claims to issue and said in the accompanying reasons for allowance that Palepu “teaches a non-sterile stable liquid formulation having vancomycin hydrochloride together with either propylene glycol or polyethylene glycol in the liquid formulation. The instant claims exclude the presence of propylene glycol or polyethylene glycol in view of the consisting of language, and thus overcome the teachings of Palepu which requires the propylene glycol or polyethylene glycol to be present with the vancomycin hydrochloride.”
The examiner repeatedly cited Palepu as prior art. And at every opportunity, Azurity clearly and unmistakably distinguished its invention from Palepu by asserting that the claimed formulations did not contain propylene glycol. Azurity did so by adding negative limitations, submitting witness affidavits, and limiting the transitional phrases in its prosecuted claims. “The prosecution history leaves no room to doubt that Azurity adopted the ‘consisting of’ transition specifically to narrow the claims and overcome Palepu and its disclosure of propylene glycol.” The Federal Circuit was not convinced of Azurity’s argument that the disclaimer of propylene glycol applied only to the carrier and not to the flavoring agent. “The record reflects that Azurity tried multiple routes to satisfy the examiner that unlike Palepu, its claimed invention lacked propylene glycol. The examiner insisted on clarity, and Azurity acquiesced by abandoning the ‘carrier’ distinction and adopting the ‘consisting of’ transition.”
Before trial, the parties stipulated to 143 undisputed facts that did not require proof at trial. One of those facts was: “Suitable flavoring agents for use in the Asserted Claims include flavoring agents with or without propylene glycol.” Azurity argued that the stipulation means that Alkem surrendered its disclaimer argument at least with respect to the claimed “flavoring agent.” Alkem disagreed, arguing when the stipulation was understood in the context of its origin, it merely confirmed that in this field, the relevant flavoring agents need not have propylene glycol. The district court and the Federal Circuit agreed with Alkem’s interpretation for multiple reasons. First, the undisputed facts begin with a statement that Alkem does not dispute infringement except that it “contends that it does not infringe the Asserted Claims due to [the] presence of propylene glycol in Alkem’s ANDA Products.” Second, the disputed stipulation is markedly different than the other undisputed facts under the “Infringement” heading; its general in scope and does not direct itself to any asserted claim. Third, Alkem’s interpretation was more consistent with the origin of the disputed stipulation.
With Azurity’s disclaimer clear and unmistakable, the Federal Circuit turned to Alkem’s ANDA to compare the asserted claim with the Alkem’s ANDA product. There was no dispute that the ANDA indicates that Alkem’s proposed generic contained propylene glycol, either through the flavoring agent or the separately listed propylene glycol. “The infringement inquiry here is very simple: propylene glycol was disclaimed; the ANDA contains propylene glycol; therefore there is no infringement.”
[View source.]
