On July 16, 2025, a U.S. federal judge denied Novartis’ bid for a preliminary injunction aimed at preventing India’s MSN Pharmaceuticals from launching a generic version of its heart drug, Entresto. The court ruled that Novartis had not demonstrated that MSN’s product would cause “irreparable harm,” emphasizing that public access to affordable, life-saving treatments is a priority.
This decision overturned an earlier finding that Novartis could potentially demonstrate that MSN’s tablets were too similar to Entresto, leading to consumer confusion. MSN has already announced that it will move forward with plans to sell the generic under the brand name Novadoz.
The expiration of Entresto’s primary U.S. patent has accelerated global competition, with China granting approval to at least 13 domestic pharmaceutical companies to market their own versions of the drug.
Response to patent expiry
In 2024, Entresto was Novartis’ top-selling therapy, generating $4.05 billion in the U.S. and $7.82 billion globally. With the loss of patent exclusivity expected to pressure revenues, the company is reshaping its cardiovascular business strategy, and trimming its workforce in the process. A Worker Adjustment and Retraining Notification (WARN) filed in New Jersey shows the laying off of 427 U.S. employees laid off between June and late October.
This move adds to a series of recent workforce reductions in the U.S. In November 2024, Novartis announced the elimination of 139 commercial field-sales roles at its East Hanover, New Jersey headquarters, after cutting 103 positions in 2023. Earlier, in April 2023, the company also disclosed broader restructuring plans that would reduce its headcount by 680 jobs across its U.S. and Swiss operations.
Patents that make up Entresto
Entresto is still protected by a portfolio of combination patents set to expire between 2023 and 2036. Since 2019, Novartis has pursued a string of patent infringement lawsuits against numerous Abbreviated New Drug Application (ANDA) filers seeking FDA approval to market generic versions of the therapy.
Core composition patent for Entresto
Heart failure remains one of the leading causes of hospitalization worldwide, driving demand for therapies that target both blood pressure regulation and cardiac protection. Traditional treatments often focused on a single mechanism, limiting their effectiveness in managing complex cardiovascular conditions. A combination approach offered a way to address multiple pathways simultaneously, improving outcomes for patients with chronic heart disease.
U.S. Patent No. 8,101,659 describes the foundational formulation of Novartis’ Entresto. The composition combines valsartan, an angiotensin receptor blocker (ARB), with a neprilysin (NEP) inhibitor, with or without a carrier, to treat cardiovascular conditions. The patent also extends to methods for preventing or managing hypertension, heart failure, left ventricular dysfunction, arrhythmias, myocardial infarction, and other cardiac disorders.
The patent, titled “Methods of treatment and pharmaceutical composition,” was filed on June 27, 2008, and granted on January 24, 2012. It was originally set to expire on January 14, 2023, but Novartis secured a two-year extension in 2015, plus pediatric exclusivity, extending protection to July 15, 2025. Despite this exclusivity, the FDA began approving generic versions of Entresto in May 2024, setting the stage for direct competition.
The patent lists Gary Ksander and Randy Webb as inventors. Legal representation was provided by the Novartis Pharmaceutical Corporation IP Department, with attorneys Jean Silveri, Timothy Witkowski, Peter Waibel et al. named on the application.
Stabilizing the chemical compounds that compose Ernesto
Sacubitril/valsartan, the active ingredients in Entresto, present challenges in their non-crystalline form due to high moisture sensitivity, which can affect stability, storage, and performance. To address these issues, pharmaceutical cocrystals are used as a way to improve solubility, dissolution, and stability while preserving therapeutic effects. Research has determined that cocrystal technology offers high dissolution and thermal stability, potentially influencing both the clinical effectiveness and regulatory outlook for sacubitril/valsartan formulations in heart failure treatment.
U.S. Patent No. 8,877,938, covers a compound combining an angiotensin receptor blocker (ARB), a neprilysin inhibitor (NEPi), and one or more monovalent cations, such as sodium, for use in treating hypertension and heart failure. This patent covers a specific crystal form of the drug known as the 2.5-hydrate, which contains bound water molecules and uses calcium salt co-crystals that allow for easier storage and use.
However, some of the patents protecting the described hydrate form have already been partly overturned in different countries. Particularly in China, companies have gotten around the patent protection by filing alternative hydrate compositions, such as Nanjing Yixinhe Pharmaceutical’s trihydrate version of the compound. Despite these challenges, the patent protection of the original crystal patent covering sacubitril/valsartan sodium tablets still remains only partially overturned.
The patent, titled “Compounds containing S-N-valeryl-N-{[2′-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations”, was filed on November 9, 2005 and was granted on November 4, 2014. The surviving claims were initially set to expire on November 8, 2026. Novartis has since filed a request for patent term extension, raising the possibility that the patent’s protection period could be lengthened.
The patent lists Lili Feng, Sven Erik Godtfredsen, Bin Hu, Yugang Liu, Piotr Karpinski, Paul Allen Sutton, Mahavir Prashad, Michael J. Girgis, Thomas J. Blacklock as inventors. Legal representation was provided by Novartis Pharmaceutical Corporation IP Department with attorneys Jean Silveri, Timothy Witkowski, Peter Waibel et. al.
