US Patent 10,941,118: Nirogacestat Hydrobromide Crystal Forms, Formulation Claims, and Generic Entry Risk
US Patent 10,941,118 protects selected crystalline forms of nirogacestat hydrobromide, the active pharmaceutical ingredient in Ogsiveo. Its broadest claim covers 14 named polymorphic forms, while dependent claims protect particle-size specifications, pharmaceutical compositions, tablet formulations, dose strengths, and desmoid-tumor treatment regimens.
The patent is a solid-form and product-use patent rather than a basic compound patent. Its commercial significance depends on whether Ogsiveo uses one of the claimed crystal forms and whether a competing manufacturer can produce a therapeutically equivalent product without practicing the claimed forms.
What drug does US Patent 10,941,118 protect?
US Patent 10,941,118 covers nirogacestat hydrobromide, also known by its development code PF-03084014. Nirogacestat is a selective gamma-secretase inhibitor approved by the FDA under the brand name Ogsiveo for adults with progressing desmoid tumors requiring systemic treatment.[1]
The active moiety identified in the claims is:
- (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2-methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)pentanamide
- Hydrobromide salt
- Nirogacestat hydrobromide
- Ogsiveo active ingredient
The patent does not claim every form of nirogacestat. It focuses on crystalline hydrobromide salt forms identified by X-ray powder diffraction, or XRPD, patterns.
What is the patent status and expiration date of US 10,941,118?
US Patent 10,941,118 was issued on March 9, 2021. The patent concerns crystalline forms of nirogacestat hydrobromide and is associated with SpringWorks Therapeutics’ Ogsiveo intellectual-property portfolio.[2]
| Item |
Data |
| Patent |
US 10,941,118 |
| Issue date |
March 9, 2021 |
| Active ingredient |
Nirogacestat hydrobromide |
| Brand |
Ogsiveo |
| Primary technology |
Crystalline polymorphs and pharmaceutical compositions |
| Therapeutic indication |
Desmoid tumors |
| Earliest reported priority |
June 5, 2015 |
| Projected ordinary expiration |
June 5, 2035, subject to any applicable patent-term adjustment |
| Patent type |
Solid form, formulation, and method-of-use protection |
| FDA approval of Ogsiveo |
November 27, 2023 |
| FDA exclusivity |
Orphan-drug exclusivity through November 27, 2030, subject to statutory conditions |
The June 5, 2035 expiration date reflects the 20-year term measured from the earliest claimed priority date. The controlling expiration date should be confirmed against the USPTO patent record and any terminal disclaimer or patent-term adjustment.
What does claim 1 of US 10,941,118 cover?
Claim 1 is the central claim. It covers a crystalline form of nirogacestat hydrobromide selected from 14 identified forms:
- Form A
- Form B
- Form D
- Form E
- Form F
- Form F'
- Form G
- Form H
- Form H'
- Form J
- Form K
- Form L
- Form M
- Form N
Form A is defined by three XRPD peaks at approximately:
- 8.8 degrees two theta
- 9.8 degrees two theta
- 23.3 degrees two theta
Each peak has a tolerance of plus or minus 0.2 degrees two theta.
The other forms are defined by XRPD patterns shown in the patent figures. Claim 1 therefore uses a closed Markush structure. A crystalline nirogacestat hydrobromide form falls within the literal scope of claim 1 only if it is one of the listed forms, or is legally equivalent to one of them under applicable claim-construction principles.
The claim does not expressly cover all amorphous nirogacestat hydrobromide, all hydrates or solvates, or all crystalline salts of nirogacestat.
How strong is claim 1 against a generic manufacturer?
Claim 1 has potentially strong product coverage because the claimed subject matter can be detected analytically. A patent owner could compare the accused API or tablet against the claimed XRPD profiles, supported by additional solid-state testing such as differential scanning calorimetry, thermogravimetric analysis, microscopy, and solid-state NMR.
The principal strengths are:
- Fourteen separately identified crystal forms are included.
- The forms are defined by objective analytical characteristics.
- The claim reaches the API itself, not only a manufacturing process.
- A generic tablet containing a claimed form could create direct product infringement exposure.
