US Patent 11,673,877: Niraparib Tosylate Form I Claims, Scope, Expiry and Patent Landscape
US Patent 11,673,877 is a solid-state patent covering crystalline Form I of niraparib tosylate monohydrate, the active pharmaceutical ingredient used in ZEJULA. Its principal limitation is not the niraparib molecule itself, but a defined crystalline form containing less than about 6% combined Form II and Form III material. The patent also claims analytical fingerprints, a conversion process, and treatment methods using the specified Form I.
The strongest infringement risk concerns commercial niraparib tosylate manufactured or sold as Form I within the claimed impurity threshold. The patent is materially narrower than a compound patent and may be vulnerable to non-infringement arguments based on polymorph identity, analytical overlap, impurity percentage, or use of a different salt or solid form.
What drug and pharmaceutical form does US 11,673,877 protect?
The claimed compound is niraparib, chemically identified as:
2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide
The patent claims the tosylate monohydrate salt in crystalline Form I. Niraparib tosylate is the active ingredient in ZEJULA, marketed by GSK for selected ovarian, fallopian tube and primary peritoneal cancer indications. The claims do not cover every physical form of niraparib, every niraparib salt, or the free base as such.
| Feature |
Claimed subject matter |
| Active moiety |
Niraparib |
| Salt |
Tosylate |
| Hydration state |
Monohydrate for Form I |
| Solid form |
Crystalline Form I |
| Excluded or controlled forms |
Form II non-stoichiometric hydrate and Form III anhydrate |
| Purity requirement |
Less than about 6% combined Form II and Form III |
| Primary analytical limitation |
XRPD peaks at 9.5, 24.9 and 26.0 degrees 2θ, each ±0.2 |
| Additional analytical tools |
XRPD, DSC, Raman, infrared spectroscopy and dynamic vapor sorption |
| Therapeutic use |
Specified cancers |
| Process scope |
Conversion of Form II, Form III or mixtures into Form I using a high-water solvent system |
[1]
What are the independent claims in US 11,673,877?
The patent has three substantive independent claim groups.
Claim 1: crystalline Form I
Claim 1 covers the crystalline material itself. It requires all of the following:
- Niraparib tosylate.
- Crystalline Form I.
- A monohydrate.
- Substantial freedom from Form II and Form III.
- Less than about 6% combined Form II and Form III by weight.
- XRPD reflections at 9.5±0.2, 24.9±0.2 and 26.0±0.2 degrees 2θ.
The claim is therefore a product-by-form claim with both structural and compositional limitations. A material may contain niraparib tosylate and still fall outside claim 1 if it is Form II, Form III, an amorphous form, another polymorph, a different hydrate, a different salt, or Form I containing at least about 6% combined Form II and Form III.
Claim 10: preparation of Form I
Claim 10 covers a process that:
- dissolves Form II, Form III, or a mixture of those forms;
- uses a solvent system having a water-to-organic-solvent ratio of approximately 10:1 to 400:1 by volume; and
- crystallizes Form I.
The claim is narrower than a general process for making niraparib tosylate. It focuses on conversion or recrystallization from specified starting forms through a highly aqueous solvent system.
Claim 11: treatment methods
Claim 11 covers administering the claimed Form I to a patient diagnosed with one of the following:
- ovarian cancer;
- fallopian tube cancer;
- epithelial ovarian cancer;
- recurrent ovarian cancer;
- prostate cancer;
- colon cancer; or
- rectal cancer.
The treatment claim incorporates the same Form I identity, XRPD peaks and less-than-6% combined Form II/Form III threshold found in claim 1.
How do dependent claims narrow the patent?
