United States Patent 10,869,924: Avelumab-Axitinib Combination Patent Scope, Expiration and Competitive Landscape
US Patent No. 10,869,924 protects specific methods of treating renal cell carcinoma with the combination of avelumab, an anti-PD-L1 antibody, and axitinib, a VEGFR inhibitor. The broadest commercially relevant claims cover the regimen of avelumab administered approximately every two weeks with axitinib administered twice daily. The patent is directed to treatment methods, not to avelumab or axitinib composition-of-matter protection.
The patent’s practical value is concentrated in the avelumab-plus-axitinib regimen for renal cell carcinoma, including the 10 mg/kg avelumab and 5 mg axitinib dosing schedule associated with the JAVELIN Renal 101 program and Bavencio/Inlyta labeling.
What does US Patent 10,869,924 protect?
The patent contains three principal claim groups:
| Claim group |
Protected subject matter |
Commercial relevance |
| Claims 1-13 |
Renal cell carcinoma treatment using an anti-PD-L1 antibody with axitinib, with antibody sequence and dosing limitations |
Broad biological combination claim, narrowed by antibody CDR limitations |
| Claims 14-20 |
Renal cell carcinoma treatment using avelumab plus axitinib, with dosing and treatment-management limitations |
Core regimen claims |
| Claims 21-24 |
Renal cell carcinoma treatment using avelumab administered every two weeks, including 1-hour infusion, with axitinib dosing limitations |
Most directly aligned with the labeled regimen |
Claim 1 identifies axitinib by its chemical name:
N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide
That chemical definition covers axitinib and its pharmaceutically acceptable salts. Claims 2 and 14 onward expressly identify the commercial antibody as avelumab and the VEGFR inhibitor as axitinib.
The patent therefore has two layers of protection:
- An antibody-structure layer, based on the claimed heavy- and light-chain CDRs.
- A named-drug regimen layer, based on avelumab plus axitinib.
The second layer is more important for enforcement against a conventional competing product or treatment protocol because it does not require the patent owner to prove every antibody sequence detail if the accused method uses avelumab.
How broad are the claims to avelumab and axitinib?
Claims 14 through 24 are the principal commercial claims. Claim 14 covers:
- treatment of renal cell carcinoma;
- avelumab;
- axitinib;
- avelumab administered about once every two weeks; and
- axitinib administered twice daily.
Dependent claims add:
- avelumab at approximately 10 mg/kg;
- axitinib at 5 mg;
- a 1-hour intravenous infusion for avelumab;
- discontinuation for unacceptable toxicity; and
- discontinuation for disease progression.
Claims 21 through 24 provide an alternative claim structure. Claim 21 requires avelumab to be administered approximately every two weeks as a 1-hour intravenous infusion, while the dependent claims add the 10 mg/kg avelumab dose and twice-daily 5 mg axitinib administration.
The claims are method-of-treatment claims. They generally require proof that:
- a human patient has renal cell carcinoma;
- the patient receives both claimed agents;
- the agents are administered using the claimed schedule; and
- the treatment is performed for the claimed therapeutic purpose.
A manufacturer would not necessarily infringe merely by selling avelumab or axitinib. The principal risk is induced infringement or contributory infringement based on labeling, promotional materials, clinical protocols, treatment-center instructions, or other evidence showing that the patented combination regimen is encouraged or supplied.
What renal cell carcinoma populations are covered?
Claim 1 expressly covers renal cell carcinoma and dependent claim 5 narrows the disease to advanced renal cell carcinoma. Claim 6 further narrows the population to previously untreated advanced renal cell carcinoma.
Claims 14 through 24 do not expressly require the cancer to be advanced or previously untreated. On their face, those claims cover renal cell carcinoma more broadly, provided the claimed avelumab and axitinib regimen is administered.
| Patient population |
Claim coverage |
| Renal cell carcinoma generally |
Claims 1 and 14-24 |
| Advanced renal cell carcinoma |
Claim 5 |
| Previously untreated advanced renal cell carcinoma |
Claim 6 |
| Previously treated renal cell carcinoma |
Potentially claims 1 and 14-24, subject to the other limitations |
| Non-renal solid tumors |
Not covered by the issued claims as provided |
| Urothelial carcinoma or Merkel cell carcinoma |
Not covered by the claims as provided |
The narrow disease limitation materially reduces the patent’s scope compared with a patent claiming all PD-L1/VEGFR inhibitor combinations across solid tumors.
