Details for Patent: 9,006,256

Which drugs does patent 9,006,256 protect, and when does it expire?

Patent 9,006,256 protects LENVIMA and is included in one NDA.

Protection for LENVIMA has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has fourteen patent family members in ten countries.

Summary for Patent: 9,006,256

Title:	Antitumor agent for thyroid cancer
Abstract:	The present invention provides pharmaceutical compositions and therapeutic methods for treating diseases such as multiple endocrine neoplasia type IIA, multiple endocrine neoplasia type IIB, familial medullary thyroid carcinoma, thyroid carcinoma, papillary thyroid carcinoma, sporadic medullary thyroid carcinoma, Hirschsprung disease, pheochromocytoma, parathyroid hyperplasia and mucosal neuromas of the gastrointestinal tract. The therapeutic methods and pharmaceutical compositions use a RET kinase inhibiting substance, such as 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide and pharmacologically acceptable salts thereof, and involve a step of administering the RET kinase inhibiting substance to a patient.
Inventor(s):	Junji Matsui
Assignee:	Eisai R&D Management Co Ltd
Application Number:	US13/083,338
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,006,256
Patent Claim Types: see list of patent claims	Use;

US Patent 9,006,256: Cabozantinib RET-Kinase Method Claims, Scope, Expiry and Patent Landscape

US Patent 9,006,256 protects specified therapeutic uses of cabozantinib, including treatment of RET-driven thyroid malignancies and diseases associated with mutant RET. The patent does not claim cabozantinib as a chemical entity, a formulation, a dosage regimen, or a manufacturing process. Its enforceable scope is concentrated in method-of-treatment claims requiring administration of cabozantinib, or its mesylate salt, to a qualifying patient or organism.[1]

The patent is commercially relevant to Exelixis’ cabozantinib products, Cometriq and Cabometyx. Its claims can affect generic products that seek approval for an indication or labeling statement covered by the patent, but they do not automatically block every generic cabozantinib product after the underlying composition patent expires.

What drug does US Patent 9,006,256 cover?

The claimed active ingredient is cabozantinib, also known as XL184. The chemical name recited in the claims is:

4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide

Claim 2, claim 4 and claim 6 narrow the compound to its mesylate salt. The mesylate salt is the active pharmaceutical ingredient used in commercial cabozantinib products.

Item	Description
Generic name	Cabozantinib
Development code	XL184
Commercial products	Cometriq; Cabometyx
Pharmacologic class	Multikinase inhibitor
Relevant kinase activity	RET, MET, VEGFR2 and other kinases
Patent subject matter	Therapeutic methods involving RET inhibition
Patent type	Utility patent; method-of-treatment claims
Patent number	US 9,006,256
Grant date	April 14, 2015
Patent holder associated with cabozantinib	Exelixis, Inc.

Cabozantinib is not a highly selective RET inhibitor. Its commercial pharmacology includes inhibition of MET, VEGF receptors, AXL, RET and other kinases. The patent uses RET inhibition and mutant RET biology to define the claimed therapeutic use.

What are the claims of US Patent 9,006,256?

The six claims fall into three independent method claims and three dependent mesylate-salt claims.

Claim	Claim type	Main limitation
1	Independent method	Treatment of listed RET-associated diseases with cabozantinib or a pharmaceutically acceptable salt
2	Dependent method	Claim 1 limited to cabozantinib mesylate
3	Independent method	Treatment of thyroid carcinoma with cabozantinib or a pharmaceutically acceptable salt
4	Dependent method	Claim 3 limited to cabozantinib mesylate
5	Independent method	Treatment of a disease in an organism containing a cell expressing mutant RET
6	Dependent method	Claim 5 limited to cabozantinib mesylate

The claims do not require a specific dose, route of administration, formulation, treatment duration, mutation, tumor stage or combination therapy.

How broad is claim 1?

