Details for Patent: 11,814,368

Which drugs does patent 11,814,368 protect, and when does it expire?

Patent 11,814,368 protects XOCOVA and is included in one NDA.

This patent has forty-one patent family members in twenty-six countries.

Summary for Patent: 11,814,368

Title:	Triazine derivatives having virus replication inhibitory activity and pharmaceutical composition comprising the same
Abstract:	The present invention provides a compound exhibiting coronavirus 3 CL protease inhibitory activity or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same. Furthermore, the present invention provides a crystalline form useful as an active pharmaceutical ingredient, and a pharmaceutical composition comprising the same.A compound represented by Formula:or a pharmaceutically acceptable salt thereof.
Inventor(s):	Yuki Tachibana, Shota UEHARA, Yuto Unoh, Kenji Nakahara, Yoshiyuki Taoda, Yukiko YAMATSU, Shigeru Ando, Michihito SASAKI
Assignee:	Hokkaido University NUC , Shionogi and Co Ltd
Application Number:	US17/733,366
Patent Claim Types: see list of patent claims	Use; Composition;

U.S. Patent 11,814,368: Ensitrelvir Fumaric Acid Cocrystal Scope, Claims, and Patent Landscape

U.S. Patent No. 11,814,368 protects ensitrelvir, also known as S-217622, and pharmaceutical forms based on its fumaric acid cocrystal. The patent covers the active compound, pharmaceutically acceptable salts, compositions, coronavirus 3CL protease inhibition, coronavirus replication inhibition, therapeutic use, and a defined fumaric acid cocrystal Form I. The strongest product-facing claims are claims 1, 9-15. Claims 2-8 create composition, mechanism, pathogen, and treatment-use layers around the compound.

The patent is assigned to Shionogi & Co., Ltd. and relates to the oral SARS-CoV-2 antiviral marketed in Japan as Xocova. Because Xocova has not received U.S. FDA approval, the patent does not currently have the commercial significance of an Orange Book-listed U.S. drug patent. Its principal U.S. value is as a blocking patent against development, manufacture, importation, or commercial use of ensitrelvir or the claimed fumaric acid cocrystal.

What drug does U.S. Patent 11,814,368 protect?

U.S. Patent 11,814,368 protects ensitrelvir and selected solid-state forms of ensitrelvir fumarate.

The claim set identifies the compound through a structural Formula I rather than by the generic name “ensitrelvir.” The compound is a noncovalent coronavirus main protease inhibitor. Coronavirus 3CL protease is also called the main protease, or Mpro, and is encoded by the coronavirus ORF1a/ORF1b polyprotein.

The principal protected subject matter is:

Protected subject matter	Claims	Commercial relevance
Core compound and pharmaceutically acceptable salts	1	Broadest product claim
Pharmaceutical composition	2	Covers drug products containing the compound
Coronavirus 3CL protease inhibitor	3	Mechanism-based product claim
Coronavirus replication inhibitor	4-6	Covers use against coronavirus classes, including SARS-CoV-2
Treatment and prevention methods	7	Method-of-treatment protection
Medical-use claim	8	European-style use formulation presented in U.S. claim format
Ensitrelvir-fumaric acid complex	9-10	Salt/cocrystal and stoichiometry protection
Fumaric acid cocrystal Form I	11	Solid-form product claim
PXRD-defined Form I	12-13	Analytical identity and solid-state claim
Raman-defined Form I	14	Additional solid-form characterization
Pharmaceutical composition containing Form I	15	Product formulation protection

The claim structure indicates that the patent was designed to protect both the active pharmaceutical ingredient and the commercially usable solid form.

What are the independent claims in U.S. Patent 11,814,368?

Claims 1, 2, 3, 4, 7, 8, and 9 are the principal independent claims.

Claim 1: core compound

Claim 1 covers the compound represented by Formula I and pharmaceutically acceptable salts. This is the most important chemical claim. A party would potentially infringe claim 1 if it makes, uses, sells, offers to sell, or imports the claimed compound or a covered salt, subject to the statutory infringement provisions and claim construction.

