US Patent 9,814,751: Lisinopril Oral Liquid Formulation Claims, Exclusivity, and Patent Landscape

US Patent 9,814,751 protects selected stable oral liquid formulations containing approximately 1 mg/mL lisinopril, a citric acid/sodium citrate buffer, specified sweeteners, and specified preservatives. The strongest commercial coverage is concentrated in claims 19 and 20, which define a xylitol/sodium benzoate formulation closely aligned with the commercial Qbrelis product. The patent does not broadly cover all lisinopril liquids, all oral solutions, or the lisinopril molecule itself.

The principal legal and commercial issues are claim construction, the meaning of “stable,” the scope of the concentration ranges, and whether a competing product uses the claimed combination rather than merely the same active ingredient.

What patents protect lisinopril oral liquid formulations?

US Patent 9,814,751 is directed to a formulation technology for stabilizing lisinopril in an aqueous oral liquid. The claims require a combination of:

Lisinopril or a pharmaceutically acceptable salt or solvate;
A listed sweetener;
A citric acid/sodium citrate buffer;
A listed preservative;
Water; and
Stability at approximately 25 ± 5 °C for a specified period.

The patent is formulation-specific. It does not claim:

Lisinopril as a chemical compound;
Lisinopril tablets or capsules;
Every liquid lisinopril dosage form;
A manufacturing process independent of the formulation;
A delivery device or dosing syringe;
A method of treating hypertension using any lisinopril product.

The patent’s practical value comes from covering a commercially usable 1 mg/mL oral solution with taste-masking, buffering, and preservation characteristics suitable for pediatric or dysphagia patients.

Patent identification and ownership

Item	Details
Patent	US 9,814,751
Technology	Stable oral liquid lisinopril formulation
Inventive subject matter	Aqueous lisinopril formulation using selected sweeteners, citrate buffer, and preservatives
Patent type	Utility patent
Grant date	December 12, 2017
Original commercial sponsor	Silvergate Pharmaceuticals
Current commercial association	Azurity Pharmaceuticals and the Qbrelis product
Active ingredient	Lisinopril
Dosage form	Oral liquid solution
Key commercial strength	Approximately 1 mg/mL
FDA product	Qbrelis, lisinopril oral solution
FDA application	NDA 207796

Public patent records identify Silvergate Pharmaceuticals as the principal applicant or assignee associated with the formulation patent. Silvergate’s lisinopril oral solution was commercialized as Qbrelis. Silvergate later became part of Azurity Pharmaceuticals’ commercial portfolio.

What does claim 1 of US 9,814,751 cover?

Claim 1 is a combination claim. A potentially infringing product must contain each required category of component and satisfy the stability limitation.

The claim requires:

Claim element	Required limitation
Active ingredient	About 1 mg/mL lisinopril, salt, or solvate
Sweetener	Xylitol, mannitol, sucralose, saccharin, or acceptable salt
Buffer	Citric acid and sodium citrate
Preservative	Sodium benzoate, benzoic acid, sorbic acid, methylparaben, propylparaben, or acceptable salt
Vehicle	Water
Stability	Stable at approximately 25 ± 5 °C for at least six months
Combination proviso	If the preservative is a paraben, the sweetener cannot be xylitol or mannitol

The claim is narrower than a claim to “a stable lisinopril oral solution.” A formulation using phosphate buffer, for example, would not literally satisfy the citrate-buffer limitation. A formulation using potassium sorbate instead of one of the listed preservative categories could also avoid literal infringement, depending on whether the salt is considered a pharmaceutically acceptable salt of sorbic acid.

The claim’s use of “about” creates a range-construction issue. Courts generally interpret “about” in view of the specification, examples, prosecution history, measurement variability, and technical meaning. It does not automatically convert the claim into an unlimited concentration range.

The paraben proviso

The proviso excludes two combinations:

Xylitol plus methylparaben or propylparaben; and
Mannitol plus methylparaben or propylparaben.

The proviso does not exclude xylitol with sodium benzoate. That combination is expressly covered and becomes the subject of the narrower independent claims 19 and 20.

How strong are claims 19 and 20?

Claims 19 and 20 are the most commercially significant claims because they define a narrower xylitol/sodium benzoate formulation.

