United States Patent 11,957,662: Nirogacestat Desmoid Tumor Treatment Claims, Scope and Patent Landscape

U.S. Patent No. 11,957,662 is a narrow, high-value method-of-treatment patent directed to the clinical use and dose-management protocol for nirogacestat in desmoid tumors. Its core limitations require a 150 mg twice-daily dose, no concomitant CYP3A4 inhibitor, a patient-specific exposure threshold, solid oral dosage forms, and specified dose interruption or reduction rules for serious adverse reactions.

The patent does not broadly claim nirogacestat, gamma-secretase inhibition, or all treatment of desmoid tumors. Its commercial importance depends on whether the marketed OGSIVEO regimen and any generic label reproduce the claimed dosing, pharmacokinetic, formulation, and toxicity-management conditions.

What does U.S. Patent 11,957,662 cover?

The patent covers methods of treating desmoid tumors with oral nirogacestat or a pharmaceutically acceptable salt, including nirogacestat dihydrobromide. The independent claims require the following elements:

Limitation	Requirement
Disease	Desmoid tumor
Patient	Patient in need of treatment
Dose	150 mg free-base equivalent twice daily
Drug interaction	No concomitant CYP3A4 inhibitor
Pharmacokinetics	AUClast below 4,000 ng·h/mL after initial 150 mg administration
Dosage form	One or more solid dosage forms
Composition	Pharmaceutically acceptable excipient
Safety management	At least one specified interruption, dose reduction, or discontinuation protocol

Claims 1 and 6 are independent method claims with substantially overlapping subject matter. Claim 1 covers one or more of the adverse-event management procedures in paragraphs (a) through (d). Claim 6 includes the same base regimen and requires the ALT or AST discontinuation provision in paragraph (e).

Claims 3 through 5 narrow claim 1 to individual toxicity-management procedures. Claim 7 adds a dermatologic-reaction protocol. Claims 8 through 14 narrow the patient population. Claim 15 specifies the dihydrobromide salt. Claims 16 and 17 narrow the pharmacokinetic profile.

The claim set therefore combines four distinct protection layers:

The therapeutic indication.
The 150 mg twice-daily regimen.
Patient exposure requirements.
Clinical dose-modification rules.

How broad are the claims of Patent 11,957,662?

The claims are commercially important but legally constrained by cumulative limitations.

Core regimen limitations

A potentially infringing method must use 150 mg free-base equivalent of nirogacestat twice daily. A regimen using 100 mg twice daily as the initial dose would not satisfy the initial-dose limitation, although the claims expressly contemplate restarting treatment at 100 mg twice daily after toxicity.

The no-CYP3A4-inhibitor limitation excludes patients receiving a CYP3A4 inhibitor concomitantly. A generic label that permits or recommends coadministration with such an inhibitor could create a noninfringement position for those patients, although the same product could still be used in infringing circumstances.

Pharmacokinetic limitation

The patient must exhibit an AUClast below 4,000 ng·h/mL after initial administration of 150 mg. Claims 16 and 17 provide narrower alternatives:

Claim 16: Cmax of approximately 480 to 950 ng/mL.
Claim 17: AUClast of approximately 2,000 to 4,000 ng·h/mL.

These limitations create proof issues. Exposure is a patient-specific fact rather than a simple product characteristic. In ordinary clinical practice, AUClast and Cmax may not be measured for every patient. That can make direct infringement difficult to establish unless the prescribing information, clinical protocol, or pharmacokinetic study demonstrates that the limitation is inherently satisfied.

The phrase "less than 4000 ng·h/mL" is broader than claim 17's approximate 2,000-to-4,000 range. Claim 17 is narrower and potentially more vulnerable to noninfringement where exposure falls below approximately 2,000 ng·h/mL or outside the claimed Cmax range.

Solid dosage-form limitation

The patent requires one or more solid dosage forms containing a pharmaceutically acceptable excipient. Capsules, tablets, and similar oral solid products are likely within this limitation. A liquid formulation would present a stronger noninfringement position under the claim language, although it could implicate separate formulation or composition patents.

