United States Patent 9,815,835: Scope, Claims, Expiration and Influenza Antiviral Patent Landscape
US 9,815,835 is a Shionogi patent directed to a broad genus of substituted heterocyclic compounds, pharmaceutical compositions containing those compounds, and their use for treating influenza infection. The claim structure is consistent with the cap-dependent endonuclease inhibitor program that produced baloxavir marboxil, marketed by Roche and Shionogi as Xofluza. The patent’s principal commercial significance is its potential coverage of baloxavir-related compounds and structurally related influenza antivirals, rather than a narrow claim limited to one marketed molecular species.
The patent issued on November 14, 2017. Based on the apparent priority date in the patent family, its nominal U.S. patent term runs into March 2033, subject to any patent-term adjustment, terminal disclaimer, or other term modification shown in the USPTO record.[1]
What does US 9,815,835 claim?
The patent contains three operative claim categories:
| Claim category |
Claims |
Legal subject matter |
| Chemical compounds |
1-10 |
Formula II compounds, salts and solvates |
| Pharmaceutical composition |
11 |
Composition containing a claim 1 compound and a pharmaceutically acceptable ingredient |
| Therapeutic method |
12 |
Administration of a claim 1 compound for influenza infectious disease |
Claim 1 is the controlling independent claim. Claims 2 through 10 narrow substituent selections and ring structures. Claim 11 depends on the compound genus. Claim 12 covers treatment activity and does not require a separate formulation limitation.
The compound claims include pharmaceutically acceptable salts and solvates. A generic or follow-on product could therefore face infringement risk even if it uses a salt, hydrate, or other solvate rather than the free compound, provided the underlying molecular structure falls within the claim.
How broad is claim 1 of US 9,815,835?
Claim 1 is a Markush genus claim with extensive substituent flexibility. Its scope is determined by the combination of:
- The formula II molecular scaffold.
- The definitions of R1a and R2a.
- The B1/B2 ring and substitution arrangement.
- The requirement that R3a and R6a form a substituted heterocycle.
- The permitted R5a and R7a substituents.
- The definitions of substituent groups C and D.
- The inclusion of salts and solvates.
The claim is broad because each variable includes multiple structural classes. R1a and R2a can independently include hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, carbonyl-containing groups, carbocyclic groups, heterocyclic groups, amino derivatives, sulfonyl groups and other functionalized substituents.
The claim also permits linker groups through Z and Y. Those linkers may be a direct bond or lower alkylene chains. This allows substantial variation in the distance and orientation between the core scaffold and peripheral substituents.
What structural features limit the genus?
The claim is broad, but it is not an unrestricted claim to all influenza polymerase inhibitors. The principal limitations are structural:
- The compound must conform to formula II.
- B1 must be NR7a.
- B2 must be CR5aR6a.
- R3a and R6a must form a heterocycle.
- The R5a and R7a substitution pattern must fall within the enumerated alternatives.
- Any substituents must remain within substituent groups C and D.
- The compound must be a pharmaceutically acceptable salt or solvate only where that form corresponds to a covered compound.
A molecule can have influenza antiviral activity and still avoid the patent if its central ring system, heterocyclic fusion, nitrogen placement, or substituent topology falls outside formula II.
What do dependent claims 2 through 10 add?
The dependent claims progressively reduce the breadth of claim 1. Their practical importance is highest in validity analysis and in evaluating design-around options.
| Claim |
Principal narrowing feature |
| 2 |
Narrows R1a while retaining several amino, sulfonyl, thioether and carbamate alternatives |
| 3 |
Removes several R1a options and focuses on selected alkyl, alkoxy, heterocyclic and amino substituents |
| 4 |
Narrows R1a to a smaller set, including hydrogen, halogen, hydroxy, carboxy, alkyl and amino groups |
| 5 |
Limits R1a to hydrogen or carboxy |
| 6 |
Limits R2a to hydrogen, substituted alkyl, carbocyclic or heterocyclic alkyl, or dialkylamino-type groups |
| 7 |
Limits R2a to hydrogen or substituted lower alkyl |
| 8 |
Requires formula II'' with a 5- to 7-membered heterocycle |
| 9 |
Narrows R7a to a specifically illustrated group defined through RE6 and m |
| 10 |
Narrows substituent group D to carbocyclic, heterocyclic and related alkyl-linked groups |
Claims 5 and 7 are particularly useful from a prosecution and validity perspective because they identify materially narrower subgenus positions. If claim 1 were challenged for undue breadth, lack of written description or lack of enablement, narrower claims could provide fallback protection if their specific structures and examples are adequately supported in the specification.
Does US 9,815,835 cover baloxavir or Xofluza?
The patent is part of the broader Shionogi influenza antiviral patent program associated with baloxavir marboxil and Xofluza. Whether a particular marketed compound literally falls within claim 1 depends on mapping the exact baloxavir structure to formula II, including the stereochemistry, ring system and substituent definitions in the issued patent.
The commercial relevance is nevertheless clear:
- Xofluza contains baloxavir marboxil.
- Baloxavir is converted in vivo to the active moiety baloxavir.