Claims 2 through 9 add analytical limitations to claim 1. Claims 12 through 19 apply corresponding limitations to the treatment claim. Claims 10 and 20 add the crystallization process.
| Claims |
Limitation |
| 2, 12 |
XRPD pattern substantially according to Figure 1 |
| 3, 13 |
Seven additional specified XRPD peaks |
| 4, 14 |
At least three peaks selected from the seven-peak group |
| 5, 15 |
At least four peaks selected from the seven-peak group |
| 6, 16 |
DSC pattern substantially according to Figure 2 |
| 7, 17 |
Raman pattern substantially according to Figure 3 |
| 8, 18 |
Dynamic water vapor sorption pattern substantially according to Figure 5 |
| 9, 19 |
Infrared spectroscopy pattern substantially according to Figure 4 |
| 10, 20 |
Preparation from Form II, Form III or a mixture using a 10:1 to 400:1 water-to-organic-solvent ratio |
The dependent claims create evidentiary layers. XRPD is likely to be the principal screening method because claim 1 already identifies three primary diffraction peaks. DSC, Raman, infrared and vapor-sorption data provide corroborating evidence but may be less practical for routine market surveillance.
What analytical features define Form I?
The claim uses a combination of positive and negative definitions.
Form I XRPD profile
The mandatory Form I peaks in claims 1 and 11 are:
| Peak |
Claimed position |
| Peak 1 |
9.5±0.2° 2θ |
| Peak 2 |
24.9±0.2° 2θ |
| Peak 3 |
26.0±0.2° 2θ |
Additional peaks identified for Form I are:
12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2 and 26.9±0.2 degrees 2θ.
The patent does not require every possible Form I reflection in claim 1. It requires the three primary peaks and the specified purity condition. Claims 3 through 5 provide narrower alternatives based on additional peaks.
Form II and Form III exclusion
Form II is defined by reflections at:
9.7±0.3, 12.8±0.3, 17.9±0.3, 19.7±0.3 and 21.8±0.3 degrees 2θ.
Form III is defined by reflections at:
17.8±0.2, 19.0±0.2 and 22.8±0.2 degrees 2θ.
The exclusion is quantitative: combined Form II and Form III must be less than about 6% by weight relative to the combined weight of Forms I, II and III. This creates a potential dispute over:
- the validation of the quantitative XRPD method;
- whether the 6% threshold is measured on a dry or hydrated basis;
- how overlapping peaks are deconvoluted;
- whether unidentified forms are included in the denominator;
- whether “about 6%” permits a range above 6%; and
- whether the accused material is actually Form I monohydrate.
How broad is the product claim?
The product claim is narrow in chemical scope but potentially important commercially.
It does not require a particular particle size, morphology, tablet composition, excipient, dose, packaging configuration or manufacturing site. A commercial API batch can therefore infringe claim 1 regardless of its downstream formulation if it has the claimed Form I characteristics.
The claim also does not expressly require a specific therapeutic use. Infringement of the product claim could occur through making, using, offering for sale or selling the claimed crystalline material, subject to the applicable statutory framework.
The claim is narrower than a claim directed to:
- niraparib generally;
- niraparib tosylate generally;
- any niraparib monohydrate;
- any niraparib crystalline form;
- any pharmaceutical composition containing niraparib; or
- any method of treating cancer with niraparib.
What is the scope of the process claims?
Claims 10 and 20 cover a specific polymorph-conversion strategy. The process must begin with Form II, Form III or a mixture and must use a water-to-organic-solvent ratio from approximately 10:1 to 400:1 by volume.
The process limitations create several design-around routes:
- begin with a different solid form;
- use direct crystallization from an intermediate rather than conversion from Form II or Form III;
- use a water-to-organic ratio outside the stated range;
- use a substantially anhydrous solvent system;
- use a different salt formation sequence; or
- produce an alternative solid form.
A process that uses the claimed ratio but produces Form I through a different starting material may raise claim-construction issues, because the claim expressly requires a composition comprising Form II or Form III, or a mixture of them.
What is the scope of the treatment claims?
Claims 11 through 20 are method-of-treatment claims limited by the physical identity of the administered product. The patient must receive Form I meeting the less-than-6% combined Form II/Form III requirement.
The cancer list is broader than the principal current ZEJULA regulatory indications. The claims expressly include prostate, colon and rectal cancer, but patent enforceability and practical commercial relevance depend on the supporting disclosure, written-description and enablement record, prosecution history, and the actual use being accused.
