Details for Patent: 9,616,096

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Which drugs does patent 9,616,096 protect, and when does it expire?

Patent 9,616,096 protects QBRELIS and is included in one NDA.

This patent has ten patent family members in eight countries.

Summary for Patent: 9,616,096

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:	US15/268,095
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,616,096
Patent Claim Types: see list of patent claims	Use; Formulation;

US Patent 9,616,096: Scope, Claim Construction, Expiration, and Lisinopril Patent Landscape

US Patent 9,616,096 protects methods of treating hypertension, heart failure, and acute myocardial infarction with a specific stable lisinopril oral liquid formulation. The patent does not broadly claim lisinopril, lisinopril dihydrate, or oral lisinopril products generally. Its principal protection is a formulation-and-use combination requiring defined concentrations of lisinopril, xylitol, citrate buffer, sodium benzoate, water, pH, and long-term stability.

The patent is associated with the 1 mg/mL lisinopril oral solution marketed as Qbrelis. Public patent records identify Silvergate Pharmaceuticals, Inc. as the original patent owner or applicant, with the product later associated with Azurity Pharmaceuticals. The reported patent expiration date is March 14, 2034, subject to any applicable patent-term adjustment, pediatric extension, or other statutory modification.[1][2]

What drug and formulation does US Patent 9,616,096 protect?

The patent protects a stable, ready-to-use oral liquid containing the following core composition:

Component	Claimed amount or characteristic
Lisinopril or pharmaceutically acceptable salt or solvate	About 1 mg/mL
Sweetener	About 150 mg/mL xylitol
Citric acid	About 0.86 mg/mL
Sodium citrate	About 1.44 mg/mL
Preservative	About 0.8 mg/mL sodium benzoate
Vehicle	Water
pH	About 4 to about 5
Stability	At least 12 months at approximately 25 ± 5°C

The claims cover a formulation that is administered therapeutically for specified cardiovascular indications. This structure is important. The patent is primarily a method-of-treatment patent tied to a narrowly defined formulation, rather than a standalone composition claim.

Qbrelis is a lisinopril oral solution containing 1 mg/mL lisinopril. FDA labeling identifies its use for hypertension in adults and pediatric patients six years of age and older, as well as adjunctive treatment of heart failure and treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction.[2]

How many independent claims does US 9,616,096 contain?

The supplied claims contain three independent claims:

1. Claim 1: treatment of hypertension.
2. Claim 11: treatment of heart failure.
3. Claim 16: treatment of a hemodynamically stable patient within 24 hours of acute myocardial infarction.

Each independent claim requires substantially the same formulation. The claims differ primarily in the therapeutic indication and, for hypertension, the patient and combination-treatment limitations added by dependent claims.

Independent claim	Indication	Required formulation	Minimum stability
Claim 1	Hypertension	1 mg/mL lisinopril, xylitol, citrate buffer, sodium benzoate, water, pH 4-5	12 months
Claim 11	Heart failure	Same formulation	12 months
Claim 16	Hemodynamically stable patient within 24 hours of acute myocardial infarction	Same formulation	12 months

Claims 4, 14, and 19 narrow the formulation by requiring at least 24 months of stability. Claims 3, 13, and 18 narrow the pH to approximately 4.9.

What are the key limitations in claim 1?

Claim 1 requires proof of each material element:

• A method of treating hypertension.
• A subject receiving the formulation.
• A therapeutically effective amount.
• Approximately 1 mg/mL lisinopril or an accepted salt or solvate.
• Approximately 150 mg/mL xylitol.
• A buffer containing approximately 0.86 mg/mL citric acid and 1.44 mg/mL sodium citrate.
• Approximately 0.8 mg/mL sodium benzoate.
• Water.
• A pH between approximately 4 and 5.
• Stability at approximately 25 ± 5°C for at least 12 months.

An accused product or use would generally need to satisfy the formulation limitations and the treatment limitation. A product containing lisinopril but using sucrose instead of xylitol would not literally satisfy the xylitol limitation. A formulation using potassium sorbate instead of sodium benzoate would present a similar literal-infringement issue.

The word “about” creates numerical flexibility, but it does not eliminate the requirement for the claimed formulation architecture. The scope of “about” would be assessed in light of the specification, analytical precision, manufacturing tolerances, formulation practice, and prosecution history.

Do the claims cover lisinopril tablets or generic lisinopril products?