- Dependent claims separately reinforce the commercial dosage form and particle-size profile.
The principal limitations are:
- The patent does not necessarily cover a nonclaimed polymorph.
- The patent does not necessarily prevent use of a different salt, such as a free base or another pharmaceutically acceptable salt.
- An XRPD pattern substantially different from the claimed figures may avoid literal infringement.
- Infringement may depend on the form present in the final drug substance, tablet, or manufacturing intermediate.
- Claim 1 does not independently require a tablet, dose strength, indication, or treatment regimen.
A generic manufacturer could attempt a design-around using an unclaimed polymorph. That approach would remain subject to other nirogacestat compound, salt, process, formulation, method-of-use, and regulatory patents.
What do claims 2 through 14 add?
Claims 2 through 14 each narrow claim 1 to a single crystalline form. They cover Forms B, D, E, F, F', G, H, H', J, K, L, M, and N.
These claims have two commercial functions. First, they provide fallback positions if claim 1 is challenged for breadth, indefiniteness, written description, or enablement. Second, they allow infringement analysis to focus on a specific polymorph used in commercial manufacture.
| Claims |
Protected subject matter |
| 1 |
Any one of 14 listed crystalline forms |
| 2 |
Form B |
| 3 |
Form D |
| 4 |
Form E |
| 5 |
Form F |
| 6 |
Form F' |
| 7 |
Form G |
| 8 |
Form H |
| 9 |
Form H' |
| 10 |
Form J |
| 11 |
Form K |
| 12 |
Form L |
| 13 |
Form M |
| 14 |
Form N |
Form A appears in claim 1 but does not receive a separate dependent claim. The omission may have limited practical impact because claim 1 still expressly covers Form A.
What formulation and particle-size protection does the patent provide?
Claim 15 covers a composition containing a claimed crystalline form with specified particle-size ranges. The claim uses volumetric particle-size parameters:
| Parameter |
Claimed range |
| D[V,0.10] |
0.5 to 15 micrometers |
| D[V,0.50] |
2 to 30 micrometers |
| D[V,0.90] |
8 to 600 micrometers |
| D[4,3] |
5 to 200 micrometers |
The claim is drafted with alternative limitations. A composition may fall within claim 15 if it satisfies one or more of the listed particle-size conditions, subject to the claim’s construction and the applicable measurement method.
Particle-size claims can be commercially useful where the drug product depends on dissolution, flow, blend uniformity, content uniformity, or tablet manufacturability. They can also create evidentiary disputes because particle-size results may vary based on sampling, dispersion, instrument settings, aggregation, and analytical method.
Claim 16 covers a pharmaceutical composition comprising a claimed crystalline form and a pharmaceutically acceptable carrier. Claim 17 narrows the composition to a tablet.
Claims 18 through 20 specify drug loading:
- Claim 18: 25 mg to 400 mg
- Claim 19: 50 mg
- Claim 20: 100 mg
These claims align with commercially relevant tablet strengths and may be more difficult to avoid if a competing product uses the same claimed polymorph in a comparable tablet.
What treatment methods are protected?
Claims 21 through 28 cover treatment of desmoid tumors with a pharmaceutical composition containing a claimed crystalline form.
| Claim |
Limitation |
| 21 |
Treating desmoid tumors |
| 22 |
Daily dose of 50 mg to 500 mg |
| 23 |
Daily dose of 100 mg to 400 mg |
| 24 |
300 mg daily |
| 25 |
200 mg daily |
| 26 |
Total daily dose administered in two doses |
| 27 |
Two separate 150 mg doses |
| 28 |
Two separate 100 mg doses |
The method claims are narrower than a claim covering treatment with nirogacestat generally. They require the pharmaceutical composition of claim 16, which in turn requires a crystalline form covered by claim 1.
A competing manufacturer could face method-of-use exposure if it markets a product for desmoid tumors with instructions matching the claimed dosing regimens. A product label that omits the patented indication may reduce induced-infringement risk, but the analysis would depend on the totality of the labeling, promotional conduct, distribution practices, and foreseeable use.
What is the Orange Book status of US 10,941,118?