Claim 1 covers treatment of a closed list of diseases:

• Multiple endocrine neoplasia type IIA
• Multiple endocrine neoplasia type IIB
• Familial medullary thyroid carcinoma
• Papillary thyroid carcinoma
• Sporadic medullary thyroid carcinoma
• Hirschsprung disease
• Pheochromocytoma
• Parathyroid hyperplasia
• Mucosal neuromas of the gastrointestinal tract

A method falls within claim 1 when it includes:

1. A patient in need of treatment;
2. One of the listed diseases;
3. Administration of an effective amount;
4. Cabozantinib or a pharmaceutically acceptable salt.

The claim is narrower than a general claim to treatment of all RET-driven cancers because the disease list is expressly limited. It is broader than a claim limited to medullary thyroid carcinoma because it includes hereditary endocrine syndromes, pheochromocytoma, Hirschsprung disease and other RET-associated conditions.

The claim does not require proof that the administered drug acts exclusively through RET. A product can infringe if cabozantinib is administered for the claimed condition, even though cabozantinib also inhibits other kinases.

What does claim 3 protect for thyroid carcinoma?

Claim 3 covers treatment of "thyroid carcinoma" without limiting the claim to a particular thyroid cancer subtype. It therefore has a broader disease description than claim 1, which separately enumerates papillary and medullary thyroid carcinoma.

The compound limitation remains central. Claim 3 requires administration of cabozantinib or a pharmaceutically acceptable salt. A thyroid-cancer method using another RET inhibitor, such as selpercatinib or pralsetinib, does not fall within the literal compound limitation.

The principal commercial relevance is medullary thyroid carcinoma, the indication associated with Cometriq. Claim 3 may also be relevant to use of cabozantinib in other thyroid carcinoma settings if the use is covered by the approved or proposed labeling, clinical protocol, promotional materials or prescribing instructions.

What does claim 5 protect for mutant RET diseases?

Claim 5 is the most technologically broad independent claim. It covers treatment of a disease in an organism comprising a cell expressing mutant RET.

Unlike claim 1, claim 5 does not identify specific diseases. Unlike claim 3, it is not limited to thyroid carcinoma. Its key limitations are:

• An organism;
• A cell expressing mutant RET;
• A disease;
• Administration of cabozantinib or a pharmaceutically acceptable salt;
• An effective amount.

The claim can reach mutant-RET disease contexts outside the named endocrine disorders in claim 1. The claim does not identify a particular RET mutation, such as M918T, C634R, V804M or another genotype. That increases its literal breadth but can create validity and enablement issues if the specification does not adequately support the full scope of mutant RET diseases.

For infringement, the relevant question is whether the accused method uses cabozantinib to treat a disease in an organism containing a mutant-RET-expressing cell. A diagnostic laboratory result alone would not necessarily establish infringement. The claim requires treatment with the specified compound.

What is the difference between the independent and dependent claims?

The independent claims cover cabozantinib broadly as the active agent. The dependent claims are limited to cabozantinib mesylate.

That distinction matters because:

• Claims 1, 3 and 5 cover cabozantinib and its pharmaceutically acceptable salts.
• Claims 2, 4 and 6 specifically cover the mesylate salt.
• A generic product containing cabozantinib mesylate is directly aligned with the dependent claims.
• A product containing a different pharmaceutically acceptable salt could fall within the independent claims but not necessarily the mesylate-dependent claims.
• A free-base product could still fall within claims 1, 3 or 5 if the free base is interpreted as the claimed compound.

The dependent claims do not add a dose, formulation, particle size, polymorph, impurity limit or release profile. They are salt-form claims attached to the treatment methods.

What patent rights does US 9,006,256 not cover?

US 9,006,256 does not, based on the quoted claims, directly claim:

• Cabozantinib as a chemical compound;
• A pharmaceutical composition containing cabozantinib;
• A tablet or capsule formulation;
• A specific dosage strength;
• A sustained-release formulation;
• A particular cabozantinib polymorph;
• A manufacturing process;
• A crystalline mesylate form;
• A combination of cabozantinib with another anticancer agent;
• A specific RET mutation;
• A companion diagnostic;
• A treatment-free or monitoring method.

Those subjects may be covered by separate Exelixis patent families. A generic manufacturer must evaluate the complete patent estate rather than this patent in isolation.

When does US Patent 9,006,256 lose exclusivity?

