Case Name: Novartis Pharms. Corp. v. Mylan Pharms. Inc., Civ. No. 19-cv-201, 2023 WL 4375445 (N.D.W.V. July 6, 2023) (Kleeh, J.)

Drug Product and Patent(s)-in-Suit: Entresto® (sacubitril / valsartan); U.S. Patents Nos. 8,877,938 (“the ’938 patent”) and 9,388,134 (“the ’134 patent”)

Nature of the Case and Issue(s) Presented: Mylan filed an ANDA seeking approval to market a generic sacubitril/valsartan tablet for the treatment of heart failure. The parties dispute whether claims 1 and 11 of the ’938 patent and claim 5 of the ’134 patent are valid and enforceable. The parties also dispute whether Mylan’s ANDA product infringes the asserted claims. After a bench trial, the court found that Novartis had shown by a preponderance of the evidence that Mylan’s API is a substantially pure hemipentahydrate and Mylan’s API and ANDA products would infringe the patents-in-suit.

Why Novartis Prevailed: The patents-in-suit recited substantially pure trisodium sacubitril-valsartan (“TSVH”) hemipentahydrate in crystalline form. Mylan argued that its API was not substantially pure and that it was not hemipentahydrate.

The court construed “substantially pure” to mean that the API had at least 90% chemical purity. Mylan’s ANDA specification required that its Form II API had not more than 2.95% w/w impurities and residual solvents. Further, Plaintiff’s expert tested Mylan’s finished dosage form, finding that it had less than 0.50% w/w total impurities and residual solvents. Plaintiff’s expert also explained that although Mylan’s Form II contained amorphous material, he found that there was not a substantial amount in the final product (i.e., less than about 0.5% w/w.). Finally, the court concluded that the additional XRPD peaks not corresponding to Form II were from inactive ingredients (i.e., excipients) used to make the final formulation and did not corresponding to impure Form II.

Mylan also argued that its API was not hemipentahydrate. In so doing, it relied on a single crystal analysis performed by the DMF holder to posit that its Form II API was a trihydrate, not a hemipentahydrate. Plaintiff’s expert analyzed the Form II single crystal structure proffered by Mylan and found that the occupancies for certain water molecules were chemically impossible. Instead, when the occupancies for those water molecules were corrected based on known chemistry, Plaintiff’s expert found that the single crystal structure for Form II was hemipentahydrate. In particular, hemipentahydrate in TSVH refers to 2.5 bound water molecules per molecule of trisodium sacubitril-valsartan. As summarized by Plaintiff’s expert, Mylan’s Form II contained an estimated 4.70% to 4.71% w/w bound water, which was within 0.01% of the theoretical 4.70% w/w for 2.5 bound waters.