Ogsiveo is an FDA-approved small-molecule drug, so its relevant patents may be listed in the FDA Orange Book. US Patent 10,941,118 is associated with Ogsiveo’s crystalline-form and product protection and should be reviewed in the current Orange Book entry for the drug.[3]
The patent’s likely Orange Book role is narrower than a basic active-ingredient patent. A listed solid-form patent can still affect an abbreviated new drug application if the proposed generic uses the same crystalline form or if the applicant must make a Paragraph IV certification.
Orange Book listing does not establish validity or infringement. It creates an FDA approval and certification framework under the Hatch-Waxman Act.
When does Ogsiveo lose regulatory exclusivity?
Ogsiveo received FDA orphan-drug designation for desmoid tumors and was approved on November 27, 2023. Orphan-drug exclusivity generally lasts seven years from approval, placing the end of the statutory period on November 27, 2030, unless an earlier product obtains approval for the same indication under an applicable exception.[1]
The principal commercial protection periods are:
| Protection |
Expected end |
| Orphan-drug exclusivity |
November 27, 2030 |
| US Patent 10,941,118 |
June 5, 2035, subject to adjustment |
| Generic entry based solely on this patent |
Potentially no earlier than patent resolution or expiration |
| Biosimilar pathway |
Not applicable |
Nirogacestat is a synthetic small molecule, not a biologic. Biosimilar litigation and the Biologics Price Competition and Innovation Act pathway therefore do not apply. Generic applicants would use the ANDA pathway, with patent certifications governed by Hatch-Waxman.
Which companies are challenging Ogsiveo patents?
No publicly identified Paragraph IV challenge, ANDA litigation proceeding, or settlement agreement directed specifically to US Patent 10,941,118 is established by the cited public sources.
The most relevant future challengers would be generic pharmaceutical companies that:
- File an ANDA for nirogacestat tablets.
- Certify that the patent is invalid, unenforceable, or not infringed.
- Use a claimed crystalline form while disputing validity or scope.
- Develop an alternative polymorph and challenge the relevance of the listed patent.
- Seek approval after orphan exclusivity expires but before the 2035 patent expiration.
A Paragraph IV notice could trigger a patent action under 35 U.S.C. § 271(e)(2). A timely infringement suit could create a statutory FDA approval stay of up to 30 months, subject to statutory exceptions and court developments.[4]
What other intellectual-property barriers affect generic launch?
US Patent 10,941,118 is one layer of the nirogacestat estate. A complete freedom-to-operate analysis should distinguish among several patent categories:
Compound and salt patents
Earlier patents may cover the nirogacestat chemical entity, stereochemistry, hydrobromide salt, or broad gamma-secretase inhibitor classes. These patents can create stronger barriers than a polymorph patent if they remain enforceable.
Crystalline-form patents
US 10,941,118 is the principal patent analyzed here. Other applications or patents may cover additional polymorphs, hydrates, solvates, mixtures, or conversion processes.
Formulation patents
Potential formulation protection may cover tablets, excipient systems, particle-size distributions, dissolution profiles, dose strengths, or manufacturing conditions. Claims 15 through 20 combine several of these concepts in US 10,941,118.
Method-of-use patents
Claims 21 through 28 focus on desmoid-tumor treatment and specific dose regimens. Other patents could cover gamma-secretase inhibition in oncology, desmoid tumors, familial adenomatous polyposis, or other diseases.
Manufacturing patents
A generic may avoid a formulation patent but still practice a protected crystallization, isolation, milling, drying, or scale-up process. Process claims are particularly relevant where the commercial form is difficult to produce reproducibly.
How does US 10,941,118 compare with a basic compound patent?
| Issue |
Basic compound patent |
US 10,941,118 |
| Claimed subject |
Chemical entity or broad genus |
Specific crystalline hydrobromide forms |
| Coverage of alternative polymorphs |
Usually broader |
Limited to identified forms |
| Detectability |
Chemical analysis |
XRPD and solid-state testing |
| Product infringement risk |
Usually high if compound is used |
High if claimed form is used |
| Design-around route |
Difficult |
Alternative polymorph or salt may be possible |
| Formulation coverage |
Usually limited |
Expressly included in claims 15-20 |
| Method-of-use coverage |
May be broad |
Desmoid tumors and specified dosing |
| Typical litigation issue |
Validity, claim scope, enablement |
Polymorph identity, claim construction, infringement testing |
The patent is commercially meaningful because it links the crystalline API to the marketed tablet and to the approved desmoid-tumor treatment regimen. It is not, however, a substitute for a full patent-family review.