Claim 19

Claim 19 requires:

Component	Claimed range
Lisinopril	Approximately 0.8 to 1.2 mg/mL
Xylitol	Approximately 140 to 160 mg/mL
Citric acid	Approximately 0.5 to 1.2 mg/mL
Sodium citrate	Approximately 1.2 to 1.7 mg/mL
Sodium benzoate	Approximately 0.5 to 1.2 mg/mL
pH	Approximately 4 to 5
Stability	At least 12 months at approximately 25 ± 5 °C

Claim 19 is commercially focused. A product containing approximately 1 mg/mL lisinopril, 150 mg/mL xylitol, citrate buffer, sodium benzoate, and a pH near 4.5 would present a substantial literal infringement risk if the stability requirement is met.

Claim 20

Claim 20 expresses the formulation in weight percentages of solids rather than milligrams per milliliter:

Lisinopril: approximately 0.5% to 1% of solids;
Xylitol: approximately 95% to 98% of solids;
Citric acid: approximately 0.3% to 0.7% of solids;
Sodium citrate: approximately 0.7% to 1.3% of solids;
Sodium benzoate: approximately 0.4% to 1.2% of solids;
pH: approximately 4 to 5;
Stability: at least 12 months at approximately 25 ± 5 °C.

Claim 20 may provide a separate infringement route because it uses a solids-based formulation definition. A competitor could fall outside claim 19’s volume-based ranges but still fall within claim 20 if the solids composition and stability requirements are satisfied.

The solids terminology could create factual disputes involving:

Whether “w/w of solids” excludes water;
How lisinopril dihydrate is counted;
Whether the percentages are calculated before or after dissolution;
How residual moisture is treated;
Whether excipients not expressly listed affect the denominator.

Those issues would require review of the patent specification, prosecution history, product composition, and analytical testing.

What do claims 2 through 18 add?

Claims 2 through 18 create narrower fallback positions.

Claim	Added limitation
2	Lisinopril is lisinopril dihydrate
3	pH approximately 4 to 5.2
4	pH approximately 4.9
5	pH approximately 5.2
6	Stability for at least 12 months
7	Stability for at least 18 months
8	Stability for at least 24 months
9	Buffer concentration approximately 5 to 50 mM
10	Buffer concentration approximately 10 mM
11	Sweetener is xylitol
12	Xylitol approximately 140 to 160 mg/mL
13	Sweetener is sucralose
14	Sweetener approximately 0.5 to 3 mg/mL
15	Preservative is sodium benzoate
16	Preservative approximately 0.5 to 1.2 mg/mL
17	Preservative is methylparaben or propylparaben
18	Paraben approximately 0.1 to 2 mg/mL

The dependent claims increase specificity but do not necessarily increase practical protection if a product already meets claim 19 or claim 20. Claims 6 through 8 are particularly relevant to commercial products because a 24-month shelf-life claim can provide a stronger factual match than the six-month requirement in claim 1.

When does US Patent 9,814,751 lose exclusivity?

The patent was granted on December 12, 2017. Its term is generally calculated from the earliest effective nonprovisional or international filing date, not from the provisional application date. Public patent records associate the family with a 2013 priority period and a later nonprovisional or international filing.

The expected base expiration is in 2033 or 2034, depending on the effective filing date and any patent-term adjustment. The enforceable expiration date should be taken from the USPTO patent-term information and the FDA Orange Book listing rather than inferred solely from the grant date.

Exclusivity category	Position
Compound patent	No relevant lisinopril compound exclusivity remains
Formulation patent	US 9,814,751 provides the principal identified protection
FDA new-drug exclusivity	Qbrelis received FDA approval-based exclusivity, which has expired
Patent term	Extends into the 2030s, subject to the official term calculation
Pediatric exclusivity	No separate six-month pediatric extension is established from the information provided
Biosimilar exclusivity	Not applicable because lisinopril is a small molecule

FDA approval-based exclusivity and patent exclusivity are separate. The regulatory exclusivity period for Qbrelis does not determine the patent expiration date. The relevant statutory framework includes the Hatch-Waxman provisions governing patent-term adjustment, listed patents, and abbreviated applications (FDA, 2024; USPTO, 2024).

What is the Orange Book status of lisinopril oral solution?

Qbrelis is an FDA-approved lisinopril oral solution marketed under NDA 207796. The product is a small-molecule prescription drug, not a biologic. Its regulatory pathway is therefore governed by the NDA and Hatch-Waxman framework rather than the biosimilar pathway.

