US Patent 10,722,471: Sacubitril/Valsartan Minitablet Scope, Expiration, and Patent Landscape

US Patent No. 10,722,471 protects a pediatric and low-dose oral dosage platform for sacubitril/valsartan. Its strongest protection is directed to a narrow combination of physical dimensions, dose, coating chemistry, excipient composition, and patient-use applications. The patent does not broadly claim every sacubitril/valsartan tablet, capsule, pellet, or pediatric formulation.

The patent issued on July 28, 2020, from an application claiming priority to August 11, 2015. On that priority basis, the nominal 20-year patent term runs to August 11, 2036, subject to any patent-term adjustment, terminal disclaimer, or other USPTO term calculation. The patent is assigned to Novartis-related entities and is associated with the pediatric formulation strategy for Entresto, whose active pharmaceutical ingredient is sacubitril/valsartan sodium hemipentahydrate. [1]

What does US Patent 10,722,471 protect?

The independent product claim protects a coated minitablet meeting all of the following limitations:

Limitation	Requirement in claim 1
Dosage form	Minitablet for oral administration
Physical size	Diameter of 1 mm to 4 mm
Core	Sacubitril and valsartan in a 1:1 molar ratio plus at least one pharmaceutically acceptable excipient
Dose	About 2 mg to about 5 mg, calculated as the combined free-acid equivalents
Coating	Controlled-release and/or protective film coating
Coating polymer	Basic butylated methacrylate copolymer
Polymer concentration	50% to 70% by weight of the film coating

A product must satisfy every limitation of claim 1 to infringe that claim literally. A formulation that contains sacubitril/valsartan but uses a different dosage form, a diameter outside the claimed range, a different coating polymer, or a polymer concentration outside the stated range would not literally meet claim 1.

The dependent claims add narrower commercial embodiments, including:

A 1 mm to 3 mm diameter;
A 3.125 mg active-ingredient dose;
The sacubitril/valsartan sodium hemipentahydrate complex;
A 1:2:1 butyl methacrylate, dimethylaminoethyl methacrylate, and methyl methacrylate copolymer;
Talc, stearic acid or magnesium stearate, and sodium lauryl sulfate in specified ranges;
A coating weight of about 4% to 8% of total minitablet weight;
Core active-ingredient content of 30% to 70%;
A defined excipient system based on microcrystalline cellulose, hydroxypropylcellulose, stearate, colloidal silicon dioxide, and talc;
Capsules containing between one and 20 minitablets;
A minitablet-and-dispenser combination;
Pediatric heart-failure treatment;
Low-dose treatment for multiple cardiovascular and renal indications;
A coating that dissolves only at pH 5 or lower.

How narrow is claim 1?

Claim 1 is materially narrower than a conventional composition-of-matter claim. It is a formulation claim requiring the interaction of five technical parameters:

Sacubitril and valsartan in a 1:1 molar ratio.
A low total dose of approximately 2 mg to 5 mg.
A minitablet diameter between 1 mm and 4 mm.
A basic butylated methacrylate copolymer coating.
A polymer concentration of 50% to 70% by coating weight.

The claim is likely to be most relevant to pediatric or swallowing-impaired patients requiring individualized dosing. It is less likely to cover standard adult Entresto tablets, ordinary immediate-release tablets, sachets, conventional capsules filled with powder, or liquid formulations.

The phrase “about 2 mg to about 5 mg” is potentially important in enforcement. The patent describes the amount by reference to the combined free-acid equivalents of sacubitril and valsartan, while dependent claim 4 identifies 3.125 mg. Product testing would need to establish the applicable assay basis and whether the accused product falls within the claimed range.

What formulation details are protected?

What polymer is claimed?

Claims 6 and 7 identify a basic butylated methacrylate copolymer formed from:

Butyl methacrylate;
(2-dimethylaminoethyl)methacrylate; and
Methyl methacrylate.

Claim 7 narrows the polymer to a 1:2:1 monomer ratio. This corresponds to a basic methacrylate coating system commonly used for acid-soluble protective coatings. Claim 18 further requires dissolution only at pH 5 or lower.

This combination creates a meaningful design-around issue. A competitor could potentially reduce infringement risk by using:

A non-methacrylate polymer;
A neutral or enteric polymer;
A coating with less than 50% or more than 70% of the claimed basic polymer;
A different monomer ratio;
A non-film-coated minitablet;
A polymer coating that dissolves above pH 5.

