Case Name: In re Entresto (Sacubitril/Valsartan) Patent Litigation, C.A. Nos. 19-1979, 19-2021, 19-2053, 2023 WL 4405464 (D. Del. July 7, 2023) (Andrews, J.)

Drug Product and Patent(s)-in-Suit: Entresto® (sacubitril/valsartan); U.S. Patent No. 8,101,659 (“the ’659 patent”)

Nature of the Case and Issue(s) Presented: Novartis holds the NDA for Entresto, which the FDA approved “to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction,” “for treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older,” and “to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure.” The ’659 Orange Book-listed patent has a priority date of January 17, 2002. It claims compositions of valsartan and sacubitril and the use of those compositions to treat hypertension and heart failure. Defendants seek FDA approval to market generic equivalents of Entresto. They have stipulated that their ANDA products would infringe the ’659 patent, and assert that the claims are invalid as obvious, lacking adequate written description, not enabled, and indefinite. After a three-day bench trial, the court found that the asserted claims lacked adequate written description and were therefore invalid.

Why Defendants Prevailed: The court noted that the touchstone of written description is possession as of the priority date. Defendants argued that because sacubitril/valsartan complexes were unknown as of the 2002 priority date, Plaintiff did not possess such complexes and therefore could not have described them. Plaintiffs responded that the ’659 patent satisfied the written description requirement by disclosing valsartan and sacubitril—the structural features (i.e. chemical names and/or chemical formulas) common to the members of the claimed genus of the pharmaceutical composition containing the valsartan and sacubitril combination. Plaintiff further pointed out that physical mixtures of valsartan and sacubitril, and complexes of valsartan and sacubitril, are mere subsets of the claimed genus. But “Plaintiff’s trouble is that written description also requires that common structural features be described ‘with enough precision that a relevant artisan can visualize or recognize the members of the genus.’” The ’659 patent specification described physical mixtures only. It did not, and could not, allow a POSA to visualize the members of the entire genus sufficient to show possession of complexes, which, to a POSA’s knowledge, had not yet been discovered.