United States Patent 9,598,376: Scope, Claims, Expiration and Patent Landscape for Binimetinib

US Patent No. 9,598,376 protects selected methods of using crystallized binimetinib, the active ingredient in Mektovi, for treating melanoma and several solid tumors. The strongest commercial claims cover a crystallized binimetinib tablet, including a 15 mg formulation with specified excipients, for BRAF V600- or NRAS-mutant melanoma. The patent does not claim binimetinib as a chemical compound generally, nor does it independently claim the tablet composition or a manufacturing process.

The patent was assigned to Array BioPharma Inc., now part of Pfizer, and was granted March 21, 2017.[1] The Orange Book-listed patent term is reported to extend to June 16, 2030, subject to any applicable patent-term adjustment or regulatory exclusivity.[2]

What drug does US Patent 9,598,376 protect?

US 9,598,376 covers methods using crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide. This compound is binimetinib, also known as MEK162.

Item	Detail
Generic name	Binimetinib
Brand name	Mektovi
Drug class	Mitogen-activated protein kinase kinase 1/2, or MEK1/2, inhibitor
Patent holder/originator	Array BioPharma Inc.; acquired by Pfizer
FDA approval	June 27, 2018
FDA-approved use	With encorafenib for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
Dosage form	Oral tablets
Commercial strength	15 mg
Patent at issue	US 9,598,376
Grant date	March 21, 2017
Reported Orange Book expiration	June 16, 2030

The FDA-approved Mektovi indication is narrower than claim 1 of the patent. The patent claims cover melanoma, pancreatic, ovarian, fallopian tube, peritoneal, biliary, colon and rectal cancers. The approved Mektovi label, by contrast, identifies use with encorafenib in BRAF V600E or V600K-mutant unresectable or metastatic melanoma.[3]

What are the independent and dependent claims in US 9,598,376?

Claim 1 is the principal independent claim. It requires four elements:

A method of treating one of eight specified cancers.
A patient in need of treatment.
Administration to the patient.
A pharmaceutical composition containing crystallized binimetinib and a pharmaceutically acceptable carrier or excipient.

The claim is a method-of-treatment claim, not a product-by-itself claim. A party generally must be shown to practice, induce, or contribute to the claimed treatment method. Merely possessing or selling an unformulated binimetinib molecule does not, by itself, satisfy every limitation of claim 1.

The dependent claims narrow the disease, patient population, dosage form, formulation, and combination regimen.

Claim	Added limitation	Commercial or legal effect
1	Eight listed cancers; crystallized binimetinib composition	Broadest asserted method claim
2	Melanoma	Narrows the disease
3	BRAF V600 or NRAS-mutant melanoma	Defines biomarker-selected melanoma
4	Tablet formulation	Requires tablet dosage form
5	Approximately 15 mg crystallized binimetinib	Tracks the commercial strength
6	Lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium and magnesium stearate	Tracks the marketed tablet excipient system
7	NRAS-mutant melanoma	Narrow biomarker subgroup
8	Additional therapeutic agent	Combination-treatment requirement
9	Chemotherapeutic or anti-tumor agent	Defines the second therapy category
10	Separate administration	Sequential or separately administered combination
11	BRAF V600-mutant melanoma	Biomarker-specific separate administration
12	Simultaneous administration	Concomitant combination
13	Colon cancer	Disease-specific method
14	Ovarian cancer	Disease-specific method

The claim language supplied identifies “approximately 15 mg” rather than an exact 15 mg limitation. That wording can create a scope issue over the acceptable quantitative range. A generic product with a materially different strength, dosage form or excipient profile may avoid claims 4 through 6 while remaining exposed to the broader treatment claims.

How broad is the scope of claim 1?

Claim 1 is materially broader than the commercial Mektovi indication. It is not limited to:

BRAF-mutant disease;
NRAS-mutant disease;
melanoma;
a 15 mg dose;
tablets;
use with encorafenib;
a particular administration schedule; or
the specific excipient combination in claim 6.

A product could therefore fall within claim 1 if it administers crystallized binimetinib in a composition for treating one of the listed cancers, even where the treatment does not use the commercial 15 mg tablet.