Because the structural drawing is omitted from the supplied text, the precise substitution pattern cannot be reproduced here. The claim must be read against the patent’s Formula I, definitions, stereochemical disclosures, and specification examples. The structural formula controls over the compound’s commercial name.

Claim 2: pharmaceutical composition

Claim 2 covers a pharmaceutical composition containing the claim 1 compound or salt and a pharmaceutically acceptable carrier or diluent.

This claim is narrower than claim 1 because it requires a composition. It can reach tablets, capsules, granules, powders, suspensions, or other dosage forms if the composition contains the claimed compound and a qualifying carrier or diluent.

A generic developer could avoid infringement of claim 2 only if its product does not contain the claimed compound or salt, or if the claim construction excludes the particular composition. Changing inactive ingredients generally would not avoid claim 2 if the active compound remains within its scope.

Claims 3-6: antiviral activity

Claims 3 and 4 characterize the compound as a coronavirus 3CL protease inhibitor and coronavirus replication inhibitor. Claims 5 and 6 narrow claim 4 to alphacoronaviruses and/or betacoronaviruses, and specifically to SARS-CoV-2.

These claims are product-use claims rather than additional composition claims. Their practical value depends on how an accused product is labeled, promoted, tested, or used. Claim 6 is directed specifically to SARS-CoV-2 and is commercially aligned with Xocova’s COVID-19 indication.

Claims 7-8: therapeutic use

Claim 7 covers administering an effective amount of the compound or salt to treat or prevent a disease associated with coronavirus 3CL proteases.

Claim 8 covers the compound for use in treating or preventing such disease. It is closely related in substance to claim 7 but uses a product-for-use format.

The claims are not limited to COVID-19 unless the claim language or incorporated definitions impose that limitation. Claim 6 is specifically SARS-CoV-2-focused, while claims 7 and 8 may extend to diseases associated with coronavirus 3CL proteases more broadly.

Claims 9-15: fumaric acid cocrystal

Claim 9 covers a complex comprising Formula I-B and fumaric acid. Claim 10 requires a 1:1 molar ratio. Claim 11 narrows the subject matter to fumaric acid cocrystal Form I.

Claims 12 and 13 define Form I by powder X-ray diffraction peaks. Claim 14 defines it by Raman spectral peaks. Claim 15 covers a pharmaceutical composition containing that Form I cocrystal.

These claims create a solid-state barrier even if a competitor disputes the broader compound claim. A product containing the same active ingredient in the claimed fumaric acid cocrystal form could face infringement risk under multiple overlapping claims.

How broad is the scope of the claims?

The patent has layered scope, but the claims do not all have equal breadth.

Claim group	Relative breadth	Main limitation
Claim 1	Broad	Specific molecular structure and salt scope
Claim 2	Medium	Requires pharmaceutical composition
Claims 3-4	Medium	Requires inhibitor characterization
Claims 5-6	Narrower	Coronavirus taxonomy or SARS-CoV-2
Claims 7-8	Medium	Treatment/prevention use
Claim 9	Medium	Requires fumaric acid complex
Claim 10	Narrower	Requires 1:1 molar ratio
Claim 11	Narrower	Requires Form I cocrystal
Claims 12-14	Narrow	Requires analytical characteristics
Claim 15	Narrower	Requires pharmaceutical composition with Form I

Claim 1 is the central blocking claim. Claims 9-15 are important because they may remain relevant even if a competing party develops a different formulation strategy. A competitor using a different salt, polymorph, amorphous form, coformer, or free-base formulation would require a separate claim-by-claim analysis.

The PXRD and Raman claims are not merely descriptive. If the recited analytical characteristics are limitations, a solid product that exhibits the claimed peaks may fall within the claims even if the manufacturer uses a different manufacturing process or assigns a different internal form designation.

What formulations are protected by U.S. Patent 11,814,368?