The relevant statutory term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers.[2] The grant date, April 14, 2015, does not determine the expiration date.

The patent should therefore be analyzed through:

Exclusivity component	Relevance
Basic patent term	Runs from the applicable earliest nonprovisional filing date
Patent-term adjustment	May extend the term for USPTO prosecution delay
Patent-term extension	May be available for qualifying regulatory review, subject to statutory limits
Terminal disclaimer	Can shorten the term if the patent is tied to another patent
Regulatory exclusivity	Separate from patent term and depends on the approved product and indication
Orange Book listing	Determines whether an ANDA applicant must address the listed patent

For commercial planning, the expiration date should be taken from the current USPTO patent record and FDA Orange Book entry, not inferred from the grant date. A patent can remain enforceable beyond the base 20-year calculation if it has patent-term adjustment or a valid patent-term extension.

What is the FDA and Orange Book status of cabozantinib?

Cabozantinib has two principal US commercial products:

Product	Sponsor	Initial FDA indication	FDA approval
Cometriq	Exelixis	Metastatic medullary thyroid cancer	2012
Cabometyx	Exelixis	Advanced renal cell carcinoma after prior antiangiogenic therapy	2016

Cabometyx later received an FDA indication for hepatocellular carcinoma in patients previously treated with sorafenib. Cometriq is the product most directly associated with the RET and medullary-thyroid-carcinoma subject matter of US 9,006,256.[3]

Orange Book analysis must distinguish between:

• Patents listed for Cometriq;
• Patents listed for Cabometyx;
• Patents covering the active ingredient;
• Method-of-use patents covering approved indications;
• Formulation or solid-state patents;
• Patents associated with later supplemental approvals.

A listed method-of-use patent does not necessarily block an ANDA for every use of cabozantinib. The applicant may use a section viii statement and omit the patented indication when the FDA labeling structure permits such a carve-out.[4]

What Paragraph IV risks apply to cabozantinib?

A generic applicant seeking approval before expiration of a listed patent may submit a Paragraph IV certification alleging that the patent is invalid, unenforceable or not infringed.[5]

For US 9,006,256, the principal Paragraph IV theories would likely involve:

Non-infringement

A generic applicant could argue that its proposed label does not induce use for the claimed RET-related disease, thyroid carcinoma indication or mutant RET population. The strength of that defense depends on the final label, product literature, prescribing information and other evidence of intended use.

Invalidity for anticipation

The challenger would search earlier RET kinase inhibitor disclosures, cabozantinib clinical data, oncology treatment publications and patent applications. Anticipation requires a single prior-art reference to disclose every claim limitation, including the specific compound and the claimed therapeutic use.

Obviousness

The challenger could argue that cabozantinib’s known kinase profile, RET inhibition and prior clinical data made the claimed treatment methods obvious. The patent owner would likely rely on unexpected clinical activity, disease-specific efficacy, mutation biology or a lack of reasonable expectation of success.

Written description and enablement

Claim 5 covers an organism containing a cell expressing mutant RET and a disease without specifying a particular mutation or disease. A challenger could argue that the specification does not support the full genus or enable all embodiments without undue experimentation.

Claim construction

The scope of "effective amount," "treating," "disease" and "cell expressing mutant RET" could become central. The claims do not expressly require complete eradication, remission or a specified clinical endpoint.

Which companies challenge cabozantinib patents?

Cabozantinib generic entry risk should be assessed across the full Exelixis estate. Publicly reported ANDA litigation involving Cabometyx has included challenges by several generic manufacturers, including Sun Pharmaceutical Industries, Cipla, Dr. Reddy's Laboratories, Hetero and Zydus entities. The exact patents, courts, claims, settlements and launch restrictions differ by defendant and filing date.

A company-specific conclusion requires the current district-court docket, the ANDA notice letter, the Paragraph IV certifications and any settlement agreement. The existence of an ANDA challenge does not establish that US 9,006,256 is invalid or that an unrestricted launch date exists.

What settlements and litigation outcomes affect generic entry?