A generic or follow-on manufacturer could face a method-of-use issue if its product is labeled for a patented indication. A “skinny label” or carve-out may reduce risk for an indication that is protected by method-of-use claims, but it would not eliminate risk under a separately enforceable product-by-form claim.
When does US 11,673,877 lose exclusivity?
The patent’s expiration date cannot be calculated from the claim text alone. The relevant calculation requires the patent’s earliest effective nonprovisional priority date, any patent-term adjustment, any patent-term extension, and terminal-disclaimer information.
The patent was granted as US 11,673,877. Its enforceable term is generally measured from the earliest effective nonprovisional filing date under 35 U.S.C. §154, subject to adjustment and extension rules. A reliable expiry analysis must distinguish:
| Exclusivity category |
Relevance |
| Patent term |
Applies to the granted claims, subject to PTA, PTE and terminal disclaimers |
| New chemical entity exclusivity |
Applies to the active ingredient’s FDA approval history, not automatically to this polymorph patent |
| Orphan-drug exclusivity |
Depends on the approved indication and orphan designation |
| Pediatric exclusivity |
May add six months to qualifying exclusivity periods |
| Regulatory exclusivity |
May expire separately from the patent |
[2][3][4]
US 11,673,877 should not be treated as the expiration date for all niraparib exclusivity. Earlier compound, salt, formulation, use or manufacturing patents may expire at different times.
What is the Orange Book status of US 11,673,877?
Orange Book listing must be verified against the FDA’s current Approved Drug Products with Therapeutic Equivalence Evaluations database and the patent-listing information submitted for ZEJULA.
A patent covering a crystalline active ingredient may be submitted for listing if it claims the drug substance or an approved drug product and satisfies FDA listing requirements. A method-of-use patent may be listed with an indication code. Listing does not determine validity or infringement, but it can trigger Hatch-Waxman certification obligations for an ANDA applicant.
The key commercial questions are:
- Is US 11,673,877 listed against ZEJULA?
- Is it listed as a drug-substance, drug-product or method-of-use patent?
- Does the listing carry an indication code?
- Is the patent eligible for a Paragraph IV certification?
- Has GSK or another NDA holder submitted a timely patent-listing amendment?
The claim text alone does not establish the patent’s current Orange Book listing status.
Which companies are challenging niraparib exclusivity?
ANDA applicants challenging a listed patent generally may file a Paragraph IV certification alleging that the patent is invalid, unenforceable or not infringed. The existence, identity and timing of a Paragraph IV challenge require review of FDA ANDA litigation records, district-court complaints, docket entries and any notice letters.
The relevant competitive group includes:
- generic pharmaceutical companies pursuing niraparib tosylate tablets;
- contract manufacturers supplying API or finished dosage forms;
- specialty oncology companies developing PARP-inhibitor combinations; and
- sponsors developing alternative PARP inhibitors or next-generation DNA-damage-response agents.
No biosimilar pathway applies. Niraparib is a chemically synthesized small molecule, so competitive entry proceeds through the ANDA or, in some cases, the 505(b)(2) pathway rather than a biosimilar application.
What patent litigation and settlement issues matter?
For a Paragraph IV dispute involving this patent, the principal litigation issues would likely be:
Infringement
The patent owner would need to prove that the accused material is:
- niraparib tosylate;
- crystalline Form I;
- a monohydrate;
- characterized by the required XRPD peaks; and
- below the stated impurity threshold.
For process claims, the evidence would focus on the starting polymorph, solvent ratio and crystallization sequence.
Validity
Potential validity challenges may target:
- anticipation by prior-art solid forms;
- obviousness based on known niraparib tosylate hydrates and routine polymorph screening;
- indefiniteness of “substantially free” and “about 6%”;
- written description of the defined Form I and impurity threshold;
- enablement across the full solvent-ratio range; and
- whether analytical characteristics adequately distinguish the claimed form.
Settlement
A settlement could establish an authorized generic date, a licensed launch date, a restriction on Form I manufacture, or a supply arrangement. No settlement terms should be inferred without a filed agreement, consent judgment, or public litigation record.
How strong is the patent estate for niraparib?