The patent protects compositions containing the compound of claim 1 and compositions containing fumaric acid cocrystal Form I.

The supplied claims do not expressly recite:

• A particular tablet strength
• A specific dosage regimen
• A specific excipient
• A specific release profile
• A particular coating
• A specific particle-size distribution
• A specific manufacturing process
• A fixed-dose combination
• A particular packaging configuration

Claim 2 is therefore compositionally broad but chemically dependent on the claim 1 compound. Claim 15 is narrower because it requires the Form I cocrystal.

The cocrystal claims are directed to a specific solid-state entity. They can protect a commercial formulation even where the final dosage form contains conventional excipients, provided the active solid form remains the claimed fumaric acid cocrystal Form I.

How do the PXRD and Raman claims affect infringement analysis?

Claims 12-14 establish analytical fingerprints for fumaric acid cocrystal Form I.

Powder X-ray diffraction limitations

Claim 12 recites peaks at approximately:

• 9.5° 2θ
• 10.9° 2θ
• 18.6° 2θ
• 23.5° 2θ
• 24.6° 2θ

Claim 13 recites a broader peak set that includes:

• 7.8°
• 9.5°
• 10.1°
• 10.9°
• 13.8°
• 14.7°
• 18.6°
• 22.6°
• 23.5°
• 24.6°

Each peak is subject to a ±0.2° tolerance.

Raman limitations

Claim 14 recites Raman peaks at approximately:

• 676.3 cm⁻¹
• 748.0 cm⁻¹
• 1,029.3 cm⁻¹
• 1,374.4 cm⁻¹
• 1,515.5 cm⁻¹
• 1,665.7 cm⁻¹
• 1,715.7 cm⁻¹
• 1,739.1 cm⁻¹

Each peak is subject to a ±2 cm⁻¹ tolerance.

In a product dispute, analytical testing would likely compare the accused material against the claim limitations. Testing conditions, instrument calibration, sample preparation, preferred orientation, hydrate or solvate content, and peak-intensity interpretation may affect the analysis. A product can carry a different internal form name and still present infringement risk if it meets the claimed structural and analytical limitations.

When does U.S. Patent 11,814,368 lose exclusivity?

The patent’s statutory expiration depends on the patent family’s earliest effective nonprovisional filing date and any applicable patent-term adjustment or terminal disclaimer.

The patent was granted on November 21, 2023, according to U.S. Patent and Trademark Office patent records. Grant date does not determine expiration. For a post-June 8, 1995 U.S. utility patent, the ordinary term is generally 20 years from the earliest effective U.S. nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments (35 U.S.C. §§ 154, 156).

The commercially relevant exclusivity date therefore requires confirmation from the patent’s USPTO Patent Center record and the relevant family priority data. The claims are associated with the ensitrelvir development program, which originated during the 2020 coronavirus pandemic and includes Japanese and international priority filings. A 2040-2042 base-term window is commercially plausible for the early compound family, but the exact expiration date should not be treated as established without the patent’s term calculation and any terminal-disclaimer information.

Patent-term extension

A patent-term extension under 35 U.S.C. § 156 is available only for qualifying regulatory review and is limited by statutory conditions. Xocova’s Japanese approval does not create a U.S. patent-term extension. A U.S. extension would require qualifying FDA regulatory review for the patented product.

Patent-term adjustment

Patent-term adjustment under 35 U.S.C. § 154 can add days for certain USPTO examination delays. The final expiration date may therefore be later than the nominal 20-year term.

What is the Orange Book status of ensitrelvir and U.S. Patent 11,814,368?

As of the latest established public regulatory information, ensitrelvir has not received FDA approval in the United States. Xocova received Japanese regulatory approval in November 2022 for COVID-19 treatment and prevention-related use under Japan’s regulatory framework (Shionogi, 2022).

