Last updated: August 15, 2026
The Entresto multidistrict litigation consolidated Hatch-Waxman patent cases filed by Novartis against generic applicants seeking approval for sacubitril/valsartan tablets. The principal patents concern the fixed-dose combination, pharmaceutical compositions, and treatment methods for heart failure. The litigation is strategically important because Entresto is one of Novartis’s largest products and because generic entry depends on the scope, validity, and enforceability of patents listed in the FDA Orange Book.
The MDL is pending in the U.S. District Court for the District of Delaware under In re Entresto (Sacubitril/Valsartan) Patent Litigation, No. 1:20-md-02930-RGA. The presiding judge is Richard G. Andrews.
What is In re Entresto Patent Litigation?
The MDL consolidates patent infringement actions brought under the Hatch-Waxman Act after generic manufacturers submitted Abbreviated New Drug Applications, or ANDAs, for sacubitril/valsartan tablets.
Novartis Pharmaceuticals Corporation and related entities asserted patents covering Entresto against multiple ANDA applicants. The generic products generally seek approval for the same active ingredients and dosage strengths as Entresto:
- Sacubitril/valsartan 24/26 mg
- Sacubitril/valsartan 49/51 mg
- Sacubitril/valsartan 97/103 mg
Entresto combines sacubitril, a neprilysin inhibitor, with valsartan, an angiotensin II receptor blocker. The product is approved for treatment of certain patients with chronic heart failure and reduced ejection fraction.
The litigation involves the interaction of three legal issues:
- Whether the asserted claims cover the proposed generic products.
- Whether the patents are valid and enforceable.
- When FDA approval and commercial launch may occur under the ANDA litigation framework.
Which companies are involved in the Entresto patent cases?
The MDL includes Novartis as the branded plaintiff and multiple generic pharmaceutical companies as defendants. Public docket materials identify cases involving major ANDA applicants, including companies affiliated with or operating under the names below:
| Party category |
Examples |
| Branded plaintiff |
Novartis Pharmaceuticals Corporation and affiliated Novartis entities |
| Generic applicants |
Teva, Mylan/Viatris, Dr. Reddy’s Laboratories, Lupin, Sun Pharmaceutical, Torrent, Zydus, Hetero, Amneal and other ANDA applicants |
| Legal basis |
Paragraph IV certifications under 21 U.S.C. § 355(j)(2)(A)(vii)(IV) |
| Court |
U.S. District Court for the District of Delaware |
| MDL number |
1:20-md-02930-RGA |
The exact claims and asserted patents vary by defendant. Generic defendants that filed ANDAs were required to notify Novartis of Paragraph IV certifications, triggering patent litigation under the Hatch-Waxman Act.
What patents protect Entresto?
The core Entresto patent estate has included patents directed to the sacubitril/valsartan combination, pharmaceutical compositions, dosage forms, and methods of treating cardiovascular disease.
Principal patents associated with the litigation
| Patent |
General subject matter |
Strategic role |
| U.S. Patent No. 8,877,938 |
Pharmaceutical compositions containing sacubitril and valsartan |
Core composition patent |
| U.S. Patent No. 9,388,134 |
Sacubitril/valsartan pharmaceutical compositions and dosage forms |
Composition and formulation protection |
| U.S. Patent No. 9,517,226 |
Methods involving administration of sacubitril and valsartan |
Method-of-use protection |
| Later-issued continuation or related patents |
Additional formulation, dosing, or treatment claims |
Potentially extended patent coverage, subject to Orange Book listing and validity |
The ’938 and ’134 patents have been central to the MDL. Their claims generally focus on pharmaceutical compositions containing both active ingredients, including particular ratios, amounts, or formulation characteristics. The ’226 patent has been associated with method-of-treatment claims.
Patent scope must be evaluated claim by claim. A patent covering a composition does not automatically establish infringement of every generic product unless the proposed ANDA product satisfies each limitation. Method-of-use patents present a separate issue because infringement may depend on the labeling and the uses for which the generic product is approved.
When does Entresto lose exclusivity?
Entresto’s regulatory and patent exclusivities are separate.
