US Patent 10,570,202: Pembrolizumab-Axitinib Combination Patent Scope, Expiration and Competitive Landscape
US Patent 10,570,202 protects specific methods and kits combining pembrolizumab, marketed as Keytruda, with axitinib, marketed as Inlyta. Its strongest commercial claims cover treatment of renal cell carcinoma, particularly advanced renal cell carcinoma, using pembrolizumab and axitinib at specified dosing schedules. The patent does not broadly block all pembrolizumab products, all axitinib products, or every PD-1/VEGFR combination.
The patent is strategically important because it covers the Keytruda-Inlyta regimen approved by the FDA for first-line advanced renal cell carcinoma. Its principal risk is directed at competitors seeking to market the same combination, label, dosing regimen, or coordinated product kit.
What does US Patent 10,570,202 cover?
The patent covers two principal categories:
- Methods of treating cancer with a PD-1 antagonist and a VEGFR inhibitor.
- Kits containing separate PD-1 and VEGFR medicaments with instructions for combination use.
The relevant commercial products are:
| Patent element |
Commercial product |
| Anti-PD-1 monoclonal antibody |
Pembrolizumab, Keytruda |
| VEGFR inhibitor |
Axitinib, Inlyta |
| Principal cancer indication |
Advanced renal cell carcinoma |
| Principal regimen |
Pembrolizumab 200 mg every three weeks plus axitinib 5 mg twice daily |
| Patent owner and commercial sponsor |
Merck, in collaboration with Pfizer for the marketed combination |
Claim 1 uses antibody sequence definitions rather than naming pembrolizumab. The heavy and light chains identified by SEQ ID NO:21 and SEQ ID NO:22 function as a structural definition of the antibody. Claim 5 then expressly identifies the antibody as pembrolizumab and the VEGFR inhibitor as axitinib.
Claim 26 further narrows claim 1 to pembrolizumab while retaining the axitinib limitation inherited from claim 1.
How broad are the independent treatment claims?
Claim 1: broad combination-treatment claim
Claim 1 requires all of the following:
- Treating cancer in an individual.
- Administering a combination therapy.
- Using an anti-PD-1 monoclonal antibody with the specified heavy and light chains.
- Using N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide or a pharmaceutically acceptable salt.
The chemical compound is axitinib. Because claim 1 structurally defines both components, it is narrower than a claim covering any anti-PD-1 antibody and any VEGFR inhibitor.
The cancer limitation is initially broad. Dependent claims narrow the field to solid tumors, renal cell carcinoma, advanced renal cell carcinoma and a lengthy list of hematologic and solid-tumor cancers.
Claims 24 and 25: commercially focused RCC claims
Claims 24 and 25 are among the most commercially significant claims:
- Claim 24 covers pembrolizumab plus axitinib for renal cell carcinoma.
- Claim 25 covers the same combination for advanced renal cell carcinoma.
These claims do not recite the specific dosing schedules found in claim 12. They therefore provide broader regimen coverage than claims 12 and 15 through 21, assuming the claims remain valid and enforceable as issued.
Claim 12: dose-specific regimen claim
Claim 12 covers pembrolizumab plus axitinib in a human diagnosed with cancer using either:
- Axitinib 5 mg twice daily plus pembrolizumab at 1 mg/kg, 2 mg/kg, or 200 mg every three weeks; or
- Axitinib 3 mg twice daily plus pembrolizumab at 1 mg/kg, 2 mg/kg, or 200 mg every three weeks.
Claims 16 through 21 separately recite each dosing combination. Claim 18 is the key marketed regimen:
- Axitinib: 5 mg twice daily.
- Pembrolizumab: 200 mg every three weeks.
The 3 mg twice-daily alternatives create additional coverage for dose-reduced axitinib regimens. That is relevant because dose reductions are common in axitinib treatment and can occur because of hypertension, fatigue, diarrhea, hepatotoxicity or other adverse events.