Whether such alternatives remain pharmaceutically acceptable and provide equivalent stability or taste-masking performance is a separate technical question.

What excipients are protected?

Claim 12 recites the core excipient classes:

Microcrystalline cellulose;
Hydroxypropylcellulose;
Magnesium, calcium, or aluminum stearate;
Anhydrous colloidal silica; and
Talc.

Claim 13 narrows the composition to the following core ranges:

Core component	Claimed amount
Microcrystalline cellulose	35% to 45%
Hydroxypropylcellulose	2% to 8%
Magnesium stearate	1.0% to 5.0%
Colloidal silicon dioxide	1.0% to 2.0%
Talc	0.5% to 1.0%

The claims create multiple infringement pathways. A product may infringe claim 1 without meeting claim 12 or 13. Conversely, a product that meets the narrow excipient ranges would still need to satisfy the independent minitablet, dose, coating, and polymer limitations.

What are the principal claim vulnerabilities?

The patent’s commercial value depends on whether the claimed combination was non-obvious over prior sacubitril/valsartan formulations, pediatric dosage technologies, and known methacrylate coating systems.

Obviousness risk

The most likely validity challenge would combine:

Prior art disclosing sacubitril/valsartan;
Prior art disclosing pediatric minitablets;
Prior art teaching low-dose multiparticulate dosing;
Prior art describing basic methacrylate coatings;
Routine excipient and coating optimization.

The patent’s strongest response would be evidence that the claimed combination solved a formulation problem that was not predictable, such as poor content uniformity, dose accuracy at very low strengths, stability degradation, unacceptable taste, or difficulty manufacturing 1 mm to 4 mm minitablets.

Written-description and enablement risk

The most vulnerable limitations may be the broad numerical ranges in claim 1, particularly:

2 mg to 5 mg;
1 mm to 4 mm;
50% to 70% polymer content; and
“controlled release and/or a protective film-coating.”

A challenger could argue that the specification does not enable the full scope of those ranges without undue experimentation. That argument would depend on the number of working examples, formulation data, dissolution profiles, stability results, and manufacturing disclosure in the patent specification.

Indefiniteness considerations

The terms “about,” “controlled release,” “protective film-coating,” and “dissolves only at a pH of 5 or lower” may require construction in litigation. The specification and prosecution history would determine how those terms are measured.

The phrase “only at a pH of 5 or lower” may create an analytical issue because dissolution depends on test conditions, agitation, temperature, coating thickness, and buffer composition. A clear validated dissolution method would strengthen enforcement.

When does US Patent 10,722,471 expire?

The patent claims priority to August 11, 2015. Assuming no terminal disclaimer and no unusual term adjustment, the baseline expiration date is August 11, 2036. The actual expiration date should be confirmed against the USPTO patent-term record before relying on it for a launch, transaction, or litigation position. The governing patent-term framework is 35 U.S.C. § 154, which generally provides a term of 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments. [2]

The patent issued after the original sacubitril/valsartan composition-of-matter estate. That distinction matters. The earlier core compound and formulation patents may expire substantially earlier, while the minitablet patent can extend protection for the specific pediatric dosage technology into the mid-2030s.

What is the Orange Book status of US Patent 10,722,471?

The Orange Book status must be evaluated by product and dosage form. A patent is not automatically relevant to every FDA-approved sacubitril/valsartan product merely because it claims the same active ingredient.

For Orange Book purposes, the key questions are:

Whether US 10,722,471 is listed against a specific FDA-approved minitablet, pellet, sprinkle, or capsule product;
Whether it is listed as a formulation, drug-product, or method-of-use patent;
Whether the approved product’s labeling identifies the claimed pediatric or low-dose use;
Whether the product is eligible for an FDA patent listing under 21 C.F.R. § 314.53.

The patent’s claims are primarily drug-product and method-of-use claims. They do not appear to be limited to a manufacturing process. If listed against a pediatric sacubitril/valsartan dosage form, an ANDA applicant seeking approval for a therapeutically equivalent product could need to address it through a Paragraph IV certification, unless the applicant waits until patent expiration or uses a non-infringing design. FDA’s Orange Book provides the controlling listed-patent record. [3]

What Paragraph IV challenges and litigation affect this patent?

