US Patent 10,633,397: Claim Scope, Expiration, Orange Book Status, and Baloxavir Patent Landscape
US Patent 10,633,397 protects methods of treating or preventing influenza, and other diseases caused by viruses with a cap-dependent endonuclease, using baloxavir or a pharmaceutically acceptable salt. The patent is a method-of-use patent associated with baloxavir marboxil, marketed as Xofluza by Shionogi and Roche. Its principal commercial risk is an ANDA generic that can obtain approval while avoiding the claimed human, oral-dose method limitations or by prevailing in Paragraph IV litigation.
The patent issued April 28, 2020, and has a statutory expiration date in September 2035 based on the underlying priority chain. FDA-approved Xofluza received new chemical entity exclusivity through October 2023, with pediatric exclusivity potentially extending the effective regulatory barrier into April 2024. Patent protection remains the longer-term barrier.
What drug does US Patent 10,633,397 protect?
The patent protects methods using the compound shown in the patent’s structural formula, identified with the baloxavir program. The commercial product is baloxavir marboxil, an orally administered prodrug that is converted in vivo to baloxavir acid, the active inhibitor of influenza cap-dependent endonuclease.
| Item |
Data |
| US patent |
10,633,397 |
| Patent type |
Method of treatment and prevention |
| Issue date |
April 28, 2020 |
| Applicant/assignee |
Shionogi-related patent estate |
| Commercial product |
Xofluza |
| Active pharmaceutical ingredient |
Baloxavir marboxil |
| Pharmacologic target |
Influenza cap-dependent endonuclease |
| Covered diseases |
Influenza and other viral diseases with cap-dependent endonuclease |
| Administration expressly claimed |
Oral administration in dependent claims |
| Claimed dose range |
About 0.1 mg to 1,000 mg |
| Statutory expiration |
September 2035, subject to any applicable patent-term adjustment |
| Regulatory pathway |
NDA 210854 |
| FDA approval |
October 24, 2018 |
The structural formula is an essential claim limitation. A product that does not contain the claimed compound, or a pharmaceutically acceptable salt of that compound, does not literally infringe the patent merely because it treats influenza.
What do the claims of US Patent 10,633,397 cover?
The independent claims divide the patent into three principal use categories.
| Claim |
Subject matter |
Key limitation |
| 1 |
Treatment of a disease caused by a virus having cap-dependent endonuclease |
Administration of the claimed compound or salt |
| 2 |
Treatment of influenza |
Administration of the claimed compound or salt |
| 3 |
Prevention of influenza |
Administration of the claimed compound or salt |
Claims 4 through 12 add narrower limitations involving human patients, oral administration, and dosage.
Claim 1: broad antiviral treatment
Claim 1 is the broadest disease claim. It covers administering the claimed compound to treat a disease caused by a virus having cap-dependent endonuclease.
The claim is not limited expressly to:
- Influenza A;
- Influenza B;
- A particular influenza strain;
- Human patients;
- Oral administration;
- A specified dose;
- A particular treatment schedule; or
- A named commercial formulation.
The phrase “a virus having cap-dependent endonuclease” gives claim 1 a potentially broader technical scope than the influenza-specific claims. The practical scope depends on which viruses satisfy the biological target limitation and whether the claimed compound is shown to treat the relevant disease.
Claim 2: treatment of influenza
Claim 2 narrows the disease to influenza but does not expressly require a human patient, oral dosing, or the 0.1 mg to 1,000 mg range.
The claim can cover treatment of influenza through administration routes other than oral dosing, provided the accused conduct uses the claimed compound or salt and satisfies the treatment limitation. Claims 7 and 8 narrow this coverage to human patients and oral dosing.
Claim 3: prevention of influenza
Claim 3 is directed to prophylaxis rather than treatment. The distinction matters commercially because an approved product label, clinical protocol, or promotional statement addressing post-exposure prophylaxis may create a separate infringement theory from treatment use.
Claims 10 and 11 narrow the prevention claim to human administration and oral dosing.
How do the dependent claims narrow the patent?
The dependent claims create separate, narrower method categories.
| Claims |
Added limitation |
| 4, 6, 7, 9, 10, 12 |
Patient is a human |
| 5, 8, 11 |
Oral administration of about 0.1 mg to 1,000 mg |
| 6, 9, 12 |
Human patient plus oral dose range |
The dose limitations do not appear in claims 1 through 3. A generic applicant therefore cannot avoid all claims merely by selecting a dose outside the stated range. Such a strategy would avoid claims 5, 8, and 11, but it would not necessarily avoid claims 1, 2, or 3.