What patent claims cover the Keytruda-Inlyta regimen?
| Claim |
Subject matter |
Commercial relevance |
| 1 |
PD-1 antibody plus axitinib structural combination |
Broadest independent method claim |
| 5 |
Pembrolizumab plus axitinib |
Direct product-specific dependent claim |
| 12 |
Pembrolizumab and axitinib at specified doses |
Core dose-regimen claim |
| 14 |
Claim 12 limited to renal cell carcinoma |
RCC regimen coverage |
| 15 |
Claim 12 with pembrolizumab 200 mg Q3W |
Matches current standard dosing |
| 18 |
Axitinib 5 mg BID plus pembrolizumab 200 mg Q3W |
Most important marketed regimen claim |
| 24 |
Pembrolizumab plus axitinib for RCC |
Broad RCC claim |
| 25 |
Pembrolizumab plus axitinib for advanced RCC |
Direct FDA-label indication coverage |
| 6 |
Two-container combination kit |
Product-packaging and instruction coverage |
| 9 |
Liquid pembrolizumab plus 1 mg or 5 mg axitinib tablets |
Matches commercial dosage forms |
| 22-23 |
Kit with 1 mg or 5 mg axitinib tablets |
More specific kit claims |
What formulations and kits are protected?
Claims 6 through 9 and 13, 22 and 23 cover coordinated kits rather than ordinary independent sales of the two drugs.
The kit claims require:
- A first container containing a PD-1 antagonist medicament.
- A second container containing a VEGFR inhibitor medicament.
- A package insert with treatment instructions.
- The specified pembrolizumab antibody and axitinib.
- In certain claims, liquid pembrolizumab and axitinib tablets.
Claim 9 corresponds closely to the commercial dosage forms:
- Pembrolizumab as a liquid medicament.
- Axitinib as a 1 mg or 5 mg tablet.
Claims 22 and 23 separate the 1 mg and 5 mg tablet alternatives.
A manufacturer selling pembrolizumab and axitinib as separate products would not necessarily practice the kit claims. The kit claims require the specified containers and package insert. A coordinated co-pack, branded regimen package, or combination-support package is more likely to implicate these claims than ordinary separate distribution.
When does US Patent 10,570,202 expire?
The patent was granted on February 25, 2020. The relevant patent term is generally measured from the applicable nonprovisional or international filing date, subject to patent-term adjustment, terminal disclaimers and any other statutory adjustments.
Public patent records identify the patent as originating from a 2014 priority filing. On that basis, the unadjusted patent term is expected to extend into 2035. The precise enforceable expiration date must be taken from the USPTO patent-term calculation, including any patent-term adjustment.
| Event |
Date or status |
| Earliest priority period |
2014 |
| US patent grant |
February 25, 2020 |
| Patent number |
US 10,570,202 |
| Expected ordinary term |
Into 2035, subject to USPTO adjustment |
| Patent type |
Combination method, dosing regimen and kit patent |
| Patent term extension relevance |
No basis is established here for a separate Hatch-Waxman patent-term extension |
The patent should be distinguished from the basic composition patents for pembrolizumab and axitinib. Those patents have separate expiration dates and do not automatically determine the expiration of the combination patent.
What is the FDA and Orange Book status of the patent?
The FDA approved Keytruda in combination with Inlyta for patients with advanced renal cell carcinoma in April 2019. The approval was based principally on the KEYNOTE-426 study, which evaluated pembrolizumab plus axitinib against sunitinib in previously untreated advanced RCC patients.[1]
The FDA-approved regimen is:
- Pembrolizumab 200 mg intravenously every three weeks.
- Axitinib 5 mg orally twice daily.
The patent claims closely track this FDA-approved use, particularly claims 18, 24 and 25.
A patent’s Orange Book status is separate from its validity and infringement scope. The FDA Orange Book lists patents submitted by an NDA holder for an approved drug and does not adjudicate whether a patent is valid or infringed. A method-of-use patent may be listed against a drug if it meets the statutory listing requirements, but listing does not create a presumption that every use of the drug infringes.
For a generic axitinib applicant, the commercial significance depends on:
- Whether US 10,570,202 is listed for the relevant NDA.
- Whether the applicant’s proposed label includes the patented pembrolizumab combination.