What dosing and administration schedules are protected?
The core dosing limitations are:
| Agent |
Claimed regimen |
| Avelumab |
Approximately once every two weeks |
| Avelumab dose |
About 10 mg/kg |
| Avelumab administration |
1-hour intravenous infusion |
| Axitinib |
Twice daily |
| Axitinib dose |
5 mg |
Claims 3, 4, 8, 10, 11, 15-18, and 21-24 create multiple dependent claim combinations around these parameters.
The use of “about” and “approximately” creates ordinary claim-construction questions regarding acceptable clinical variation. A regimen that departs materially from 10 mg/kg, a two-week interval, 5 mg axitinib, or twice-daily dosing would have a stronger noninfringement position. Small practical deviations may remain within the scope of the claims depending on the intrinsic evidence, prosecution history, and expert testimony.
The toxicity and disease-progression limitations in claims 12, 13, 19, and 20 are treatment-management limitations. They are unlikely to be the primary commercial barrier because discontinuation for toxicity or progression is standard oncology practice and may be difficult to use as a meaningful distinction from the labeled regimen.
When does US Patent 10,869,924 lose exclusivity?
US Patent 10,869,924 issued on December 22, 2020. Its ordinary patent term is generally 20 years from the earliest effective nonprovisional or international filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any disclaimer or post-grant order recorded in the official file.
The relevant term estimate is approximately 2035, based on the patent family’s 2015-era filing chronology. The enforceable expiration date should be taken from the USPTO Patent Center term record rather than calculated solely from the issue date. Patent expiration does not remove separate patents covering avelumab, axitinib, manufacturing processes, formulations, or other uses.
| Exclusivity element |
Relevance to US 10,869,924 |
| Patent type |
Treatment-method patent |
| Issue date |
December 22, 2020 |
| Expected statutory term |
Approximately 2035 |
| FDA new-drug exclusivity |
Separate from this patent |
| Composition-of-matter protection |
Not provided by the claims supplied |
| Formulation protection |
Not provided by the claims supplied |
| Manufacturing protection |
Not provided by the claims supplied |
| Biosimilar exclusivity |
Not applicable to axitinib; avelumab is a biologic |
The patent does not itself create FDA regulatory exclusivity. FDA exclusivity is determined under the applicable NDA and biologics provisions, while patent rights are determined under the Patent Act.
What is the FDA and Orange Book status of the protected regimen?
Avelumab is marketed as Bavencio by EMD Serono and Pfizer. Axitinib is marketed as Inlyta by Pfizer. The FDA approved Bavencio in combination with axitinib for patients with advanced renal cell carcinoma in 2019. The FDA-approved regimen uses avelumab 800 mg intravenously every two weeks and axitinib 5 mg orally twice daily, subject to dose modification and clinical management. [2]
The 10 mg/kg dose in the patent claims is not identical to the current fixed 800 mg every-two-week labeling commonly associated with Bavencio. For an adult weighing 80 kg, 10 mg/kg corresponds to 800 mg. The distinction matters:
- claims 14-24 do not all require the 10 mg/kg dose;
- claims 14 and 21 independently protect the two-week avelumab/axitinib combination structure;
- fixed-dose administration may still fall within claims that do not require the weight-based dose; and
- infringement cannot be assessed from dose equivalence alone.
Avelumab is a biologic. Its primary regulatory pathway for competition is biosimilar approval under the Public Health Service Act, not an ANDA Paragraph IV filing. Axitinib is a small molecule and can be challenged through the ANDA pathway.
What Paragraph IV challenges and biosimilar risks affect this patent?
Axitinib generic risk
A generic axitinib applicant could file an ANDA with a Paragraph IV certification against listed patents covering axitinib, its use, or its approved labeling. A Paragraph IV challenge directed to a separate axitinib patent would not automatically invalidate or remove US 10,869,924.
