Details for Patent: 10,039,800

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Which drugs does patent 10,039,800 protect, and when does it expire?

Patent 10,039,800 protects QBRELIS and is included in one NDA.

This patent has ten patent family members in eight countries.

Summary for Patent: 10,039,800

Title:	Lisinopril formulations
Abstract:	Provided herein are stable lisinopril oral liquid formulations. Also provided herein are methods of using lisinopril oral liquid formulations for the treatment of certain diseases including hypertension, heart failure and acute myocardial infarction.
Inventor(s):	Gerold L. Mosher, David W. Miles
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US15/805,934
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,039,800
Patent Claim Types: see list of patent claims	Use; Formulation;

U.S. Patent 10,039,800: Lisinopril Oral Solution Claims, Exclusivity, and Patent Landscape

U.S. Patent No. 10,039,800 protects specific stable liquid lisinopril formulations when used to treat hypertension, heart failure, or patients shortly after acute myocardial infarction. Its core technical limitation is a 1 mg/mL aqueous formulation containing lisinopril, a defined sweetener, a citric acid/sodium citrate buffer, a defined preservative, and demonstrated stability for at least six months at approximately room temperature.

The patent is formulation-specific rather than molecule-specific. It does not prevent all lisinopril products, tablets, capsules, or liquid formulations. A competing product must avoid at least one required formulation element, avoid the claimed therapeutic use, or establish that the patent is invalid or unenforceable.

What does U.S. Patent 10,039,800 protect?

The patent protects three independent method-of-treatment claims:

Independent claim	Disease or clinical setting	Required formulation
Claim 1	Hypertension	1 mg/mL lisinopril liquid meeting the listed excipient and stability limitations
Claim 11	Heart failure	Same formulation requirements
Claim 16	Hemodynamically stable patient within 24 hours after acute myocardial infarction	Same formulation requirements

Each independent claim requires all of the following:

1. About 1 mg/mL lisinopril, or a pharmaceutically acceptable salt or solvate.
2. An aqueous oral liquid formulation.
3. A sweetener selected from xylitol, mannitol, sucralose, saccharin, or acceptable salts.
4. A buffer comprising citric acid and sodium citrate.
5. A preservative selected from sodium benzoate, benzoic acid, sorbic acid, methylparaben, propylparaben, or acceptable salts.
6. No combination of a paraben preservative with xylitol or mannitol.
7. Stability at approximately 25 ± 5°C for at least six months.

The claims are method claims. Infringement generally requires both use of a covered formulation and administration for one of the claimed indications or clinical settings.

What are the important limitations in the claims?

Concentration and active ingredient

The concentration is “about 1 mg/ml,” which creates a range rather than an absolute numerical requirement. The scope will depend on claim construction, specification support, product labeling, analytical testing, and the degree to which a competing concentration is equivalent to 1 mg/mL.

The claims expressly cover lisinopril dihydrate through dependent claims 2, 12, and 17. A formulation containing another pharmaceutically acceptable lisinopril salt or solvate may still fall within the independent claims.

The patent does not claim every lisinopril concentration. A materially different concentration could avoid literal infringement, although the doctrine of equivalents may remain relevant depending on the evidence.

Sweetener and preservative combinations

The sweetener limitation creates five alternatives:

• Xylitol
• Mannitol
• Sucralose
• Saccharin
• Pharmaceutically acceptable salts of those substances

The preservative limitation creates six principal alternatives:

• Sodium benzoate
• Benzoic acid
• Sorbic acid
• Methylparaben
• Propylparaben
• Pharmaceutically acceptable salts

The proviso narrows the permissible combinations. If the preservative is methylparaben or propylparaben, the sweetener cannot be xylitol or mannitol. The patent therefore permits, for example:

Sweetener	Sodium benzoate or benzoic acid	Sorbic acid	Methylparaben or propylparaben
Xylitol	Yes	Yes	No
Mannitol	Yes	Yes	No
Sucralose	Yes	Yes	Yes
Saccharin	Yes	Yes	Yes

A formulation using a different sweetener or preservative may avoid literal infringement, subject to the doctrine of equivalents. Excipients such as glycerin, flavoring agents, coloring agents, or additional stabilizers are not excluded by the claims if the claimed ingredients are also present.