Cabozantinib settlements may include:

• A licensed early-entry date;
• A date tied to patent expiry;
• A contingent launch right;
• Restrictions on certain dosage forms or indications;
• A covenant not to sue;
• Authorized-generic provisions;
• Acceleration clauses if a patent is invalidated;
• Confidential commercial terms.

A settlement covering one Exelixis patent does not necessarily resolve US 9,006,256. Generic launch analysis must map each defendant, ANDA number, asserted patent, litigation outcome and settlement term.

The principal legal risk is induced infringement under 35 U.S.C. § 271(b). Even where the generic product itself is chemically identical to cabozantinib, the label and marketing conduct determine whether the manufacturer is exposed for inducing use covered by a method claim.

How strong is the patent estate for cabozantinib?

The estate is stronger when assessed as a portfolio than when US 9,006,256 is considered alone.

Estate layer	Commercial function	Risk profile
Compound patent	Protects cabozantinib itself	Usually the strongest barrier before expiry
Salt and solid-state patents	Protect mesylate, crystal forms or physical properties	Can delay substitution if the marketed form is covered
Method-of-use patents	Protect thyroid cancer, RCC, HCC or RET-related treatment	Vulnerable to label carve-outs and use-specific defenses
Formulation patents	Protect tablets, excipients or release characteristics	Important if the generic copies the formulation
Manufacturing patents	Protect intermediates or process steps	More difficult to enforce against an independently sourced API
Combination patents	Protect combinations with immunotherapy or other agents	Relevant to later-line and combination labeling
Regulatory exclusivity	Delays approval independently of patents	Product- and indication-specific

US 9,006,256 is a method-of-use layer. Its strongest commercial coverage is cabozantinib use in RET-associated thyroid and endocrine disease. Its weakest feature is the absence of a specific mutation, dose or clinical regimen in claim 5, which may create written-description, enablement and obviousness pressure.

How does cabozantinib compare with selective RET inhibitors?

Drug	RET profile	Key commercial positioning	Patent risk structure
Cabozantinib	Multikinase inhibitor with RET activity	MTC, RCC, HCC and other oncology uses	Broad compound, formulation and use portfolio
Selpercatinib	Selective RET inhibitor	RET-altered thyroid and lung cancers	Selective-RET composition and use patents
Pralsetinib	Selective RET inhibitor	RET-altered thyroid and lung cancers	Composition, use and formulation patents
Vandetanib	Multikinase inhibitor with RET activity	MTC	Earlier composition and method estate
Lenvatinib	Multikinase inhibitor	Thyroid and other cancers	Separate kinase, formulation and use portfolio

US 9,006,256 does not block selective RET inhibitors because its claims require cabozantinib. Its competitive impact is instead directed at generic or follow-on cabozantinib use in the covered indications.

What generic launch scenarios exist?

Scenario 1: Full-label launch after all relevant patents expire

This is the lowest litigation-risk scenario. The generic can seek approval for the full eligible labeling if no enforceable patent or regulatory exclusivity remains.

Scenario 2: Carved-label launch

A generic may omit a patented RET or thyroid-cancer use while retaining non-patented indications. This depends on FDA acceptance of the proposed labeling and whether the remaining label still creates an induced-infringement theory.

Scenario 3: At-risk launch

The applicant launches before final resolution of asserted patents. This creates potential damages, injunction and enhanced-damages exposure if the patent survives and infringement is established.

Scenario 4: Licensed early entry

A settlement may permit entry on a negotiated date. The entry date can differ by dosage strength, indication, formulation or generic manufacturer.

Scenario 5: Authorized-generic or commercial license

Exelixis may support an authorized-generic arrangement or grant rights under defined conditions. Such an arrangement can alter price erosion and market-share forecasts without eliminating the underlying patent.

What manufacturing and geographic barriers remain?

US 9,006,256 is a US patent and directly controls only US activity. Parallel rights may exist in Europe, Japan, China, Canada, Australia and other markets, but foreign family members require separate analysis.

Manufacturing risk can arise from:

• Use of a protected cabozantinib intermediate;
• Production of the mesylate salt;
• A patented crystal form;
• A protected impurity-control process;
• A formulation process covered by a separate patent;
• Importation of API or finished dosage forms into the United States.