- The active moiety inhibits influenza virus cap-dependent endonuclease, a subunit of the viral polymerase complex.
- US 9,815,835 is directed to compounds in the same technical and chemical field.
- Patent protection for Xofluza is likely distributed across compound, formulation, therapeutic-use and manufacturing-related patent families rather than resting on this patent alone.[2][3]
A definitive infringement opinion requires a structure-to-claim chart. The claim text supplied does not include the chemical drawings for formula II and formula II'', which are essential for confirming literal coverage of baloxavir marboxil.
When does US 9,815,835 lose exclusivity?
The apparent nominal expiration date is in March 2033, based on a 20-year term measured from the relevant 2013 priority or international filing chain.[1] The final enforceable expiration date must be taken from the USPTO patent record because patent-term adjustment can add days to the term.
| Event |
Date or status |
| Earliest apparent priority period |
March 2013 |
| U.S. patent issue |
November 14, 2017 |
| Nominal 20-year expiration |
Approximately March 2033 |
| Patent-term adjustment |
Must be confirmed in USPTO Patent Center |
| Patent-term extension under 35 U.S.C. § 156 |
No extension established from the supplied record |
| Small-molecule regulatory exclusivity |
Separate from patent term |
The patent does not receive a new 20-year term merely because the FDA approved Xofluza after issuance. Patent term and FDA exclusivity operate independently.
What is the FDA and Orange Book status of the patent?
Xofluza was approved by the FDA on October 24, 2018, for treatment of acute uncomplicated influenza in patients aged 12 years and older who had been symptomatic for no more than 48 hours.[2] The FDA later expanded the indication to younger pediatric patients and approved post-exposure prophylaxis in specified populations.[3]
The relevant regulatory protections are:
| Regulatory protection |
Status |
| New chemical entity exclusivity |
Applied to the original approval |
| Five-year NCE exclusivity |
Expired in October 2023, subject to statutory calculation |
| Pediatric exclusivity |
Requires confirmation against the FDA exclusivity record |
| Orange Book patent listing |
Must be checked against the current Orange Book entry for Xofluza |
| Patent term |
Extends materially beyond ordinary NCE exclusivity |
A patent can be important to Xofluza without being listed in the Orange Book. The Orange Book generally lists patents claiming the drug substance, drug product or approved method of use. Broad research-platform patents, manufacturing patents and claims that do not read on the approved product may not qualify for listing under FDA regulations.[4]
What Paragraph IV challenges and litigation affect the patent?
A Paragraph IV certification would be relevant only if an ANDA applicant identifies the patent in the Orange Book and asserts that the patent is invalid, unenforceable or not infringed. The supplied information does not establish an ANDA filing, a Paragraph IV notice letter, a 30-month stay, or a district-court action involving US 9,815,835.
For commercial diligence, the patent should be separated into three risk categories:
| Risk category |
Assessment |
| Direct product risk |
High if the generic compound maps literally to formula II |
| Formulation risk |
Depends on separate claims directed to dosage form, excipients, particle size or solid state |
| Method-of-use risk |
Depends on the approved indication and whether the applicant uses a section viii carve-out |
A generic applicant could pursue a Paragraph IV challenge against a listed compound patent, a formulation patent, or both. If the patent is not listed, the applicant could still seek approval while accepting potential infringement exposure, but the Orange Book’s statutory stay mechanism would not operate for that unlisted patent.
No settlement agreement, authorized generic arrangement or litigation outcome involving US 9,815,835 is established by the supplied record.
What formulations are protected by US 9,815,835?
Claim 11 is a functional composition claim. It requires:
- A compound of claim 1, or its pharmaceutically acceptable salt or solvate; and
- At least one pharmaceutically acceptable ingredient.
The claim does not identify a particular tablet, capsule, suspension, excipient, dosage strength, release profile or manufacturing process. It therefore has broader theoretical coverage than a formulation claim limited to a defined excipient ratio or solid form, but it may also face greater validity scrutiny if the claim is challenged across the full chemical genus.
Claim 11 does not automatically cover every product that contains an influenza antiviral. The active ingredient must be a claim 1 compound. A formulation using a chemically distinct endonuclease inhibitor would not infringe merely because it has the same mechanism of action.
Does the patent cover methods of treating influenza?
Yes. Claim 12 covers administering a claim 1 compound, salt or solvate to treat influenza infectious disease. The claim does not appear limited to:
- A particular influenza strain.
- A particular age group.
- A particular dosing schedule.
- A particular route of administration.
- A particular treatment window.
- Outpatient or inpatient use.
The method claim may therefore overlap with multiple approved or investigational influenza-treatment settings if the administered compound falls within claim 1.
Its practical value depends on enforceability against the relevant actor. Direct infringement generally requires performance of each method step. Liability theories can differ for manufacturers, prescribers, pharmacies and patients under the Hatch-Waxman framework and 35 U.S.C. § 271(e)(2), § 271(b) and § 271(c).[5]
How strong is the patent estate?
Chemical scope
The chemical scope is potentially strong against close analogues because claim 1 covers a large set of substituent combinations and expressly includes salts and solvates. The principal weakness is breadth. A challenger could focus on written description, enablement, indefiniteness or anticipation if the prior art discloses a sufficiently similar genus or representative compound.