Buffer and pH

The independent claims require a buffer comprising citric acid and sodium citrate. This limitation is narrower than a generic “citrate buffer” limitation. A formulation using only citric acid, only sodium citrate, a phosphate buffer, or another buffer system would present a noninfringement position based on the claim language.

Claims 3, 13, and 18 narrow the formulation to a pH of approximately 4.9. The pH limitation is not required by the independent claims. A product outside the approximate 4.9 range can still infringe an independent claim if it satisfies the other limitations.

Stability requirement

The formulation must be stable at approximately 25 ± 5°C for at least six months. Claims 4, 14, and 19 extend this requirement to at least 24 months.

Stability is a substantive claim limitation, not merely a product-performance statement. Relevant testing may include assay, degradation products, appearance, pH, microbial quality, preservative effectiveness, and other specifications described in the patent or regulatory file.

A product with six months of qualifying stability may fall within claims 1, 11, or 16 but not necessarily claims 4, 14, or 19. A product with 24 months of qualifying stability can satisfy both the six-month and 24-month limitations if the other elements are present.

How do the dependent claims expand the protected uses?

The dependent claims add patient populations, disease subtypes, coadministration, and clinical circumstances.

Claims	Added limitation
2, 12, 17	Lisinopril dihydrate
3, 13, 18	pH of approximately 4.9
4, 14, 19	Stability for at least 24 months
5	Primary or essential hypertension
6	Secondary hypertension
7	Blood pressure of at least 140/90 mm Hg
8	Elderly subject
9	Pediatric subject
10	Combination with specified antihypertensive agents
15	Heart-failure patient inadequately responding to diuretics and digitalis
20	Post-myocardial-infarction use with beta blockers, aspirin, or thrombolytics

Claims 5 through 9 do not broaden claim 1. They narrow it. The formulation still must meet every limitation of claim 1, and the patient must also satisfy the additional condition.

Claim 10 covers combination administration with diuretics, beta blockers, alpha blockers, mixed alpha and beta blockers, calcium channel blockers, angiotensin II receptor antagonists, ACE inhibitors, aldosterone antagonists, or alpha-2 agonists. The claim does not require a specific fixed-dose combination. Separate administration of lisinopril liquid and another agent may be sufficient if the claim’s administration requirement is met.

When does U.S. Patent 10,039,800 lose exclusivity?

The patent issued on August 7, 2018. Public patent records identify a September 2013 priority date, producing a nominal 20-year patent term that reaches approximately September 2034, subject to any patent-term adjustment, terminal disclaimer, or other USPTO term calculation. Google Patents, U.S. Patent and Trademark Office records, and FDA Orange Book data should be read together for the controlling expiration information.[1][2]

Event	Date or period
Earliest reported priority	September 2013
Patent grant	August 7, 2018
Nominal 20-year term endpoint	Approximately September 2034
FDA product approval associated with lisinopril oral solution	2016
Patent term remaining after approval	Approximately eight years from approval, before any adjustment

Patent expiration is separate from FDA regulatory exclusivity. Lisinopril is an established active ingredient, so the product does not receive new chemical entity exclusivity. FDA approval of an oral solution does not itself create a 12-year biologic exclusivity period or a five-year NCE period.

Any pediatric exclusivity, patent-term extension, or patent-term adjustment would need to be confirmed in the USPTO and FDA records. The patent’s commercial importance therefore depends primarily on patent protection and the absence of a successful Paragraph IV challenge, rather than on long statutory drug exclusivity.

What is the Orange Book status of the lisinopril oral solution?

The commercial product associated with this technology is Qbrelis, a 1 mg/mL lisinopril oral solution approved by FDA under NDA 209158. The FDA-approved labeling identifies lisinopril oral solution for hypertension, heart failure, and reduction of mortality in hemodynamically stable patients within 24 hours of acute myocardial infarction.[3]

The labeled indications align closely with independent claims 1, 11, and 16. That alignment increases the risk that a generic oral solution with the same concentration, excipient architecture, and labeled uses would face a patent-listing issue.

FDA Orange Book analysis should distinguish:

• The listed drug and NDA.
• Any patent listed for the drug product.
• The patent’s expiration date.
• Whether a future abbreviated new drug application must make a Paragraph IV certification.
• Whether a generic applicant uses a section viii statement to omit a patented method of use.

