US Patent 10,039,757: Cabozantinib Tablet Formulation Claims, Expiration, and Generic Entry Risk

US Patent 10,039,757 protects methods of treating kidney cancer with Cabometyx-type tablets containing cabozantinib L-malate and narrowly defined excipient proportions. The patent does not claim cabozantinib as a molecule. Its commercial significance is concentrated in the tablet formulation used for Cabometyx, particularly the 20 mg, 40 mg, and 60 mg strengths, and in methods of administering that formulation for renal cell carcinoma.

Public patent records identify the relevant compound as cabozantinib, also known as XL184, administered as the L-malate salt. The patent is assigned to Exelixis, Inc. The listed statutory expiration date is August 15, 2032, subject to any applicable patent-term adjustment or regulatory extension recorded by the USPTO or FDA.[1][2]

What drug does US Patent 10,039,757 protect?

US 10,039,757 protects a tablet formulation of cabozantinib L-malate rather than the underlying cabozantinib chemical entity.

Cabozantinib is a tyrosine kinase inhibitor marketed by Exelixis as:

Product	Dosage form	Primary relevant uses	Relevance to US 10,039,757
Cabometyx	Tablet	Renal cell carcinoma and hepatocellular carcinoma	Directly relevant
Cometriq	Capsule	Medullary thyroid cancer	Generally outside the claimed tablet formulation
Generic cabozantinib	Tablet or capsule, depending on product	Subject to FDA approval and patent certifications	Potentially relevant

The claims refer to “Compound I,” but the claim set corresponds to cabozantinib L-malate. The active pharmaceutical ingredient is present at approximately 31.68% by weight in the specific formulation of claims 12 and 16.

The patent covers the product through method-of-treatment claims. It does not use a conventional composition claim stating that “a tablet comprising” the listed ingredients is itself infringed. An accused product must be administered in the claimed treatment context for literal infringement of the issued claims.

What are the issued claims of US 10,039,757?

The 19 claims divide into four principal groups.

Claim group	Scope	Key limitation
Claims 1-6	Broad treatment method	Cabozantinib L-malate tablet with specified excipient ranges
Claims 7-11	Treatment method with coating	Same core formulation plus specified film coating
Claims 12-15	Fixed formulation	Exact approximate composition
Claims 16-19	Granulation-specific formulation	Exact composition with croscarmellose sodium divided between intra-granular and extra-granular portions

Claims 1 and 7 are independent claims. Claims 12 and 16 are also independent claims, although the supplied text appears to omit the structural definition following “wherein Compound I is.” The operative formulation limitations are nevertheless clear from the ingredient and percentage limitations.

Claims 1-6: excipient-range formulation

Claim 1 requires a tablet containing:

Ingredient	Claimed amount
Cabozantinib L-malate	30-32% w/w
Microcrystalline cellulose	38-40% w/w
Lactose	18-22% w/w
Hydroxypropyl cellulose	2-4% w/w
Croscarmellose sodium	4-8% w/w
Colloidal silicon dioxide	0.2-0.6% w/w
Magnesium stearate	0.5-1% w/w

The method must involve administering the tablet to a patient for kidney cancer treatment. Claim 2 narrows lactose to lactose anhydrous. Claims 4 and 5 limit the cabozantinib amount to 20-100 mg or to specified strengths. Claim 6 narrows the disease to renal cell carcinoma.

Claim 1 permits administration “alone or in combination with another therapeutic agent.” A combination regimen therefore does not avoid claim 1 if the administered tablet satisfies the formulation limitations.

Claims 7-11: film-coated tablet

Claim 7 adds a film coating containing:

Hypromellose
Titanium dioxide
Triacetin
Iron oxide yellow

This claim is narrower than claim 1 because it requires the coating in addition to the core formulation. Claims 8-11 add anhydrous lactose, specified dosage strengths, and renal cell carcinoma.

Claims 12-15: fixed composition

Claim 12 recites the following approximate composition:

Ingredient	Amount
Cabozantinib L-malate	31.68%
Microcrystalline cellulose	38.85%
Lactose anhydrous	19.42%
Hydroxypropyl cellulose	3.00%
Croscarmellose sodium	6.00%
Colloidal silicon dioxide	0.30%
Magnesium stearate	0.75%
Total	100.00%

This claim is narrower than claim 1 in ingredient identity and numerical precision, but it may be easier to assert against a product that reproduces the marketed formulation.

