US Patent 11,253,474: Amlodipine Liquid Formulation Scope, Exclusivity and Patent Landscape

US Patent 11,253,474 protects a low-water, glycerin-based liquid formulation of amlodipine besylate, including formulations containing maltitol, butylated hydroxyanisole, flavor, and ethanol. The broadest composition claim requires four core elements: approximately 0.10% to 0.12% w/w amlodipine besylate, a pharmaceutically acceptable excipient, 80% to 96% w/w glycerin, and water content of no more than approximately 5% w/w. The patent also covers a container presentation and treatment of hypertension and angina-related conditions.

The claims are formulation-specific. A conventional amlodipine tablet, capsule, aqueous solution outside the claimed ranges, or glycerin-free product would not meet claim 1. The principal commercial risk is directed at an oral liquid that reproduces the claimed excipient architecture, particularly a 0.11% w/w amlodipine besylate product with maltitol, BHA, ethanol, flavor, low water, and high glycerin.

What does US Patent 11,253,474 protect?

The patent protects an oral liquid formulation rather than amlodipine besylate generally. Its claim structure creates a layered formulation estate.

Claim group	Subject matter	Principal limitations
Claim 1	Broad liquid formulation	0.10%-0.12% w/w amlodipine besylate; 80%-96% w/w glycerin; water <=5% w/w
Claims 2-3	Excipient composition	4%-7% sweetener; antioxidant; optional flavor; optional ethanol
Claims 4-6	Narrower concentration and ingredient combinations	Approximately 0.11% amlodipine; maltitol and BHA in certain embodiments
Claims 7-8	Narrow commercial formulation	5%-7% maltitol; 0.03% BHA; 0.008%-0.010% flavor; 2.5% ethanol; 80%-92% glycerin
Claim 9	Liquid maltitol syrup formulation	Approximately 11% liquid maltitol syrup; 0.03% BHA; flavor; 2.5% ethanol; 80%-92% glycerin
Claim 10	Container and labeling	Bottle containing claim 1 formulation plus written material
Claims 11-15	Method of treatment	Administration for hypertension, chronic stable angina, vasospastic angina, or coronary artery disease
Claims 16-17	Lower water embodiments	Water <=4% or <=3%
Claims 18-19	Low-water claim 9 embodiments	Claim 9 formulation with water <=4% or <=3%

The patent uses “comprising” language. That generally means the presence of additional ingredients does not avoid infringement if all recited elements remain present. A competing product containing the claimed ingredients plus preservatives, buffers, additional flavor, or other excipients could still fall within the claims.

How broad is claim 1?

Claim 1 is the principal enforcement claim. It requires:

A liquid pharmaceutical formulation.
About 0.10% to about 0.12% w/w amlodipine besylate.
At least one pharmaceutically acceptable excipient.
A vehicle containing about 80% to about 96% w/w glycerin.
Water content of no more than about 5% w/w.

The claim does not expressly require maltitol, BHA, ethanol, or flavor. Those ingredients appear in dependent claims. A product can therefore potentially infringe claim 1 without infringing claims 2 through 9.

The claim is materially narrower than a claim to “an oral liquid amlodipine formulation.” The following design choices may avoid claim 1 if implemented outside the claim boundaries:

Amlodipine besylate concentration below approximately 0.10% or above approximately 0.12% w/w.
Glycerin concentration below approximately 80% or above approximately 96% w/w.
Water content above approximately 5% w/w.
A nonliquid dosage form.
A formulation using a different amlodipine salt, subject to the patent’s specification and claim construction.
A formulation that does not contain a pharmaceutically acceptable excipient, although a pharmaceutical liquid would ordinarily contain one.

The terms “about” create a fact-sensitive boundary. Courts generally interpret “about” in view of the specification, prosecution history, analytical precision, and technical understanding. A formulation at 0.099% or 79.9% glycerin should not be assumed to be outside the claim without an infringement analysis based on the patent record.

Which formulations are protected by the dependent claims?

Claims 2 through 9 progressively narrow the formulation and increase overlap with a specific commercial product profile.

Claims 2 and 3: excipient ranges

Claims 2 and 3 require a sweetening agent at 4%-7% w/w, an antioxidant, and optional flavor and ethanol. Claim 3 narrows the antioxidant to 0.03%-0.04% w/w.

