US Patent 9,539,214: Scope, Claims, Expiration, and Patent Landscape for Aspirin/Omeprozole
US Patent 9,539,214 protects a method of administering a fixed-dose aspirin and immediate-release omeprazole product that produces defined intragastric-pH and pharmacokinetic results. The patent is directed to use of the combination, not merely to aspirin, omeprazole, or a generic co-packaged product. Its strongest coverage is concentrated on a 325 mg aspirin/40 mg omeprazole unit dose, multilayer tablet architecture, immediate gastric release of omeprazole, and treatment courses lasting at least seven or 14 days.
The patent issued January 10, 2017, from the Pozen aspirin/omeprazole development program associated with Yosprala. Its nominal patent term appears to run to approximately December 2029, subject to the recorded patent-term adjustment and any applicable terminal disclaimer. FDA approval of Yosprala occurred September 14, 2016. FDA approval did not create new chemical-entity exclusivity because both active ingredients were previously approved; the relevant regulatory exclusivity was based on clinical investigations and was materially shorter than the patent term (FDA, 2016a, 2016b).
What does US Patent 9,539,214 protect?
The patent claims a treatment method requiring all of the following core elements:
| Claim element |
Requirement |
| Dosage form |
Pharmaceutical composition in unit-dose form |
| Active ingredients |
Acetylsalicylic acid, or a pharmaceutically acceptable salt, and omeprazole, or a pharmaceutically acceptable salt |
| Omeprazole release |
Immediate-release omeprazole released at a pH from about 0 or greater |
| Gastric-pH objective |
Mean time with intragastric pH at about 4.0 or greater for at least about 50% of a 24-hour period after steady state |
| Aspirin PK |
Defined aspirin and/or salicylic-acid Cmax and Tmax ranges |
| Omeprazole PK |
AUC0-12 of about 0.8 to 2.5 hr·µg/mL |
| Administration |
At least one unit dose administered to a patient |
| Treatment duration in dependent claims |
At least seven days or at least 14 days |
| Specific dose |
325 mg aspirin and 40 mg omeprazole in claim 9 |
| Specific dosage form |
Multilayer tablet with aspirin core, pH-responsive coating, and omeprazole-containing layer |
The patent therefore combines structural limitations, release-profile limitations, pharmacodynamic objectives, and pharmacokinetic limitations. A competing product would not necessarily infringe merely because it contains aspirin and omeprazole. It would need to satisfy the claimed administration method and the specified release and PK limitations.
How broad is independent claim 1?
Claim 1 is broad in dosage-form terminology but narrow in functional performance.
It does not expressly require a multilayer tablet, a 325 mg aspirin dose, or a 40 mg omeprazole dose. Those restrictions appear in dependent claims. Claim 1 can therefore reach other unit-dose presentations if they deliver aspirin and immediate-release omeprazole while achieving the stated gastric-pH and PK targets.
The claim contains several important limitations:
- The omeprazole must be immediate release.
- The omeprazole must be released under strongly acidic conditions beginning at approximately pH 0 or greater.
- The composition must target sustained intragastric pH of at least about 4.0.
- The aspirin or salicylic-acid exposure must fall within specified ranges.
- Omeprazole exposure must have an AUC0-12 between approximately 0.8 and 2.5 hr·µg/mL.
The phrase “and/or” in the aspirin PK clause creates a claim-construction issue. The most natural reading is that the aspirin PK requirement can be satisfied by the acetylsalicylic-acid profile, the salicylic-acid profile, or both, while the omeprazole AUC limitation remains mandatory. A court could examine the specification and prosecution history to determine whether “and/or” was intended to provide alternative pathways or was treated as a drafting error.
What do claims 2 through 8 add?