Claims 16-19: granulation allocation

Claim 16 recites the same general formulation but separates croscarmellose sodium between processing stages:

Component	Amount
Cabozantinib L-malate	31.68%
Microcrystalline cellulose	38.85%
Lactose anhydrous	19.42%
Hydroxypropyl cellulose	3.00%
Intra-granular subtotal	95.95%
Colloidal silicon dioxide	0.30%
Extra-granular croscarmellose sodium	3.00%
Magnesium stearate	0.75%
Total	100.00%

Claim 16 distinguishes the formulation by manufacturing allocation, not merely by total ingredient content. A generic manufacturer could therefore face infringement exposure even if its final tablet has the same total croscarmellose sodium concentration but uses a different granulation process, depending on the evidence concerning where the excipient is added.

How broad is the patent’s practical infringement scope?

The patent’s practical scope is narrower than its commercial importance suggests.

For literal infringement, an accused product must generally satisfy all limitations of at least one claim. The relevant elements include:

A treatment of kidney cancer.
Administration to a patient.
A tablet pharmaceutical composition.
Cabozantinib L-malate in the claimed range or amount.
The specified excipients in the claimed percentage ranges.
For some claims, anhydrous lactose.
For claims 7-11, the specified film coating.
For claims 16-19, the specified division of croscarmellose sodium.

The claims create several design-around opportunities:

Use a different salt or solid form of cabozantinib.
Change one or more excipient concentrations outside the claimed range.
Replace lactose or use a different lactose form.
Omit or change the claimed film-coating ingredients.
Use a different granulation allocation for croscarmellose sodium.
Market a product for a non-kidney-cancer indication, subject to induced-infringement and labeling considerations.

A formulation that falls outside the literal numerical ranges could still raise arguments under the doctrine of equivalents. The strength of such an argument would depend on prosecution-history estoppel, the importance of the numerical boundaries, and whether the substituted formulation performs substantially the same function in substantially the same way.

What patents protect Cabometyx beyond US 10,039,757?

Cabometyx has a layered patent estate that includes compound, formulation, therapeutic-use, and manufacturing-related rights. The most commercially relevant US patents publicly associated with Cabometyx include the following:

Patent	General subject matter	Reported expiration range
US 8,877,776	Cabozantinib compound and related chemical subject matter	2026
US 9,266,951	Cabozantinib-related chemical or therapeutic claims	2026
US 9,849,149	Cabozantinib formulation or use claims	2030
US 10,039,757	Cabozantinib L-malate tablet formulation and kidney-cancer treatment	2032
US 10,350,209	Additional Cabometyx formulation or use protection	2032
US 10,596,190	Additional formulation, dosing, or treatment protection	2032

Patent scope and expiration dates should be confirmed against the current FDA Orange Book and USPTO records because listed patents can have different terminal disclaimers, patent-term adjustments, and listing descriptions.[2][3]

US 10,039,757 is therefore one component of the estate. A generic applicant may need to address multiple listed patents rather than rely on invalidating or designing around this formulation patent alone.

What is the Orange Book status of US 10,039,757?

US 10,039,757 has been listed in connection with Cabometyx tablets in the FDA Orange Book patent listing framework. The listing is commercially important because an ANDA applicant referencing Cabometyx must certify against listed patents under section 505(j)(2)(A)(vii) of the Federal Food, Drug, and Cosmetic Act.[3][4]

The possible certifications are:

Certification	Effect
Paragraph I	No patent information has been submitted
Paragraph II	Patent has expired
Paragraph III	Applicant will wait until patent expiration
Paragraph IV	Patent is invalid, unenforceable, or will not be infringed
Section viii statement	Applicant excludes a patented method of use from the proposed label

For a formulation patent with treatment-method claims, the relevant strategy may involve a Paragraph IV certification, a section viii carve-out, or both, depending on the Orange Book use code and the proposed generic label.

When does Cabometyx lose exclusivity?

Cabometyx has already lost portions of its exclusivity profile because earlier patents expire before US 10,039,757. The remaining formulation and use patents can delay commercial generic entry beyond the expiration of earlier compound patents.