Because there is no U.S. FDA-approved ensitrelvir NDA, U.S. Patent 11,814,368 is not expected to have an Orange Book listing associated with an approved ensitrelvir product. The absence of an Orange Book listing has several consequences:

1. A generic applicant cannot rely on the ordinary ANDA Paragraph IV pathway against an approved ensitrelvir reference product.
2. The patent does not receive the standard Orange Book notice and 30-month-stay framework tied to an ANDA patent certification.
3. Any U.S. generic or follow-on challenge would depend on a future FDA approval pathway, an applicable reference product, or independent litigation and regulatory strategies.
4. The patent can still be asserted under 35 U.S.C. § 271 against unauthorized commercial activity.

If Shionogi later obtains U.S. approval, the listing status would depend on the approved product, the patent’s claims, FDA listing determinations, and the timing of any listing submission.

Are there Paragraph IV challenges to U.S. Patent 11,814,368?

No established Paragraph IV challenge against this patent can be identified from the claim information supplied.

A Paragraph IV certification is tied to an ANDA referencing an approved drug and a patent listed for that drug in the Orange Book under the Hatch-Waxman framework. Without an FDA-approved U.S. ensitrelvir reference product, a conventional Paragraph IV dispute is unlikely to be operational.

The more relevant pre-launch risks are:

• A declaratory-judgment action seeking noninfringement or invalidity
• An abbreviated or alternative FDA pathway if a lawful reference-product route becomes available
• A 35 U.S.C. § 271(e)(2) action after a qualifying ANDA filing
• Post-launch patent litigation
• Trade-secret or manufacturing disputes
• Inter partes review or post-grant review challenges, subject to statutory timing and eligibility

Which companies are challenging ensitrelvir patents?

Shionogi is the principal identified originator and commercial rights holder associated with ensitrelvir. No major U.S. generic challenger or biosimilar company is publicly established as having launched a Paragraph IV challenge to U.S. Patent 11,814,368.

The competitive landscape is driven more by competing COVID-19 antivirals than by a public U.S. patent challenge:

Product	Active ingredient	Company	Mechanism	U.S. status
Xocova	Ensitrelvir	Shionogi	SARS-CoV-2 3CL protease inhibitor	Not FDA-approved
Paxlovid	Nirmatrelvir/ritonavir	Pfizer	SARS-CoV-2 3CL protease inhibitor plus pharmacokinetic booster	FDA-approved
Lagevrio	Molnupiravir	Merck and Ridgeback	Polymerase-directed mutagenesis	FDA EUA status; not equivalent to full approval
Veklury	Remdesivir	Gilead Sciences	RNA-dependent RNA polymerase inhibitor	FDA-approved

Paxlovid is the closest commercial comparator because both products target SARS-CoV-2 3CL protease. Nirmatrelvir, however, is structurally distinct from ensitrelvir and is not covered by the claims described for U.S. Patent 11,814,368.

How does the ensitrelvir patent estate compare with Paxlovid’s patent estate?

Ensitrelvir and Paxlovid have different patent-risk profiles.

Issue	Ensitrelvir	Paxlovid
Primary protease inhibitor	Ensitrelvir	Nirmatrelvir
Booster requirement	No ritonavir requirement in the marketed product	Ritonavir coadministration is central to Paxlovid
U.S. approval	No established FDA approval	FDA-approved
Orange Book exposure	No established listing for this patent	Significant Orange Book and related patent exposure
Product claim in this patent	Core ensitrelvir structure	Not applicable
Solid-form claim	Fumaric acid cocrystal Form I	Separate Paxlovid-related formulation and process estate
Generic pathway	No conventional reference-product pathway established	ANDA and patent-certification pathway available
Main commercial barrier	Compound and cocrystal IP plus regulatory status	Compound, formulation, process, and listed-patent estate

Ensitrelvir’s chemical structure claim may be highly effective against a direct copy. Its commercial blocking power is reduced in the United States by the absence of an approved reference product and by the possibility that competitors use different protease inhibitors.

How strong is the patent estate for ensitrelvir?

