United States Patent 9,186,411: Claim Scope, Vonoprazan Formulation Protection, and Patent Landscape
U.S. Patent No. 9,186,411 protects stabilized solid pharmaceutical compositions containing vonoprazan or specified related pyrrole derivatives, fumaric acid, and an excipient with a water-dissolved or water-dispersed pH of at least 4.5. The patent is formulation-focused. It does not broadly claim the vonoprazan molecule, all vonoprazan salts, or every vonoprazan dosage form.
The strongest commercial relevance is to vonoprazan fumarate solid formulations, including tablets and other solid preparations that use fumaric acid as a stabilizer and meet the excipient-pH limitation.
What does U.S. Patent 9,186,411 protect?
U.S. Patent 9,186,411 covers a composition combining four core elements:
| Required element |
Scope under independent claim 1 |
| Active ingredient |
One of three specified nonpeptidic amine-containing pyrrole derivatives, including vonoprazan |
| Excipient |
An excipient having a pH of at least 4.5 when dissolved or dispersed in water |
| Acidic compound |
Fumaric acid or a fumaric acid salt |
| Product type |
A stabilized pharmaceutical composition |
The first listed active ingredient is vonoprazan, also known as TAK-438:
- 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine, or a salt thereof.
Vonoprazan fumarate is a potassium-competitive acid blocker used for acid-related gastrointestinal disorders and Helicobacter pylori eradication regimens. The claim also covers two structurally related compounds identified in the patent, subject to the same composition requirements.
The patent therefore protects a formulation architecture rather than the pharmacological class as a whole.
How broad is independent claim 1?
Claim 1 is chemically narrow but formulation-wise meaningful. It requires all of the following:
- One of three expressly identified active ingredients or a salt thereof.
- Fumaric acid or a salt of fumaric acid.
- An excipient meeting the pH threshold.
- A stabilized pharmaceutical composition.
The claim does not require:
- A particular dosage strength.
- A particular tablet weight.
- A particular manufacturing process.
- A particular dissolution profile.
- A specific release profile.
- A specified ratio of active ingredient to fumaric acid.
- A particular pharmaceutical indication.
- A particular tablet coating.
- A particular excipient from the list in dependent claim 4.
Because claim 1 does not specify a solid dosage form, it can theoretically cover liquids, suspensions, powders, granules, and other compositions if the remaining limitations are met. Dependent claim 6 narrows the scope to a solid preparation.
The active-ingredient limitation prevents the claim from covering unrelated proton-pump inhibitors, potassium-competitive acid blockers, or other amine-containing drugs. A competing product containing tegoprazan, vonoprazan analogs not listed in the claim, or another acid-suppressing agent would not fall within claim 1 solely because it uses fumaric acid.
What formulations are protected by claim 4?
Claim 4 identifies the following excipients:
- Mannitol
- Croscarmellose sodium
- Hydroxypropylcellulose
- Hydroxypropylmethylcellulose
- Polyethylene glycol
- Polyvinylpyrrolidone
- Crystalline cellulose
- Lactose
- Sucrose
- Starch
- Cornstarch
- Titanium dioxide
- Light anhydrous silicic acid
The claim language permits “any one kind or more” of these excipients. A formulation using multiple listed excipients can satisfy claim 4 if the excipient-pH requirement inherited from claim 1 is also met.
Claim 4 does not automatically cover every formulation containing one of these materials. The selected excipient must still satisfy the pH condition in claim 1. The claim also remains subject to the requirements for the specified active ingredient and fumaric acid.
What is the importance of the pH 4.5 limitation?
The pH limitation is a central technical restriction. It requires that the excipient, when dissolved or dispersed in water, have a pH of at least 4.5.
This limitation appears directed to controlling degradation or instability of the active ingredient. It may exclude acidic excipients or excipient systems that produce an aqueous pH below 4.5. The claim raises analytical questions concerning:
- The amount of excipient tested.
- Water volume.
- Temperature.
- Dissolution or dispersion time.
- Whether the test applies to an individual excipient or the combined excipient system.
- Whether pH is measured before or after addition of the active ingredient and fumaric acid.
For infringement analysis, the pH test protocol can be as important as the formulation’s ingredient list. A composition using the same active ingredient and fumaric acid may avoid literal infringement if the relevant excipient system does not meet the pH threshold.