No. The claims are directed to a stable oral liquid formulation administered for specified cardiovascular treatments.

Conventional lisinopril tablets would ordinarily lack at least the following limitations:

• A liquid formulation.
• Approximately 150 mg/mL xylitol.
• The specified citric acid and sodium citrate buffer.
• Approximately 0.8 mg/mL sodium benzoate.
• The claimed pH and stability profile.

Generic lisinopril tablets can therefore coexist with the patent without practicing the claimed method, provided they do not involve the claimed liquid formulation and method of administration.

The patent has greater relevance to:

• Generic lisinopril oral solutions.
• Compounded or commercial liquid lisinopril products.
• Authorized-generic or licensed versions of Qbrelis.
• Pediatric and geriatric liquid dosage forms.
• Formulations designed to substitute for Qbrelis.

What do the dependent claims add?

Lisinopril dihydrate claims

Claims 2, 12, and 17 specify lisinopril dihydrate. These claims may be easier to prove against a product whose active pharmaceutical ingredient is expressly identified as lisinopril dihydrate. They are narrower than the corresponding independent claims because they exclude other lisinopril forms that might otherwise fall within the broader “salt or solvate” language.

pH 4.9 claims

Claims 3, 13, and 18 require a pH of approximately 4.9. These claims provide a narrower target than the pH 4-to-5 range. They may be useful where a product’s pH is tightly controlled near 4.9, but they are less useful against a formulation maintained near the edge of the broader range.

Twenty-four-month stability claims

Claims 4, 14, and 19 require at least 24 months of stability at approximately 25 ± 5°C. These claims are commercially significant because a product with a two-year shelf life is more likely to compete directly with an approved commercial oral solution.

The stability limitation also creates an evidentiary burden. Infringement analysis may require review of:

• Long-term stability protocols.
• Accelerated stability data.
• Assay and degradation-product specifications.
• Container-closure studies.
• Batch records.
• Expiration dating.
• Regulatory submissions.

A formulation that has the same ingredients but lacks evidence of the claimed stability may not satisfy the stability limitation.

Combination-treatment claims

Claim 10 covers hypertension treatment in combination with categories including diuretics, beta blockers, alpha blockers, calcium channel blockers, angiotensin II receptor antagonists, other ACE inhibitors, aldosterone antagonists, and alpha-2 agonists.

Claim 20 covers acute myocardial infarction treatment in combination with beta blockers, aspirin, or thrombolytics.

These claims are method claims. They require administration of both the patented lisinopril liquid and the specified co-therapy. They do not independently claim the co-therapy or the treatment regimen without the patented formulation.

What indications are covered by US 9,616,096?

Indication or patient population	Claim coverage
Primary or essential hypertension	Claim 5
Secondary hypertension	Claim 6
Blood pressure of at least 140/90 mmHg	Claim 7
Elderly subjects	Claim 8
Pediatric subjects	Claim 9
Heart failure	Claim 11
Heart failure with inadequate response to diuretics and digitalis	Claim 15
Hemodynamically stable patient within 24 hours of acute myocardial infarction	Claim 16
Acute myocardial infarction with specified combination therapy	Claim 20

The indication claims overlap with established clinical uses of lisinopril. Their commercial value comes from linking those uses to the specific liquid formulation.

The pediatric claims are important because liquid delivery is particularly relevant where tablets are difficult to swallow or dose adjustments are required. The claims do not, however, create a separate pediatric exclusivity period. FDA pediatric exclusivity is a regulatory extension that depends on completion of an FDA-requested pediatric study and is separate from the patent claims.[2][3]

When does US Patent 9,616,096 lose exclusivity?

Public patent databases report an expiration date of March 14, 2034.[1] The statutory term is generally 20 years from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment and other statutory rules.[4]

Milestone	Reported event
Patent family priority	2013
U.S. patent issuance	2017
Reported expiration	March 14, 2034
Regulatory product	Qbrelis, lisinopril oral solution
FDA NDA	208161

Patent expiration does not necessarily establish the earliest lawful commercial entry date for an ANDA applicant. Entry may occur earlier through:

• A successful Paragraph IV challenge.
• A court decision finding the patent invalid or not infringed.
• A settlement with an agreed entry date.
• A license from the patent owner.
• A product that does not practice the patent claims.
• A regulatory pathway that avoids the listed patent.

What is the Orange Book status of US 9,616,096?

