US Patent 9,993,476: Claim Scope, Vericiguat Patent Landscape, Exclusivity and Generic Entry Risk
US Patent 9,993,476 is a Bayer method-of-use patent covering administration of vericiguat, its defined salts and N-oxide forms, for cardiovascular and renal disorders. The patent is materially narrower than a composition-of-matter patent because it requires both the covered compound and treatment of a listed disease. Its commercial relevance is high because vericiguat is the active ingredient in Verquvo, approved by the FDA to reduce cardiovascular death and heart-failure hospitalization in adults with symptomatic chronic heart failure and reduced ejection fraction.[1][2]
The strongest practical protection is the combination of:
- Vericiguat or a specified salt or N-oxide.
- Treatment of one of the claimed cardiovascular or renal conditions.
- In certain dependent claims, coadministration with selected PDE5 inhibitors or blood-pressure-lowering agents.
- Potential Orange Book listing and Paragraph IV litigation exposure.
The patent does not independently prevent all manufacture, sale or use of vericiguat. Those activities are primarily addressed by composition, formulation, solid-state, manufacturing and other method-of-use patents.
What does US Patent 9,993,476 cover?
The patent covers methods of treating or preventing specified cardiovascular and renal disorders with a compound of formula (I). Based on the claimed species, the commercially relevant compound is vericiguat:
Methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate
Vericiguat is a soluble guanylate cyclase stimulator. The claim structure is summarized below.
| Claim |
Subject matter |
Commercial significance |
| 1 |
Treatment or prevention of listed cardiovascular and renal disorders using formula (I), including salts and N-oxides |
Principal broad method claim |
| 2 |
R1 is hydrogen or methyl, with optional trifluoromethyl substitution |
Narrows the chemical genus |
| 3 |
Enumerated vericiguat compounds and salts, including hydrochloride, sulfate, phosphate, mesylate, ethane-1,2-disulfonate, maleate and nitrate |
Directly targets specific chemical forms |
| 4 |
A specific compound of formula (I), with salts and N-oxides |
Likely species-level vericiguat claim; the supplied text omits the structural drawing |
| 5 |
Treatment of angina pectoris |
Disease-specific method claim |
| 6 |
Treatment of vascular disorders |
Disease-specific method claim |
| 7 |
Treatment of kidney failure |
Disease-specific method claim |
| 8 |
Combination with sildenafil, vardenafil or tadalafil |
Combination-use claim |
| 9 |
Combination with listed antihypertensive, endothelin-receptor or mineralocorticoid agents |
Combination-use claim |
| 10 |
Treatment of coronary heart disease |
Disease-specific method claim |
| 11 |
Treatment of systolic or diastolic heart failure |
Commercially important disease-specific claim |
| 12 |
Treatment of renal insufficiency |
Disease-specific method claim |
| 13 |
Treatment of increased microalbuminuria |
Renal biomarker and disease-management claim |
The claims are method claims, not claims to the vericiguat molecule itself. A claim requires administration to a human or animal "in need thereof" of a therapeutically effective amount for a covered condition.
What compound is protected by US 9,993,476?
Vericiguat is the principal commercial compound
The species listed in claim 3 corresponds to vericiguat and its identified acid-addition salts. Vericiguat has the following relevant characteristics:
| Attribute |
Detail |
| Active ingredient |
Vericiguat |
| Brand |
Verquvo |
| Developer and commercial parties |
Bayer and Merck |
| Pharmacology |
Soluble guanylate cyclase stimulator |
| FDA approval |
January 19, 2021 |
| Approved use |
Reduction of cardiovascular death and heart-failure hospitalization in adults with symptomatic chronic heart failure and ejection fraction below 45% following a recent worsening event |
| Dosage form |
Oral tablets |
| Relevant patent |
US 9,993,476, among other patent rights |
Claim 3 is unusually important because it recites the commercial active pharmaceutical ingredient in multiple salt forms. A generic applicant cannot avoid the claim merely by selecting a different listed salt if the administered active moiety falls within the relevant claim construction.
The supplied text for claim 4 omits the structural drawing. That omission prevents a complete assessment of the precise species limitation in claim 4. Claims 1 through 3, however, clearly identify the vericiguat chemical series and several commercially relevant salt forms.