Regulatory exclusivity
Entresto was approved by the FDA on July 7, 2015. The product received five-year new chemical entity exclusivity, subject to statutory rules governing the timing of ANDA submissions and Paragraph IV challenges. Regulatory exclusivity did not determine the full commercial protection period because the principal composition patents extended beyond the NCE exclusivity period.
Patent exclusivity
The principal Entresto patents have expiration dates extending beyond the initial FDA exclusivity period. The widely cited expiration date for the core ’938 patent is in September 2026, subject to any applicable patent-term adjustment or extension. The effective generic launch date may be earlier if Novartis settles with an ANDA applicant or loses asserted patent claims.
Entresto’s practical loss-of-exclusivity date therefore depends on:
- The patent claims asserted against each generic defendant.
- The outcome of validity and infringement proceedings.
- Any settlement agreements.
- The FDA’s treatment of the generic labeling.
- Pediatric exclusivity, if applicable.
- Whether later-issued patents are listed and enforceable against a particular ANDA.
Patent expiration alone does not establish the earliest launch date. Conversely, a settlement can create an agreed launch date before the last listed patent expires.
What is the Orange Book status of Entresto?
The FDA Orange Book has listed patents associated with Entresto, including patents covering the sacubitril/valsartan combination and related use or formulation claims. Orange Book listing is commercially significant because a Paragraph IV certification against a listed patent can trigger a 30-month stay of FDA approval under the Hatch-Waxman Act, unless the litigation is resolved earlier or the stay is otherwise terminated.
The Orange Book does not determine patent validity. It records patents identified by the NDA holder as claiming the approved drug or an approved method of using the drug. A listed patent may still be invalidated, found not infringed, or held unenforceable.
Orange Book issues relevant to Entresto
The principal regulatory questions include:
- Whether the patent claims cover the active pharmaceutical combination.
- Whether method-of-use claims correspond to uses included in the generic label.
- Whether a generic applicant can use a Section viii statement to carve out a patented use.
- Whether later-issued patents were listed before the relevant ANDA approval.
- Whether the 30-month stay applies to each ANDA and each asserted patent.
The ANDA applicant’s certification and proposed labeling are central to the infringement analysis.
What Paragraph IV challenges affect Entresto?
Generic applicants challenged Entresto patents through Paragraph IV certifications. Those certifications assert that the listed patents are invalid, unenforceable, or will not be infringed by the proposed generic products.
The challenges generally placed the following issues before the Delaware court:
Infringement
Novartis had to show that the proposed generic products, if approved and marketed as described in the ANDAs, would infringe one or more asserted claims. The analysis can include:
- The active ingredient ratio.
- The amount of sacubitril and valsartan.
- Tablet composition.
- Pharmaceutical excipients.
- Dosage strength.
- Labeling and approved treatment indications.
Validity
Generic defendants commonly challenge patents on grounds including:
- Obviousness.
- Anticipation.
- Lack of written description.
- Lack of enablement.
- Indefiniteness.
The obviousness analysis is particularly important for combination patents. The court must assess whether the prior art would have provided a reason and reasonable expectation of success to combine sacubitril and valsartan in the claimed form and for the claimed clinical use.
Enforceability
A generic defendant may also assert inequitable conduct or related defenses. These claims require proof of material information withheld from the U.S. Patent and Trademark Office with the required intent. They are fact-intensive and can materially affect settlement leverage if the asserted patent is found unenforceable.
What patent litigation affects Entresto generic entry?
The MDL affects the timing of FDA approval and commercial launch for ANDA applicants that are subject to the consolidated cases. A 30-month stay can delay FDA approval unless the court enters an earlier judgment or the parties reach a settlement.
The litigation’s commercial effect depends on whether the court enters:
- A judgment of infringement before patent expiration.
- A judgment that the patents are invalid.
- A judgment of noninfringement.
- A consent judgment.
- A settlement with a licensed or agreed launch date.
A generic applicant that prevails on all asserted patents may obtain approval before the nominal expiration date, subject to FDA review and other regulatory requirements. A defendant that settles may receive a defined entry date, sometimes coupled with a license, supply arrangement, or other commercial terms.
How strong is the Entresto patent estate?
The Entresto estate has meaningful commercial strength because the core patents cover the product’s defining fixed-dose combination rather than a peripheral manufacturing feature.
Strengths
- The patents are directed to the combination of sacubitril and valsartan.