The word “about” gives the dose limitations some numerical flexibility. The scope would ordinarily be assessed using the specification, prosecution history, technical meaning of the dose, and any relevant Federal Circuit claim-construction precedent.
What is the infringement risk for a generic version of Xofluza?
The primary risk is induced infringement rather than direct infringement by the manufacturer alone.
A generic manufacturer may sell tablets with a label that recommends treatment or prevention of influenza. If the label instructs physicians and patients to use the claimed compound for a patented indication, the label can support an induced-infringement theory under 35 U.S.C. §271(b).
The risk is highest where the proposed generic label includes:
- Treatment of uncomplicated influenza;
- Post-exposure prevention;
- Oral administration;
- Human patients;
- Doses within the claimed range; or
- The same dosing regimen used in the Xofluza label.
A “skinny label” that omits a patented use can reduce induced-infringement exposure, but it does not eliminate all risk. Plaintiffs may rely on prescribing behavior, promotional activity, product instructions, medical literature, or evidence that the patented use is an intended use of the product.
When does US Patent 10,633,397 lose exclusivity?
The expected statutory expiration is September 2035.
| Exclusivity layer |
Approximate end date |
Commercial significance |
| FDA NCE exclusivity |
October 24, 2023 |
Blocked submission of an ANDA or 505(b)(2) application for five years, subject to statutory exceptions |
| Pediatric exclusivity |
Approximately April 24, 2024, if granted and applicable |
Added six months to qualifying exclusivity |
| US Patent 10,633,397 |
September 2035 |
Method-of-use protection |
| Earlier compound and composition patents |
Generally also tied to the 2035 patent-term window |
May block non-infringing product development even if the method patent is avoided |
FDA approval of a generic does not automatically authorize a generic applicant to market for every use covered by a listed method-of-use patent. Patent certifications and label carve-outs determine the regulatory path.
What is the Orange Book status of US Patent 10,633,397?
US Patent 10,633,397 is associated with the Xofluza patent estate and is identified in FDA patent-listing materials for the product. The relevant regulatory issue is not only whether the patent is listed, but also which use code and expiration information FDA records assign to it.
For an ANDA applicant, a listed method-of-use patent can produce:
- A Paragraph III certification accepting delayed approval until patent expiration;
- A Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed; or
- A section viii statement seeking approval for uses outside the patented indication.
A Paragraph IV notice can trigger a 30-month stay if the patent holder files suit within the statutory period under the Hatch-Waxman Act. The stay does not itself establish patent validity. It delays approval while the dispute proceeds, subject to statutory exceptions.
Which patents are likely to matter alongside US Patent 10,633,397?
The commercial patent position for Xofluza is broader than this single method patent. The relevant estate generally includes compound, salt, formulation, dosage, treatment, prevention, and manufacturing claims.
| Patent category |
Commercial function |
Generic exposure |
| Active compound patents |
Protect baloxavir chemical structure and related compounds |
High |
| Salt and solid-form patents |
Protect crystalline, salt, or polymorphic forms |
Medium to high |
| Prodrug patents |
Protect baloxavir marboxil and related ester forms |
High |
| Method-of-treatment patents |
Cover influenza treatment |
High where the label includes treatment |
| Prophylaxis patents |
Cover prevention or post-exposure use |
High for broad labels |
| Formulation patents |
Cover tablet composition, stability, or release properties |
Depends on product design |
| Manufacturing patents |
Cover synthesis, intermediates, purification, or process conditions |
Depends on process and sourcing |
| Pediatric or dosing patents |
Cover age groups, regimen, or dose schedules |
Relevant to label strategy |
A generic company can potentially design around a formulation or manufacturing patent. Designing around the active compound or core prodrug patent is substantially more difficult if the product must be pharmaceutically equivalent to Xofluza.
What formulations are protected by the patent?
US Patent 10,633,397 does not appear, based on the supplied claims, to require a particular tablet, excipient, coating, particle size, dissolution profile, or release mechanism.
Its claims are directed to administering the compound or salt. The patent therefore differs from a conventional formulation patent, which would typically require elements such as:
- A defined amount of active ingredient;
- Specific excipients;
- A tablet or capsule;
- A dissolution profile;
- A particle-size distribution;
- A stabilizer or coating; or
- A specified bioavailability parameter.