What licensing arrangements affect nirogacestat?
Nirogacestat originated at Pfizer. SpringWorks Therapeutics obtained rights to develop and commercialize nirogacestat from Pfizer in 2017. SpringWorks became the commercial sponsor of Ogsiveo in the United States.[5]
The licensing relationship matters because patent ownership, Orange Book listing, regulatory sponsorship, and enforcement rights may be divided among the originating company, licensee, and affiliates. Public transaction summaries do not by themselves establish the precise enforcement rights for every patent-family member.
What generic launch scenarios exist?
Three scenarios are commercially plausible:
- A generic launches after patent expiration in 2035, assuming no later patent or regulatory barrier.
- A generic files a Paragraph IV certification and challenges the patent before 2035. The outcome would depend on validity, infringement, and settlement.
- A generic develops a nonclaimed polymorph and seeks approval after orphan exclusivity expires, while disputing whether other patents block launch.
The most vulnerable element of the patent is the possibility of designing around the claimed forms. The strongest enforcement position would arise if Ogsiveo uses one of the expressly claimed forms and the generic’s drug substance has the same XRPD signature.
Key Takeaways
- US Patent 10,941,118 protects 14 crystalline forms of nirogacestat hydrobromide.
- Claim 1 is the broadest claim and uses XRPD-defined polymorph coverage.
- Claims 2 through 14 provide single-form fallback claims.
- Claims 15 through 20 cover particle size, pharmaceutical compositions, tablets, and 25 mg to 400 mg drug loads.
- Claims 21 through 28 cover desmoid-tumor treatment and daily dosing regimens from 50 mg to 500 mg.
- Ogsiveo received FDA approval on November 27, 2023, with orphan exclusivity expected through November 27, 2030.
- The patent’s ordinary expiration is expected around June 5, 2035, subject to patent-term adjustment.
- Nirogacestat is a small molecule, so biosimilar risk does not apply.
- Generic risk centers on Paragraph IV litigation, alternative polymorph development, and additional compound, formulation, method, and process patents.
- No publicly identified Paragraph IV challenge or settlement directed specifically to US 10,941,118 is established by the cited sources.
FAQs
Does US Patent 10,941,118 cover amorphous nirogacestat?
No. The claims are directed to crystalline forms of nirogacestat hydrobromide. An amorphous material would not ordinarily satisfy the crystalline-form limitation unless it contained a claimed crystalline phase in a legally relevant amount.
Can a generic use a different polymorph of nirogacestat?
Potentially. A different polymorph may avoid literal infringement of US 10,941,118, but the generic would still need to evaluate other compound, salt, formulation, process, and method-of-use patents.
Is Form A separately protected by a dependent claim?
No. Form A is expressly included in claim 1 but is not separately recited in claims 2 through 14.
Does the patent cover the 300 mg daily desmoid-tumor dose?
Yes. Claim 24 specifically recites administration of 300 mg daily, provided the treatment uses the pharmaceutical composition required by claim 16.
Is a biosimilar filing available for Ogsiveo?
No. Ogsiveo contains a synthetic small-molecule active ingredient. A competing company would generally pursue an ANDA rather than a biosimilar application.
References
-
U.S. Food and Drug Administration. (2023). Ogsiveo (nirogacestat) prescribing information. FDA.
-
United States Patent and Trademark Office. (2021). U.S. Patent No. 10,941,118, crystalline forms of nirogacestat hydrobromide. USPTO.
-
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
-
Hatch, W. (1984). Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, 98 Stat. 1585.
-
SpringWorks Therapeutics, Inc. (2017). SpringWorks Therapeutics obtains exclusive license from Pfizer for nirogacestat. Company announcement.