A Paragraph IV challenge would likely target one or more of the following:

Challenge	Likely theory
Non-infringement	Accused product uses a different polymer, dose, size, or coating concentration
Anticipation	Single prior-art reference discloses the complete minitablet combination
Obviousness	Combination of known sacubitril/valsartan, pediatric minitablet, and methacrylate-coating disclosures
Indefiniteness	“About,” “controlled release,” or pH-dissolution language lacks objective boundaries
Written description	Specification does not support the full breadth of the claimed ranges
Enablement	Full claimed range cannot be practiced without undue experimentation

A Paragraph IV notice directed specifically to US 10,722,471 would create a potential Hatch-Waxman litigation pathway if the patent is listed for the reference product. A 30-month approval stay would depend on the timing of the notice, the listing, and the filing of an infringement action under the applicable FDA and patent statutes. [4]

No specific Paragraph IV challenge, settlement agreement, or final court judgment concerning US 10,722,471 is established by the claim text supplied. The broader Entresto patent estate has generated generic-entry activity and patent disputes, but those proceedings must be distinguished from a challenge to this particular minitablet patent.

Is biosimilar risk relevant to this patent?

No. Sacubitril/valsartan is a chemically synthesized small-molecule combination, not a biologic. A competitor would generally use the ANDA pathway for a generic version rather than the biosimilar pathway under the Public Health Service Act.

The principal regulatory risks are therefore:

Paragraph IV patent certification;
Product-by-product Orange Book listing;
Bioequivalence or pharmaceutical-equivalence requirements;
Pediatric dosage-form comparability;
Demonstration of equivalent dissolution and delivery;
Labeling and dosage-strength differences.

A generic adult tablet sponsor would face a different risk profile from a sponsor developing a pediatric minitablet or sprinkle product. The latter is more likely to encounter US 10,722,471.

How does this patent compare with the core Entresto patent estate?

Estate segment	Typical protection	Strategic relevance
Composition-of-matter patents	Sacubitril/valsartan or related compounds	Broadest active-ingredient protection, generally earlier expiration
Salt and solid-state patents	Sodium hemipentahydrate, crystal or hydrate forms	Protects API form and manufacturing supply
Adult tablet patents	Conventional strengths and excipient systems	Relevant to standard Entresto tablets
Minitablet patent, US 10,722,471	1 mm to 4 mm low-dose coated minitablets	Targets pediatric and individualized dosing
Method-of-use patents	Heart failure and cardiovascular indications	May affect labeling and skinny-label strategies
Manufacturing patents	API synthesis, purification, and formulation processes	Can raise supply-chain and reverse-engineering barriers

US 10,722,471 is narrower than a composition patent but potentially longer-lived than early active-ingredient patents. Its value is concentrated in the pediatric and low-dose segment rather than the entire sacubitril/valsartan market.

What generic launch scenarios exist?

Adult tablet launch

A generic adult tablet may avoid direct infringement if it does not use the claimed minitablet geometry, low dose, or basic methacrylate coating. Its principal exposure would arise from other listed Entresto patents.

Pediatric minitablet or sprinkle launch

This is the highest-risk scenario. A product using 3.125 mg units, 1 mm to 3 mm minitablets, a 1:2:1 basic methacrylate copolymer, and the claimed excipient system could fall within multiple claims.

Capsule-filled minitablets

Claims 14 and 15 extend protection to a dispenser combination and capsules containing one to 20 covered minitablets. Changing the outer capsule does not avoid infringement if the capsule contains minitablets that satisfy claim 1.

Alternative polymer formulation

Replacing the basic butylated methacrylate copolymer is the clearest design-around route. The alternative must still meet stability, taste, dissolution, and pediatric administration requirements.

Liquid or powder formulation

A liquid or powder product would generally fall outside the minitablet claims, although other patents, regulatory exclusivities, or method-of-use claims may remain relevant.

What manufacturing and geographic barriers exist?

The patent has its strongest practical impact in jurisdictions where equivalent family members are granted and enforceable. The United States is commercially important because FDA approval, Orange Book listings, and Hatch-Waxman litigation can delay ANDA entry.