A different formulation may avoid a separate formulation patent but would not necessarily avoid the method claims if the formulation delivers the claimed compound for influenza treatment or prevention.
Does US Patent 10,633,397 create biosimilar risk?
No conventional biosimilar pathway applies. Baloxavir marboxil is a chemically synthesized small molecule, not a biologic subject to the Biologics Price Competition and Innovation Act.
The relevant competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, or potentially a 505(b)(2) application for a product that differs from Xofluza in formulation, dosage form, or clinical use.
This distinction affects timing:
- Generics rely on pharmaceutical equivalence and bioequivalence.
- Biosimilars require a biologic reference product and comparative analytical and clinical evidence.
- Xofluza competitors face Hatch-Waxman patent certifications rather than biosimilar patent-exchange procedures.
How does baloxavir compare with competing influenza antivirals?
Baloxavir has a differentiated mechanism. It inhibits cap-dependent endonuclease, while the principal older influenza antivirals inhibit neuraminidase.
| Product |
Active ingredient |
Target |
Typical regulatory competitor |
| Xofluza |
Baloxavir marboxil |
Cap-dependent endonuclease |
ANDA generic |
| Tamiflu |
Oseltamivir |
Neuraminidase |
Multiple generics |
| Relenza |
Zanamivir |
Neuraminidase |
Limited generic competition |
| Rapivab |
Peramivir |
Neuraminidase |
Potential injectable competition |
Baloxavir’s single-dose oral regimen is commercially relevant. It also creates a claim-enforcement risk because a simple label can directly communicate the patented treatment method.
Resistance-associated substitutions in the influenza polymerase acidic protein can affect baloxavir susceptibility. Those substitutions do not eliminate patent coverage if the accused product and use otherwise satisfy the claim elements.
What licensing deals affect the Xofluza patent estate?
Shionogi and Roche entered a collaboration covering baloxavir development and commercialization outside Japan and Taiwan. Roche markets Xofluza in multiple territories under the collaboration, while Shionogi retains important rights in Japan and Taiwan.
The commercial rights structure means that patent enforcement, regulatory filings, and settlements may involve different entities depending on jurisdiction. It also means that a US patent challenge may be pursued by the listed patent owner, an exclusive licensee, or another party with enforcement rights.
The licensing arrangement does not change the patent’s claim scope. It affects who commercializes the product and who may have standing to enforce or defend the patent.
What is the geographic coverage of the patent?
US Patent 10,633,397 is enforceable only in the United States. Parallel patent families may exist in:
- Japan;
- Europe;
- Canada;
- China;
- South Korea;
- Australia; and
- Other major pharmaceutical markets.
Patent term, claim scope, opposition procedures, and use-code treatment differ by jurisdiction. A US Paragraph IV outcome does not invalidate corresponding foreign patents.
For global launch planning, the relevant questions are whether the jurisdiction has:
- A corresponding baloxavir compound patent;
- A method-of-use patent;
- A supplementary protection certificate or patent-term extension;
- A pre-grant opposition system;
- A regulatory patent linkage mechanism; and
- A local compulsory-license or Bolar exemption.
What patent litigation affects US Patent 10,633,397?
The key litigation trigger would be an ANDA Paragraph IV notice identifying the patent. If Shionogi or its relevant licensee sues within 45 days, FDA approval may be stayed for up to 30 months, subject to court action and statutory exceptions.
The supplied record does not establish an adjudicated decision invalidating, narrowing, or unenforcing US Patent 10,633,397. The patent should therefore be treated as an active method-of-use asset unless a later court order, terminal disclaimer, reexamination certificate, or post-grant proceeding changes its status.
Potential litigation issues include:
-
Written description and enablement. A defendant could challenge the breadth of the cap-dependent-endonuclease disease language if the specification does not support the full claimed viral scope.
-
Indefiniteness. The terms “about,” “treating,” “preventing,” and “virus having cap-dependent endonuclease” may receive scrutiny, although each is commonly used in pharmaceutical method claims.
-
Induced infringement. The central dispute may concern whether a generic label encourages the patented treatment or prevention use.
-
Obviousness. Defendants may rely on prior art relating to influenza polymerase inhibition, antiviral screening, dosing, and prodrug design.
-
Double patenting. The patent estate may face obviousness-type double-patenting arguments if related patents claim overlapping treatment methods or compounds.
How strong is the patent estate for Xofluza?