How do claims 2 through 7 narrow the patent?
| Claim |
Added limitation |
Commercial significance |
| 2 |
Active ingredient has a pKa higher than fumaric acid or its salt |
Adds an acid-base relationship that may require comparative pKa analysis |
| 3 |
Active ingredient is an organic acid salt |
Covers salt forms beyond the free base, while claim 1 still requires fumaric acid or a fumarate salt in the composition |
| 4 |
Excipient selected from a defined list |
Targets conventional tablet and solid-dosage excipients |
| 5 |
Active ingredient is a salt with an unsaturated carboxylic acid |
Particularly relevant to fumarate-type active salts |
| 6 |
Composition is a solid preparation |
Applies to tablets, powders, granules, capsules, and related solid forms |
| 7 |
Fumaric acid is 0.01% to 50% of the total composition |
Creates a quantitative concentration range |
What does claim 7 cover?
Claim 7 requires fumaric acid content of 0.01% to 50% of the whole pharmaceutical composition. The claim appears to express the range as a percentage by weight, although the supplied claim text does not expressly state “w/w.”
The range is broad. It covers low-level stabilizer use and formulations in which fumaric acid is a substantial component. A product outside the stated range may avoid claim 7 but could still infringe claim 1 or another dependent claim if all applicable elements are present.
The lower endpoint is inclusive on its face. The upper endpoint is also inclusive unless claim construction or prosecution history indicates otherwise.
Does the patent cover vonoprazan fumarate?
Yes, potentially. Vonoprazan fumarate is within the practical center of the claim set because:
- Vonoprazan is one of the expressly named active ingredients.
- Vonoprazan contains a basic amine and can form an organic acid salt.
- Fumaric acid is expressly required by claim 1.
- Claim 5 expressly addresses salts with unsaturated carboxylic acids.
- Claim 6 covers solid preparations.
- Claim 7 covers a broad fumaric-acid concentration range.
A vonoprazan fumarate tablet would present the highest claim-overlap risk if it also uses a listed excipient and the excipient system has a pH of at least 4.5 in water.
The patent does not establish that every vonoprazan fumarate tablet infringes. A complete infringement analysis would require product-specific data on composition, excipient identity, pH, fumaric-acid content, salt form, and dosage form.
What is the relationship between claims 3 and 5?
Claims 3 and 5 address the salt state of the active ingredient but differ in breadth.
Claim 3 requires that the active ingredient be an organic acid salt. It does not restrict the organic acid to an unsaturated carboxylic acid.
Claim 5 is narrower. It requires a salt with an unsaturated carboxylic acid. Fumaric acid is an unsaturated dicarboxylic acid, making vonoprazan fumarate a direct commercial example.
Because both claims depend on claim 1, the composition must still contain fumaric acid or a fumaric acid salt as the acidic compound. Claim 3 should not be read as eliminating that claim 1 requirement.
When does U.S. Patent 9,186,411 lose exclusivity?
U.S. Patent 9,186,411 was issued on November 17, 2015. Public patent records identify Takeda Pharmaceutical Company Limited as the patent owner or original assignee for the stabilized-composition invention. The patent arose from an international pharmaceutical formulation filing with an early-2010s priority date.
The ordinary patent term is generally 20 years from the earliest effective nonprovisional or international filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable patent-term extension. The relevant formulation patent term is expected to extend into the early 2030s, rather than expiring with earlier vonoprazan compound patents.
| Exclusivity layer |
Likely effect |
| Vonoprazan compound patents |
Protect the active molecule or core pyrrole chemistry for an earlier period |
| U.S. Patent 9,186,411 |
Protects selected stabilized fumaric-acid formulations |
| Later formulation patents |
May cover dosage strength, tablet architecture, combinations, or manufacturing parameters |
| FDA regulatory exclusivity |
Depends on the approved NDA, indication, and approval pathway |
The patent’s exact expiration date should be taken from the USPTO Patent Center record and the patent face, including any patent-term adjustment. A priority date alone does not establish the final enforceable expiration date.
What is the Orange Book status of U.S. Patent 9,186,411?
The Orange Book status must be evaluated against the specific approved vonoprazan products and NDA listings. A patent can be relevant to an approved drug without being listed for every dosage form or indication.
For vonoprazan products, Orange Book analysis should distinguish:
- Vonoprazan tablets marketed as Voquezna.