A generic applicant may attempt to carve out one or more patented uses through a section viii statement. That strategy would not eliminate formulation patent risk if the product itself is covered by a product or formulation claim. Here, the issued claims are method claims, so the strength of a use carve-out depends on the final label, prescribing information, distribution practices, and the actual formulation.

Which companies are challenging U.S. Patent 10,039,800?

No widely reported district-court litigation or publicly prominent Paragraph IV dispute involving U.S. Patent 10,039,800 is identified in the patent record and FDA materials cited here. The absence of reported litigation is not equivalent to an adjudication of validity or noninfringement.

Potential challengers would most likely include:

• Generic manufacturers developing lisinopril oral solution.
• Specialty pharmaceutical companies targeting pediatric or elderly patients who have difficulty swallowing tablets.
• Contract manufacturers supplying a competing oral liquid.
• Companies seeking to market an oral solution under a different concentration or excipient system.

A Paragraph IV challenge could attack the patent on anticipation, obviousness, lack of written description, enablement, indefiniteness, or improper claim scope. A challenger could also pursue a noninfringement position based on a different buffer, preservative, sweetener, concentration, or stability profile.

How strong is the patent estate for lisinopril oral solution?

The patent estate appears strongest against a product that copies the commercial 1 mg/mL formulation architecture and uses the same labeled indications.

Strengths

• The claims cover three commercially relevant clinical uses.
• The concentration matches the approved oral solution.
• The excipient lists capture common pharmaceutical preservatives and sweeteners.
• The citric acid/sodium citrate buffer limitation identifies a defined formulation platform.
• The six-month stability limitation can be demonstrated through product testing.
• The patent term extends into approximately 2034 on a nominal basis.

Vulnerabilities

• The claims are not composition claims that cover the formulation independent of use.
• A competitor may design around the sweetener or preservative.
• A phosphate or non-citrate buffer may avoid the express buffer limitation.
• A different concentration may avoid the “about 1 mg/mL” limitation.
• The formulation concept may face obviousness arguments based on known lisinopril liquids, conventional preservatives, citrate buffers, sweeteners, and routine stability testing.
• The “about” language and stability standard may generate claim-construction disputes.
• The medical-use limitations may permit label-based design-around strategies.

The patent is therefore commercially meaningful but narrower than a composition patent covering all lisinopril oral solutions.

What generic launch risks exist?

A generic launch could follow several paths.

Same formulation and full label

A generic using approximately 1 mg/mL lisinopril, citrate buffer, a listed sweetener, and a listed preservative would face the highest risk if it also seeks the patented hypertension, heart-failure, and post-myocardial-infarction indications.

The applicant would likely need to certify against the listed patent or wait until expiration, unless it establishes noninfringement or invalidity.

Same formulation with a carved-out label

A section viii strategy could remove one or more patented uses. The approach is more credible where the remaining label does not encourage use within the patent claims. It is less effective if the formulation itself is treated as inseparable from the labeled indication or if marketing materials promote the carved-out use.

Reformulated oral solution

A competitor could reduce risk by using:

• A different buffer system.
• A sweetener outside the claimed group.
• A preservative outside the claimed group.
• A concentration materially different from 1 mg/mL.
• A formulation that does not demonstrate the claimed stability period.
• A different route or dosage form.

Each change can create regulatory, palatability, microbial-control, dosing, or shelf-life complications. The patent is most valuable because its limitations overlap with a commercially practical formulation.

What biosimilar risk applies to lisinopril?

No biosimilar pathway applies. Lisinopril is a synthetic small-molecule ACE inhibitor, not a biologic subject to the Public Health Service Act’s biosimilar framework.

The relevant competitive pathway is an ANDA for a generic drug product or, depending on the product’s regulatory classification, another FDA pathway for an oral solution. The main risks are formulation patent challenges, labeling carve-outs, bioequivalence requirements, and manufacturing validation.

How does U.S. Patent 10,039,800 compare with other lisinopril patent protection?