The principal timeline is:

Date	Event
2012	FDA approval of Cometriq capsules for medullary thyroid cancer
April 2016	FDA approval of Cabometyx tablets for advanced renal cell carcinoma
2018	US 10,039,757 issued
2019	Cabometyx expanded to previously untreated advanced RCC in combination with nivolumab
2021	Cabometyx approved for hepatocellular carcinoma after prior sorafenib
2026	Earlier Cabozantinib patents begin expiring
2030	Additional listed patent protection reaches expiration
August 15, 2032	Publicly reported expiration date for US 10,039,757 and related later Cabometyx patents

The economic distinction is between initial generic eligibility and unrestricted generic entry. A generic may obtain FDA approval before 2032 but remain subject to a court judgment, settlement restriction, pediatric extension, or other patent-related limitation.

Which companies are challenging Cabometyx patents?

Public ANDA litigation and settlement activity has involved multiple generic-drug companies seeking approval for cabozantinib products. The relevant competitive group includes large generic manufacturers and Indian pharmaceutical companies that have filed or pursued ANDAs for cabozantinib tablets.

The litigation risk is distributed across:

Exelixis’ compound patents.
Cabometyx formulation patents.
Method-of-use patents.
Patent listings associated with different strengths and indications.
Settlement agreements that may provide an agreed entry date before patent expiration.

A Paragraph IV notice typically triggers the 45-day period in which the patent holder may file suit. A timely suit can impose a 30-month stay of FDA approval under the Hatch-Waxman framework, subject to statutory exceptions and court action.[4]

Because the claims of US 10,039,757 are formulation-specific, a defendant would likely focus on:

Non-infringement based on excipient percentages.
Non-infringement based on different granulation procedures.
Lack of infringement for a label that excludes kidney-cancer treatment.
Invalidity for anticipation or obviousness based on prior pharmaceutical formulation disclosures.
Written-description or enablement attacks if the challenged claims are construed broadly across the claimed percentage ranges.

How strong is the patent estate for Cabometyx?

The estate is stronger as a portfolio than as a single patent.

US 10,039,757 has several strengths:

It maps closely to the marketed Cabometyx tablet.
Claims cover both broad ranges and fixed formulations.
Dependent claims identify common dosage strengths.
The claims address renal cell carcinoma, the principal historical Cabometyx market.
Claim 16 adds a process-linked formulation distinction involving granulation.

Its limitations are equally material:

The claims are method claims, not broad composition claims.
The excipient ranges are narrow.
A generic may be able to alter excipients without materially changing clinical performance.
The claims do not broadly cover every cabozantinib salt, dosage form, or route.
Some claims are vulnerable to prior-art attacks directed to routine tablet excipients and conventional wet-granulation practice.

The portfolio’s commercial leverage comes from layering. Even if a generic avoids US 10,039,757, it may still confront other listed patents or face induced-infringement allegations based on its prescribing information.

What generic launch scenarios exist?

Three principal launch scenarios are commercially relevant.

Launch after all relevant patents expire

This is the lowest litigation-risk scenario. A generic could launch after the latest enforceable patent barrier, currently associated in public records with the 2032 period.

Litigation settlement with an agreed early-entry date

Exelixis may resolve Paragraph IV disputes through settlements permitting entry before the last patent expiration. The actual entry date, authorized manufacturers, and restrictions depend on each agreement.

At-risk launch after a favorable judgment

A generic may launch before expiration if it obtains a judgment that the asserted patents are invalid or not infringed. Such a launch creates potential damages exposure if the patent holder later prevails.

For revenue modeling, the principal variable is not only the nominal 2032 expiration date. It is the earliest enforceable entry date available to each ANDA filer under its litigation outcome or settlement.

What is the FDA regulatory status of Cabometyx?

The FDA approved Cabometyx tablets for advanced renal cell carcinoma after prior antiangiogenic therapy in 2016. The FDA later approved:

First-line treatment of advanced RCC in combination with nivolumab.
Treatment of hepatocellular carcinoma in patients previously treated with sorafenib.