The patent creates a distinct method-use risk if a generic axitinib label expressly or implicitly encourages combination use with avelumab for renal cell carcinoma. A skinny-label strategy could attempt to omit the patented combination indication. The success of that strategy would depend on the final label, prescribing information, promotional conduct, and the scope of any FDA-approved use retained in the generic application.
A generic axitinib product could also be used off-label in the patented combination. That would raise inducement issues if the generic manufacturer encourages the combination or supplies information directed to the claimed regimen.
Avelumab biosimilar risk
Avelumab biosimilars would face a biologics patent landscape rather than an ANDA Paragraph IV process. The relevant risks include:
- composition patents covering the antibody;
- cell-line and production patents;
- purification and manufacturing patents;
- formulation patents;
- treatment-method patents such as US 10,869,924; and
- settlement or license agreements under the Biologics Price Competition and Innovation Act.
A biosimilar applicant may pursue a noninfringement or invalidity position against the combination claims while retaining a label that omits renal cell carcinoma use. Whether that approach reduces risk depends on the product’s label, the reference-product indications, and evidence of induced use.
How does this patent compare with competing renal cell carcinoma patents?
US 10,869,924 covers one specific immuno-oncology/VEGFR pairing. It does not block competing combinations using different checkpoint inhibitors or different VEGFR or tyrosine kinase inhibitors.
| Combination |
Representative commercial products |
Relationship to US 10,869,924 |
| Avelumab + axitinib |
Bavencio + Inlyta |
Directly within the claimed regimen |
| Pembrolizumab + axitinib |
Keytruda + Inlyta |
Different PD-1 antibody; outside the named-avelumab claims |
| Pembrolizumab + lenvatinib |
Keytruda + Lenvima |
Different checkpoint antibody and VEGFR inhibitor |
| Nivolumab + cabozantinib |
Opdivo + Cabometyx |
Different checkpoint antibody and kinase inhibitor |
| Nivolumab + ipilimumab |
Opdivo + Yervoy |
Different immunotherapy combination |
The patent does not prevent treatment providers from using alternative approved renal cell carcinoma combinations. Its competitive effect is narrower: it can constrain the avelumab-plus-axitinib regimen during the patent term.
How strong is the patent estate for avelumab and axitinib?
The supplied claims have moderate commercial strength but limited technological breadth.
Strengths
- Claims 14 and 21 directly recite avelumab and axitinib.
- The dosing schedule corresponds closely to the approved clinical regimen.
- The claims target a specific renal cell carcinoma treatment rather than an untested broad genus.
- Dependent claims provide multiple fallback positions around dose, frequency, infusion duration, and treatment discontinuation.
Weaknesses
- The claims are limited to renal cell carcinoma.
- The claims do not cover avelumab or axitinib as products.
- The claims do not cover manufacturing, formulation, salt selection, or tablet composition.
- The treatment-management limitations may add little practical distinction.
- The “about” and “approximately” language may create claim-construction disputes.
- The sequence-based antibody limitation in claim 1 may require detailed CDR mapping and antibody identity evidence.
- The regimen’s public clinical and regulatory disclosure may create prior-art and obviousness issues, depending on the earliest priority date and the references considered during prosecution.
The strongest enforcement position is likely against a label or treatment protocol that expressly recommends avelumab every two weeks with axitinib twice daily for renal cell carcinoma.
What patent litigation and settlement issues are relevant?
No litigation conclusion follows from the patent number alone. The principal potential disputes would involve:
- validity challenges based on anticipation or obviousness;
- claim construction of “about” and “approximately”;
- whether fixed-dose avelumab falls within claims using a weight-based dose;
- whether a generic or biosimilar label induces the patented use;
- whether treatment-center administration constitutes direct infringement;
- whether the claims are invalid for lack of written description or enablement; and
- whether a settlement permits entry before the estimated 2035 patent-term endpoint.
Any settlement involving an axitinib generic or avelumab biosimilar would need to be analyzed separately from the patent claims. A license to one patent family would not necessarily resolve other patents held by Pfizer, EMD Serono, Merck KGaA, or affiliated entities.