The estate is strongest when the generic product uses the same active prodrug and carries an unrestricted influenza-treatment label. US Patent 10,633,397 alone is less comprehensive than a compound patent because a defendant may seek a label carve-out or dispute the induced-infringement theory.
| Risk factor |
Assessment |
| Core compound substitution |
High barrier |
| Oral influenza treatment label |
High infringement exposure |
| Prophylaxis indication |
Separate, significant exposure |
| Alternative formulation |
May avoid formulation claims, not necessarily method claims |
| Alternative manufacturing process |
May avoid process claims, not compound or method claims |
| Off-label prescribing |
Fact-specific induced-infringement risk |
| Biosimilar competition |
Not applicable |
| ANDA competition |
Primary pathway |
| Patent expiration |
2035 statutory endpoint |
| Regulatory exclusivity |
Expired, subject to pediatric extension history |
Generic launch scenarios for baloxavir
Scenario 1: Paragraph III delay
An ANDA applicant accepts the listed patents and seeks approval after the relevant expiration dates. This is the lowest litigation-risk route but delays entry until the patent barriers expire.
Scenario 2: Paragraph IV challenge
The applicant asserts that the patent is invalid, unenforceable, or not infringed. A timely suit can create a 30-month FDA stay. The likely commercial objective is approval before September 2035.
Scenario 3: Section viii carve-out
The applicant omits a patented method from the label. This strategy is more credible if the generic label excludes prophylaxis or another separately claimed use. It is more difficult if the remaining label instructions inherently encourage the patented treatment method.
Scenario 4: Settlement with licensed entry
The parties may agree to an entry date before patent expiration, subject to antitrust review and the terms of the settlement. A settlement can include a license, supply arrangement, restricted indication, or launch date.
Key Takeaways
- US Patent 10,633,397 is a method-of-use patent for baloxavir-related treatment and prevention.
- Claims 1 through 3 cover broad antiviral treatment, influenza treatment, and influenza prevention.
- Claims 4 through 12 narrow the methods to human patients and, in selected claims, oral doses of about 0.1 mg to 1,000 mg.
- The patent does not require a particular tablet formulation based on the supplied claims.
- Xofluza is a small-molecule product, so generic competition proceeds through Hatch-Waxman, not biosimilar regulation.
- The expected US patent expiration is September 2035.
- A generic label covering influenza treatment or prevention would face the greatest induced-infringement risk.
- The commercial assessment must include related compound, prodrug, formulation, dosing, and manufacturing patents, not this patent in isolation.
- Shionogi and Roche’s collaboration is relevant to commercialization and enforcement rights outside Japan and Taiwan.
- No adjudicated invalidity or noninfringement outcome is established here for US Patent 10,633,397.
FAQs About US Patent 10,633,397
Is US Patent 10,633,397 a compound patent?
No. Based on the supplied claims, it is a method-of-treatment and method-of-prevention patent. Related compound or prodrug patents may provide separate protection for baloxavir marboxil.
Can a generic avoid the patent by using a dose below 0.1 mg?
That could avoid the specific dependent dose claims, but it would not necessarily avoid claims 1, 2, or 3, which do not include the 0.1 mg to 1,000 mg limitation.
Does the patent cover influenza prophylaxis?
Yes. Claim 3 expressly covers preventing influenza, with claims 10 through 12 adding human-patient and oral-dose limitations.
Does a nonoral baloxavir product avoid all claims?
No. Nonoral administration may avoid certain dependent claims, but claims 1 through 3 do not expressly require oral administration.
What is the main commercial weakness of this patent?
The principal weakness is that it is use-based rather than solely product-based. A generic may pursue a narrowed label, challenge induced infringement, or attack validity while relying on separate arguments against the broader Xofluza patent estate.
References
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Food and Drug Administration. (2018). Xofluza (baloxavir marboxil) prescribing information. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov
-
Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov/scripts/cder/ob/
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Roche. (2016). Roche and Shionogi enter into a collaboration agreement for the development and commercialization of a novel influenza treatment. https://www.roche.com
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Shionogi & Co., Ltd. (2023). Annual report. https://www.shionogi.com
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United States Patent and Trademark Office. (2020). US Patent No. 10,633,397, method for treating or preventing influenza. https://patents.google.com/patent/US10633397B2
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U.S. Code, Title 35, §§ 154, 271, and 281-285.
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U.S. Code, Title 21, §§ 355(j) and 355(c)(3).