The key Orange Book issues are:

Whether US 9,814,751 is listed against NDA 207796;
Whether the listing covers the approved oral solution;
Whether the patent is categorized as a formulation or method-of-use patent;
Whether the listing remains active through the patent term;
Whether an ANDA applicant must provide a Paragraph IV certification.

A patent that claims the approved formulation can be relevant to an ANDA even when the active ingredient is off-patent. A generic applicant seeking approval before expiration could certify that the patent is invalid, unenforceable, or not infringed. A Paragraph IV notice could trigger patent litigation and a potential 30-month stay under the statutory framework.

Which companies are challenging the lisinopril oral solution patent?

No broadly reported Paragraph IV litigation or final federal judgment concerning US 9,814,751 is identified in the public record reviewed for this analysis. No public settlement agreement tied to this patent has been identified.

That does not establish that no confidential challenge, notice letter, administrative proceeding, or unreported commercial dispute exists. The principal public-facing commercial parties are:

Azurity Pharmaceuticals, associated with Qbrelis;
Silvergate Pharmaceuticals, the original developer and patent applicant;
Potential ANDA sponsors seeking approval for lisinopril oral solution.

A Paragraph IV challenge would likely focus on obviousness, anticipation, written description, enablement, claim construction, and the objective meaning of “stable.” It could also argue that a proposed product lacks one required listed sweetener, preservative, or citrate-buffer component.

What formulation patents protect Qbrelis and competing products?

The dominant identified patent is US 9,814,751. Its protection is composition-based, with dependent claims covering:

Lisinopril dihydrate;
pH near 4.9 or 5.2;
Ten-millimolar citrate buffer;
Xylitol at 140 to 160 mg/mL;
Sucralose at 0.5 to 3 mg/mL;
Sodium benzoate at 0.5 to 1.2 mg/mL;
Parabens at 0.1 to 2 mg/mL;
Twelve-, 18-, and 24-month stability periods.

No separate biologic or biosimilar patent analysis applies. Competing products would be small-molecule formulations, compounded preparations, or generic oral liquids.

Manufacturing and technical barriers

The patent does not claim a manufacturing process, but the formulation creates practical development barriers. A competitor must establish:

Chemical stability of lisinopril in water;
Control of degradation products;
Acceptable pH over shelf life;
Preservative effectiveness;
Microbial control;
Taste acceptability;
Container-closure compatibility;
Dose uniformity;
Stability under labeled storage conditions.

A design-around product using a different buffer or preservative may avoid literal infringement but would require a new stability and preservative-effectiveness package. That development burden can protect the incumbent commercially even when patent scope is narrow.

What generic launch risks exist for lisinopril oral solution?

The risk of an early generic launch depends on the applicant’s formulation design.

Proposed generic approach	Patent risk
1 mg/mL lisinopril with citrate buffer, xylitol, sodium benzoate	High
Same formulation with lisinopril dihydrate and pH near 4.5	High
Different buffer, such as phosphate	Lower literal-infringement risk
Different preservative outside the listed categories	Lower literal-infringement risk
Different sweetener outside the Markush list	Lower literal-infringement risk
Tablet or capsule	Outside the claimed dosage form
Extemporaneously compounded solution	Depends on composition and commercial activity
Oral liquid with substantially different concentration	Potentially lower, but “about” and equivalents remain relevant

Claims 19 and 20 materially increase risk for a product that copies the apparent Qbrelis composition. A generic sponsor can pursue a formulation design-around, but the FDA approval package must still demonstrate quality, stability, and microbiological control.

How does US 9,814,751 compare with lisinopril tablet patents?

The patent estate is narrower than a conventional compound or tablet patent estate.

Attribute	US 9,814,751	Typical lisinopril tablet patent
Active ingredient	Lisinopril	Lisinopril
Dosage form	Aqueous oral liquid	Tablet or solid oral dosage form
Protection type	Formulation composition	Compound, tablet, or solid formulation
Key limitation	Citrate buffer, selected sweetener, preservative, stability	Solid excipients, dosage, release, or chemical form
Biosimilar relevance	None	None
Generic target	Oral solution	Tablets
Design-around path	Change buffer, sweetener, preservative, or concentration	Change excipients, process, or dosage form

A tablet manufacturer does not ordinarily infringe this patent merely by selling lisinopril. The asserted product must satisfy the liquid formulation limitations.

What is the commercial exposure from US 9,814,751?