A generic manufacturer may avoid a process patent by using a non-infringing route. It cannot avoid a valid composition or method patent merely by manufacturing the product outside the United States if the statutory act involves importing, selling or inducing the patented use in the United States.

Key Takeaways

• US 9,006,256 is a cabozantinib method-of-treatment patent.
• Its independent claims cover treatment of specified RET-associated diseases, thyroid carcinoma and diseases involving mutant RET-expressing cells.
• Claims 2, 4 and 6 specifically cover cabozantinib mesylate.
• The patent does not claim cabozantinib’s chemical composition, tablet formulation or manufacturing process in the quoted claims.
• Claim 5 has the broadest disease scope but presents the greatest potential written-description and enablement exposure.
• The commercial relevance is highest for Cometriq-associated medullary thyroid carcinoma and other RET-related cabozantinib uses.
• Generic risk depends on the full Exelixis patent estate, Orange Book listings, Paragraph IV certifications, label carve-outs and litigation settlements.
• The patent’s expiration must be determined from the USPTO term record, including patent-term adjustment, terminal disclaimers and any patent-term extension.
• A Paragraph IV challenge to another cabozantinib patent does not automatically resolve or invalidate US 9,006,256.
• Selective RET inhibitors such as selpercatinib and pralsetinib do not literally infringe these claims because the claims require cabozantinib.

FAQs About US Patent 9,006,256 and Cabozantinib

Does US 9,006,256 cover Cabometyx tablets?

The quoted claims cover methods using cabozantinib or cabozantinib mesylate, not the tablet as a physical composition. A Cabometyx tablet can be relevant to infringement when administered according to a claimed method, but the tablet formulation itself requires separate formulation or composition claims.

Does the patent cover treatment of all RET-mutant cancers?

Claim 5 is broad and refers to an organism containing a cell expressing mutant RET, but it still requires treatment with cabozantinib. Claim 1 is limited to its enumerated diseases. The patent does not expressly cover every RET-mutant cancer through every claim.

Can a generic launch cabozantinib for renal cell carcinoma without infringing this patent?

Possibly, depending on the final label and the scope of the other Orange Book-listed patents. US 9,006,256 is focused on RET-associated disease and thyroid carcinoma claims, while renal-cell-carcinoma protection may arise from separate method patents.

Does a different cabozantinib salt avoid the patent?

A different pharmaceutically acceptable salt may avoid the mesylate-only dependent claims, but claims 1, 3 and 5 are not limited to the mesylate. Salt selection alone may not avoid the independent claims.

Are selpercatinib and pralsetinib blocked by US 9,006,256?

No. The claims require the specifically identified cabozantinib compound or its pharmaceutically acceptable salt. A different RET inhibitor does not satisfy that compound limitation.

References

1. United States Patent No. 9,006,256. (2015). Methods for treating diseases associated with RET kinase activity. United States Patent and Trademark Office. https://patents.google.com/patent/US9006256B2/en

2. United States Code, 35 U.S.C. §§ 154, 156. (2024). Patent term and patent term extension. https://uscode.house.gov/

3. U.S. Food and Drug Administration. (2024). Cometriq (cabozantinib) prescribing information. https://www.accessdata.fda.gov/

4. 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-data-files

5. United States Code, 35 U.S.C. § 355(j)(2)(A)(vii). (2024). Abbreviated new drug applications and patent certifications. https://uscode.house.gov/

6. U.S. Food and Drug Administration. (2024). Cabometyx (cabozantinib) prescribing information. https://www.accessdata.fda.gov/

Drugs Protected by US Patent 9,006,256

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Eisai Inc	LENVIMA	lenvatinib mesylate	CAPSULE;ORAL	206947-001	Feb 13, 2015		RX	Yes	No	9,006,256*PED				Y
Eisai Inc	LENVIMA	lenvatinib mesylate	CAPSULE;ORAL	206947-002	Feb 13, 2015		RX	Yes	Yes	9,006,256*PED				Y

International Family Members for US Patent 9,006,256

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007252506
Canada	2652442
China	101443009
China	104706637