Manufacturing barriers include:

Uniform blending at a 2 mg to 5 mg dose;
Content uniformity in 1 mm to 4 mm units;
Reliable compression of very small cores;
Consistent application of a 4% to 8% coating weight;
Control of polymer concentration within the claimed range;
Verification of pH-dependent dissolution;
Prevention of dose segregation during capsule filling or dispensing.

The patent does not by itself prevent manufacture of sacubitril/valsartan API or standard tablets. It targets a particular finished-dosage-form architecture.

Are licensing deals disclosed for this patent?

The patent record does not establish a separate licensing transaction for US 10,722,471. The commercial rights appear connected to the Novartis sacubitril/valsartan product franchise. Any third-party license, settlement license, or supply agreement would need to be assessed from SEC filings, court records, transaction documents, or the relevant patent-family records rather than inferred from the claims.

How strong is the patent estate for pediatric sacubitril/valsartan?

The patent is strongest when used as part of a layered estate:

A core active-ingredient patent;
Salt or solid-state protection;
Pediatric formulation claims;
Method-of-use claims;
FDA regulatory exclusivity;
Manufacturing and supply-control measures.

Standing alone, US 10,722,471 is vulnerable to a formulation design-around. A competitor that changes the dosage form or coating polymer may avoid the most specific claims. As part of a broader pediatric product strategy, however, the patent can create meaningful launch friction because the claimed formulation corresponds closely to a practical low-dose administration format.

Key Takeaways

US 10,722,471 is a formulation and dosage-form patent, not a broad sacubitril/valsartan composition patent.
Claim 1 requires a 1 mm to 4 mm coated minitablet, a 2 mg to 5 mg low dose, a 1:1 sacubitril/valsartan ratio, and a basic butylated methacrylate copolymer at 50% to 70% of the coating.
Claims 4, 7, 9, 13, 15, 16, and 18 define commercially important narrower embodiments.
The patent is most relevant to pediatric, individualized, and swallowing-impaired patient products.
The baseline term is August 11, 2036, subject to the USPTO’s final term calculation.
Generic risk depends on whether the competitor pursues an equivalent pediatric minitablet rather than a conventional adult tablet.
The principal legal vulnerabilities are obviousness, enablement, written description, indefiniteness, and formulation design-around.
Sacubitril/valsartan is a small molecule, so biosimilar litigation is not the relevant pathway.
Orange Book relevance depends on the specific FDA-approved product and any patent listing associated with that product.

FAQs

Does US 10,722,471 cover ordinary Entresto tablets?

Not necessarily. Its independent claim requires a small coated minitablet, a low 2 mg to 5 mg dose, and a specified basic methacrylate coating. Conventional adult tablets may be outside its literal scope.

Can a generic use a different methacrylate polymer?

Potentially. A different polymer may avoid literal infringement of claims requiring the basic butylated methacrylate copolymer, but other patents and regulatory requirements may still apply.

Does putting the minitablets inside a capsule avoid the patent?

No. Claim 15 expressly covers capsules containing one to 20 covered minitablets.

Is a pediatric sacubitril/valsartan liquid covered by this patent?

A liquid would generally fall outside the minitablet claims. It could remain subject to separate patents, exclusivities, or method-of-use rights.

What is the most important infringement test for a competing product?

The critical test is whether the product contains every limitation of claim 1, especially the minitablet size, low-dose range, 1:1 active ratio, basic methacrylate coating, and 50% to 70% polymer concentration.

References

United States Patent and Trademark Office. (2020). U.S. Patent No. 10,722,471 B2, Minitablets comprising sacubitril and valsartan.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patents; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
United States Code. (2023). 21 U.S.C. § 355(j): Abbreviated applications for new drugs.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-001	Apr 12, 2024		RX	Yes	No	⤷ Start Trial	⤷ Start Trial	Y			TREATMENT OF HEART FAILURE WITH ORAL PELLETS	⤷ Start Trial
Novartis	ENTRESTO SPRINKLE	sacubitril; valsartan	CAPSULE, PELLETS;ORAL	218591-002	Apr 12, 2024		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y			TREATMENT OF HEART FAILURE WITH ORAL PELLETS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2017215530	⤷ Start Trial
Australia	2019280026	⤷ Start Trial
Canada	3010778	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,722,471

Which drugs does patent 10,722,471 protect, and when does it expire?

Summary for Patent: 10,722,471