United States Drug Patent 8,618,141: Sorafenib Scope, Claims, Expiry and Patent Landscape

U.S. Patent No. 8,618,141 covers methods of using sorafenib, including sorafenib tosylate, to block tumor angiogenesis in specified solid tumors. The claims focus on renal, breast, gastrointestinal, ovarian and cervical tumors, with narrower limitations directed to VEGFR-2/KDR-mediated angiogenesis, non-RAF and non-p38 mechanisms, combination therapy and a 0.01-200 mg/kg dose range. The patent does not broadly claim sorafenib as a chemical compound.

What drug does U.S. Patent 8,618,141 protect?

The claimed active ingredient is sorafenib, chemically identified as:

N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea.

Sorafenib is marketed as sorafenib tosylate under the brand Nexavar by Bayer and Onyx Pharmaceuticals, now part of Bayer and Amgen-related historical commercial structures. Nexavar tablets contain sorafenib tosylate, equivalent to 200 mg of sorafenib per tablet. FDA approved Nexavar for unresectable hepatocellular carcinoma, advanced renal cell carcinoma and radioactive iodine-refractory differentiated thyroid cancer, while the claims of Patent 8,618,141 identify a different and broader group of tumor sites, including kidney, breast, gastrointestinal, ovarian and cervical tumors. [1]

The patent therefore protects selected therapeutic uses rather than the molecule itself.

What are the independent claims in Patent 8,618,141?

Claims 1, 6 and 7 are the principal independent claims.

Claim	Core subject matter	Key limitations
1	Angiogenesis inhibition	Sorafenib or a pharmaceutically acceptable salt; human or other mammal; breast, gastrointestinal, kidney, ovarian or cervical tumor
6	Angiogenesis inhibition using tosylate	Sorafenib tosylate; same tumor categories
7	Kidney-tumor treatment	Sorafenib tosylate; renal tumor; blocking angiogenesis

Claim 1 is the broadest independent claim in the set because it covers sorafenib or a pharmaceutically acceptable salt. Claim 6 narrows the salt form to sorafenib tosylate. Claim 7 narrows the disease setting further to kidney tumors.

The claims use the transitional term “comprising.” That language generally permits the presence of additional treatment steps, agents, excipients or therapies, provided the claimed elements are present.

How broad is the scope of claim 1?

Claim 1 requires proof of five principal elements:

Administration to a human or another mammal.
Treatment of a tumor.
The tumor must be located in the breast, gastrointestinal tract, kidney, ovary or cervix.
The administered compound must be sorafenib or a pharmaceutically acceptable salt.
The amount must be effective to block tumor angiogenesis.

The claim does not require:

A particular route of administration.
A specific tablet, capsule or injectable formulation.
A particular dosing schedule.
A specified tumor stage.
A requirement that the tumor be VEGFR-2 positive.
A requirement that the tumor be refractory to another therapy.
A requirement that the treatment produce a specified response rate.

The absence of a route or dosage limitation gives claim 1 substantial breadth within the listed tumor sites. The tumor-site limitation, however, prevents the claim from covering every possible cancer. A use in hepatocellular carcinoma, thyroid cancer or another unlisted malignancy would not literally satisfy the express site limitation unless the tumor also falls within the claimed gastrointestinal category under the relevant claim construction.

What limitations do claims 2 through 5 add?

Claim 2: Combination angiogenesis therapy

Claim 2 covers simultaneous administration of sorafenib with another angiogenesis-inhibiting agent. The agents may be provided:

In the same formulation; or
In separate formulations.

The claim is directed to combination treatment and does not identify the second angiogenesis inhibitor by name. A competing product could face risk if its labeling or clinical use instructs combination administration of sorafenib with another agent that inhibits angiogenesis.

The word “simultaneously” creates a timing limitation. Sequential administration separated by a meaningful interval may fall outside the literal scope, although the practical interpretation would depend on the treatment protocol and infringement evidence.

Claim 3: KDR or VEGFR-2-mediated disease

Claim 3 requires a tumor characterized by abnormal angiogenesis or hyperpermeability mediated by KDR, also known as VEGFR-2. This is a mechanism-based limitation. It can narrow infringement disputes to evidence concerning:

VEGFR-2 expression or activation;
VEGF signaling;
Tumor vascular permeability; and
The relationship between the mechanism and the treated tumor.

The claim does not require a particular diagnostic test, biomarker threshold or laboratory method.

Claims 4 and 5: Non-RAF and non-p38 disease

Claim 4 requires angiogenesis or hyperpermeability processes that are not RAF-mediated. Claim 5 adds the requirement that the processes are also not p38-mediated.

