The Federal Circuit recently reversed a District of Delaware decision that invalidated claims of Novartis’s Orange Book listed patent, U.S. Patent No. 8,101,659 (the “’659 patent”), for its blockbuster drug Entresto®, a combination drug used to treat heart failure.

Following a three-day bench trial, Judge Andrews found the ’659 patent not invalid for obviousness, lack of enablement, or indefiniteness, but invalid for lack of written description.[1] On appeal, the Federal Circuit reversed the district court’s finding of inadequate written description and affirmed the other findings that the patent was not invalid.[2]

While not specific to biosimilar law, this case addresses the effect of post-filing discoveries on written description in the pharmaceutical context. The ruling reinforces the principle that inventions or discoveries arising after the filing date do not necessarily invalidate claims directed to an earlier underlying invention that is described and enabled by the specification.

Background

Novartis’s Entresto®, approved by the U.S. Food & Drug Administration (FDA) in 2015, combines valsartan, an angiotensin receptor blocker (ARB), and sacubitril, a neutral endopeptidase (NEP) inhibitor. Entresto® 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.[3] Entresto® was initially approved with an indication to treat heart failure ejection fraction. In 2019, the drug was additionally approved for the treatment of heart failure in children, and, in 2021, it was approved for the treatment of heart failure with preserved ejection fraction.[4] In 2023, sales of Entresto® in the U.S. totaled more than $3 billion.[5]

In 2019, MSN Pharmaceuticals, among other generic manufacturers, submitted an Abbreviated New Drug Application (ANDA) seeking FDA approval to market and sell a generic version of Estresto®.[6] Novartis sued MSN and other generic companies, alleging infringement of the ’659 patent, which covers a pharmaceutical composition comprising valsartan and sacubitril.[7] The sole independent claim of the ’659 patent recites:

1. A pharmaceutical composition comprising:

(i) the AT 1-antagonist valsartan or a pharmaceutically acceptable salt thereof;

(ii) the NEP inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic acid ethyl ester or (2R,4S)-5-biphenyl-4-yl-4(3-carboxy-propionyl amino)-2-methyl-pentanoic acid or a pharmaceutically acceptable salt thereof; and

(iii) a pharmaceutically acceptable carrier;

wherein said (i) AT 1-antagonist valsartan or pharmaceutically acceptable salt thereof and said (ii) NEP inhibitor N-(3-carboxy-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-2R-methylbutanoic acid ethyl ester or (2R,4S)-5-biphenyl-4-yl-4(3-carboxy-propionyl amino)-2-methyl-pentanoic acid or pharmaceutically acceptable salt thereof, are administered in combination in about a 1:1 ratio.[8]

During claim construction, the court construed the claim term “in combination” as bolded above. The construction dispute centered on whether “in combination” limited the claim to administration of valsartan and sacubitril “as two separate components,” which MSN proposed to support its non-infringement argument.[9] Novartis argued, and the district court agreed, that the claim was not so limited, and that the term should be given its plain and ordinary meaning.[10] After Markman, MSN, whose proposed generic comprised a “complex” of non-covalently bonded valsartan and sacubitril, stipulated to infringement.

The District Court’s Decision

The district court was unpersuaded by MSN’s obviousness arguments because, despite the known synergistic effects of ARB-NEP inhibitor combinations, the court found MSN failed to provide clear and convincing evidence that a person of ordinary skill in the art (POSA) would have been motivated to combine valsartan and sacubitril in 2002.[11] Specifically, the court found that sacubitril had never been tested on humans or in an animal model of hypertension and heart failure, and results for other NEP inhibitors that had been tested were discouraging.[12]

As to written description and enablement, “guided by the understanding that the court had ‘construed the asserted claims to cover valsartan and sacubitril as a physical combination and as a complex,’ the parties’ dispute centered on whether the ’659 patent was required to enable and describe such complexes.”[13]

MSN argued that the patent failed to enable and describe the full scope of the claims, while Novartis argued that a complex of valsartan and sacubitril was an after-arising invention that need not have been enabled or described.[14] Specifically, Novartis argued that its “later, nonobvious discovery of valsartan and sacubitril in the form of a complex should not invalidate the ’659 patent claims to Novartis’s earlier invention: the novel combination of valsartan and sacubitril.”[15] The district court agreed with Novartis on enablement, but disagreed on written description.