The principal narrowing feature is “crystallized” binimetinib. The patent does not merely recite binimetinib in any physical form. A party contesting infringement may examine whether the active pharmaceutical ingredient is the claimed crystalline material, whether the administered composition contains that form, and whether the product documentation induces treatment of a listed cancer.

The claim also requires a pharmaceutical composition with a carrier or excipient. Administration of neat active ingredient, if practically relevant, would raise a claim-construction issue. Commercial oral tablets ordinarily contain excipients and would likely satisfy this limitation.

What formulations are protected by US 9,598,376?

Claims 4 through 6 are directed to the commercial-style tablet formulation.

The narrowest formulation chain requires:

crystallized binimetinib;
a tablet;
approximately 15 mg binimetinib;
lactose monohydrate;
microcrystalline cellulose;
colloidal silicon dioxide;
croscarmellose sodium; and
magnesium stearate.

This formulation coverage is narrower than the treatment coverage in claim 1. A competing manufacturer may avoid claims 4 through 6 by changing one or more of the following:

dose strength;
dosage form;
excipient selection;
excipient concentration;
crystalline form;
product labeling;
indication language.

That design-around analysis would not necessarily avoid claim 1. A different tablet composition containing crystallized binimetinib could still be used in a way that practices claim 1 or another surviving method claim.

The patent does not, based on the quoted claims, independently claim:

a process for producing crystallized binimetinib;
a polymorph as a composition of matter;
a pharmaceutical composition regardless of use;
a method of manufacturing the tablet; or
a specific combination product containing binimetinib and encorafenib.

Those protections may exist in related patents, but they should not be attributed to US 9,598,376 without separate claim support.

What melanoma populations are covered?

Claim 3 covers both BRAF V600-mutant and NRAS-mutant melanoma. Claim 7 narrows the coverage to NRAS-mutant melanoma. Claim 11 covers BRAF V600-mutant melanoma when the additional therapeutic agent is administered separately.

The claim structure creates different risk levels:

Population or regimen	Relevant claim exposure
BRAF V600-mutant melanoma treated with binimetinib alone	Claims 1-6 and potentially 11 if a separately administered agent is used
NRAS-mutant melanoma treated with binimetinib alone	Claims 1-7
Melanoma with an unspecified mutation	Claims 1-2
Melanoma treated with binimetinib plus another anti-tumor agent	Claims 8-12, depending on timing
BRAF V600 melanoma treated with binimetinib and a separately administered agent	Claims 8-11
BRAF V600 melanoma treated with simultaneous combination therapy	Claims 8-9 and 12

The patent’s NRAS coverage is commercially significant because the FDA-approved Mektovi indication is focused on BRAF V600E/K-mutant melanoma in combination with encorafenib, while the patent separately claims NRAS-mutant melanoma. The patent therefore reaches a population outside the principal approved label.

What cancers beyond melanoma are covered?

Claim 1 covers the following non-melanoma indications:

pancreatic cancer;
ovarian cancer;
carcinoma of the fallopian tubes;
peritoneal cancer;
biliary cancer;
colon cancer; and
rectal cancer.

Claims 13 and 14 separately narrow the method to colon cancer and ovarian cancer. These claims could be relevant to off-label use, clinical development, investigator-sponsored trials, combination studies and future label expansion.

The practical enforceability of these claims depends heavily on product labeling and treatment evidence. A generic applicant may seek to omit patented indications from its label through a section viii “skinny label” approach under the Hatch-Waxman Act. That strategy can reduce induced-infringement exposure for carved-out uses, but it does not eliminate risk where the remaining label, promotional activity, clinical materials or standard prescribing practice encourages the patented treatment method.[4]

When does binimetinib lose patent exclusivity?

The reported expiration date for US 9,598,376 is June 16, 2030.[2] The relevant timeline is:

Date	Event
June 16, 2010	Reported earliest relevant priority date for the binimetinib patent family
March 21, 2017	US 9,598,376 granted
June 27, 2018	FDA approved Mektovi with encorafenib for BRAF V600E/K-mutant melanoma
June 16, 2030	Reported expiration date for the Orange Book-listed patent
After June 16, 2030	Generic launch becomes materially less exposed to this patent, subject to other unexpired patents and regulatory exclusivity

The 2030 date is not necessarily the complete US exclusivity endpoint for binimetinib. Related composition, formulation, polymorph, combination or use patents may expire on different dates. A generic launch analysis must review the complete Orange Book listing and any relevant patent-term adjustment, pediatric extension, litigation settlement or later-issued patent.