What adverse-event management is protected?

The patent protects treatment protocols that interrupt treatment and restart at 100 mg twice daily after specified adverse reactions.

Event	Interruption threshold	Restart condition	Restart dose
Grade 3 diarrhea	Persists at least three days despite medical therapy	Resolves to Grade 1 or baseline	100 mg twice daily
Grade 3 hypophosphatemia	Persists at least seven days despite replacement therapy	Resolves to Grade 1 or baseline	100 mg twice daily
Grade 3 hypokalemia	Despite replacement therapy	Resolves to Grade 1 or baseline	100 mg twice daily
ALT or AST elevation	Three to five times ULN	Resolves to no more than three times ULN or baseline	100 mg twice daily
ALT or AST elevation	Greater than five times ULN	Permanent discontinuation	Not applicable
Severe or life-threatening reaction	Reaction resolves to Grade 1 or baseline	Benefit-risk assessment completed	100 mg twice daily
Recurrence at 100 mg twice daily	Severe or life-threatening reaction recurs	Permanent discontinuation	Not applicable
Grade 3 dermatologic reaction	Grade 3 event	Resolves to Grade 1	100 mg twice daily

Claims 3, 4, and 5 isolate the diarrhea, hypophosphatemia, and hypokalemia procedures. Claim 7 isolates the dermatologic-reaction procedure. Claim 2 adds permanent discontinuation for ALT or AST greater than five times ULN and the severe or life-threatening adverse-reaction protocol.

The claim language in claim 1 contains a duplicated paragraph (d), and claim 6 repeats the ALT/AST limitation in its final clause. These drafting features do not automatically invalidate the claims, but they can affect claim construction, prosecution history analysis, and written-description or definiteness arguments.

What patient populations are covered?

Claims 8 through 14 add patient characteristics:

APC mutation.
CTNNB1 or beta-catenin mutation.
Prior tyrosine kinase inhibitor treatment.
Intra-abdominal tumors.
Adult patients.
Refractory or recurrent disease.
Post-menopausal women.

These claims are narrower than claims 1 and 6. They do not require all listed characteristics. Each dependent claim adds one characteristic to the base method.

The commercial relevance of these limitations differs. Adult patients and recurrent or refractory disease are likely to overlap substantially with the FDA-approved population. APC and CTNNB1 mutation status may not be routinely required before treatment, which limits the practical reach of those dependent claims. The post-menopausal-woman limitation has a narrower population and may have particular relevance to risk-management and reproductive-toxicity evidence.

What is the FDA regulatory status of nirogacestat?

The FDA approved OGSIVEO (nirogacestat) on November 27, 2023, for adults with progressing desmoid tumors who require systemic treatment. SpringWorks Therapeutics commercializes the product in the United States. The approved regimen is 150 mg orally twice daily, consistent with the central dosing limitation in Patent 11,957,662 (FDA, 2023).

The FDA labeling includes dose interruption and reduction instructions for diarrhea, hypophosphatemia, hypokalemia, hepatotoxicity, and other adverse reactions. Those instructions materially overlap with the procedures recited in the patent (FDA, 2023).

What is the Orange Book status?

The Orange Book is the relevant FDA database for approved drug products and listed patents. Patent 11,957,662 may be listed against OGSIVEO if the NDA holder submitted it for listing and FDA accepted the listing. Patent issuance alone does not establish Orange Book listing.

For an ANDA applicant, an Orange Book-listed method-of-use patent can require a Paragraph IV certification, a section viii statement, or another certification depending on the listed use and the proposed labeling. A generic applicant that seeks an indication or label containing the patented desmoid-tumor regimen faces greater litigation exposure than an applicant that carves out the patented use.

The relevant regulatory distinction is:

Issue	Effect
Patent listed in Orange Book	May trigger certification and 30-month-stay litigation consequences
Patent not listed	Patent rights remain enforceable but do not create the same ANDA certification pathway
Method-of-use patent	Can be addressed through labeling carve-out if the patented use is separable
Product or formulation patent	Usually harder to avoid through a section viii carve-out

When does nirogacestat lose exclusivity?