Claim hierarchy
The claim set has useful fallback positions. Claims 5, 7, 8 and 9 provide narrower subgenera that may be easier to defend than claim 1. The strength of those claims depends on whether the specification provides representative examples across each claimed category.
Regulatory leverage
The patent’s value is highest if:
- It is listed in the Orange Book.
- The approved active ingredient falls within the issued claims.
- No terminal disclaimer or term adjustment issue materially shortens its duration.
- The claims survive a Paragraph IV challenge.
- Separate formulation or method patents do not expire earlier and create an easier design-around.
How does US 9,815,835 compare with competing influenza antiviral patents?
| Product |
Active ingredient |
Mechanism |
Main competitive patent issue |
| Xofluza |
Baloxavir marboxil |
Cap-dependent endonuclease inhibition |
Compound, prodrug, formulation and use claims |
| Tamiflu |
Oseltamivir phosphate |
Neuraminidase inhibition |
Core patents largely expired; generic competition established |
| Relenza |
Zanamivir |
Neuraminidase inhibition |
Older patent estate; broad generic and alternative-treatment competition |
| Rapivab |
Peramivir |
Neuraminidase inhibition |
Product-specific and method protection |
| FluMist and other vaccines |
Various antigens and platforms |
Immune prevention |
Biologic and manufacturing patent issues rather than small-molecule Orange Book risk |
US 9,815,835 is differentiated by targeting a viral polymerase function rather than neuraminidase. That distinction reduces direct chemical overlap with oseltamivir, zanamivir and peramivir patents. Competitive pressure is more likely to arise from alternative mechanisms, next-generation polymerase inhibitors and new formulations of baloxavir than from literal infringement by existing neuraminidase generics.
What generic launch scenarios exist?
Scenario 1: Paragraph IV challenge
An ANDA applicant challenges the listed patent before the nominal 2033 expiration date. The principal arguments would likely involve noninfringement based on the applicant’s molecular structure, invalidity based on prior art, or an assertion that the listed patent does not claim the approved product.
Scenario 2: Section viii carve-out
If only an influenza indication is patented and other approved uses are unpatented, an applicant may carve out the protected use from its labeling. This route is less useful where the patent claims the active compound itself.
Scenario 3: Post-expiration launch
A generic waits for expiration and avoids litigation. This is the lowest legal-risk path but leaves substantial time between NCE exclusivity expiration and patent expiry.
Scenario 4: Non-infringing compound
A competitor develops an endonuclease inhibitor outside formula II. This is the most durable design-around strategy because it avoids dependence on a narrow interpretation of the substituent definitions.
Key Takeaways
- US 9,815,835 is a broad compound-genus patent with associated composition and influenza-treatment claims.
- Claim 1 is the commercial center of gravity and covers a complex Markush family of heterocyclic compounds, salts and solvates.
- Claims 5, 7, 8 and 9 provide narrower fallback positions.
- The patent is associated with Shionogi’s baloxavir/Xofluza influenza antiviral program, but exact literal coverage of baloxavir requires the missing formula drawings and a structure-to-claim analysis.
- The apparent nominal expiration is approximately March 2033, subject to USPTO patent-term adjustment.
- FDA NCE exclusivity for Xofluza expired in 2023, but patent protection can continue substantially longer.
- No Paragraph IV litigation, settlement or 30-month stay involving this patent is established by the supplied record.
- Formulation and method-of-use risks must be evaluated separately from the broad chemical genus.
- The primary generic defense is a molecular design-around or a Paragraph IV challenge directed to claim breadth, written description, enablement, anticipation or noninfringement.
FAQs
Is US 9,815,835 a compound patent or a method patent?
It is both. Claims 1 through 10 cover compounds, claim 11 covers compositions, and claim 12 covers treatment of influenza.
Does a pharmaceutically acceptable salt infringe US 9,815,835?
It can. Claim 1 expressly includes pharmaceutically acceptable salts and solvates of covered compounds.
Can a generic launch after Xofluza’s FDA exclusivity expires?
Not necessarily. FDA exclusivity and patent rights are separate. A generic may face patent-based approval or litigation barriers after regulatory exclusivity ends.
Does the patent cover all cap-dependent endonuclease inhibitors?
No. It covers only compounds falling within formula II and the associated substituent definitions. Mechanism alone is insufficient for infringement.
What is the main design-around strategy?
The strongest design-around is a compound with a core scaffold, ring configuration or substituent arrangement outside the literal boundaries of formula II and its dependent claims.
References
- United States Patent and Trademark Office. (2017). U.S. Patent No. 9,815,835. https://patents.google.com/patent/US9815835B2/en
- U.S. Food and Drug Administration. (2018). FDA approves new drug to treat influenza. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treat-influenza
- U.S. Food and Drug Administration. (2022). Xofluza prescribing information. Genentech, Inc. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/210854s006lbl.pdf
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
- Legal Information Institute. (2024). 35 U.S.C. § 271: Infringement of patent. Cornell Law School. https://www.law.cornell.edu/uscode/text/35/271