The patent estate is strongest when viewed as a layered structure:
| Layer |
Strategic function |
| Compound patents |
Protect niraparib across salts and solid forms, depending on claim language |
| Salt and polymorph patents |
Protect commercial API forms such as the claimed Form I |
| Formulation patents |
Protect tablets, excipients, release characteristics or stability profiles |
| Method-of-use patents |
Protect specified cancer indications or treatment combinations |
| Manufacturing patents |
Protect routes, crystallization, impurity control and scale-up |
| Regulatory exclusivity |
Delays or restricts ANDA approval independently of patent validity |
US 11,673,877 is a solid-state layer. Its commercial value depends on whether ZEJULA is manufactured and distributed in Form I, whether alternative forms have acceptable quality and bioequivalence, and whether the patent is listed against the approved product.
What generic launch scenarios exist?
Three launch scenarios are commercially plausible:
- Entry after patent expiry. The ANDA applicant avoids Paragraph IV litigation and launches after all blocking patents and regulatory exclusivities expire.
- Paragraph IV launch after litigation or settlement. The applicant challenges the patent and obtains a court judgment, settlement license or agreed launch date.
- Non-infringing alternative form. The applicant develops a different niraparib salt or crystalline form and supports it through the applicable FDA pathway.
The third route may be difficult if the alternative form has different dissolution, stability, hygroscopicity or bioavailability characteristics. The patent’s Form I claim does not automatically block every alternative form, but FDA chemistry, manufacturing and controls requirements can make solid-form switching operationally costly.
Key Takeaways
- US 11,673,877 targets crystalline Form I of niraparib tosylate monohydrate.
- Claim 1 requires three XRPD peaks and less than about 6% combined Form II and Form III.
- Claims 2 through 9 add XRPD, DSC, Raman, infrared and vapor-sorption fingerprints.
- Claims 10 and 20 cover conversion from Form II or Form III using a 10:1 to 400:1 water-to-organic-solvent ratio.
- Claims 11 through 19 cover treatment of specified cancers using the claimed Form I.
- The patent does not broadly claim niraparib, niraparib tosylate, or every niraparib formulation.
- The principal technical dispute will be polymorph identification and quantitative impurity measurement.
- No biosimilar pathway applies because niraparib is a small-molecule drug.
- Orange Book listing, Paragraph IV activity, litigation and patent expiry require verification against current FDA and court records.
- Generic risk is highest for a product using Form I niraparib tosylate and lower for a genuinely different salt or polymorph.
FAQs
Does US 11,673,877 cover ZEJULA tablets?
It may cover the niraparib tosylate API used in ZEJULA if that API is crystalline Form I within the claimed impurity threshold. The claim does not require a particular tablet formulation.
Can a generic avoid US 11,673,877 by using amorphous niraparib?
Potentially, but the alternative material must satisfy FDA quality, stability, dissolution and bioequivalence requirements. The generic would also need to avoid separate compound, salt, formulation and method-of-use patents.
Does the 6% threshold apply to impurities other than Form II and Form III?
The express quantitative limitation concerns the combined total weight of Form II and Form III relative to Forms I, II and III. It does not expressly quantify unrelated impurities or other solid forms.
Are the ovarian-cancer treatment claims limited to FDA-approved ZEJULA indications?
No. The patent claims recite specific cancer diagnoses, including prostate, colon and rectal cancer. Enforceability depends on the patent record and the accused conduct, not solely on the current FDA label.
Is a Paragraph IV certification required for this patent?
Only if the patent is listed in the Orange Book for the relevant reference-listed drug and the ANDA applicant is making the applicable certification. A patent’s existence alone does not establish a Paragraph IV obligation.
References
- United States Patent No. 11,673,877. U.S. Patent and Trademark Office.
- U.S. Food and Drug Administration. (n.d.). ZEJULA (niraparib) prescribing information.
- U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- 35 U.S.C. §§ 154, 156, 271(e), 282.
- U.S. Patent and Trademark Office. (n.d.). Manual of Patent Examining Procedure, chapters addressing patent term, infringement-related claim interpretation and pharmaceutical patent listing considerations.
