United States Patent 10,961,251: Scope, Claim Boundaries, and Competitive Patent Landscape for Crystalline Ibrutinib
What does US 10,961,251 claim, in enforceable terms?
US 10,961,251 is directed to pharmaceutical compositions containing a specific crystalline form of ibrutinib defined by XRPD 2-theta peak sets, where that crystalline form is produced by a solvent-mediated process using an alcohol (methanol or ethanol), optionally with water, and then combined with pharmaceutically acceptable excipients. The claims are framed as product-by-process: the composition is claimed by the resulting crystalline form plus the process that produced it.
Independent claim 1 (core claim scope)
Claim 1 covers a pharmaceutical composition comprising:
- A crystalline form of ibrutinib having XRPD 2-theta peaks at:
- 7.0 ± 0.1°
- 14.0 ± 0.1°
- 15.7 ± 0.1°
- 18.2 ± 0.1°
- plus a pharmaceutically acceptable excipient
- where that crystalline form is produced by a process comprising:
- combining a solvent solution comprising alcohol with
- crystalline ibrutinib having the same peak set (as a starting crystalline material)
- and the solvent solution includes alcohol (methanol or ethanol are specified in dependent claims).
Enforcement implication: To infringe claim 1, an accused product must (i) contain a crystalline form matching the specified XRPD peak pattern and (ii) be produced by the claimed solvent-alcohol process (at least as characterized by the claim’s product-by-process language).
Alcohol selection (claims 2–4)
- Claim 2: alcohol is methanol or ethanol
- Claim 3: alcohol is ethanol
- Claim 4: alcohol is methanol
Enforcement implication: Alcohol choice is a key limiter. A product produced using a different alcohol (e.g., isopropanol, n-propanol, tert-butanol) is outside these dependent claim pathways, and likely also outside the independent claim’s typical construction if “alcohol” is construed narrowly to those recited options in the family record (courts often treat specific dependent claims as clarifying the independent claim’s practical scope when the spec supports it).
Additional, narrower crystalline forms (claims 5, 7)
-
Claim 5 (dependent on claim 3/ethanol) specifies another crystalline form of ibrutinib with XRPD peaks at:
- 5.7 ± 0.1°
- 13.6 ± 0.1°
- 16.1 ± 0.1°
- 18.9 ± 0.1°
- 21.3 ± 0.1°
-
Claim 7 (dependent on claim 6, which adds water) further narrows to peaks at:
- 5.2 ± 0.1°
- 10.2 ± 0.1°
- 16.5 ± 0.1°
- 18.5 ± 0.1°
- 20.8 ± 0.1°
Enforcement implication: These dependent claims create separate crystallographic “design spaces”. Competitors can attempt to avoid by targeting a crystalline form whose XRPD peak pattern does not match these sets within the stated tolerances.
Recovery language (claims 8–14)
- Claims 8–14 add that the crystalline form is recovered from the solvent solution.
- This is essentially a process step tying the product to isolation from the crystallization medium.
Enforcement implication: “Recovered from the solvent solution” tends not to be a narrow differentiator if standard manufacturing necessarily isolates the solid phase from solvent. It does, however, create a handle for proving that the accused material came from an alcohol solvent crystallization workflow rather than, for example, milling-only or solid-state transformations without solvent recovery.
What is the practical claim “map” competitors will underwrite?
Below is a structured view of what must be present for each claim group.
Claim-by-claim enforceable elements
| Claim |
Product element (XRPD 2-theta peaks) |
Process element (solvent/process constraints) |
Key limiter |
| 1 |
7.0±0.1, 14.0±0.1, 15.7±0.1, 18.2±0.1 |
Combine solvent solution comprising alcohol with crystalline ibrutinib having same peak set |
alcohol-containing solvent; crystalline starting material seed |
| 2 |
same as 1 |
alcohol is methanol or ethanol |
alcohol set |
| 3 |
same as 1 |
alcohol is ethanol |
ethanol only |
| 4 |
same as 1 |
alcohol is methanol |
methanol only |
| 5 |
5.7±0.1, 13.6±0.1, 16.1±0.1, 18.9±0.1, 21.3±0.1 |
alcohol is ethanol |
second crystalline pattern tied to ethanol |
| 6 |
(as in 3) |
solvent solution further comprises water |
water addition |
| 7 |
5.2±0.1, 10.2±0.1, 16.5±0.1, 18.5±0.1, 20.8±0.1 |
alcohol is in claim 6 context (via claim 3) and includes water |
third crystalline pattern tied to water condition |
| 8–14 |
XRPD pattern per the dependency |
recovery from solvent solution |
isolation step |
Key boundary conditions embedded in the claims
- XRPD matching is the primary product discriminator. The tolerance is tight: ±0.1° on each recited 2-theta peak.
- Alcohol solvent is central. Dependent claims explicitly tie ethanol or methanol to specific crystallographic outcomes.
- Water changes the crystalline identity. Claims 6 and 7 create a water-dependent crystallization/isolation path.
- Seeded transformation is implied. Claim 1 uses “combining” a solvent solution with crystalline ibrutinib having a defined XRPD set. That reads as a transformation or recrystallization workflow using crystalline seed material.
How does this patent likely sit in the ibrutinib crystallization landscape?
US 10,961,251 is best understood as a crystalline form control patent with process-defined generation (alcohol/water solvent crystallization). In most ibrutinib patent portfolios, crystalline form claims cluster around:
- identification of polymorphs/solvates/hydrates by XRPD peak patterns,
- claims to manufacturing processes (solvent selection, crystallization conditions),
- and then downstream formulation composition claims that add excipient-based “composition” limitations.