- Whether the applicant uses a section viii statement to carve out a patented method of use.
- Whether the applicant makes statements or distributes materials that support combination use.
What Paragraph IV challenges and generic-entry risks exist?
US 10,570,202 is not a composition-of-matter patent covering axitinib or pembrolizumab individually. Its principal risk is therefore label and conduct based.
Axitinib ANDA risk
An ANDA applicant seeking approval for generic axitinib could attempt to omit the pembrolizumab combination indication from its label. A successful section viii carve-out would reduce direct infringement risk for the patented method claims.
The risk increases if the generic applicant:
- Includes the pembrolizumab combination in its proposed labeling.
- Promotes axitinib for use with pembrolizumab.
- Provides dosing materials that reproduce the patented regimen.
- Supplies a coordinated kit.
- Relies on instructions that induce physicians to practice claims 18, 24 or 25.
A generic axitinib approval would not, by itself, authorize the generic company to market the patented combination method.
Pembrolizumab biosimilar risk
Pembrolizumab is a biologic. A biosimilar applicant would use the Biologics Price Competition and Innovation Act pathway rather than an ANDA. The combination patent could be relevant if the biosimilar label includes:
- Pembrolizumab plus axitinib for advanced RCC.
- The 200 mg Q3W pembrolizumab regimen.
- Combination-use instructions or promotional materials.
The patent does not prevent a biosimilar applicant from seeking approval for pembrolizumab alone. It creates a separate method-of-use issue for the covered combination.
Which companies compete with the Keytruda-Inlyta regimen?
The principal competitive products in first-line advanced RCC include:
| Regimen |
Companies |
Competitive position |
| Pembrolizumab plus axitinib |
Merck and Pfizer |
FDA-approved first-line RCC regimen |
| Nivolumab plus cabozantinib |
Bristol Myers Squibb and Exelixis |
Competing PD-1 plus tyrosine kinase inhibitor regimen |
| Pembrolizumab plus lenvatinib |
Merck and Eisai |
Competing PD-1 plus VEGFR-targeted regimen |
| Nivolumab plus ipilimumab |
Bristol Myers Squibb |
Dual immune-checkpoint regimen |
| VEGFR-targeted monotherapy |
Multiple sponsors |
Later-line or alternative treatment option |
The key competitive distinction is that US 10,570,202 is combination-specific. It does not cover competing regimens using nivolumab, cabozantinib, lenvatinib or ipilimumab unless those products somehow satisfy the issued claim limitations. They generally do not.
How strong is the patent estate?
Strengths
- Claims 24 and 25 directly cover pembrolizumab plus axitinib for RCC and advanced RCC.
- Claim 18 matches the commercially important 200 mg Q3W and 5 mg BID regimen.
- The antibody is identified by sequence-defined limitations, reducing ambiguity over the PD-1 component.
- Kit claims cover coordinated packaging and instructions.
- The claims are aligned with the FDA-approved combination indication.
Vulnerabilities
- The claims are method and kit claims, not basic composition claims.
- A generic applicant may pursue a non-infringing label that omits the patented combination.
- Claim 1's broad cancer language is narrowed by the specific antibody and axitinib limitations.
- The kit claims require specific physical and instructional elements that ordinary commercial distribution may not include.
- Validity challenges could focus on written description, enablement, obviousness, anticipation and whether the claimed combination and dosing schedules were adequately supported by the priority disclosure.
The most defensible commercial position is likely against an actor that markets pembrolizumab and axitinib together for advanced RCC using the FDA-approved dosing regimen. The position is weaker against a company selling either drug independently with a carved-out label.
What litigation and settlement issues affect the patent?
The principal litigation exposure would arise from:
- An axitinib ANDA containing a Paragraph IV certification to an Orange Book listing.
- A pembrolizumab biosimilar notice and patent-exchange process.
- Promotional conduct supporting the patented combination.
- A co-pack or combination kit that satisfies claims 6 through 9.
- A competing RCC regimen that uses the same claimed products and dosing.