The patent represented by U.S. Patent 11,814,368 has several strengths:

• Claim 1 targets the active molecular entity.
• Claims 2-8 provide multiple composition and use theories.
• Claims 9-15 protect a specific fumaric acid cocrystal and its analytical identity.
• The claim set covers both the active ingredient and a commercially relevant solid form.
• SARS-CoV-2 is expressly recited in claim 6.
• The cocrystal claims can create a separate infringement pathway even if a dispute narrows the broader compound claim.

The principal vulnerabilities are structural and legal:

• Claim 1 depends on the precise Formula I structure and its written-description support.
• The cocrystal claims require proof that the accused material is the claimed complex or Form I.
• PXRD and Raman claims can face claim-construction disputes concerning peak tolerances and measurement conditions.
• Treatment claims may raise divided-infringement, inducement, labeling, and medical-use issues.
• The patent’s effective exclusivity period may be limited by the family’s earliest priority date, terminal disclaimers, and related patents.
• Validity may be tested against earlier coronavirus protease inhibitor disclosures, medicinal-chemistry references, cocrystal prior art, and enablement or written-description arguments.

The estate is strongest against a product that uses both ensitrelvir and the claimed fumaric acid Form I. It is weaker against a product using a different active compound, a non-fumarate solid form, or a formulation that does not contain the claimed compound.

What manufacturing and intellectual-property barriers exist?

Manufacturing a competing ensitrelvir product may require more than reproducing the final chemical structure. The relevant barriers can include:

Active pharmaceutical ingredient synthesis

A competitor may need to develop a noninfringing synthetic route. A different process does not avoid a composition claim if the final product is the claimed compound. It can, however, reduce exposure to separate process patents.

Solid-state control

The fumaric acid cocrystal claims create a solid-state barrier. Process conditions such as solvent, temperature, water activity, crystallization rate, seeding, and drying can influence whether the final material forms Form I or another form.

Analytical characterization

A competitor would need to characterize its material using PXRD, Raman spectroscopy, thermal analysis, microscopy, and related methods. Analytical differences may affect whether claims 12-14 read on the product.

Regulatory documentation

A U.S. applicant must establish the identity, quality, stability, manufacturing controls, and clinical or regulatory basis for its product. The absence of a U.S. reference product can make a conventional generic route more difficult than a standard ANDA program.

International rights

The U.S. patent is one part of a broader international patent strategy. National rights may differ in claim scope, validity, expiration, prosecution history, and regulatory linkage. A company planning supply across the United States, Japan, Europe, or other markets must conduct country-specific freedom-to-operate analysis.

What litigation and licensing issues affect U.S. Patent 11,814,368?

No established U.S. infringement action, Paragraph IV settlement, or public license specific to U.S. Patent 11,814,368 is identified in the supplied record.

Shionogi has entered broader collaborations and commercialization arrangements for COVID-19 products and related technologies, but a license or collaboration involving ensitrelvir does not automatically establish rights under every U.S. patent in the family. Patent rights, regulatory rights, manufacturing rights, and territorial commercialization rights must be analyzed separately.

A future license would likely require review of:

• Field-of-use restrictions
• U.S. and foreign territory
• Patent-by-patent grant language
• Sublicensing rights
• Manufacturing rights
• Royalty and milestone terms
• Patent-prosecution control
• Enforcement control
• Generic-entry or launch provisions
• Rights after patent expiration or termination

A settlement with a future generic entrant could also include a date-certain launch, authorized-generic rights, supply arrangements, or restrictions limited to particular formulations. No such settlement is established for this patent.

What generic launch scenarios exist for ensitrelvir?

A direct generic launch before patent expiration would face compound and cocrystal risks if the product uses the claimed ensitrelvir structure and fumaric acid Form I.