Your provided claim text shows the strongest enforceable hooks are:
- exact peak lists and tolerances, and
- solvent system identity (methanol/ethanol, and optional water),
- with recovery from solvent.
Competitor “escape routes” implied by the claim language
Because infringement hinges on XRPD peak sets, competitors can generally explore:
- Alternative polymorph/solvate families whose XRPD peaks do not match within ±0.1°,
- Different alcohol systems outside methanol/ethanol (for the relevant dependent claims),
- Solvent system modifications that avoid the water-included crystallization pathway recited in claims 6 and 7,
- Different crystallization mechanisms where the accused material’s crystalline identity is formed without matching the claimed solvent-alcohol “produced by process” characterization.
Whether these routes actually avoid infringement depends on claim construction, prosecution history, and the patent’s specification (not provided here). Still, the claim text itself creates clear “design-out” levers: XRPD matching and solvent identity.
What is the likely scope of protection (and what is not) based on claim structure?
Protection scope: broad on composition, narrow on crystalline identity
- Broad: The claims cover a “pharmaceutical composition” with any pharmaceutically acceptable excipient. That can include typical tablet/capsule/suspension excipients depending on the specification.
- Narrow: The crystalline identity is tightly constrained to specific XRPD peak lists. Even if excipients differ, crystalline form must match.
Protection scope: tied to solvent-alcohol production
- The independent claim is product-by-process. If an accused crystalline form matches the peak set but is made by a different process, courts may still treat it as infringing depending on how the process language is interpreted and whether identity can be proven to be the same.
- Practically, competitors will assume that proving matching XRPD peaks is often the decisive evidentiary question, followed by process provenance.
Not covered (based strictly on the provided claim text)
- Non-alcohol solvents as the key solvent system (unless still construed as “solvent solution comprising alcohol”).
- Other alcohols beyond methanol and ethanol in the dependent claims.
- Crystalline forms not matching the listed peak sets, even if the material is still “ibrutinib” and still crystalline.
How to evaluate a freedom-to-operate risk reading of US 10,961,251
Even without the rest of the application record, the claims as provided create a concrete testing and evidence plan for litigation readiness and for manufacturing risk scoring.
Risk factors for potential challengers (manufacturers/generics)
- Use of methanol or ethanol in crystallization/recrystallization of iibrutinib.
- Use of water co-solvent leading to a different crystalline form with the claim-7-type peak set.
- XRPD results that, after considering instrument/reporting conditions, land within ±0.1° for the key peaks.
Evidence most likely to be determinative
- XRPD patterning of the accused bulk material compared to:
- Claim 1 peaks: 7.0, 14.0, 15.7, 18.2 (±0.1 each)
- Claim 5 peaks: 5.7, 13.6, 16.1, 18.9, 21.3
- Claim 7 peaks: 5.2, 10.2, 16.5, 18.5, 20.8
- Process documentation showing solvent system:
- alcohol present (methanol or ethanol)
- water present or not (depending on which crystalline form is being claimed)
What does the “claim numbering” signal about exclusivity vs incremental coverage?
- Claims 2–4 create a straightforward ladder from claim 1 to specific alcohols.
- Claims 5 and 7 are crystallographically distinct and depend on the alcohol/water conditions, signaling the patent is not only claiming “any crystalline ibrutinib made with ethanol,” but rather specific XRPD-defined outcomes.
- Claims 8–14 are largely procedural/handling (recovery from solvent solution), suggesting the patent is trying to close a common product manufacturing gap: ensuring that isolated solid from that solvent system still falls within the composition claim.
This architecture is consistent with a strategy to cover both:
- downstream commercial material (composition with excipients), and
- upstream crystallization steps that justify the material’s identity.
Key Takeaways
- US 10,961,251 claims pharmaceutical compositions containing XRPD-defined crystalline ibrutinib, with crystallinity characterized by tight 2-theta peak lists (±0.1°).
- The crystalline form is produced by combining crystalline ibrutinib with a solvent solution containing alcohol, with dependent claims narrowing alcohol identity to methanol or ethanol and introducing water for specific crystalline outcomes.
- The enforceable “decision points” are: (1) XRPD peak matching and (2) solvent system identity (alcohol type, water presence), with an added “recovery from solvent solution” isolation element.
- For competitive positioning or risk scoring, focus on whether the target process yields a crystalline form matching the specific peak sets recited in claims 1, 5, and 7.
FAQs
1) What crystalline identification is required for independent claim 1?
A crystalline ibrutinib form with XRPD 2-theta peaks at 7.0±0.1°, 14.0±0.1°, 15.7±0.1°, and 18.2±0.1°.
2) Which alcohols are explicitly covered in dependent claims?
Ethanol and methanol.
3) Do claims 5 and 7 cover different crystalline forms than claim 1?
Yes. Claim 5 has a distinct five-peak set (5.7, 13.6, 16.1, 18.9, 21.3). Claim 7 adds a different five-peak set (5.2, 10.2, 16.5, 18.5, 20.8) and is tied to the water-containing solvent scenario.
4) Does the patent require water for all claimed forms?
No. Water is introduced in claim 6, which then narrows to the specific crystalline pattern of claim 7.
5) What does “recovered from the solvent solution” add?
It ties the crystalline form to isolation from the solvent medium used in the alcohol (and possibly water) process, aligning the claimed solid with standard crystallization and recovery workflows.
References
No external sources were provided or cited in the prompt.