FDA Orange Book records identify patents associated with approved drug products and their approved uses. US 9,616,096 has been publicly associated with the Qbrelis lisinopril oral solution approval.[2]

The relevant Orange Book issue is not whether lisinopril itself remains patent-protected. Lisinopril tablets have long been available generically. The issue is whether an ANDA applicant seeking approval for the same or a therapeutically equivalent oral solution must address the listed formulation-and-use patent.

An applicant filing an ANDA may need to submit a certification concerning the listed patent, including:

• Paragraph I: no patent information has been submitted.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will not market until patent expiration.
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

The commercial consequences of a Paragraph IV notice depend on whether the NDA holder brings suit within the statutory period. A timely patent infringement action can trigger a 30-month stay of approval under the Hatch-Waxman framework, subject to statutory exceptions and court action.[5]

Are there known Paragraph IV challenges or patent litigation?

No established public Paragraph IV litigation or settlement involving US 9,616,096 should be inferred solely from the existence of the patent or the Qbrelis approval.

A complete litigation assessment would require current review of:

• FDA Paragraph IV notice records.
• PACER and district-court dockets.
• ANDA litigation complaints.
• Declaratory-judgment actions.
• Patent Trial and Appeal Board proceedings.
• FDA Orange Book updates.
• Corporate disclosures by Qbrelis, Azurity, and generic applicants.

The absence of a publicly identified case is not equivalent to a finding that no Paragraph IV notice has ever been sent. Paragraph IV notices are generally served on the NDA holder and patent owner, while the public record becomes more visible if litigation follows.

Which companies are challenging the Qbrelis patent estate?

The supplied information does not identify a specific ANDA applicant, Paragraph IV challenger, licensee, or settlement counterparty. The visible competitive set consists of:

Competitor category	Product or approach	Relevance to US 9,616,096
Branded oral solution	Qbrelis	Primary commercial product associated with the patent
Generic lisinopril tablets	Multiple manufacturers	Compete in active ingredient, but generally do not practice the liquid formulation claims
Compounded lisinopril liquids	Pharmacy or outsourcing-facility preparations	Potential formulation and enforcement issue
Other liquid ACE inhibitors	Epaned, enalapril oral solution	Therapeutic alternative, not a lisinopril formulation competitor
Future generic oral solution	ANDA applicant	Direct patent and regulatory challenger

How strong is the patent estate for Qbrelis?

The patent is strong against an exact or near-exact copy of the claimed formulation, but narrower than a composition patent covering all lisinopril liquids.

Strengths

• The formulation is defined by multiple quantitative limitations.
• The claims cover three commercially important cardiovascular indications.
• The 24-month stability claims align with commercial shelf-life requirements.
• Pediatric and elderly populations are expressly addressed.
• A generic oral solution may need to disclose enough formulation information to create an infringement risk.
• The patent extends well beyond the original approval date.

Limitations

• The claims require a method of treatment, not merely manufacture or sale of a formulation.
• A liquid product using a materially different sweetener, buffer, preservative, concentration, or pH may avoid literal infringement.
• The claim requires the specified stability period.
• The clinical indication and administration requirement matter.
• “About” limitations may create claim-construction disputes.
• Lisinopril’s active-ingredient and tablet markets are not protected by this patent.

The most important design-around variables are the sweetener system, buffer composition, preservative, lisinopril concentration, pH, and stability profile. A formulation change must still satisfy FDA quality, safety, palatability, preservative-effectiveness, and shelf-life requirements.

What manufacturing and intellectual-property barriers exist?

The patent is only one barrier. A competing oral solution would also face:

• Development of a reproducible liquid formulation.
• Control of lisinopril degradation.
• Taste masking without xylitol.
• Microbiological preservation.
• Container-closure compatibility.
• Dose-measurement accuracy.
• Long-term stability at labeled storage conditions.
• FDA bioequivalence or comparative-quality requirements.
• Labeling and indication alignment.
• Orange Book patent certifications.

A manufacturer could avoid direct patent overlap but still face regulatory complexity. Conversely, a formulation that appears commercially different may remain vulnerable under the doctrine of equivalents if the substituted ingredient performs substantially the same function in substantially the same way to achieve substantially the same result. The doctrine is fact-specific and cannot be determined from the claim text alone.[6]

How does US 9,616,096 compare with competing lisinopril products?