These negative limitations are legally significant. A party asserting infringement would need to establish that the relevant process is not mediated by RAF, and for claim 5, not mediated by p38. The limitations may create evidentiary challenges because angiogenesis can involve overlapping signaling pathways. The claims do not require that sorafenib have no RAF or p38 activity in all biological contexts. They address the mechanism characterizing the treated tumor process.

What does the sorafenib tosylate claim cover?

Claim 6 covers the use of sorafenib tosylate in breast, gastrointestinal, kidney, ovarian or cervical tumors. Claim 7 is narrower and covers kidney tumors only.

The distinction between claims 1 and 6 is important:

Claim 1 covers sorafenib and pharmaceutically acceptable salts.
Claim 6 expressly requires the tosylate salt.
Claim 7 requires the tosylate salt and a kidney tumor.

A generic sponsor selling sorafenib tosylate tablets would not automatically infringe these method claims merely by manufacturing or selling the product. Risk depends on the intended use, product labeling, prescribing instructions, promotional conduct and any applicable induced-infringement theory.

What dosing range is protected?

Claims 10 and 11 specify an effective amount of 0.01 to 200 mg/kg of total body weight.

Feature	Claimed range
Lower bound	0.01 mg/kg
Upper bound	200 mg/kg
Unit	mg/kg of total body weight
Applicable compound	Sorafenib tosylate
Claim context	Claims 6 and 7

The range is very broad compared with standard adult Nexavar dosing. The labeled Nexavar regimen is generally 400 mg twice daily, equivalent to approximately 800 mg per day. For a 70 kg adult, that is roughly 11.4 mg/kg/day, before accounting for dosing modifications. [1]

A dose below 0.01 mg/kg or above 200 mg/kg would fall outside the literal numerical range, subject to applicable claim-construction and equivalents analysis. The claim does not specify whether the range is per administration, per day or over another dosing period. That ambiguity could become material in litigation.

What is the FDA and Orange Book status?

Nexavar is FDA-approved under NDA 021923. FDA-approved uses include:

Unresectable hepatocellular carcinoma;
Advanced renal cell carcinoma; and
Locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer. [1]

Patent 8,618,141 should not be treated as synonymous with the entire Nexavar Orange Book estate. Orange Book listing is tied to patents submitted for an approved drug and its approved uses. A method-of-use patent may be listed if it meets FDA listing requirements, but issuance alone does not establish Orange Book listing. [2]

The patent’s claimed tumor categories overlap most directly with renal cancer, but the claim language also reaches breast, gastrointestinal, ovarian and cervical tumors. Its method claims are broader in disease-site coverage than the original FDA-approved label, while the approved indication for renal cell carcinoma provides the clearest commercial overlap.

When does Patent 8,618,141 lose exclusivity?

Patent term cannot be determined from the issued patent number alone. The controlling calculation depends on the earliest effective nonprovisional priority date, patent-term adjustment, patent-term extension, terminal disclaimers and any applicable disclaimer or reexamination history. The patent issued on December 31, 2013. [3]

The relevant commercial analysis is:

Exclusivity component	Relevance to sorafenib
Compound patent	Protects sorafenib itself and may have expired earlier
Use patent 8,618,141	Protects specified angiogenesis-treatment methods
FDA regulatory exclusivity	Separate from patent term
Orange Book listings	Can support Paragraph IV litigation
Label carve-outs	May reduce use-code exposure for generics

The base patent term for modern U.S. patents is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments. [4] Patent 8,618,141 should therefore be evaluated as one layer in a patent family rather than as the sole expiry date controlling generic entry.

What Paragraph IV and generic-entry risks exist?

A generic applicant seeking approval for sorafenib tosylate can challenge listed patents through an Abbreviated New Drug Application and a Paragraph IV certification. The applicant may assert that a listed patent is:

Invalid;
Unenforceable; or
Not infringed.

For this patent, common noninfringement theories would include:

The proposed label does not direct treatment of the claimed tumor sites.
The label omits angiogenesis-blocking language.
The proposed use does not require KDR-mediated angiogenesis.
The method is not limited to a non-RAF or non-p38 process.
The proposed regimen falls outside the claimed dose range.
The product label uses a permitted skinny-label carve-out.

Invalidity theories could include anticipation, obviousness, written-description deficiencies, enablement and indefiniteness, depending on the asserted claim and prosecution history. The genus-like tumor-site language and mechanism-based limitations would be central to claim construction and validity analysis.

How strong is the patent estate for sorafenib?

The estate has several distinct layers:

Estate layer	Protection target	Business significance
Composition patents	Sorafenib molecule and salts	Core chemical exclusivity
Formulation patents	Tablets, solid forms, excipients or release characteristics	Product-specific barriers
Method-of-use patents	Angiogenesis, tumor types and signaling pathways	Label and prescribing risk
Combination patents	Sorafenib with angiogenesis inhibitors or anticancer agents	Combination regimens
Manufacturing patents	Synthesis, intermediates and purification	API supply and process risk
Regulatory exclusivity	NDA-specific approval rights	Separate from patent rights

Patent 8,618,141 is strongest when the accused conduct involves sorafenib tosylate, renal tumors, angiogenesis inhibition and a label that directs the claimed use. It is weaker against a generic label that omits the covered uses and against off-label use lacking evidence of inducement.