What is the Orange Book status of US 9,598,376?

US 9,598,376 is listed in FDA Orange Book materials for Mektovi. Its listed use-code coverage is directed to methods involving binimetinib treatment rather than a simple product-by-process claim.[2]

The Orange Book listing matters because it creates the statutory framework for ANDA patent certifications. A generic applicant must address listed patents through:

a Paragraph I certification, where no patent information is listed;
a Paragraph II certification, where the patent has expired;
a Paragraph III certification, accepting delayed approval until expiration; or
a Paragraph IV certification, asserting that the patent is invalid, unenforceable or will not be infringed.

The patent’s method-of-use character may permit a generic applicant to pursue a section viii statement for indications that can be omitted from the proposed labeling. That option is fact-specific and does not automatically remove all Paragraph IV or induced-infringement exposure.

Which companies are challenging the Mektovi patent?

No publicly identified Paragraph IV litigation involving US 9,598,376 is reflected in the FDA patent records and publicly available federal docket sources cited here.[2,5] The absence of an identified case does not establish that no ANDA has been filed or that no confidential notice has been served. FDA approval timing and patent litigation timing can diverge.

Pfizer is the current commercial owner of the Array-originated Mektovi franchise. Array developed binimetinib and entered into a collaboration with Pierre Fabre for development and commercialization in certain territories before Pfizer acquired Array in 2019.[6]

What litigation and settlement issues affect generic entry?

A Paragraph IV dispute over US 9,598,376 would likely focus on four issues:

Whether the accused product contains the claimed crystalline form.
Whether the proposed label induces treatment of a listed cancer.
Whether the product is directed to the claimed biomarker population.
Whether the generic applicant can omit patented indications or combination instructions.

A generic company could pursue several launch positions:

Launch strategy	Main benefit	Main exposure
Wait until patent expiry	Avoids infringement litigation under this patent	Delays market entry
Paragraph III certification	Preserves a defined post-expiration launch	No earlier entry
Paragraph IV challenge	Potential early approval and launch	Invalidity, noninfringement and induced-infringement litigation
Section viii carve-out	Removes selected patented uses from labeling	Remaining label or conduct may still induce infringement
Formulation redesign	May avoid claims 4-6	Broader claim 1 may remain relevant
Non-crystalline API strategy	May avoid the crystallized-form limitation	Must establish physical-form characteristics and regulatory equivalence

The patent’s method claims may be more vulnerable to label-based design-around than a composition-of-matter patent. Its commercial value remains significant because the claims track common clinical uses and the marketed tablet formulation.

How strong is the patent estate for binimetinib?

US 9,598,376 is a meaningful use patent, but it is not equivalent to a foundational chemical patent. Its strength is highest when the accused product:

contains the claimed crystallized binimetinib;
is labeled for melanoma or another listed cancer;
uses the 15 mg tablet;
includes the named excipients; and
promotes use in BRAF V600 or NRAS-mutant melanoma.

Its relative weaknesses are:

the absence of a product-by-itself claim in the quoted claims;
reliance on method-of-treatment proof;
potential section viii label carve-outs;
possible design-around through dosage form, strength or excipient changes;
the need to prove the relevant crystalline form; and
the limited scope of claims 4 through 6 compared with broader treatment claims.

The patent has stronger commercial relevance when combined with unexpired related patents covering binimetinib’s chemical structure, crystalline forms, formulations, combinations or additional approved uses. A single patent should not be treated as the entire Mektovi exclusivity estate.

How does binimetinib compare with competing MEK inhibitors?