What geographic coverage does the patent provide?
US 10,869,924 has territorial effect only in the United States. Corresponding foreign patents may protect the same combination in Europe, Japan, China, Canada, Australia, and other jurisdictions, but each country applies its own claim scope, validity rules, patent-term adjustments, supplementary protection certificate framework, and litigation procedures.
The US patent does not directly block:
- manufacture outside the United States for non-US markets;
- treatment conducted entirely outside the United States;
- foreign sales absent a corresponding foreign patent; or
- alternative checkpoint inhibitor/VEGFR combinations.
Export activity involving components or products may create separate US infringement questions under 35 U.S.C. § 271, particularly where a patented combination is supplied for assembly or use abroad.
What generic launch scenarios exist?
| Scenario |
Risk under US 10,869,924 |
| Generic axitinib with a label excluding the avelumab combination |
Lower direct label risk, subject to actual marketing conduct |
| Generic axitinib with an RCC combination indication |
High method-use risk |
| Off-label physician use of generic axitinib with avelumab |
Potential indirect-infringement exposure for the manufacturer; direct-use issues for providers |
| Avelumab biosimilar excluding RCC use |
Reduced method-use risk, but other antibody and manufacturing patents remain relevant |
| Avelumab biosimilar retaining RCC use |
Directly targets claims 14-24 |
| Alternative immunotherapy/VEGFR regimen |
Outside the claims provided |
Key Takeaways
- US 10,869,924 is a method-of-treatment patent covering avelumab plus axitinib for renal cell carcinoma.
- Claims 14-24 are the most commercially important claims.
- The central regimen is avelumab approximately every two weeks with axitinib twice daily.
- The patent does not claim avelumab, axitinib, their formulations, or their manufacturing processes.
- The ordinary patent-term endpoint is expected to fall around 2035, subject to the USPTO term record.
- Generic axitinib risk depends heavily on the ANDA label and any inducement evidence.
- Avelumab competition would proceed through the biosimilar pathway, not a conventional Paragraph IV ANDA.
- Competing regimens such as pembrolizumab/axitinib, pembrolizumab/lenvatinib, and nivolumab/cabozantinib are not covered by the claims provided.
- The patent’s strongest enforcement case is an express US treatment protocol or product label recommending the claimed avelumab-axitinib RCC regimen.
FAQs
Does US Patent 10,869,924 cover Bavencio alone?
No. The claims require a combination involving avelumab or an anti-PD-L1 antibody and axitinib. Avelumab monotherapy is outside the claims provided.
Does the patent cover Inlyta alone?
No. The claims are directed to combination treatment. Axitinib monotherapy is outside the claimed methods.
Does an 800 mg fixed dose of avelumab infringe the 10 mg/kg claims?
Claims that expressly require approximately 10 mg/kg raise a dose-specific question. Claims 14 and 21 do not independently require the 10 mg/kg limitation, so fixed-dose administration may still fall within those broader regimen claims.
Can a generic axitinib launch before the patent expires?
Potentially, if its approved labeling and conduct avoid inducing the patented avelumab combination use and if other applicable axitinib patents do not block launch. A Paragraph IV certification or settlement could materially change the timing.
Is avelumab subject to biosimilar competition?
Yes. Avelumab is a biologic, so future competitors would generally use the biosimilar pathway. US 10,869,924 could be one patent considered in the biosimilar applicant’s patent strategy, alongside antibody, manufacturing, formulation, and other method patents.
References
- United States Patent and Trademark Office. (2020). U.S. Patent No. 10,869,924, methods for treating cancer using an anti-PD-L1 antibody and a VEGFR inhibitor. https://patents.google.com/patent/US10869924B2/en
- U.S. Food and Drug Administration. (2019). FDA approves avelumab plus axitinib for advanced renal cell carcinoma. https://www.fda.gov
- U.S. Food and Drug Administration. (2024). BAVENCIO (avelumab) prescribing information. EMD Serono, Inc. https://www.accessdata.fda.gov
- U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/
- U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov
- United States Code. (2024). 35 U.S.C. §§ 154, 271. https://uscode.house.gov