A Paragraph IV certification could trigger Hatch-Waxman litigation if the patent is properly listed and the NDA holder brings suit within the statutory period. The resulting litigation would concern both patent validity and infringement. A section viii carve-out would shift the dispute toward whether the generic company’s actual label, marketing and conduct induce the claimed combination use.
No settlement terms should be inferred from the existence of the patent. A settlement could include a delayed-entry date, label carve-out, license, covenant not to sue or restrictions on promotional materials. Those terms require a specific public agreement or court filing.
What geographic coverage does the patent provide?
US Patent 10,570,202 provides rights only in the United States. Parallel patent families may protect the pembrolizumab-axitinib combination in Europe, Japan, China, Canada and other jurisdictions, but foreign claims, prosecution outcomes and expiration dates must be assessed separately.
A US patent can be infringed by:
- Treatment administered in the United States.
- Sale or offer for sale of a covered kit in the United States.
- Importation of a product or kit that practices an issued claim.
- Inducing US physicians or patients to practice the claimed method.
It does not directly control treatment performed entirely outside the United States.
Key Takeaways
- US 10,570,202 is a combination patent for pembrolizumab plus axitinib.
- Claims 24 and 25 directly target renal cell carcinoma and advanced renal cell carcinoma.
- Claim 18 covers the commercially important regimen of pembrolizumab 200 mg every three weeks plus axitinib 5 mg twice daily.
- Claims 6 through 9 and 22 through 23 cover coordinated kits, liquid pembrolizumab and 1 mg or 5 mg axitinib tablets.
- The patent is expected to remain relevant into 2035, subject to the official USPTO term calculation.
- The patent does not block pembrolizumab or axitinib monotherapy.
- Generic axitinib risk depends heavily on labeling, promotional conduct and any section viii carve-out.
- Pembrolizumab biosimilar applicants face a separate method-of-use issue if their label includes the axitinib combination.
- The strongest infringement case involves marketing the FDA-approved Keytruda-Inlyta regimen for advanced RCC.
- Competing regimens using nivolumab, cabozantinib, lenvatinib or ipilimumab generally fall outside the literal product limitations.
FAQs
Does US 10,570,202 cover Keytruda by itself?
No. The relevant claims require pembrolizumab together with axitinib. The patent does not independently cover pembrolizumab monotherapy.
Does the patent cover generic axitinib for all cancer uses?
No. The patent covers specific combination-treatment and kit uses involving pembrolizumab and axitinib. Generic axitinib marketed for non-pembrolizumab uses may not practice the claims.
Is the 200 mg pembrolizumab dose specifically protected?
Yes. Claims 12, 15 and 18 through 21 include pembrolizumab at 200 mg every three weeks. Claim 18 is the most commercially relevant 200 mg/5 mg regimen claim.
Can a generic axitinib company omit the RCC combination indication?
A generic applicant may seek a label that omits a patented method of use, subject to FDA requirements and the applicant’s actual conduct. The omission does not eliminate risk if marketing or instructions still induce the patented combination use.
Does the patent cover pembrolizumab plus lenvatinib?
No. The claims identify axitinib, including its chemical structure. Lenvatinib is a different VEGFR-targeted compound and does not satisfy the axitinib limitation.
References
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U.S. Food and Drug Administration. (2019). FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma. FDA Oncology Center of Excellence.
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U.S. Food and Drug Administration. (2024). Keytruda (pembrolizumab) prescribing information. Merck Sharp & Dohme LLC.
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U.S. Food and Drug Administration. (2024). Inlyta (axitinib) prescribing information. Pfizer Laboratories Div Pfizer Inc.
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U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,570,202, Combination therapy.
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA Center for Drug Evaluation and Research.
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Rini, B. I., Plimack, E. R., Stus, V., Gafanov, R., Hawkins, R., Nosov, D., Pouliot, F., Alekseev, B., Soulières, D., Melichar, B., Vynnychenko, I., Kopyltsov, E., Bondarenko, I., Bykov, V., Staehler, M., Kailing, M., Bair, A. H., Chen, M., Shih, C., ... Powles, T. (2019). Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. New England Journal of Medicine, 380(12), 1116-1127.