What licensing and litigation issues matter?

Sorafenib was developed through Bayer’s research program and commercialized through the Bayer-Onyx collaboration. Commercial rights, development obligations and regional arrangements have changed over time and should be separated from patent ownership. A license to commercialize Nexavar does not necessarily transfer ownership of every patent family member.

The material litigation questions are:

Whether Patent 8,618,141 was listed for the relevant NDA;
Whether an ANDA applicant certified Paragraph IV against it;
Whether the sponsor accepted a section viii carve-out;
Whether litigation triggered a 30-month stay;
Whether any settlement restricted generic launch; and
Whether later agreements preserved authorized-generic or licensee entry rights.

The patent number alone does not establish a Paragraph IV case, a settlement or a current injunction. Those events must be tied to a specific ANDA, district-court docket and FDA regulatory record.

How does Patent 8,618,141 compare with competing drug patents?

Drug	Primary target profile	Patent-risk distinction
Sorafenib	RAF, VEGFR and other kinases	This patent focuses on angiogenesis and selected tumor sites
Sunitinib	VEGFR, PDGFR and related kinases	Separate composition, formulation and use estates
Pazopanib	VEGFR, PDGFR, FGFR	Different chemical and label-specific patent barriers
Axitinib	Primarily VEGFR inhibition	Narrower targeted mechanism and separate use claims
Lenvatinib	VEGFR, FGFR and related kinases	Later-generation composition and method patents
Cabozantinib	MET, VEGFR and other kinases	Distinct composition, combination and use estate

Patent 8,618,141 does not block competitors from selling other VEGFR inhibitors. It also does not generally block treatment of the same tumors with a different kinase inhibitor. Its practical value depends on whether generic sorafenib use can be separated from the claimed angiogenesis indications.

Key Takeaways

U.S. Patent 8,618,141 is a method-of-use patent for sorafenib and sorafenib tosylate.
The core claims cover angiogenesis inhibition in breast, gastrointestinal, kidney, ovarian and cervical tumors.
Claims 3 through 5 add KDR/VEGFR-2, non-RAF and non-p38 mechanism limitations.
Claims 7 through 11 concentrate on sorafenib tosylate treatment of kidney tumors and a 0.01-200 mg/kg dose range.
The patent does not broadly claim sorafenib as a chemical compound.
FDA approval of Nexavar does not, by itself, establish that every claim in the patent is an Orange Book-listed barrier.
Generic risk depends on the ANDA label, use-code scope, Paragraph IV certification and inducement evidence.
The patent should be assessed alongside sorafenib composition, formulation, manufacturing and other method-of-use patents.
The renal-cell-carcinoma claims present the closest overlap with the FDA-approved Nexavar market.

FAQs

Does Patent 8,618,141 cover Nexavar tablets?

It covers specified methods of using sorafenib tosylate, the active salt in Nexavar tablets. It does not independently claim the tablet dosage form as a product.

Does the patent cover sorafenib treatment of liver cancer?

The listed claims identify breast, gastrointestinal, kidney, ovarian and cervical tumors. Liver cancer is not expressly listed in the supplied claims.

Can a generic sell sorafenib if this patent remains in force?

Potentially. A generic may seek approval with a label that omits patented uses, subject to FDA rules and litigation risk. Commercial sale alone does not automatically establish infringement of a method claim.

Is sorafenib tosylate different from sorafenib?

Sorafenib is the active molecular moiety. Sorafenib tosylate is its tosylate salt form, used in the marketed product and expressly required by claims 6 through 11.

Does a KDR-positive tumor automatically satisfy claim 3?

No. Claim 3 requires that the abnormal angiogenesis or hyperpermeability process be mediated by KDR/VEGFR-2. A mere finding of KDR expression may not establish that the claimed disease process is KDR-mediated.

References

U.S. Food and Drug Administration. (2024). Nexavar (sorafenib tosylate) prescribing information. https://www.accessdata.fda.gov
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
United States Patent and Trademark Office. (2013). U.S. Patent No. 8,618,141. https://patents.google.com/patent/US8618141
United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section154

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2003209116	⤷ Start Trial
Canada	2475703	⤷ Start Trial
Cyprus	1114314	⤷ Start Trial
Denmark	1478358	⤷ Start Trial
European Patent Office	1478358	⤷ Start Trial
European Patent Office	2324825	⤷ Start Trial
Spain	2425739	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,618,141

Summary for Patent: 8,618,141