These claims create protection around a high-glycerin liquid that uses a sweetener and antioxidant while retaining the low-water requirement of claim 1. The difference between claims 2 and 3 is principally the antioxidant concentration.

Claims 4 through 6: maltitol and BHA

Claim 4 fixes amlodipine besylate at approximately 0.11% w/w while retaining the broader excipient ranges.

Claim 5 identifies maltitol as the sweetener and BHA as the antioxidant. Claim 6 narrows the formulation further by requiring:

5%-7% w/w maltitol;
0.03% w/w BHA;
0.008%-0.010% w/w flavor;
optional 2%-4% w/w ethanol.

A competitor using sucrose, sorbitol, sucralose, or another sweetener might avoid claims 5 and 6 while still potentially falling within claim 1 or claim 4.

Claims 7 and 8: concentrated commercial formulation

Claims 7 and 8 are the most commercially specific claims before claim 9. They require:

Approximately 0.11% w/w amlodipine besylate;
5%-7% w/w maltitol;
0.03% w/w BHA;
0.008%-0.010% w/w flavor;
2.5% ethanol;
80%-92% w/w glycerin.

Claim 8 narrows the sweetener to approximately 6% w/w maltitol. These claims are vulnerable to design-around strategies involving a different sweetener, a different antioxidant, no ethanol, a materially different glycerin concentration, or a different active concentration.

Claim 9: liquid maltitol syrup

Claim 9 does not merely require maltitol as an ingredient. It requires approximately 11% w/w of a liquid maltitol syrup comprising maltitol. That distinction may matter analytically because a finished product containing 6% maltitol is not necessarily the same as a product containing 11% liquid maltitol syrup.

A generic or follow-on manufacturer would need to examine whether its raw material is a liquid maltitol syrup and whether the concentration is measured as the syrup material or as maltitol solids. The specification and prosecution history would be important to resolve that issue.

What water-content limitations matter?

Claims 1 through 15 require water content of no more than approximately 5% w/w through their dependency on claim 1. Claims 16 and 17 narrow the threshold to approximately 4% and 3%, respectively. Claims 18 and 19 apply the same thresholds to the claim 9 formulation.

The water limitation is a central technical restriction. It separates the claimed formulation from conventional aqueous amlodipine solutions and may support stability, solubility, or preservation characteristics associated with the glycerin-rich vehicle.

A formulation with 4% water would generally fall within claim 1 and claim 16, subject to the meaning of “about.” A formulation with 3% water would generally fall within claims 1, 16, and 17. Claims 18 and 19 add the liquid maltitol syrup formulation requirements.

Water measurement is likely to be an important infringement issue. Karl Fischer analysis, sample handling, raw-material water contribution, and whether water is measured on a finished-product basis can affect the result. A product specification stating “water content not more than 5%” would be relevant evidence but would not by itself resolve the legal question.

Does US 11,253,474 cover a commercial amlodipine oral liquid?

The claim architecture closely corresponds to a glycerin-based amlodipine oral solution containing maltitol, BHA, ethanol, flavor, and low water. That profile is associated with commercial liquid amlodipine products, including Norliqva, an amlodipine besylate oral solution marketed in the United States.

The claims do not cover every presentation of Norliqva by name. Infringement depends on the actual composition, concentrations, manufacturing specifications, and labeling. A branded product can practice the claims without the claims being limited to that product, and a competitor can sell an amlodipine liquid without practicing the claims if its formulation falls outside the required ranges.

What is the FDA regulatory status and Orange Book relevance?

Amlodipine besylate is an FDA-approved dihydropyridine calcium-channel blocker used for hypertension and certain angina indications. The FDA-approved liquid product is subject to the regulatory framework applicable to prescription oral solutions and to patent listing rules under the Hatch-Waxman Act.[2][4]

For an approved reference product, a formulation patent may be listed in the FDA Orange Book if it claims the drug substance, drug product, or an approved method of use and satisfies FDA listing requirements. The Orange Book entry, if present, would determine whether an abbreviated new drug application applicant must make a Paragraph IV certification or another certification against the patent.[3]

The claim set includes drug-product claims and method-of-use claims. The formulation claims are more likely to be relevant to a product-specific Orange Book listing than the broad treatment claims, although listing depends on FDA determinations and the reference product’s approved labeling.

The patent number alone does not establish the current Orange Book listing status, certification history, or whether a patent has been delisted, expired, disclaimed, or removed. Those points must be determined from the current FDA Orange Book and USPTO records.