Claims 2 through 8 narrow the PK requirements and increase the evidentiary burden for infringement.
| Claim |
Added limitation |
| 2 |
Aspirin mean Cmax of at least 2.36 µg/mL and salicylic-acid mean Cmax of at least 15.3 µg/mL |
| 3 |
Aspirin mean Cmax of about 2.91 µg/mL and salicylic-acid mean Cmax of at least 16.2 µg/mL |
| 4 |
Claim 3 plus aspirin coefficient of variation of about 54% and salicylic-acid coefficient of variation of about 29% |
| 5 |
Omeprazole AUC0-12 of about 2.174 hr·µg/mL |
| 6 |
Claim 5 plus omeprazole AUC0-12 coefficient of variation of about 88% |
| 7 |
Omeprazole AUC0-24 of about 2.187 hr·µg/mL |
| 8 |
Claim 7 plus omeprazole AUC0-24 coefficient of variation of about 88% |
These claims are narrower than claim 1 and may be easier to design around. They also raise questions concerning sample size, study population, fed or fasted state, assay methodology, steady-state definition, and statistical treatment. A generic applicant could challenge whether the numerical limitations are sufficiently reproducible across ordinary clinical or bioequivalence studies.
The coefficient-of-variation limitations in claims 4, 6, and 8 are particularly narrow. Variability can change materially with population selection, sampling schedule, assay sensitivity, compliance, food intake, and study design. A product could have a similar mean exposure while falling outside the claimed variability range.
What formulation is protected by claim 12?
Claim 12 is the principal formulation-architecture claim. It requires a multilayer tablet comprising:
- An aspirin-containing core.
- A first coating that at least begins to dissolve at approximately pH 3.5 or greater.
- A second layer containing omeprazole.
- Omeprazole release beginning at approximately pH 0 or greater.
Claim 13 narrows the omeprazole-release range to approximately pH 0 to pH 2.
This architecture is unusual because conventional omeprazole products commonly use enteric protection to prevent release in the stomach. The claimed design instead uses immediate gastric release of omeprazole to raise intragastric pH while allowing aspirin exposure to occur through a controlled multilayer structure. The claim is directed to physical arrangement and dissolution behavior, not simply ingredient identity.
A product using a separate aspirin layer and an immediate-release omeprazole layer could potentially fall within claim 12 even if its commercial name, excipients, coating thickness, or manufacturing process differs. Conversely, a two-tablet regimen or a capsule containing separate units may avoid claim 12 while remaining potentially relevant to method claims 1 through 11.
What are the strongest design-around opportunities?
The principal design-around routes are:
| Design-around route |
Potential effect |
| Use omeprazole in an enteric-release form |
May avoid the immediate-release limitation |
| Administer aspirin and omeprazole as separate dosage forms |
May avoid unit-dose and multilayer-tablet limitations |
| Use a different omeprazole dose |
May avoid dependent claim 9, but not necessarily claim 1 |
| Alter release timing or gastric-pH effect |
May fall outside the pH or intragastric-pH limitations |
| Produce materially different aspirin or salicylic-acid exposure |
May avoid the numerical PK limitations |
| Use another proton-pump inhibitor |
Avoids omeprazole-specific limitations |
| Use a non-multilayer tablet |
May avoid claim 12 while leaving method claims in issue |
| Administer for less than seven days |
May avoid claim 10, but not claim 1 |
The most commercially relevant design-around is a product that separates aspirin and acid suppression into different dosage units. That approach may weaken the combination-product argument but could reduce adherence and alter the intended pharmacokinetic relationship.
When does US Patent 9,539,214 lose exclusivity?
The patent issued January 10, 2017. Under the ordinary US patent-term framework, patent expiration is generally 20 years from the earliest effective nonprovisional filing date, not 20 years from issuance (35 U.S.C. § 154). The relevant Pozen aspirin/omeprazole family traces to a 2009 priority period. On that basis, the nominal expiration date is approximately December 2029, subject to patent-term adjustment.
| Event |
Date or period |
| Earliest family priority period |
December 2009 |
| US patent issuance |
January 10, 2017 |
| Approximate nominal expiration |
December 2029 |
| 3.5-year maintenance-fee stage |
2020 |
| 7.5-year maintenance-fee stage |
2024 |
| 11.5-year maintenance-fee stage |
2028 |
The enforceability analysis depends on whether required maintenance fees were paid and whether the USPTO record shows patent-term adjustment or other term modifications. The expiration date should therefore be taken from the current USPTO patent record rather than inferred solely from the issue date (USPTO, 2017).