How broad is the disease coverage?
Claim 1 covers a broad disease set:
- Coronary heart disease.
- Systolic and diastolic heart failure.
- Angina pectoris.
- Ischemias.
- Peripheral and cardiac vascular disorders.
- Kidney failure.
- Renal insufficiency.
- Increased microalbuminuria.
The broadest commercial overlap is heart failure. The FDA-approved Verquvo indication falls within the heart-failure language of claims 1 and 11. The FDA label describes use after a recent worsening heart-failure event in adults with symptomatic chronic heart failure and ejection fraction below 45%.[1]
The patent claim is broader than the approved label in several respects. It does not expressly require:
- A particular ejection-fraction threshold.
- A recent hospitalization.
- A recent outpatient intravenous diuretic treatment.
- A specific dose.
- A particular New York Heart Association class.
- Use in adults only, because claim 1 refers to a human or animal.
That breadth supports enforcement against uses beyond the approved indication if the accused product or conduct intentionally promotes, instructs or facilitates a covered use.
What are the strongest and weakest claim elements?
Strongest elements
The strongest practical element is the species limitation to vericiguat. A generic product containing vericiguat and labeled for chronic heart failure would create a direct overlap with claims 1 and 11.
Claim 3 also has commercial strength because it identifies specific salts rather than relying solely on a broad Markush structure. Salt selection may matter for formulation and manufacturing, but a change from one listed pharmaceutically acceptable salt to another may not remove infringement risk if the relevant claim is construed to cover the active compound and its salts broadly.
Potentially narrower elements
The method claims require a covered treatment purpose. A product distributed with a strictly carved-out label could reduce induced-infringement exposure for unapproved diseases. That strategy would not necessarily eliminate infringement risk for the FDA-approved heart-failure indication.
Claim 8 is limited to combination therapy with sildenafil, vardenafil or tadalafil. Claim 9 is limited to a specified set of blood-pressure-lowering or vascular-active agents. These claims have narrower commercial reach because they require both vericiguat and an identified coadministered agent.
The renal claims may also require a fact-specific showing that the patient has kidney failure, renal insufficiency or increased microalbuminuria and that administration is directed to treatment or prevention of that condition. They are less directly aligned with the current FDA indication than the heart-failure claims.
When does US Patent 9,993,476 expire?
The patent traces to a priority date in December 2011 and issued on June 12, 2018. Its nominal patent-term endpoint is expected to fall in December 2031, subject to the controlling patent-term calculation, any patent-term adjustment and any terminal disclaimer recorded in the patent file.[3]
| Event |
Date |
| Earliest priority period |
December 2011 |
| US grant |
June 12, 2018 |
| Expected nominal expiration |
December 2031 |
| FDA approval of Verquvo |
January 19, 2021 |
| Five-year NCE exclusivity endpoint |
January 19, 2026 |
The patent term is separate from FDA regulatory exclusivity. Vericiguat received five-year new chemical entity exclusivity from the FDA. That exclusivity blocks submission of an ANDA or 505(b)(2) application relying on the drug during the protected period, subject to statutory exceptions. After the NCE period ends, patent rights remain the principal barrier to approval and launch.[1][4]
What is the Orange Book status of US 9,993,476?
US Patent 9,993,476 has been associated with Verquvo patent protection and is relevant to Orange Book analysis. The Orange Book listing determines whether an ANDA applicant must certify against the patent and whether the NDA holder can trigger the statutory 30-month stay through a timely Paragraph IV notice and infringement action.[4]
The key regulatory consequences are:
- A Paragraph IV certification alleges that the listed patent is invalid, unenforceable or will not be infringed.
- Notice to the NDA and patent holders is required.
- A timely infringement action can impose a 30-month stay on final ANDA approval.
- The stay can terminate earlier through court judgment, settlement or other statutory events.
- A section viii statement may be available for a method-of-use patent if the generic label omits the patented use.
For this patent, a section viii strategy would be difficult if the proposed generic label includes chronic heart failure, because claims 1 and 11 directly cover heart-failure treatment. A carved-out label could be more relevant to claims directed to angina, vascular disorders, renal insufficiency and microalbuminuria, but it would not necessarily eliminate risk associated with the approved heart-failure use.