Nirogacestat has orphan-drug exclusivity associated with the FDA approval of OGSIVEO. Orphan exclusivity generally lasts seven years from approval, subject to statutory exceptions. On that basis, the principal orphan exclusivity period runs from November 27, 2023, into November 2030 (FDA, 2023; 21 U.S.C. § 360cc).

Orphan exclusivity and patent expiration are separate rights. A patent can extend beyond orphan exclusivity, while an unexpired patent can block generic approval or launch after regulatory exclusivity ends.

The patent term for Patent 11,957,662 must be determined from its effective nonprovisional filing date, terminal disclaimers, patent-term adjustment, and any applicable patent-term extension. The issue date was May 7, 2024. The patent's precise expiration date should be taken from the USPTO patent record and any applicable Orange Book entry rather than inferred solely from the issue date (USPTO, 2024).

Which companies are challenging nirogacestat exclusivity?

No challenger is identified in the claim information supplied. Public challenge analysis should distinguish among:

An ANDA Paragraph IV filing.
A declaratory judgment action.
An inter partes review petition.
A post-grant review or other USPTO proceeding.
A commercial competitor developing another desmoid-tumor therapy.

A generic company could challenge Patent 11,957,662 on several grounds:

Lack of written description for the combined dose, exposure, formulation, and safety-management limitations.
Enablement of the full range of patient-specific AUClast values.
Indefiniteness in terms such as "about," "baseline," "severe," and "life-threatening."
Obviousness based on the FDA label, clinical-trial protocols, pharmacokinetic disclosures, and known dose-reduction rules.
Noninfringement based on omission of the patented indication, altered labeling, different dose-management instructions, or absence of the claimed pharmacokinetic condition.

The patent holder could respond with induced-infringement theories if a generic label directs prescribers to use the same dose interruptions and 100 mg restart protocol.

How strong is the patent estate for OGSIVEO?

Patent 11,957,662 is strongest against a product that reproduces the full FDA-labeled regimen and adverse-event management instructions. Its strength is lower against products with:

A carved-out desmoid-tumor indication.
A different initial dose.
A liquid dosage form.
A label that omits the claimed toxicity-management instructions.
A regimen involving a CYP3A4 inhibitor.
No demonstrated or expected AUClast below 4,000 ng·h/mL.

The patent is a method-of-use and treatment-management patent, not a basic molecule patent. Its value therefore depends on the ability to enforce treatment instructions against prescribers, manufacturers, pharmacies, and generic-label sponsors.

The absence of a biosimilar pathway is significant. Nirogacestat is a chemically synthesized small molecule, so biosimilar competition is not the relevant threat. The competitive risks are ANDA-based generic entry and alternative systemic treatments for desmoid tumors, including tyrosine kinase inhibitors and other investigational agents.

What patent litigation and settlement risks affect generic entry?

A Paragraph IV notice involving Patent 11,957,662 could produce patent litigation in federal district court. If the patent is properly listed and the NDA holder timely sues, the ANDA approval process may be subject to a statutory 30-month stay, subject to court and FDA rules.

Settlement terms could include:

A fixed generic entry date.
A license limited to a carved-out indication.
A covenant not to sue for selected patient populations.
Restrictions on label language.
Authorized-generic arrangements.
Acceleration provisions tied to invalidation of related patents.

No settlement agreement is established by the claim text. Any commercial forecast should treat the patent, orphan exclusivity, other Orange Book patents, and potential pediatric exclusivity as separate barriers.

What geographic coverage does Patent 11,957,662 provide?

The patent provides rights only in the United States. It does not directly protect OGSIVEO in Europe, Japan, China, Canada, or other markets. International protection must be assessed family by family, including national-phase applications, granted counterparts, prosecution outcomes, patent-term adjustments, and local regulatory exclusivity.

The same clinical protocol may be protected by corresponding foreign method-of-treatment claims, but U.S. claim scope cannot be imported into another jurisdiction.