When does US Patent 11,253,474 lose exclusivity?

The patent issued on February 22, 2022. The ordinary United States patent term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.[1][5]

The exact expiration date cannot be calculated from the claim text or issue date. It requires the patent’s earliest effective nonprovisional priority date, PTA, terminal-disclaimer information, and any applicable PTE. The issue date does not establish the expiration date.

Regulatory exclusivity is separate from patent exclusivity. FDA new-drug exclusivity, if applicable to the reference product, may expire before the patent or may not materially affect a later ANDA if the regulatory exclusivity period has already ended. A patent challenge can also create litigation-related delay without changing the statutory patent term.

What Paragraph IV challenges and generic entry risks exist?

A generic applicant seeking approval of an equivalent amlodipine oral liquid could face several pathways:

Entry route	Likely relevance
ANDA with Paragraph IV certification	Relevant if the reference product has a listed, unexpired formulation or method patent
ANDA with section viii statement	Potentially relevant for method claims where the applicant omits patented indications from labeling
ANDA with Paragraph III certification	Relevant if the applicant accepts delayed approval until patent expiration
505(b)(2) application	Possible for a differentiated liquid formulation or reliance on published clinical information
Noninfringing formulation	May avoid the listed formulation claims if all required ranges are avoided

The most important Paragraph IV target would be claim 1 because it is the broadest composition claim. A successful Paragraph IV defense could invalidate or avoid the broad claim and materially reduce the estate’s blocking effect. Dependent claims 5 through 9 would still matter if the accused product reproduces the commercial excipient profile.

For method claims 11 through 15, a generic applicant may attempt a section viii carve-out for patented indications. That strategy depends on the approved labeling, the precise scope of the claims, and whether the remaining labeling still induces use within the patented methods.

How strong is the patent estate?

The estate has meaningful commercial value but a concentrated technical scope.

Strengths

Claim 1 covers the core glycerin-rich, low-water formulation architecture.
The 0.11% active concentration aligns with a practical commercial formulation.
Dependent claims identify maltitol and BHA, which may correspond closely to a marketed product.
Low-water claims provide additional fallback positions.
Claim 10 reaches a bottle and written material containing the formulation.
Method claims extend coverage to adult and pediatric use.

Vulnerabilities

The claims depend on multiple quantitative ranges.
“About” creates boundary and claim-construction disputes.
A competitor may substitute the sweetener, antioxidant, vehicle, or ethanol concentration.
Claim 9 depends on the characterization of liquid maltitol syrup.
The treatment claims are limited to listed conditions and patient populations.
Invalidity challenges could focus on anticipation or obviousness based on prior oral liquids, glycerin-based formulations, maltitol systems, and amlodipine stability disclosures.
The patent does not claim amlodipine besylate as a molecule or all oral liquid dosage forms.

The strongest enforcement position is likely against a product that reproduces the specific commercial formulation, not against every generic amlodipine liquid.

How does this patent compare with conventional amlodipine products?

Product type	Likely relationship to US 11,253,474
Amlodipine tablets	Usually outside the liquid-formulation claims
Amlodipine capsules	Usually outside the liquid-formulation claims
Aqueous amlodipine solution with high water	Potentially outside the low-water limitation
Glycerin-rich amlodipine solution	Potentially within claim 1
Maltitol/BHA/ethanol liquid	Higher risk under claims 5-9
Amlodipine oral suspension	Requires separate analysis; may fall outside the claimed liquid formulation
Pediatric liquid using a different vehicle	Possible design-around
505(b)(2) liquid product	Patent risk depends on composition and labeling

Katerzia, an amlodipine besylate oral suspension, is technologically distinct from the glycerin-rich liquid formulation claimed here. The products may compete for pediatric and swallowing-impaired patients, but their dosage-form and formulation patent risks are not identical.

What manufacturing and IP barriers apply?

The main manufacturing barrier is not amlodipine synthesis. It is reproducibly making a stable, homogeneous, low-water liquid with high glycerin content and controlled concentrations of sweetener, antioxidant, flavor, and ethanol.

Relevant technical controls include:

Water-content testing;
Uniform dispersion or dissolution of amlodipine besylate;
Control of glycerin and maltitol raw-material variability;
BHA assay and uniformity;
Ethanol concentration;
Flavor concentration;
Bottle compatibility and extractables;
Stability under storage and shipping conditions;
Dose-measurement accuracy.