How does US 9,993,476 compare with vericiguat composition patents?
The patent estate should be divided into separate protection layers.
| Protection layer |
Typical subject matter |
Relevance to generic entry |
| Composition of matter |
Vericiguat chemical structure and related compounds |
Usually the strongest molecule-level barrier |
| Method of use |
Cardiovascular and renal treatment claims in US 9,993,476 |
Strong where the generic label includes heart failure |
| Formulation |
Tablet composition, excipients, release characteristics or stability |
Can create additional infringement issues after molecule expiry |
| Solid state |
Polymorphs, hydrates, solvates or crystalline forms |
Can block a specific API or tablet manufacturing route |
| Manufacturing |
Intermediates, reaction sequences and purification |
Raises process-development and freedom-to-operate issues |
| Dosing regimen |
Titration, dose escalation or patient-selection methods |
May support label and induced-infringement claims |
| Regulatory exclusivity |
NCE or other FDA exclusivity |
Delays ANDA or 505(b)(2) submission and approval |
US Patent 9,993,476 is therefore not a standalone measure of the full Verquvo estate. A generic company may avoid one formulation or process patent while still facing the composition patent, the method patent or a solid-state patent.
The composition patent is generally more resistant to label carving because an ANDA product necessarily contains the protected active ingredient. A method patent is more vulnerable to non-infringement arguments based on labeling, physician behavior and the relationship between the marketed indication and the claimed disease.
What Paragraph IV challenges and litigation affect vericiguat?
A Paragraph IV challenge to US 9,993,476 would likely focus on one or more of the following issues:
- Obviousness of treating heart failure or renal disease with vericiguat in view of earlier soluble guanylate cyclase-stimulator disclosures.
- Written description and enablement across the broad disease list.
- Whether the claims adequately support the specific vericiguat species and its salts.
- Construction of "therapeutically effective amount."
- Construction of "in need thereof."
- Whether an ANDA label induces use for a patented indication.
- Whether the listed salts and N-oxide language covers the proposed generic form.
- Patent-term calculation and Orange Book listing requirements.
The expected litigation sequence is conventional:
| Stage |
Likely event |
| ANDA filing |
Generic applicant certifies under Paragraph IV against listed patents |
| Notice |
Bayer and the NDA-related patent holders receive certification notice |
| Litigation |
Suit may be filed within 45 days |
| Regulatory effect |
Potential 30-month stay of final approval |
| Merits |
Court evaluates validity, enforceability and infringement |
| Resolution |
Judgment, settlement, license, dismissal or launch after statutory protection ends |
No biosimilar pathway applies. Vericiguat is a chemically synthesized small molecule, not a biologic. The relevant competitors would file ANDAs or, depending on the product and reliance strategy, 505(b)(2) applications rather than biosimilar applications.
What generic entry risks exist for Verquvo?
Generic entry before the expected 2031 patent endpoint would require either:
- Successful invalidity or non-infringement litigation.
- A settlement providing an agreed launch date.
- A license from the relevant patent holders.
- A product and label that avoid enforceable claims.
- Regulatory approval after expiration of the applicable patent and exclusivity barriers.
The highest-risk scenario for the patent holders is a generic label that includes the FDA-approved chronic-heart-failure indication. That label would map directly onto claims 1 and 11. The principal generic defenses would be invalidity, claim construction and a challenge to the patent's written description or obviousness.
The lower-risk scenario for an ANDA applicant is a label limited to uses that do not include the patented cardiovascular indication. That approach would not address composition or formulation patents and would be commercially weaker if the principal market is chronic heart failure.
How strong is the patent estate for vericiguat?
The estate is commercially meaningful because it combines a marketed product with method claims that reach the approved indication. US 9,993,476 has the following strengths:
- It recites the vericiguat species.
- It covers heart failure in express language.
- It covers both systolic and diastolic heart failure.
- It includes salts and N-oxide forms.
- It reaches administration to humans.
- It covers prevention as well as treatment.
- It is relevant to the FDA-approved use.
Its limitations are equally important:
- It is not a pure composition claim.
- Infringement depends on the treatment use.
- Combination claims are narrower.
- Some disease categories are broader and less closely tied to the current label.