What is the FDA and Orange Book status of the aspirin/omeprazole product?
The commercial product associated with this patent family is Yosprala, a fixed-dose combination of delayed-release aspirin and immediate-release omeprazole. FDA approved Yosprala under NDA 208987 on September 14, 2016. The marketed strengths are generally identified as:
- 81 mg aspirin/40 mg omeprazole
- 325 mg aspirin/40 mg omeprazole
The product is indicated for patients requiring aspirin for secondary prevention of cardiovascular and cerebrovascular events who are at risk of developing aspirin-associated gastric ulcers. The label describes the tablet as a combination product designed to deliver immediate-release omeprazole and delayed-release aspirin (FDA, 2016a).
The patent landscape must be separated into three categories:
- FDA-listed patents covering the approved product.
- Unlisted or non-Orange-Book patents covering manufacturing, formulation, or broader method-of-use concepts.
- Expired, abandoned, or unenforceable family members that may remain relevant to validity or prosecution-history analysis.
Because US Patent 9,539,214 is method-oriented, its commercial impact depends on whether it is listed for the approved NDA and how any generic applicant addresses the listing. An ANDA applicant generally must provide a Paragraph IV certification if it seeks approval before an asserted listed patent expires and contends that the patent is invalid, unenforceable, or not infringed (FDA, 2024).
What Paragraph IV risks exist for generic entry?
A generic aspirin/omeprazole applicant faces several possible certification positions:
| Certification strategy |
Commercial consequence |
| Paragraph III |
Approval deferred until patent expiry |
| Paragraph IV |
Applicant alleges invalidity, unenforceability, or non-infringement |
| Section viii statement |
Applicant omits a patented method of use, if the labeling can be carved out |
| No certification to unlisted method patent |
Product may still face ordinary infringement litigation |
The possibility of a Section viii carve-out depends on whether the patented method is reflected in the proposed labeling and whether the remaining label can support approval. Claims 1 through 15 are method claims tied to administration, treatment, and pharmacokinetic outcomes. That structure can make a clean labeling carve-out more difficult if the FDA-approved use overlaps materially with the claimed treatment method.
A Paragraph IV case would likely focus on:
- Whether the claimed PK ranges are inherent or predictable from prior-art products.
- Whether the intragastric-pH limitation is properly measurable and sufficiently definite.
- Whether immediate-release omeprazole at low pH was disclosed or obvious.
- Whether the claimed unit-dose composition is enabled across the full claim scope.
- Whether the claims improperly recite desired results rather than patentable limitations.
- Whether prior art disclosed aspirin plus omeprazole in separate or co-formulated dosage forms.
What patent litigation and settlement risks affect generic launch?
A Paragraph IV notice would create potential patent litigation under 35 U.S.C. § 271(e)(2). Filing suit within the statutory period can trigger a 30-month stay of ANDA approval, subject to statutory exceptions and court action.
The principal litigation risk is claim overlap between the approved Yosprala product and a proposed generic. A generic applicant could argue that:
- Its omeprazole is not immediate release.
- Its product does not produce the claimed intragastric-pH duration.
- Its aspirin or salicylic-acid PK values fall outside the specified ranges.
- Its dosage form is not a unit dose or multilayer tablet.
- The claims are indefinite because “about,” “target,” “at least,” and “and/or” do not establish objective boundaries.
- The claims are obvious over prior-art aspirin and proton-pump-inhibitor combinations.
The patent owner could respond that the claim limitations are performance-defined, that the specification provides clinical data supporting the numerical ranges, and that infringement can be established through comparative PK and gastric-pH studies.
No settlement terms should be treated as established without a corresponding court docket, FDA settlement record, or company disclosure. A confidential or unreported settlement cannot be inferred from the existence of the patent.
How strong is the patent estate for Yosprala?
