Entresto® (valsartan/sacubitril)
Case Name: In re Entresto, 125 F.4th 1090 (Fed. Cir. Jan. 10, 2025) (Circuit Judges Lourie, Prost, and Reyna presiding; Opinion by Lourie, C.J.) (Appeal from D. Del., Andrews, J.)
Drug Product and Patent(s)-in-Suit: Entresto® (valsartan/sacubitril); U.S. Patent No. 8,101,659 (“the ’659 patent”)
Nature of the Case and Issue(s) Presented: Novartis sued multiple generic manufacturers, including MSN, after they filed ANDAs seeking FDA approval to market generic versions of Entresto. Entresto is a combination drug that includes valsartan and sacubitril in a specific form known as a “complex,” which combines the two drugs into a single unit-dose-form through weak, non-covalent bonds. Valsartan is an angiotensin receptor blocker (“ARB”) that prevents angiotensin II from binding to its receptor, thereby reducing the blood-vessel-constricting effects of angiotensin II, a naturally occurring hormone. Sacubitril is a neutral endopeptidase (“NEP”) inhibitor that, like valsartan, reduces blood vessel constriction but does so through a mechanism of action not involving angiotensin. The ’659 patent claims the pharmaceutical composition of valsartan and sacubitril administered “in combination.” At trial, the parties disputed whether the ’659 patent was required to enable the “pharmaceutical complex” of valsartan and sacubitril or if it simply needed to enable the physical combination of valsartan and sacubitril. The parties also disputed whether the ’659 patent needed to describe such complexes to satisfy the adequate written description requirement. The district court found the ’659 patent invalid for lack of adequate written description and not invalid for lack of enablement and obviousness. Specifically, the district court held that “Novartis scientists, by definition, could not have possession of, and disclose, the subject matter of [such complexes] in 2002, and therefore, axiomatically, [Novartis] cannot satisfy the written description requirement for such complexes.” On appeal, the Federal Circuit reversed the district court’s ruling regarding a lack of adequate written description.
Why Novartis Prevailed: The Federal Circuit first clarified the standard as applied to written description, noting that:
The issue on appeal is whether the ’659 patent describes what is claimed, viz., a pharmaceutical composition comprising valsartan and sacubitril administered “in combination.” The issue is not whether the ’659 patent describes valsartan-sacubitril complexes. Because the ’659 patent does not claim valsartan-sacubitril complexes, those complexes need not have been described.
Applying that standard, the Federal Circuit found that the invention, a physical combination of valsartan and sacubitril, was “plainly described throughout the specification.” According to the Federal Circuit, it was demonstrably clear that such a physical combination was highlighted on multiple occasions. In highlighting the district court’s error, the Federal Circuit noted that “the fact that the ’659 patent does not describe a complexed form of valsartan and sacubitril does not affect the validity of the patent” because the complex was not identified for years after the priority date of the patent. The district court erred because it “construed the claim terms to ‘cover’ complexes.” This analysis was flawed because, as the Federal Circuit described, “the district court erroneously conflated the distinct issues of patentability and infringement, which led it astray in evaluating written description. … Written description asks whether that which is claimed is adequately described.”
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