- A generic applicant may attempt a label carve-out for certain methods of use.
- Invalidity arguments can target the breadth of the disease and compound genus.
Overall, the patent is strongest against a full-label generic entering the heart-failure market and weaker against a narrowly labeled product targeting non-listed or carved-out uses.
What licensing and commercial arrangements affect the patent landscape?
Vericiguat was developed and commercialized through a Bayer-Merck collaboration. Merck’s US commercial role is associated with the Verquvo product, while Bayer remains central to the underlying intellectual-property position.[1][5]
A generic launch settlement would typically address:
- An agreed entry date.
- Authorized-generic rights.
- Patent litigation dismissal.
- Supply or licensing terms.
- Restrictions on manufacturing and distribution.
- Treatment of later-issued formulation or process patents.
No public settlement should be assumed solely from the existence of a Paragraph IV filing. The relevant FDA, district-court and appellate records control whether a settlement, license or litigation judgment affects entry.
What manufacturing and geographic barriers remain?
The patent is a US right. It directly affects manufacture, use, sale, offer for sale and importation into the United States. It does not automatically control products made and sold entirely outside the US, although US process claims, importation provisions, supply-chain conduct and corresponding foreign patents can create separate exposure.
A generic manufacturer must evaluate:
- The API route and protected intermediates.
- Salt selection.
- Crystalline form.
- Tablet formulation.
- Dissolution and stability profile.
- US importation and supply agreements.
- Foreign counterpart patents.
- FDA labeling and promotional materials.
- Physician and pharmacy substitution practices.
The commercial barrier is therefore broader than the literal text of US 9,993,476. A non-infringing process does not resolve formulation or method-of-use risk, and a non-infringing formulation does not resolve composition-of-matter risk.
Key Takeaways
- US Patent 9,993,476 is a vericiguat method-of-use patent, not the principal molecule patent.
- Claims 1 and 11 directly overlap the FDA-approved Verquvo heart-failure indication.
- Claim 3 expressly lists vericiguat and multiple salts.
- Claims 8 and 9 cover selected combination therapies but have narrower commercial value.
- The expected patent-term endpoint is December 2031, subject to the controlling USPTO term calculation.
- FDA five-year NCE exclusivity for Verquvo began on January 19, 2021 and is separate from patent protection.
- A full-label ANDA would face substantial Paragraph IV exposure.
- A section viii carve-out may reduce risk for selected non-heart-failure uses but would not solve composition, formulation or process-patent issues.
- Vericiguat is a small molecule, so biosimilar competition is not relevant.
- The complete freedom-to-operate analysis requires review of the compound, formulation, solid-state, manufacturing and additional method-of-use patent families.
FAQs
Does US 9,993,476 cover Verquvo tablets specifically?
It covers methods of administering vericiguat and specified salts for listed diseases. It does not, based on the supplied claims, claim every physical tablet formulation. Separate formulation or solid-state patents may cover the commercial tablet.
Can a generic vericiguat applicant avoid this patent by using a different salt?
Not necessarily. Claim 1 includes salts and claim 3 lists several specific salts. A different salt could still fall within the broad salt language or raise infringement under another patent family.
Does a heart-failure label create direct infringement risk?
Yes. A label directing use of vericiguat to treat systolic or diastolic heart failure would closely track claim 11 and the heart-failure portion of claim 1.
Could a 505(b)(2) applicant face the same patent?
Yes. A 505(b)(2) applicant can face Orange Book certifications, Paragraph IV litigation and a 30-month stay when relying on listed patents for a product or indication involving vericiguat.
Is kidney-disease protection commercially important for Verquvo?
It is legally relevant but less directly aligned with the current FDA-approved indication than the heart-failure claims. Its commercial value depends on future labeling, clinical development and the scope of any generic label.
References
-
U.S. Food and Drug Administration. (2021). Verquvo (vericiguat) prescribing information. FDA.
-
U.S. Patent and Trademark Office. (2018). US Patent No. 9,993,476, use of 4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl carbamic acid methyl ester for treating cardiovascular disorders. USPTO.
-
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation records for US Patent No. 9,993,476. USPTO Patent Center.
-
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
-
Merck & Co., Inc. (2021). Annual report and product information concerning Verquvo. Merck.