- Voquezna Dual Pak and Triple Pak products.
- Different strengths and dosage forms.
- Approved indications for erosive esophagitis, heartburn associated with erosive gastroesophageal reflux disease, and H. pylori eradication.
- Patents listed for drug substance, formulation, method of use, or other approved-product characteristics.
The patent’s formulation claims are potentially listable if they read on an approved product and satisfy FDA patent-listing requirements. Orange Book listing, however, is not proof that every commercial product meets every limitation of the claims.
The relevant regulatory framework includes 21 U.S.C. §355(b)(1), 21 C.F.R. §§314.53 and 314.94, and FDA Orange Book listing practices. The FDA’s Orange Book should be checked by NDA and patent number for the current listing status. [1-3]
Which companies could face infringement risk?
The principal risk group consists of companies seeking to market U.S. vonoprazan products before expiration of enforceable formulation patents.
Potentially exposed parties include:
- Generic drug manufacturers filing Abbreviated New Drug Applications for vonoprazan fumarate tablets.
- Companies developing authorized generics or licensed versions of vonoprazan.
- Contract manufacturers supplying tablets that use the claimed excipient system.
- Innovator or specialty pharmaceutical companies launching line extensions with the same formulation architecture.
Companies using a different salt, different stabilizer, or non-listed excipient may still face risk under claim 1 if the composition contains fumaric acid and the excipient meets the pH limitation. Companies that remove fumaric acid may avoid this patent but could encounter other vonoprazan composition or stability patents.
What Paragraph IV challenges are relevant?
A generic applicant may file a Paragraph IV certification alleging that a listed patent is invalid, unenforceable, or not infringed. For this patent, the principal Paragraph IV theories would likely focus on:
- Noninfringement based on an excipient pH below 4.5.
- Noninfringement based on the absence of fumaric acid or a fumaric acid salt.
- Noninfringement based on use of a different active ingredient or salt.
- Invalidity based on anticipation or obviousness.
- Lack of adequate written description or enablement for the claimed formulation scope.
- Indefiniteness of the pH testing requirement.
- Invalidity of the fumaric-acid concentration range if prior art disclosed overlapping stabilizer concentrations.
A generic company could also design around the patent by using a different acid, such as a non-fumarate organic acid, provided that alternative does not fall within another asserted patent.
A Paragraph IV notice would ordinarily trigger potential litigation under the Hatch-Waxman framework. The statutory 30-month stay depends on the timing of notice, the patent listing, and the NDA holder’s response. No specific Paragraph IV challenge or settlement agreement is established by the claim text supplied here.
How strong is the patent estate for vonoprazan?
The formulation patent has moderate commercial strength and narrower legal breadth than a core compound patent.
Strengths
- Vonoprazan is expressly named.
- Fumaric acid is expressly required.
- The patent reaches solid preparations through claim 6.
- Claim 7 covers a wide 0.01% to 50% fumaric-acid range.
- Conventional excipients are addressed in claim 4.
- The patent can create a formulation barrier after earlier compound claims expire.
Weaknesses
- Claim 1 is limited to three identified active ingredients.
- The claim requires fumaric acid or a fumaric acid salt.
- The excipient must satisfy a specific pH threshold.
- The pH testing method may create factual and claim-construction disputes.
- A competitor may be able to redesign the formulation around the acid, excipient, or salt limitations.
- The patent does not claim all dosage forms, all vonoprazan salts, or all methods of treating acid-related disease.
The most defensible commercial position is against a product that reproduces the known vonoprazan fumarate tablet formulation or a close formulation equivalent. The estate is less powerful against a deliberately engineered non-fumarate formulation.
What litigation or settlement agreements affect this patent?
The supplied claim information does not establish a litigation judgment, settlement, covenant not to sue, license, or consent order involving U.S. Patent 9,186,411. Patent ownership and enforcement rights may also have changed through Takeda’s licensing and commercialization arrangements for vonoprazan in the United States.
For commercial diligence, the relevant records are:
- USPTO Patent Center assignment and maintenance records.
- FDA Orange Book patent listings.
- Federal district court docket systems.
- ANDA litigation complaints and Paragraph IV notices.
- SEC filings by the NDA holder and commercial partners.
- License agreements involving vonoprazan U.S. rights.
No conclusion about an unreported license or settlement should be drawn from the claim language alone.