The estate is strongest against a single-tablet product that reproduces the claimed 325 mg/40 mg composition and immediate-release gastric omeprazole profile.
| Estate characteristic |
Assessment |
| Composition coverage |
Moderate; claim 1 requires both active ingredients but is not limited to one strength |
| Formulation coverage |
Stronger for the specific multilayer architecture in claim 12 |
| PK coverage |
Potentially strong factually, but vulnerable to variability and measurement disputes |
| Method-of-use coverage |
Broad in claim 1 but tied to technical outcomes |
| Manufacturing coverage |
Not established by the supplied claims |
| Biosimilar relevance |
None; both active ingredients are small molecules |
| Generic exposure |
Material for a matching fixed-dose tablet |
| Design-around flexibility |
Meaningful through separate dosage forms, altered release, or alternative acid suppression |
There is no biosimilar pathway issue because aspirin and omeprazole are small-molecule active ingredients. The principal competitive threat is an ANDA product, not a 351(k) biosimilar.
What is the competitive landscape?
The commercial competition divides into four groups:
- Fixed-dose aspirin/omeprazole products using the Yosprala design.
- Generic low-dose or full-dose aspirin sold separately.
- Generic omeprazole or other proton-pump inhibitors sold separately.
- Alternative gastroprotection regimens using pantoprazole, esomeprazole, lansoprazole, or H2-receptor antagonists.
A direct generic substitute must reproduce the clinical and regulatory profile of the fixed-dose product. Separate-pill competition can avoid this patent family more easily but does not offer the same adherence profile or necessarily the same PK relationship.
Revenue exposure is concentrated in the branded fixed-dose combination rather than in aspirin or omeprazole as molecules. Because both active ingredients are long-established generics, the commercial value of the patent estate depends on product integration, labeling, dosing convenience, and the ability to delay a directly substitutable ANDA product.
Key Takeaways
- US Patent 9,539,214 is a method patent covering administration of aspirin and immediate-release omeprazole in a unit-dose composition.
- Claim 1 requires specific intragastric-pH and PK outcomes, making the patent narrower than a simple combination-composition patent.
- Claim 9 targets the commercially important 325 mg aspirin/40 mg omeprazole dose.
- Claim 12 provides the principal structural protection for a multilayer tablet.
- The patent issued January 10, 2017, with nominal family-based expiration around December 2029, subject to USPTO term calculations.
- FDA approved Yosprala on September 14, 2016, under NDA 208987.
- Generic risk is highest for a single-tablet product using immediate-release omeprazole and a matching aspirin exposure profile.
- The principal validity issues are obviousness, indefiniteness, enablement, and the evidentiary reliability of the claimed PK and intragastric-pH parameters.
- Biosimilar risk is not relevant. The relevant pathway is ANDA approval and potential Paragraph IV litigation.
- Separate dosage forms, altered release behavior, different acid-suppression agents, and PK profiles outside the claimed ranges provide the main design-around options.
FAQs
Does US Patent 9,539,214 cover ordinary aspirin tablets?
No. The claims require a composition containing both aspirin and omeprazole, together with specified release, gastric-pH, administration, or PK limitations.
Does the patent cover omeprazole delayed-release capsules?
Not on the supplied claim language. Claim 1 requires immediate-release omeprazole, and claim 12 requires omeprazole released at approximately pH 0 or greater.
Is a separate aspirin tablet plus omeprazole capsule covered?
The separate products would present a stronger non-infringement position against the unit-dose and multilayer-tablet limitations. The method claim would still require analysis of whether the products collectively satisfy the claimed administration and performance limitations.
Can a generic avoid the patent by using 81 mg aspirin instead of 325 mg?
That may avoid dependent claim 9, which specifies approximately 325 mg aspirin, but it does not necessarily avoid claim 1 or other dependent claims that do not require the 325 mg strength.
Does the patent create biosimilar protection?
No. Aspirin and omeprazole are small-molecule drugs. Any abbreviated approval challenge would generally proceed through the ANDA framework rather than the biosimilar pathway.
References
Food and Drug Administration. (2016a). Yosprala prescribing information. U.S. Department of Health and Human Services.
Food and Drug Administration. (2016b). Approval letter for NDA 208987, Yosprala. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (2017). United States Patent No. 9,539,214: Pharmaceutical compositions comprising aspirin and omeprazole. U.S. Department of Commerce.
35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights. United States Code.
21 U.S.C. § 355(j). (2024). Abbreviated application for new drug. United States Code.