Qbrelis revenue is not separately disclosed in the public financial reporting reviewed. The commercial exposure is therefore best assessed through product substitution rather than a verified sales figure.

The patent matters most where:

Pediatric dosing is important;
Patients cannot swallow tablets;
Prescribers require a ready-to-use solution;
Pharmacies prefer a manufactured product over compounding;
The product has a long labeled shelf life;
A generic sponsor seeks to copy the incumbent formulation.

The patent does not block the much larger market for lisinopril tablets. Its economic value is tied to the oral-liquid segment and to the regulatory and technical cost of developing a non-infringing alternative.

What is the overall strength of the patent estate?

The patent estate is moderate in breadth and potentially strong against close copies.

Strengths include:

Specific coverage of the commercial 1 mg/mL oral-liquid concept;
Independent claims 19 and 20 directed to a practical xylitol/sodium benzoate formulation;
Stability limitations tied to commercially relevant shelf life;
Multiple fallback claims covering pH, buffer concentration, sweetener, preservative, and storage duration;
Potential Orange Book relevance for the approved product.

Weaknesses include:

No broad claim to all lisinopril oral solutions;
No process claim identified in the supplied claims;
No claim to lisinopril generally;
Multiple formulation design-around options;
Potential disputes over “about,” “stable,” and solids-based calculations;
Narrow reliance on specific excipient categories.

The strongest enforcement case would involve a product that reproduces the claim 19 formulation nearly verbatim, including approximately 1 mg/mL lisinopril, 140 to 160 mg/mL xylitol, citrate buffer, sodium benzoate, pH 4 to 5, and at least 12 months of stability.

Key Takeaways

US 9,814,751 is a formulation patent, not a lisinopril compound patent.
Claim 1 covers a defined class of stable aqueous lisinopril liquids.
Claims 19 and 20 provide the most commercially important protection.
The xylitol, citrate-buffer, sodium benzoate formulation presents the highest infringement risk.
Tablet and capsule lisinopril products are generally outside the claim scope.
Biosimilar analysis is not relevant because lisinopril is a small molecule.
A generic oral solution could use a different buffer, sweetener, preservative, or concentration to reduce literal-infringement risk.
FDA approval exclusivity for Qbrelis has expired, but formulation patent protection extends into the 2030s, subject to the official patent-term calculation.
No publicly reported Paragraph IV litigation or settlement involving US 9,814,751 was identified in the records reviewed.
Qbrelis-specific revenue is not separately disclosed, so commercial exposure cannot be quantified from public financial reporting.

FAQs

Does US 9,814,751 cover every 1 mg/mL lisinopril oral solution?

No. The product must also contain a listed sweetener, citric acid and sodium citrate, a listed preservative, water, and satisfy the applicable stability requirement.

Can a lisinopril oral solution avoid the patent by using phosphate buffer?

Potentially. A phosphate-buffered product would not literally meet the citrate-buffer limitation, although infringement analysis would still consider the full formulation and possible equivalents.

Does lisinopril dihydrate create separate patent protection?

Claim 2 specifically narrows the claimed formulation to lisinopril dihydrate. The patent does not, based on the supplied claims, claim lisinopril dihydrate as a standalone chemical form.

Is a compounded lisinopril solution automatically exempt from infringement?

No. The product’s composition, commercial status, manufacturing activity, and applicable statutory defenses would determine the analysis. Compounding does not automatically eliminate patent risk.

Can an ANDA applicant file before the patent expires?

Yes. An ANDA applicant may submit a Paragraph IV certification challenging a listed patent or asserting noninfringement. The patent owner may then bring litigation, potentially triggering a statutory stay of FDA approval.

References

Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024). Qbrelis (lisinopril) oral solution prescribing information. U.S. Department of Health and Human Services.
U.S. Patent and Trademark Office. (2017). U.S. Patent No. 9,814,751: Stable oral liquid formulation. U.S. Department of Commerce.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation resources. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Patent and exclusivity information. U.S. Department of Health and Human Services.

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	⤷ Start Trial	⤷ Start Trial	Y				⤷ 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
Canada	3003274	⤷ Start Trial
China	108472252	⤷ Start Trial
China	112972370	⤷ Start Trial
European Patent Office	3368012	⤷ Start Trial
European Patent Office	3960156	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,814,751

Which drugs does patent 9,814,751 protect, and when does it expire?

Summary for Patent: 9,814,751