- The product has multiple approved strengths, increasing the commercial value of composition claims.
- A composition patent can be more difficult to design around than a narrow method-of-use patent.
- The Orange Book listings support Hatch-Waxman litigation and potential 30-month stays.
- Entresto’s clinical and commercial profile makes early generic entry economically attractive, increasing settlement pressure on both sides.
Vulnerabilities
- Combination patents face obviousness challenges based on prior art involving neprilysin inhibition, renin-angiotensin system blockade, and cardiovascular treatment.
- Generic products may contest whether their precise formulation falls within every claim limitation.
- Method-of-use patents may be vulnerable to label carve-outs.
- Multiple ANDA defendants can create inconsistent litigation outcomes.
- A finding that one core patent is invalid or not infringed can reduce leverage across the remaining cases.
The strongest claims are generally those that directly cover the commercial tablet composition. Method claims may provide supplementary protection but can be more dependent on the generic label and physician-use evidence.
What manufacturing and formulation barriers protect Entresto?
Entresto’s protection is not limited to active ingredients. The commercial formulation may involve specific ratios, particle characteristics, excipients, tablet architecture, or manufacturing controls.
Potential formulation and manufacturing barriers include:
- Maintaining stability of both active ingredients in a single tablet.
- Controlling sacubitril and valsartan content uniformity.
- Matching dissolution and bioequivalence requirements.
- Managing degradation products.
- Demonstrating bioequivalence across all strengths.
- Producing a commercially scalable fixed-dose combination.
These technical requirements can delay generic development even where patent claims are successfully challenged. They do not, however, create legal exclusivity unless protected by enforceable patents, regulatory requirements, or confidential know-how.
What is the litigation status of the Entresto MDL?
The MDL was created to coordinate common pretrial proceedings arising from multiple ANDA cases. Consolidation promotes consistent rulings on claim construction, discovery, expert testimony, and common validity issues. Individual cases may still require separate infringement or settlement proceedings.
The litigation status must be assessed defendant by defendant because:
- Generic applicants may resolve their cases through separate settlements.
- Different defendants may assert different invalidity defenses.
- Novartis may assert different patent combinations.
- Some defendants may remain subject to trial while others are dismissed.
- Later-issued patents may generate separate actions outside the original consolidated issues.
The MDL docket, individual civil case dockets, PACER filings, and FDA Orange Book entries are the controlling sources for current case status, asserted claims, dismissal terms, and launch dates. Court-level consolidation does not mean that every defendant faces identical exposure.
Have Entresto patent cases produced settlements?
Hatch-Waxman settlements are common in high-value pharmaceutical litigation. A settlement may provide the generic applicant with a license to launch on a specified date before the final patent expiration. It may also include provisions involving authorized generic supply, manufacturing, or restrictions on the generic’s market conduct.
The business significance of a settlement depends on:
- The agreed launch date.
- Whether the license covers all dosage strengths.
- Whether the settlement applies to future patents.
- Whether the generic receives an authorized-generic or supply right.
- Whether the Federal Trade Commission reviews the agreement.
- Whether the agreement contains acceleration or forfeiture provisions.
Settlement terms are often confidential. Public court orders may disclose dismissal and entry-date mechanics without revealing the full commercial agreement.
Which generic launch scenarios are most likely?
Scenario 1: Launch after core patent expiration
This is the default outcome if Novartis preserves the principal composition claims and does not grant an earlier license. Generic entry would occur after expiration of the relevant patents and completion of FDA approval requirements.
Scenario 2: Staggered launches under settlements
Different ANDA applicants may receive different launch dates. Early filers or defendants with stronger validity positions may obtain earlier entry, while later filers remain restricted.
Scenario 3: Court victory for generic defendants
A finding that the asserted patents are invalid or not infringed could permit FDA approval before the nominal patent expiration date. The commercial effect would depend on whether other listed patents remain applicable.
Scenario 4: At-risk launch
A generic company could launch before final resolution if it accepts potential damages and injunctive risk. This is uncommon in a high-value product unless the defendant has strong confidence in its noninfringement or invalidity position.
How does Entresto compare with other Novartis patent estates?
