The District Court for the District of Delaware recently rejected Novartis’s effort to block MSN Pharmaceuticals from launching a generic version of Entresto® (sacubitril/valsartan), its top-selling heart failure medication. The decision, issued on July 11, 2025, potentially clears the path for generic entry before expiration of U.S. Patent No. 11,096,918 (“the ’918 patent”) on November 9, 2026. However, on July 15, 2025, the Court of Appeals for the Federal Circuit issued a temporary injunction blocking MSN’s launch and ordered expedited briefing on whether the circuit court should issue an injunction pending appeal.
While not specific to biosimilars, this case highlights the importance of data reliability in patent litigation and raises interesting issues involving a plaintiff’s discovery obligations in a multi-defendant litigation.
Background
Novartis’s Entresto®, approved by the FDA in 2015, combines valsartan, an angiotensin receptor blocker, and sacubitril, a neutral endopeptidase inhibitor. On October 24, 2022, Novartis filed C.A. No. 22-1395 against MSN, alleging infringement of the ’918 patent, which claims an amorphous solid form of a compound comprising sacubitril, valsartan, and sodium cations (“amorphous TVS”). The only independent claim of the ’918 patent recites:
1. An amorphous solid form of a compound comprising anionic (S)-N-valeryl-N-{[2’-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine [valsartan], anionic (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester [sacubitril], and sodium cations in a 1:1:3 molar ratio.
Following a bench trial in December 2024, Judge Andrews found that Novartis has not proven that MSN infringes the ’918 patent.[1] Prior to the trial, the court construed the term “amorphous solid form of a compound” in the ’918 patent 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 solid form.”[2] At trial, the question of infringement revolved around whether Novartis could prove that MSN’s generic product is predominantly amorphous TVS (an amorphous complex with chemical interactions among the compounds) rather than a physical mixture of amorphous valsartan and amorphous sacubitril sodium with no significant chemical interactions among the compounds.[3]
The Court’s Decision
To demonstrate that MSN infringes the ’918 patent, Novartis compared a Raman spectrum from MSN’s abbreviated new drug application (ANDA) to a reference Raman spectrum. Raman spectroscopy is a method that produces a unique spectrum for different compounds or mixtures of compounds. Specifically of interest here, Raman spectroscopy is capable of differentiating a physical mixture of two compounds (in which no interaction occurs between the compounds) versus an amorphous complex (e.g., amorphous TVS).
Novartis’s expert made a “mathematically-created” reference spectrum for an amorphous physical mixture (which is different from the claimed “amorphous TVS” complex) by adding together the Raman spectra of separate amorphous valsartan disodium and amorphous sacubitril sodium samples. The district court found this spectrum reliable.[4] Novartis’s expert also created a “glassy solid” sample, which Novartis argued was amorphous TVS, to compare with MSN’s ANDA spectrum. The district court found the Raman spectrum collected for this glassy solid was not reliable, and thus Novartis failed to show by a preponderance of the evidence that the resulting reference Raman spectrum corresponds to amorphous TVS.[5] Specifically, the court found the Raman spectrum for Novartis’s glassy solid sample was suspiciously similar to the spectrum for the physical mixture; the differences in the spectra appeared to be only a systematic shift of all peaks, rather than different peaks as would be expected for different samples.
Novartis argued that the Raman spectrum of the glassy solid “is different from the Raman spectrum of a[] physical mixture”, pointing to peak shifts when comparing the glassy solid spectrum to the mathematically-created spectrum of a physical mixture of sacubitril and valsartan.[6] Novartis further argued that the peak shifts indicate that the glassy solid sample is amorphous TVS.
MSN disagreed, pointing out that the entire Raman spectrum for the glassy solid “is shifted…to the right of the Raman spectrum of the physical mixture”.[7] MSN’s expert testified that “the type of systematic shift observed…is simply impossible”,[8] thus casting doubt on the reliability of the glassy solid Raman spectrum.
Further compounding this issue, the court took an adverse inference against Novartis for failing to produce the glassy solid sample during discovery. Novartis argued, in part, that an adverse inference is not applicable because MSN did not request production of the sample. However, Noratech was MSN’s co-defendant at the time of discovery and did request production of the sample. The court found that this “discovery [was] common to both Defendants,” that MSN and Noratech shared an expert witness for this issue, and that “MSN wished to test [Novartis’s] glassy solid, the material against which its ANDA was compared.”[9] The court found Novartis had the sample, knew it fell within the scope of requested discovery, and did not provide it. Thus, the court assumed that, “had Novartis produced the glassy solid sample to Defendants, it would have been unfavorable to Novartis’ case.”[10]
Novartis presented additional evidence to demonstrate that the glassy solid was amorphous TVS. However, because Novartis used Raman spectra to show infringement by MSN’s ANDA, the additional evidence was not directly considered when determining infringement. In the end, the “unreliability of Novartis’ reference Raman spectrum” lead the court “to conclude that Novartis did not meet its burden to show MSN’s ANDA infringes by a preponderance of evidence.”[11]
Implications
As a result of the decision, Novartis is denied injunctive relief based on the ’918 patent, and MSN’s generic version of Entresto® could soon receive final FDA approval.[12] MSN has previously indicated that it is poised to launch its product as soon as it is approved.[13] However, Novartis has appealed the District Court’s decision, and the Federal Circuit has issued a temporary stay preventing launch of the generic. Both Novartis and MSN have until July 21 to file briefs, at which time the Federal Circuit will determine whether a lengthier pause is warranted.
Disclaimer: The information contained in this posting does not, and is not intended to, constitute legal advice or express any opinion to be relied upon legally, for investment purposes or otherwise. If you would like to obtain legal advice relating to the subject matter addressed in this posting, please consult with us or your attorney. The information in this post is also based upon publicly available information, presents opinions, and does not represent in any way whatsoever the opinions or official positions of the entities or individuals referenced herein.
[1] In re Entresto (Sacubitril/Valsartan) Pat. Litig., No. 22-cv-1395-RGA, 2025 WL 1911823 (D. Del. July 11, 2025).
[2] Id. at *2.
[3] See id. at *3.
[4] Id. at *3.
[5] Id. at *4.
[6] Id. at *8.
[7] Id. at *10.
[8] Id. at *13.
[9] Id. at *21.
[10] Id. at *22.
[11] Id. at *22.
[12] The district court previously issued an order under 35 U.S.C. § 271(e)(4)(A) resetting the date of approval of MSN’s ANDA to July 16, 2025, after the expiration of the pediatric exclusivity period for U.S. Patent No. 8,101,659. See MSN’s Emergency Motion to Stay, Novartis Pharms. Corp. v. MSN Pharms. Inc., No. 19-cv-2053, Dkt. 511 (D. Del., filed April 2, 2025).
[13] See id. at 3.
Skip to content