Protection type	Coverage	Relevance to this patent
Compound patent	Lisinopril molecule	Expired; lisinopril is a long-established active ingredient
Tablet or capsule patents	Solid dosage forms	Generally separate from the claimed oral liquid
Formulation patent	Specific liquid composition and stability	Core subject of U.S. 10,039,800
Method-of-use patent	Hypertension, heart failure, post-MI treatment	Incorporated into the three independent claims
Manufacturing patent	Preparation, mixing, filling, or packaging	Not apparent from the supplied claims
Pediatric-use protection	Pediatric patients	Claim 9 narrows the method but is not FDA pediatric exclusivity
Biologic exclusivity	Not applicable	Lisinopril is not a biologic

The patent’s value is concentrated in the liquid formulation and its alignment with the approved Qbrelis indications. It does not create broad exclusivity over lisinopril treatment or all liquid ACE-inhibitor products.

What manufacturing and intellectual-property barriers remain after patent expiration?

Patent expiration will not automatically eliminate commercial barriers. A competitor must still establish:

• Pharmaceutical-grade lisinopril sourcing.
• Stability under ICH storage conditions.
• Preservative effectiveness.
• Microbial limits and container-closure integrity.
• Dose accuracy across pediatric and adult administration volumes.
• Acceptable taste and patient adherence.
• FDA bioequivalence or applicable product-quality requirements.
• Manufacturing controls for aqueous solutions.
• Packaging compatibility and extractables/leachables control.

The formulation claims may also be supplemented by confidential manufacturing know-how, supplier specifications, analytical methods, and process controls that are not visible in the patent claims.

Key Takeaways

• U.S. Patent 10,039,800 is a formulation-linked method patent for stable 1 mg/mL lisinopril oral liquid.
• Claims 1, 11, and 16 cover hypertension, heart failure, and treatment within 24 hours after acute myocardial infarction.
• The required formulation includes lisinopril, a specified sweetener, citric acid and sodium citrate, a specified preservative, water, and six-month room-temperature stability.
• Claims 4, 14, and 19 add a 24-month stability requirement.
• The patent does not cover all lisinopril products or all oral liquids.
• Qbrelis, the FDA-approved 1 mg/mL lisinopril oral solution, aligns closely with the claimed indications.
• The nominal patent term reaches approximately September 2034, subject to the controlling USPTO term calculation.
• No biosimilar pathway applies.
• The strongest generic design-around options involve changing the buffer, sweetener, preservative, concentration, stability profile, or labeled use.
• A formulation that copies the commercial product and seeks the same indications presents the highest infringement and Paragraph IV risk.

FAQs

Is U.S. Patent 10,039,800 a composition-of-matter patent?

No. The issued claims supplied are method-of-treatment claims. They require administration of a defined stable lisinopril oral liquid for specified clinical uses.

Does a lisinopril tablet infringe U.S. Patent 10,039,800?

Ordinarily, no. The claims require a stable oral liquid formulation containing the specified excipient and stability elements.

Does a 2 mg/mL lisinopril oral solution avoid the patent?

It may provide a noninfringement position because the claims recite about 1 mg/mL. The outcome would depend on claim construction, formulation data, and whether the concentration is considered an equivalent.

Can a generic use sucralose and propylparaben?

That combination is within the expressly permitted sweetener-preservative combinations because the exclusion applies only when a paraben is combined with xylitol or mannitol. The other claim elements must also be satisfied.

Does pediatric claim 9 create separate FDA exclusivity?

No. Claim 9 is a patent claim covering treatment of a child with the claimed formulation. It does not itself create statutory pediatric exclusivity.

References

1. United States Patent and Trademark Office. (2018). U.S. Patent No. 10,039,800.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
3. U.S. Food and Drug Administration. (2016). Qbrelis (lisinopril) oral solution prescribing information. NDA 209158.

Drugs Protected by US Patent 10,039,800

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	10,039,800					ACUTE MYOCARDIAL INFARCTION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	10,039,800					TREATMENT OF MYOCARDIAL INFARCTION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	10,039,800					REDUCTION OF MORTALITY IN ACUTE MYOCARDIAL INFARCTION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	10,039,800					METHOD OF TREATMENT OF HEART FAILURE
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	10,039,800					TREATMENT OF HEART FAILURE

International Family Members for US Patent 10,039,800

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3003274
China	108472252
China	112972370
European Patent Office	3368012
European Patent Office	3960156