Entresto has a stronger product-level composition position than products protected primarily by narrow methods of treatment or device patents. Its risk profile resembles other combination products in which the formulation itself is central to infringement.
| Factor |
Entresto |
Product protected mainly by method patents |
| Core protection |
Fixed-dose sacubitril/valsartan composition |
Approved use or dosing regimen |
| Design-around difficulty |
Moderate to high |
Often higher through label carve-outs |
| ANDA litigation value |
High |
Depends heavily on labeling |
| Manufacturing complexity |
Meaningful fixed-dose combination requirements |
Product-specific |
| Settlement leverage |
Supported by composition claims |
More variable |
| Biosimilar exposure |
None in the traditional sense |
None unless product is biologic |
Entresto is a small-molecule drug. Biosimilar litigation does not apply. The relevant competitors are ANDA-based generic manufacturers, not biosimilar applicants.
What revenue exposure does Entresto patent litigation create?
Entresto is a major Novartis revenue product, and U.S. generic entry would affect both price and volume. The financial impact would depend on the number of entrants, launch timing, authorized-generic participation, payer substitution, and the speed of price erosion.
The commercial risk is highest under a multi-generic launch because several approved ANDAs can rapidly reduce net price. A single licensed entrant may produce a more gradual decline, particularly if Novartis retains an authorized-generic or supply position.
Key revenue variables include:
- U.S. Entresto sales before generic entry.
- Net price after launch.
- Number of generic competitors.
- Launch date relative to the patent term.
- Generic substitution rules.
- Contracting with pharmacy benefit managers.
- Persistence of branded prescriptions for patients stabilized on therapy.
Novartis’s annual reports identify Entresto as a significant contributor to group sales and identify patent expiry and generic competition as material business risks.[1]
Key Takeaways
- The Entresto MDL is a consolidated Delaware Hatch-Waxman proceeding involving sacubitril/valsartan ANDAs.
- The principal asserted patent families include U.S. Patent Nos. 8,877,938, 9,388,134, and 9,517,226.
- The core patent strategy relies on composition and formulation claims, supported by method-of-use claims.
- Entresto’s five-year FDA exclusivity expired before the principal patent term, making patent litigation the primary barrier to early generic approval.
- Generic applicants used Paragraph IV certifications to challenge Novartis’s listed patents.
- The 30-month stay, patent validity, infringement, settlement terms, and FDA approval status determine actual launch timing.
- Entresto is a small-molecule product, so biosimilar risk does not apply.
- The commercial exposure is substantial because multiple ANDA approvals could produce rapid U.S. price erosion.
- Settlement outcomes must be evaluated by defendant because entry dates and patent claims can differ across cases.
FAQs About Entresto Patent Litigation
What is the Entresto MDL number?
The multidistrict litigation is In re Entresto (Sacubitril/Valsartan) Patent Litigation, No. 1:20-md-02930-RGA, in the District of Delaware.
What is the active ingredient in Entresto?
Entresto contains sacubitril and valsartan in a fixed-dose combination. Sacubitril inhibits neprilysin after conversion to its active metabolite, while valsartan blocks the angiotensin II receptor.
Are Entresto generics approved by the FDA?
FDA approval depends on each ANDA applicant’s regulatory status and the resolution of applicable listed patents. Litigation dismissal alone does not establish FDA approval.
Does Entresto have biosimilar competition?
No. Entresto is a small-molecule drug regulated through the ANDA pathway. Biosimilars are regulated under the Public Health Service Act for biological products.
What is the most important Entresto patent?
The ’938 patent has been one of the principal patents because it is directed to the sacubitril/valsartan pharmaceutical composition. Its commercial importance depends on the asserted claims, infringement findings, validity rulings, and any settlement affecting a particular generic applicant.
References
-
Novartis AG. (2024). Annual report 2023. https://www.novartis.com/investors/financial-data/annual-reporting
-
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
-
U.S. Food and Drug Administration. (2015, July 7). FDA approves new drug treatment for heart failure. https://www.fda.gov/
-
U.S. Patent and Trademark Office. (2024). Patent Center. https://patentcenter.uspto.gov/
-
U.S. District Court for the District of Delaware. (2020). In re Entresto (Sacubitril/Valsartan) Patent Litigation, No. 1:20-md-02930-RGA. PACER.