What manufacturing and design-around barriers exist?
The patent creates several practical barriers even where literal claim coverage is avoidable.
A competitor may need to develop:
- A different acidulant or stabilizer.
- A non-fumarate salt.
- An excipient system with a measured pH below 4.5.
- A different solid-state form.
- A coating or granulation process that prevents degradation without fumaric acid.
- Stability data supporting the alternative formulation.
- Bioequivalence data for the redesigned product.
The principal technical tradeoff is between avoiding the fumaric-acid limitation and maintaining chemical stability, dissolution, manufacturability, and bioequivalence. A formulation that avoids claim 1 may still encounter separate patents covering particle size, crystalline form, tablet coating, dosage regimen, or manufacturing conditions.
How does this patent compare with a vonoprazan compound patent?
| Issue |
U.S. Patent 9,186,411 |
Vonoprazan compound patent |
| Subject matter |
Stabilized pharmaceutical composition |
Active chemical entity or chemical class |
| Active ingredient scope |
Three specified pyrrole derivatives |
May cover vonoprazan and related compounds |
| Fumaric acid required |
Yes |
Usually no |
| Excipient required |
Yes, with pH at least 4.5 |
No |
| Solid dosage form required |
Only under claim 6 |
Usually no |
| Design-around potential |
Moderate to high |
Lower if the compound itself is covered |
| Commercial role |
Lifecycle and formulation protection |
Core market exclusivity |
| Typical challenger strategy |
Reformulate or attack validity |
Challenge compound scope, validity, or expiration |
The formulation patent can extend practical market protection after a compound patent expires, but it does not prevent all generic vonoprazan products. Its impact depends on whether the approved product and the proposed generic use the claimed stabilizer and excipient architecture.
Key Takeaways
- U.S. Patent 9,186,411 is a formulation patent centered on vonoprazan or two related pyrrole derivatives.
- Claim 1 requires a specified active ingredient, fumaric acid or a fumaric acid salt, and an excipient with a water-dissolved or dispersed pH of at least 4.5.
- Claim 4 targets conventional excipients used in tablets and solid dosage forms.
- Claim 6 specifically covers solid preparations.
- Claim 7 covers fumaric acid at 0.01% to 50% of the total composition.
- Vonoprazan fumarate tablets have the highest potential overlap.
- A non-fumarate formulation, different salt, or excipient system that fails the pH limitation may provide a design-around route.
- The patent is narrower than a compound patent but can remain commercially important after core vonoprazan chemical protection expires.
- Orange Book relevance must be confirmed by current FDA listing data for the applicable NDA and dosage form.
- The final expiration date requires the patent’s official term-adjustment and terminal-disclaimer records.
FAQs
Does U.S. Patent 9,186,411 cover vonoprazan free base?
Potentially, yes, if the composition contains vonoprazan free base, fumaric acid or a fumaric acid salt, and an excipient meeting the pH requirement. Claim 1 does not require the active ingredient itself to be a fumarate salt.
Can a generic avoid the patent by removing fumaric acid?
Removing fumaric acid may avoid the asserted claims because fumaric acid or a fumaric acid salt is a required element of claim 1. The redesigned product must still be evaluated against other formulation, salt, stability, and method-of-use patents.
Does the patent cover capsules containing vonoprazan fumarate?
A capsule could fall within claim 1 if it satisfies all composition limitations. Claim 6 is not required unless the capsule is being analyzed under the solid-preparation dependent claim.
Is fumaric acid concentration measured against the active ingredient or the entire tablet?
Claim 7 measures fumaric acid as a percentage of the whole pharmaceutical composition. It does not state that the percentage is calculated only against the active ingredient.
Can a competitor use mannitol and avoid infringement?
Not necessarily. Mannitol is listed in claim 4, but claim 1 controls the basic combination. Use of mannitol may increase claim overlap if the formulation also contains the specified active ingredient, fumaric acid, and an excipient system with a pH of at least 4.5.
References
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
- U.S. Patent and Trademark Office. (2015). U.S. Patent No. 9,186,411, Stabilized pharmaceutical composition.
- U.S. Food and Drug Administration. (2023). Voquezna prescribing information. Phathom Pharmaceuticals, Inc.
- 21 C.F.R. § 314.53. Patent listing requirements.
- 21 U.S.C. § 355. New drug applications and patent certifications.