A competitor that changes the vehicle or water content may reduce patent risk but create new formulation, stability, taste, and regulatory problems. A noninfringing formulation therefore may require more than substituting one excipient.

What litigation and licensing issues should be monitored?

The relevant records are:

USPTO Patent Center for prosecution history, continuation applications, terminal disclaimers, PTA, reexamination, and post-grant proceedings.
FDA Orange Book for patent listing, expiration data, and reference-product information.
Federal court dockets for Paragraph IV litigation under 35 U.S.C. §271(e)(2).
ANDA approval letters and FDA patent certifications.
SEC filings, licensing announcements, and product acquisition disclosures involving the patent owner or marketing partner.

No licensing agreement, settlement agreement, or Paragraph IV litigation outcome can be inferred from the claim language alone. Those events are separate from the patent’s substantive scope.

Key Takeaways

US 11,253,474 is a formulation patent directed to a glycerin-rich, low-water liquid amlodipine besylate product.
Claim 1 is the central blocking claim and does not require maltitol, BHA, ethanol, or flavor.
Claims 5 through 9 target increasingly specific commercial formulations using maltitol, BHA, flavor, ethanol, and 80%-92% glycerin.
Claims 16 through 19 strengthen protection for formulations with water content of approximately 4% or 3% or less.
Conventional amlodipine tablets are generally outside the claims.
A competitor can potentially reduce risk by changing the active concentration, glycerin level, water content, sweetener, antioxidant, or liquid maltitol syrup composition.
Method claims may affect labeling strategy and section viii analysis.
The exact patent expiration date, Orange Book status, Paragraph IV activity, litigation status, and licensing position require current USPTO, FDA, and court-record verification.

Frequently Asked Questions

Does US 11,253,474 cover amlodipine besylate itself?

No. The claims cover specified liquid formulations containing amlodipine besylate. They do not claim the active pharmaceutical ingredient generally.

Would an amlodipine liquid with 10% glycerin infringe claim 1?

Ordinarily, 10% glycerin would be outside the express 80%-96% glycerin range. The final analysis would depend on claim construction, the meaning of “about,” and the complete formulation.

Would removing ethanol avoid the patent?

Removing ethanol could avoid claims that expressly require ethanol, such as claims 7 and 8. It would not necessarily avoid claim 1, which does not require ethanol.

Are pediatric uses separately protected?

Yes. Claims 11 through 15 expressly cover administration to adult or pediatric patients for the listed cardiovascular conditions. Their enforceability also depends on the approved labeling and the elements required by each method claim.

Is a competing amlodipine suspension automatically outside the patent?

No. A suspension may differ technically from the claimed liquid formulation, but the answer depends on whether it satisfies the claim’s liquid-formulation, concentration, glycerin, excipient, and water limitations.

References

United States Patent and Trademark Office. (2022). U.S. Patent No. 11,253,474.
U.S. Food and Drug Administration. (n.d.). Norliqva (amlodipine besylate) oral solution prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355.
Patent Act, 35 U.S.C. §§ 154, 156, 271(e), 282.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cmp Dev Llc	NORLIQVA	amlodipine besylate	SOLUTION;ORAL	214439-001	Feb 24, 2022		RX	Yes	Yes	11,253,474	⤷ Start Trial	Y			NORLIQVA IS INDICATED FOR THE TREATMENT OF HYPERTENSION, TO LOWER BLOOD PRESSURE IN ADULTS AND CHILDREN 6 YEARS OF AGE AND OLDER	⤷ Start Trial
Cmp Dev Llc	NORLIQVA	amlodipine besylate	SOLUTION;ORAL	214439-001	Feb 24, 2022		RX	Yes	Yes	11,253,474	⤷ Start Trial	Y			NORLIQVA IS INDICATED FOR THE SYMPTOMATIC TREATMENT OF CHRONIC STABLE ANGINA	⤷ Start Trial
Cmp Dev Llc	NORLIQVA	amlodipine besylate	SOLUTION;ORAL	214439-001	Feb 24, 2022		RX	Yes	Yes	11,253,474	⤷ Start Trial	Y			NORLIQVA IS INDICATED FOR THE TREATMENT OF CONFIRMED OR SUSPECTED VASOSPASTIC ANGINA	⤷ 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

Details for Patent: 11,253,474

Which drugs does patent 11,253,474 protect, and when does it expire?

Summary for Patent: 11,253,474