As to enablement, the district court reasoned that enablement is judged as of the priority date, and therefore later-existing state of the art may not be properly considered in the enablement analysis.[16] The district court found that MSN failed to establish that pharmaceutical complexes in general were known or nascent technology in 2002, and therefore the ’659 patent need not enable them.[17]

As for written description, however, the district court found “the facts that helped [Novartis] with respect to enablement proved fatal for written description,” because it was undisputed that complexes were unknown to a POSA, and thus the Novartis scientists “by definition, could not have possession of, and disclose, the subject matter” of the complexes in 2002.[18]

The Federal Circuit’s Reversal

The Federal Circuit reversed the district court’s written description ruling. The court emphasized that the issue is “not whether the ’659 patent describes valsartan-sacubitril complexes,” because “the ’659 patent does not claim valsartan-sacubitril complexes.”[19] The court noted that the district court rejected MSN’s proposed construction which had sought to exclude from the scope of the claims the accused product: a valsartan-sacubitril complex.[20] Instead, the term was given its plain and ordinary meaning: “wherein said [valsartan and sacubitril] are administered in combination.” The Federal Circuit found such combinations were “plainly described throughout the specification.”[21]

The Federal Circuit explained: “the fact that the ’659 patent does not describe a complexed form of valsartan and sacubitril” is irrelevant to validity, because a “complex”—which was not discovered until four years after the priority date of the ’659 patent—“is not what is claimed.”[22] The court noted that if the claims had been “construed to claim valsartan-sacubitril complexes . . . that construction would have been error,” because claim interpretation must determine “the meaning of the claims to one of ordinary skill in the art at the time of the invention,” and such complexes were unknown at that time.[23]

The court also held that the district court’s reasoning that the claims were “construed to cover complexes of valsartan and sacubitril,” was erroneous because it “conflated the distinct issues of patentability and infringement, which led [the district court] to astray in evaluating written description.”[24] The court reiterated that claims are not construed “to cover” or “not to cover” the accused product.[25] ‘“It is only after the claims have been construed without reference to the accused device that the claims, as so construed, are applied to the accused device to determine infringement.’”[26]

Implications for Pharmaceutical Patents

This decision reinforces the principle that an after-arising invention does not render invalid for lack of written description a claim that is properly construed as broad enough to encompass it, provided the specification supports and enables what is claimed. This is particularly relevant in the pharmaceutical field, where later research often leads to refinements and discoveries involving existing drugs. Practitioners should carefully analyze the state of the art and the appropriate claim construction when developing arguments regarding written description.


[1] In re Entresto (Sacubitril/Valsartan) Pat. Litig., No. 20-md-2930, 2023 WL 4405464 (D. Del. July 7, 2023).

[2] In re Entresto, No. 23-2218, 2025 WL 63577, Slip Op. at 3 (Fed. Cir. Jan. 10, 2025) (precedential).

[3] Id. at 4.

[4] Id.

[5] Id.

[6] Id. at 6.

[7] Id.

[8] U.S. Patent No. 8,101,659 at Claim 1 (emphasis added).

[9] In re Entresto, 2021 WL 2856683, at *3.

[10] Id.

[11] In re Entresto, 2023 WL 4405464 at *12-13.

[12] Id.

[13] Novartis, 23-2218 at 10 (quoting In re Entresto, 2023 WL 4405464 at *17) (emphasis added)).

[14] In re Entresto, 2023 WL 4405464 at *17-21.

[15] Novartis, 23-2218 at 10.

[16] In re Entresto, 2023 WL 4405464 at *19.

[17] Id. at *20.

[18] Id. at *21-22.

[19] Novartis, 23-2218 at 12 (emphasis in original).

[20] Id. (emphasis added).

[21] Id.

[22] Id. at 13.

[23] Id. at 14, n.5 (quoting SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1338 (Fed. Cir. 2005)) (emphases in original).

[24] Id. at 13 (emphasis in original).

[25] Id. at 14.

[26] Id. (quoting SRI Int’l v. Matsushita Elec. Corp. of Am., 775 F.2d 1107, 1118 (Fed. Cir. 1985)).