The principal scenarios are:

Scenario	Patent exposure	Commercial assessment
Copy of ensitrelvir fumaric acid Form I	High	Most exposed to claims 1, 9-15
Ensitrelvir free base	High under claim 1; lower under cocrystal claims	Depends on whether claim 1 covers the free form and salt scope
Different ensitrelvir salt	Potentially high under claim 1	Requires salt and claim-construction analysis
Different ensitrelvir polymorph	Potentially high under claim 1; potentially lower under claims 11-14	Solid-form distinction may not avoid the chemical claim
Different 3CL protease inhibitor	No direct claim exposure	Competes scientifically, not through ensitrelvir claims
Non-U.S. manufacture for U.S. import	Potentially high	U.S. importation can trigger infringement under § 271
Research-only activity	Limited commercial exposure	Safe-harbor analysis depends on the statutory purpose and conduct

The most realistic early-entry path would involve either a different antiviral compound or a legally and technically distinct ensitrelvir form, followed by regulatory approval through a pathway available at the time.

Key Takeaways

• U.S. Patent 11,814,368 covers ensitrelvir, pharmaceutically acceptable salts, antiviral compositions, coronavirus treatment, and SARS-CoV-2 use.
• Claims 9-15 separately protect a 1:1 ensitrelvir-fumaric acid complex and fumaric acid cocrystal Form I.
• Claims 12-14 use PXRD and Raman signatures to define the protected solid form.
• Claim 1 is the principal broad product claim; claim 11 and the analytical claims are narrower but commercially important.
• Ensitrelvir does not have an established FDA-approved U.S. reference product, so a conventional Orange Book Paragraph IV pathway is not currently the central challenge mechanism.
• No established Paragraph IV challenge, U.S. infringement action, or settlement involving this patent is identified in the supplied record.
• Direct copying of ensitrelvir fumaric acid Form I presents the highest infringement risk.
• A competing coronavirus antiviral with a different molecular structure would generally fall outside the supplied claim set.
• Exact patent expiration requires the USPTO term calculation, including priority date, patent-term adjustment, and any terminal disclaimer.
• The patent’s U.S. commercial value depends heavily on future FDA approval, regulatory exclusivity, related family patents, and the scope of any additional Shionogi solid-form, formulation, process, or use patents.

FAQs

Is U.S. Patent 11,814,368 a patent on Xocova?

Yes. The claim set is directed to ensitrelvir and its fumaric acid cocrystal Form I, the active pharmaceutical form associated with Xocova.

Does the patent cover nirmatrelvir in Paxlovid?

No. Nirmatrelvir is a different coronavirus 3CL protease inhibitor and is not the Formula I compound described in the supplied claims.

Can a company avoid the patent by using a different ensitrelvir polymorph?

A different polymorph may avoid the Form I claims, but it may still fall within claim 1 if it contains the claimed ensitrelvir structure or a covered salt.

Do the PXRD peaks alone prove infringement?

No. The accused material must be evaluated against the full claim, including the claimed complex or cocrystal identity and the applicable analytical limitations.

Does Japanese approval create U.S. regulatory exclusivity for ensitrelvir?

No. Japanese approval does not create U.S. FDA approval, U.S. Orange Book listing, or U.S. regulatory exclusivity.

References

1. Shionogi & Co., Ltd. (2022). Xocova (ensitrelvir fumaric acid) approval information. Shionogi.

2. United States Patent and Trademark Office. (2023). U.S. Patent No. 11,814,368. Patent Center.

3. United States Code. (2024). 35 U.S.C. §§ 154, 156, 271, and 271(e)(2).

4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.

5. U.S. Food and Drug Administration. (2024). Coronavirus disease 2019 (COVID-19) drugs and biological products. FDA.

Drugs Protected by US Patent 11,814,368

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Shionogi	XOCOVA	ensitrelvir	TABLET;ORAL	220442-001	May 29, 2026		RX	Yes	Yes			Y	Y		POST-EXPOSURE PROPHYLAXIS OF CORONAVIRUS DISEASE 2019 (COVID 19) IN ADULTS AND ADOLESCENTS 12 YEARS OF AGE AND OLDER

International Family Members for US Patent 11,814,368

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2022204775
Brazil	122023002208
Canada	3195272
Chile	2023003041
China	115038696
China	115073431