Drug	Active ingredient	Principal developer	Key marketed use	Competitive patent issue
Mektovi	Binimetinib	Array/Pfizer	With encorafenib for BRAF V600E/K melanoma	Crystallized-form treatment claims in US 9,598,376
Mekinist	Trametinib	Novartis	With dabrafenib for BRAF V600 melanoma and other indications	Separate compound, formulation and method patent estate
Cotellic	Cobimetinib	Exelixis/Roche	With vemurafenib for BRAF V600-mutant melanoma	Separate MEK inhibitor patent estate
Koselugo	Selumetinib	AstraZeneca	Neurofibromatosis type 1 plexiform neurofibromas	Different indication and regulatory exclusivity profile

Binimetinib competes commercially through the encorafenib-binimetinib combination. The US 9,598,376 claims do not require encorafenib in the quoted language. That distinction gives the patent broader theoretical coverage than the principal FDA-approved combination regimen, while related patents may address the combination specifically.

What generic entry risks exist after patent expiration?

After June 16, 2030, the primary risks shift from US 9,598,376 to:

other Orange Book-listed patents;
later-issued continuation patents;
crystalline-form or polymorph patents;
formulation and tablet-process patents;
combination-use patents;
pediatric exclusivity;
regulatory exclusivity attached to later-approved indications;
manufacturing patents outside the Orange Book; and
induced-infringement theories based on the proposed label.

Binimetinib is a small molecule, so the relevant competitive pathway is an ANDA, not a biosimilar application under the Public Health Service Act. There is no biosimilar risk in the technical sense. The principal post-exclusivity threat is generic substitution.

Key Takeaways

US 9,598,376 is a method-of-treatment patent for crystallized binimetinib.
Claim 1 covers eight cancers and is broader than the current FDA-approved melanoma indication.
Claims 3, 7 and 11 specifically address BRAF V600- and NRAS-mutant melanoma.
Claims 4 through 6 track a 15 mg Mektovi tablet and its named excipients.
The patent does not, based on the quoted claims, independently claim binimetinib as a compound or a manufacturing process.
The reported Orange Book expiration date is June 16, 2030.
A generic applicant may evaluate Paragraph III, Paragraph IV and section viii strategies.
No publicly identified Paragraph IV litigation concerning this patent appears in the cited records.
The full binimetib exclusivity analysis requires review of related patents covering composition, crystalline form, formulation, combinations and additional uses.
Because binimetinib is a small molecule, generic ANDA entry, rather than biosimilar entry, is the relevant competitive pathway.

FAQs About US Patent 9,598,376 and Binimetinib

Does US 9,598,376 cover Mektovi itself?

It covers methods of treating specified cancers using a composition containing crystallized binimetinib. The quoted claims do not independently claim Mektovi as a composition of matter.

Does the patent cover binimetib use with encorafenib?

The quoted claims do not name encorafenib. They cover administration with an additional chemotherapeutic or anti-tumor agent, including separate or simultaneous administration. A separate combination patent may provide more specific encorafenib coverage.

Can a generic avoid US 9,598,376 by using a non-tablet dosage form?

That may avoid claims 4 through 6, which require a tablet and, in claim 5, approximately 15 mg. It would not necessarily avoid claim 1 or claims 2 and 3.

Does the patent cover NRAS-mutant melanoma?

Yes. Claim 3 includes NRAS-mutant melanoma, and claim 7 narrows the method specifically to NRAS-mutant melanoma.

Is binimetinib subject to biosimilar competition?

No. Binimetinib is a chemically synthesized small molecule. Competition would proceed through an ANDA generic pathway rather than a biosimilar application.

References

United States Patent and Trademark Office. (2017). US Patent No. 9,598,376, Methods of treating cancer.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Mektovi, binimetinib, Orange Book patent listing.
U.S. Food and Drug Administration. (2018). Mektovi (binimetinib) prescribing information.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j)(2)(A)(viii).
U.S. Courts. (2025). Public federal court docket records for Hatch-Waxman patent litigation involving binimetinib and Mektovi.
Pfizer Inc. (2019). Pfizer completes acquisition of Array BioPharma.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Array Biopharma Inc	MEKTOVI	binimetinib	TABLET;ORAL	210498-001	Jun 27, 2018		RX	Yes	Yes	9,598,376	⤷ Start Trial				METHOD OF TREATING MELANOMA	⤷ 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	099630	⤷ Start Trial
Brazil	112015008623	⤷ Start Trial
Canada	2888474	⤷ Start Trial
Canada	3079071	⤷ Start Trial
China	104870427	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,598,376

Which drugs does patent 9,598,376 protect, and when does it expire?

Summary for Patent: 9,598,376