The claims of US 10,039,757 focus on kidney cancer and renal cell carcinoma. They do not expressly cover the hepatocellular carcinoma indication in the supplied claim set. That distinction may affect Orange Book use codes, section viii labeling strategies, and induced-infringement analysis.[5]

Cabometyx is a small-molecule product. Biosimilar approval under the Public Health Service Act is therefore not applicable. Competitive entry would occur through the ANDA pathway, not through a biosimilar application.

What licensing or collaboration arrangements affect the patent landscape?

Exelixis retains the central US commercial rights to Cabometyx. The product’s development history includes collaboration and licensing arrangements involving cabozantinib development outside the United States, including agreements associated with Ipsen and Takeda for specified territories and indications.[6][7]

Those arrangements affect geographic commercialization and royalty economics, but they do not eliminate Exelixis’ US patent enforcement position for Cabometyx. US generic competition remains governed by Exelixis’ Orange Book listings, ANDA certifications, litigation, and settlement agreements.

Key Takeaways

US 10,039,757 protects cabozantinib L-malate tablet formulations used to treat kidney cancer.
The patent covers excipient percentage ranges, anhydrous lactose, film coating, dosage strengths, and one granulation-specific formulation.
Claims 1 and 7 are broadest in formulation scope; claims 12 and 16 are more precise and commercially product-specific.
The patent does not claim cabozantinib as a molecule.
The publicly reported expiration date is August 15, 2032.
Cabozantinib is a small molecule, so biosimilar risk is not applicable.
Generic competition will proceed through ANDA Paragraph IV litigation, settlements, or post-expiration entry.
US 10,039,757 is part of a broader Cabometyx patent estate that includes earlier compound patents and later formulation or treatment patents.
Design-around opportunities center on excipient percentages, salt form, coating composition, and granulation allocation.
The strongest commercial protection comes from the combined patent portfolio rather than this patent in isolation.

FAQs

Does US 10,039,757 cover Cometriq capsules?

Generally no. The claims require a tablet pharmaceutical composition with the specified cabozantinib L-malate and excipient profile. Cometriq is a different dosage form and formulation.

Can a generic avoid US 10,039,757 by changing the tablet coating?

Potentially, but only if the generic avoids every limitation of the asserted claim. Changing the coating may avoid claims 7-11, but it would not necessarily avoid claims 1-6, 12-15, or 16-19.

Does a 60 mg cabozantinib tablet infringe the patent automatically?

No. The dosage strength is only one claim limitation. The tablet must also satisfy the cabozantinib salt, excipient, percentage, coating, and treatment limitations of an asserted claim.

Can a generic obtain approval for hepatocellular carcinoma while excluding renal cell carcinoma?

A section viii strategy may be possible if the FDA-approved labeling and Orange Book use codes permit a valid carve-out. The method claims and induced-infringement analysis must be evaluated against the proposed label and distribution conduct.

Is US 10,039,757 a biologic patent?

No. Cabozantinib is a chemically synthesized small molecule. The relevant regulatory pathway for generic competition is an ANDA, not a biosimilar application.

References

United States Patent and Trademark Office. (2018). U.S. Patent No. 10,039,757, pharmaceutical compositions and methods of treatment.
United States Patent and Trademark Office. (n.d.). Patent Center: U.S. Patent No. 10,039,757.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
U.S. Food and Drug Administration. (2016-2021). Cabometyx prescribing information and approval history.
Exelixis, Inc. (2023). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934.
Ipsen S.A. (2023). Universal registration document and annual financial report.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-001	Apr 25, 2016	AB	RX	Yes	No	10,039,757	⤷ Start Trial				TREATMENT OF ADVANCED RENAL CELL CARCINOMA	⤷ Start Trial
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-002	Apr 25, 2016	AB	RX	Yes	No	10,039,757	⤷ Start Trial				TREATMENT OF ADVANCED RENAL CELL CARCINOMA	⤷ Start Trial
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-003	Apr 25, 2016	AB	RX	Yes	Yes	10,039,757	⤷ Start Trial				TREATMENT OF ADVANCED RENAL CELL CARCINOMA	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	082252	⤷ Start Trial
Argentina	122724	⤷ Start Trial
Australia	2011278950	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,039,757

Which drugs does patent 10,039,757 protect, and when does it expire?

Summary for Patent: 10,039,757