Attribute	Qbrelis	Generic lisinopril tablet	Epaned
Active ingredient	Lisinopril	Lisinopril	Enalapril
Dosage form	Oral solution	Tablet	Oral solution
Patent relevance	Direct	Generally outside claim scope	Outside claim scope
Pediatric liquid utility	High	Limited by swallowing and dosing	High
ACE-inhibitor class	Yes	Yes	Yes
Same patented formulation	Yes or closely associated	No	No

Qbrelis occupies a dosage-form niche rather than a molecule-exclusive market. Its commercial protection depends on formulation differentiation, pediatric and geriatric utility, physician familiarity, regulatory approval, and the ability to delay or deter a directly substitutable generic oral solution.

What generic launch risks exist?

A generic entrant has four principal paths:

1. Launch after the reported March 14, 2034 expiration date.
2. File a Paragraph IV certification and litigate.
3. Develop a non-infringing lisinopril liquid using a different formulation design.
4. Enter through a license or settlement agreement.

The highest-risk design is an oral solution that duplicates the claimed concentrations, xylitol sweetener, citrate buffer, sodium benzoate preservative, pH range, and stability profile. A materially different formulation could reduce patent exposure but may require additional development work and may produce differences in taste, dosing, stability, or regulatory comparability.

Key Takeaways

• US 9,616,096 covers methods of administering a specific stable lisinopril oral liquid.
• The core formulation is approximately 1 mg/mL lisinopril, 150 mg/mL xylitol, citrate buffer, 0.8 mg/mL sodium benzoate, water, and pH 4 to 5.
• The patent covers hypertension, heart failure, and early treatment after acute myocardial infarction.
• Dependent claims address lisinopril dihydrate, pH 4.9, 24-month stability, pediatric use, elderly use, and combination therapy.
• Conventional generic lisinopril tablets generally fall outside the claims.
• The reported patent expiration date is March 14, 2034.
• The principal competitive threat is a generic or alternative lisinopril oral solution.
• Formulation design-around opportunities exist, but they may increase development and regulatory costs.
• A current Paragraph IV, litigation, or settlement conclusion requires the latest FDA and court records; the supplied claim text does not identify a challenger or settlement.

FAQs About US Patent 9,616,096

Does US 9,616,096 cover Qbrelis?

It is publicly associated with Qbrelis and covers methods using a formulation that substantially corresponds to the claimed lisinopril oral solution.

Can a generic company sell lisinopril tablets before 2034?

Yes. The claims are directed to a specific oral liquid formulation and treatment methods. They do not broadly block generic lisinopril tablets.

Does the patent cover every lisinopril oral solution?

No. A competing oral solution would need to be evaluated against each formulation, stability, and treatment limitation. A formulation using materially different excipients or concentrations may avoid literal infringement.

Is there biosimilar risk for lisinopril?

No. Lisinopril is a synthetic small-molecule drug, not a biologic. The relevant competitive pathway is an ANDA or another small-molecule regulatory route, not a biosimilar application.

What is the most important claim for commercial enforcement?

Claim 1 is the principal claim for hypertension products. Claims 11 and 16 extend the same formulation protection to heart failure and acute myocardial infarction treatment. Claims 4, 14, and 19 may be important for commercial products carrying a 24-month shelf life.

References

1. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,616,096, Stable liquid formulation of lisinopril. https://patents.google.com/patent/US9616096B2/en

2. U.S. Food and Drug Administration. (2016). Qbrelis (lisinopril) oral solution prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/

3. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/

4. United States Code. (2024). 35 U.S.C. §§ 154 and 156: Patent term and patent term extension. https://uscode.house.gov/

5. U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/

6. Federal Circuit. (1997). Warner-Jenkinson Co. v. Hilton Davis Chemical Co., 520 U.S. 17. https://supreme.justia.com/cases/federal/us/520/17/

Drugs Protected by US Patent 9,616,096

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	9,616,096					TREATMENT OF HYPERTENSION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	9,616,096					METHOD OF TREATING HYPERTENSION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	9,616,096					TREATMENT OF HEART FAILURE
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	9,616,096					TREATMENT OF MYOCARDIAL INFARCTION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	9,616,096					REDUCTION OF MORTALITY IN ACUTE MYOCARDIAL INFARCTION
Azurity	QBRELIS	lisinopril	SOLUTION;ORAL	208401-001	Jul 29, 2016	AA	RX	Yes	Yes	9,616,096					ACUTE MYOCARDIAL INFARCTION

International Family Members for US Patent 9,616,096

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
Spain	2886869