Entresto® (valsartan/sacubitril)
Case Name: Novartis Pharms. Corp. v. MSN Pharms., Inc., Nos. 2024-2211, 2024-2212, 2024 WL 4969281 (Fed. Cir. Dec. 4, 2024) (Circuit Judges Lourie, Prost, and Reyna presiding; Opinion by Lourie, J.) (Appeal from D. Del., Andrews, J.)
Drug Product and Patent(s)-in-Suit: Entresto® (valsartan/sacubitril); U.S. Patent No. 11,096,918 (“the ’918 patent”)
Nature of the Case and Issue(s) Presented: In 2015, FDA Entresto “to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure, and for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.” The ‘’918 patent claims an amorphous solid form of trisodium valsartan sacubitril (TVS). The ’918 patent is not listed in the Orange Book for Entresto and Novartis concedes that the ’918 patent does not claim the drug product present in Entresto.
In 2019, MSN filed an ANDA for Entresto. Novartis sued. During claim construction, the district court construed “an amorphous solid form of a compound” to mean a solid form of a compound in which the amorphous form of the compound predominates; an amorphous solid form is mutually exclusive from a crystalline solid form, but not necessarily mutually exclusive from a partially crystalline form.
On July 24, 2024, the FDA granted final approval of MSN’s ANDA, which MSN claims includes crystalline TVS, or “Form-S.” Novartis moved for a preliminary injunction to stop MSN’s at-risk launch. The district court concluded that Novartis had not met its burden of showing that it is likely to succeed in proving that MSN’s ANDA product contained amorphous TVS and that it would suffer irreparable harm absent an injunction. Novartis appealed the district court’s decision, and the Federal Circuit affirmed.
Why MSN Prevailed: The Federal Circuit acknowledged that the district court’s analytical analysis compared the spectra from MSN’s API—not MSN’s final product—with a Form-S reference spectrum, and that such a comparison would not be dispositive of the ultimate infringement inquiry, which requires a showing that MSN’s final product contains amorphous TVS. However, MSN’s argument was that Novartis had not shown that MSN’s final product contained amorphous TVS because it did not consider the possibility that the regions in the Raman spectra that Novartis’s expert identified as amorphous TVS could have been a closer match to crystalline TVS. “That argument, regardless how it was characterized by the district court, properly goes to the relevant infringement inquiry.” With that clarification, the Federal Circuit saw no clear error in the district court’s analysis and consideration of the evidence.
MSN’s expert compared the spectra that Novartis’s expert obtained from the final product to a Form-S reference spectrum and found that they closely aligned. Coupling this with the fact that Novartis bore the burden of proof, the Federal Circuit agreed with the district court that Novartis did not persuasively show that it was likely to succeed in proving that MSN’s ANDA products contain amorphous TVS. “At bottom, Novartis's arguments on appeal ask us to reconsider and reweigh this highly factual evidence anew. We decline to do so.”