Dosage regimen for Entresto, and the last line of defense against generic drugs
Sacubitril/valsartan (Entresto) has proven effective in treating heart failure, with a PARADIGM-HF trial showing that a 200 mg twice-daily dose significantly lowered hospitalizations and mortality compared to enalapril. However, real-world data indicate that many patients are prescribed lower doses, often due to adherence issues or gaps in clinical practice. To address this, a Titration study evaluated different dose escalation strategies, suggesting that slower uptitration may help patients better tolerate the therapy while still gaining its benefits.
U.S. Patent No. 11,058,667, outlines a treatment method for heart failure using an angiotensin receptor neprilysin inhibitor (ARNi). The approach involves a twice-daily dosing regimen, where patients start on a lower dose and gradually increase to a target dose over a period of two to eight weeks. The filing also covers combinations of an angiotensin receptor blocker (ARB) with either a neprilysin inhibitor (NEPi) or a NEPi pro-drug.
This patent is the longest-lasting patent tied to Entresto, giving Novartis extended protection against generic rivals. The company has used this and related patents to challenge would-be competitors, both through litigation and by urging the FDA to limit generic approvals. In one example, Novartis filed a lawsuit against Torrent Pharma, alleging infringement of an Entresto dosage regimen patent that is valid until May 2036.
The patent, titled “Sacubitril-valsartan dosage regimen for treating heart failure”, was filed on May 11, 2015, and granted on July 13, 2021. It is anticipated to expire on May 9, 2036. The patent lists Adel Remond Rizkala, Victor Chengwei Shi, Fabian Chen as inventors. Legal representation was provided by Novartis Pharmaceutical Corporation IP Department with attorneys Jean Silveri, Timothy Witkowski, Peter Waibel et. al. listed on the application.
Novartis: Patenting Activity
Novartis’s patent activity intensified in 2016, following the launch of Entresto and the U.S. loss of exclusivity for its cancer drug Gleevec. In the early 2020s, the company recorded a rise in granted patents, coinciding with Entresto’s expanded approvals from the FDA.
On December 16, 2020, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted in favor of expanding Entresto’s use to patients with heart failure with preserved ejection fraction (HFpEF). The agency formally approved the new indication on February 16, 2021, allowing Entresto to be prescribed to a broader group of adults with chronic heart failure, particularly those with below-normal left ventricular ejection fraction (LVEF).
Novartis: Top Technology Areas
Novartis’s patent filings from 2015 to 2024 are heavily concentrated in preparations for medical, dental, or toiletry purposes (A61K), which account for more than 30% of its portfolio. Heterocyclic compounds (C07D) follow with 24.2%, while peptides (C07K) make up 19%, reflecting the company’s strong emphasis on pharmaceutical formulations and drug discovery at the molecular level.
Beyond these core categories, Novartis holds significant shares in specific therapeutic activity of chemical compounds (A61P) and microorganisms or enzymes (C12N), highlighting its focus on developing treatments that target particular diseases and leveraging biotechnology in drug development. Smaller shares in areas such as prostheses (A61F), diagnosis and surgery (A61B), and devices for introducing media into the body (A61M) show diversification into medical devices and delivery systems.
Novartis: Top Jurisdictions
Novartis has filed most of its patents in the United States, followed by Japan and China, highlighting the importance of these markets to its business. In the U.S., the Food and Drug Administration (FDA) approved Entresto™ (sacubitril/valsartan) on July 7, 2015. Originally known as LCZ696, the drug was first cleared for patients with heart failure with reduced ejection fraction (HFrEF), giving Novartis access to a large group of patients in need of treatment.
In Japan, Entresto was approved for heart failure in June 2020 and later for hypertension in September 2021. The most recent milestone came in February 2024, when the drug was also approved for children with chronic heart failure, marking the first approval of its kind in the country and expanding its reach to younger patients.
China has been a more complex market for Novartis. The main drug patent was canceled in 2018, and some protections for specific tablet forms were also reduced. However, certain rights remain valid until November 8, 2026, giving Entresto some ongoing protection while facing rising competition from generic drugmakers.
Novartis: Top Legal Representatives
Novartis relies on a diverse set of representatives to manage its global patent portfolio. In Japan, attorneys Hiroshi Kobayashi, Norio Ohmori, and Eiji Katayama, connected with Abe, Ikubo & Katayama, account for the largest share of filings. In China, Zhongzi Law Office and attorney Huang Gesheng play leading roles, handling a significant portion of Novartis’s work in the region.
Beyond Asia, Davies Collison Cave Pty Ltd provides representation in Australia, while Novartis Pharma AG handles a share of filings internally. In South Korea, Yang Young Jun and Kim Dong-Shin are the primary representatives, and in Canada, the company turns to Smart & Biggar LLP for legal support.
Novartis refocuses after Entresto setbacks
Novartis is moving to appeal recent court rulings and continue defending its intellectual property, while reorganizing its cardiovascular division in the U.S., a move that has led to new job cuts.
With exclusivity for Entresto nearing its end, the company is shifting attention to other drugs in its portfolio. LEQVIO® (inclisiran), a cholesterol-lowering therapy administered twice a year, has posted rising sales.
Another candidate, pelacarsen, is in phase 3 trials to test whether reducing lipoprotein(a) levels can help lower the risk of major cardiovascular events.