Key Takeaways

Patent 11,957,662 protects a specific nirogacestat treatment protocol for desmoid tumors.
The core regimen is 150 mg twice daily without a concomitant CYP3A4 inhibitor.
The claims require a patient exposure condition, including AUClast below 4,000 ng·h/mL.
Solid dosage forms and excipients are express claim limitations.
Dose interruption and restart rules for diarrhea, electrolyte abnormalities, hepatotoxicity, dermatologic reactions, and severe adverse reactions are central to the patent.
The claims overlap materially with the FDA-approved OGSIVEO dosing and safety-management instructions.
The patent is not a broad composition-of-matter patent and does not cover every use of nirogacestat.
Nirogacestat's orphan exclusivity is expected to run into November 2030, separate from patent term.
Generic risk will depend on Orange Book listing, Paragraph IV activity, label carve-outs, and any related formulation or use patents.
Biosimilar competition is not the relevant pathway because nirogacestat is a small-molecule drug.

FAQs About U.S. Patent 11,957,662 and OGSIVEO Exclusivity

Does Patent 11,957,662 cover nirogacestat itself?

No. The claims provided are method claims. They cover specified treatment methods and do not broadly claim the nirogacestat molecule or every pharmaceutical composition containing it.

Can a generic avoid Patent 11,957,662 by using a 100 mg starting dose?

Potentially, yes, if the generic method does not later practice the claimed 150 mg twice-daily initial regimen. A 100 mg restart dose alone does not satisfy the entire independent claim, but other patents or regulatory barriers may remain.

Does a patient need pharmacokinetic testing to infringe the patent?

The claim requires that the patient exhibit the stated AUClast or Cmax value. Whether routine testing is necessary for infringement depends on how the limitation is construed and whether the exposure condition is shown to be inherent or statistically expected in the treated population.

Are CTNNB1 and APC mutations required for OGSIVEO treatment?

No. They are limitations in dependent claims. The FDA-approved indication does not require that a patient have an APC or CTNNB1 mutation.

Can a generic obtain approval with a section viii carve-out?

A section viii strategy may be available if the patented use can be cleanly omitted from the proposed labeling. The feasibility depends on the exact Orange Book listing, the proposed indication, the safety instructions, and whether the patented dose-management protocol remains necessary for the approved use.

References

Food and Drug Administration. (2023). FDA approves nirogacestat for adults with desmoid tumors. U.S. Department of Health and Human Services.
Food and Drug Administration. (2023). OGSIVEO (nirogacestat) prescribing information. SpringWorks Therapeutics, Inc.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Patent and Trademark Office. (2024). U.S. Patent No. 11,957,662: Methods for therapeutic treatment of desmoid tumor. U.S. Department of Commerce.
Orphan Drug Act, 21 U.S.C. § 360cc.
Hatch-Waxman Amendments, 21 U.S.C. §§ 355 and 355(j).

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Springworks	OGSIVEO	nirogacestat hydrobromide	TABLET;ORAL	217677-001	Nov 27, 2023		DISCN	Yes	No	11,957,662	⤷ Start Trial				TREATMENT OF ADULT PATIENTS WITH PROGRESSING DESMOID TUMORS	⤷ Start Trial
Springworks	OGSIVEO	nirogacestat hydrobromide	TABLET;ORAL	217677-002	Apr 4, 2024		RX	Yes	No	11,957,662	⤷ Start Trial				TREATMENT OF ADULT PATIENTS WITH PROGRESSING DESMOID TUMORS	⤷ Start Trial
Springworks	OGSIVEO	nirogacestat hydrobromide	TABLET;ORAL	217677-003	Apr 4, 2024		RX	Yes	Yes	11,957,662	⤷ Start Trial				TREATMENT OF ADULT PATIENTS WITH PROGRESSING DESMOID TUMORS	⤷ 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
European Patent Office	4010322	⤷ Start Trial	CA 2026 00017	Denmark	⤷ Start Trial
European Patent Office	4010322	⤷ Start Trial	301374	Netherlands	⤷ Start Trial
European Patent Office	4010322	⤷ Start Trial	C20260011	Finland	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,957,662

Which drugs does patent 11,957,662 protect, and when does it expire?

Summary for Patent: 11,957,662