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Patent landscape, scope, and claims: |
United States Patent 9,309,229: Scope, Claims, and Crystalline-Form Patent Landscape for the 5-Chloro Pyrimidine-2,4-diamine
What does US 9,309,229 protect?
US Patent 9,309,229 protects crystalline forms (two distinct “Forms A and B”) of a specific API: 5-Chloro-N2-(2-isopropoxy-5-methyl-4-piperidin-4-yl-phenyl)-N4-[2-(propane-2-sulfonyl)-phenyl]pyrimidine-2,4-diamine, with protection anchored on X-ray powder diffraction (XRPD) peak position sets, plus secondary solid-state property limits (DSC melting point, decomposition point and TGA weight loss, and IR band sets), and further extended to compositions and manufacturing and interconversion methods.
The claim set is organized into:
- Product-by-crystallinity (XRPD peak maxima)
- Product-by-crystallinity + solid-state specs (melting point, decomposition, TGA loss, IR bands)
- Purity-limited variants (total impurities by weight thresholds)
- Pharmaceutical compositions
- Preparation and conversion methods (including Form B to Form A conversion)
How broad are the crystalline-form claims (Form A vs Form B)?
Protection is primarily feature-based (XRPD peak maxima at specified 2θ angles). That makes infringement largely a forensic powder characterization exercise.
Claim-1 anchor: Form A XRPD maxima (2θ)
Claim 1 requires a crystalline form exhibiting one or more XRPD peaks with maxima at selected diffraction angles listed (2θ degrees). The list in claim 1 is:
7.2, 8.1, 10.8, 12.0, 12.4, 13.4, 14.4, 14.8, 15.7, 16.9, 17.7, 18.5, 19.0, 19.5, 20.0, 20.3, 21.1, 21.6, 22.4, 22.6, 23.0, 24.1, 24.5, 25.5, 26.0, 26.2, 27.0, 27.3, 28.3, 29.0, 29.1, 30.6, 31.3, 32.8, 33.5, 34.2, 36.4.
Key breadth point: the claim says “one or more” peaks. That means not every peak must match; showing even a subset consistent with the list can be enough, depending on claim construction and the evidentiary pattern used in litigation.
Claim-8 anchor: Form B XRPD maxima (2θ)
Claim 8 similarly requires a crystalline form exhibiting one or more peaks at the listed 2θ maxima:
5.1, 5.5, 5.6, 9.5, 9.6, 10.1, 11.0, 11.8, 12.1, 12.6, 13.7, 14.5, 14.9, 15.2, 16.1, 16.6, 16.7, 17.0, 17.1, 17.5, 17.7, 18.0, 18.8, 19.0, 19.3, 19.5, 20.5, 20.9, 21.5, 21.9, 22.1, 22.4, 22.8, 23.2, 23.7, 23.9, 24.3, 24.5, 24.8, 25.1, 25.4, 25.5? (not present; list continues), 25.9, 26.4, 26.8, 27.8, 28.1, 28.6, 29.1, 29.6, 29.8, 30.6, 31.6, 32.7, 33.5, 34.2, 35.4, 35.6, 36.8.
Breadth is structurally the same: “one or more” peaks must align with the specified maxima set.
Practical implication for scope
Because both Form A and Form B use peak-position sets with “one or more” logic, the risk for generic or alternative-process producers is not just “does the polymorph exist,” but “does the measured XRPD pattern (peak picking tolerance, background handling, instrument calibration) include any of the claimed maxima.”
What secondary specs narrow (or help prove) infringement?
Claims 2-4 narrow Form A by specific thermodynamic and spectroscopic properties. Claims 9-11 narrow Form B similarly.
Form A narrowing claims
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Claim 2 (DSC): melting point 174°C
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Claim 3 (TGA): decomposition point >250°C and weight loss on drying 0.1% at 200°C
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Claim 4 (IR): characteristic infrared absorption bands at the listed wavenumbers (cm⁻¹):
3440.4, 3318.9, 2973.7, 2931.3, 2921.7, 1596.8, 1562.1, 1498.4, 1442.5, 1409.7, 1382.7, 1311.4, 1284.4, 1270.9, 1251.6, 1224.6, 1139.7, 1126.2, 1105.0, 1081.9, 1049.1, 1020.2, 1012.5, 952.7, 937.3, 894.8, 877.5, 860.1, 848.5, 817.7, 798.4, 781.0, 763.7, 756.0, 732.8, 686.6, 665.3, 644.1, 586.3, 543.8.
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Claims 5-7 (impurities): total impurities less than 1.0%, 0.5%, and 0.1% by weight, respectively.
Form B narrowing claims
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Claim 9 (DSC): melting point 162°C
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Claim 10 (TGA): decomposition point >250°C and weight loss on drying 0.05% at 200°C
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Claim 11 (IR): characteristic infrared absorption bands at:
3418.7, 3309.5, 3202.3, 2976.2, 2936.3, 2806.9, 2731.8, 1683.9, 1652.8, 1598.4, 1568.9, 1507.0, 1483.5, 1447.1, 1411.0, 1314.9, 1288.1, 1261.1, 1220.8, 1195.7, 1170.8, 1140.1, 1124.6, 1083.2, 1053.3, 1010.1, 947.1, 874.5, 776.0, 758.7, 734.5, 706.5, 678.5, 652.1, 586.3, 544.7, 519.1, 472.6, 456.8.
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Claims 12-14 (impurities): total impurities less than 1.0%, 0.5%, and 0.1% by weight.
How this changes the litigation posture
In practice:
- XRPD peak maxima claims are often the primary infringement hook.
- DSC/TGA/IR/impurity claims become evidentiary support and can also form separate limitations depending on the accused product’s measured properties.
- If a competitor argues that its solid form is different, it will typically fight on XRPD peak identity and phase purity and on whether the accused material meets the specific thermal and spectroscopic fingerprints in narrower dependent claims.
How does the patent extend beyond the crystalline solids?
US 9,309,229 covers downstream and process activities.
Pharmaceutical compositions
- Claim 15: pharmaceutical composition comprising Form A and a pharmaceutically acceptable carrier
- Claim 16: pharmaceutical composition comprising Form B and a pharmaceutically acceptable carrier
These claims add a form-based composition barrier, not just an API solids barrier. If a product formulation uses the claimed solid form, the carrier does not avoid coverage.
Preparation method (dihydrochloride base conversion with NaOH)
- Claim 17: method for preparing a crystalline form by reacting
5-Chloro...pyrimidine-2,4-diamine dihydrochloride in a solvent with at least two equivalents of aqueous sodium hydroxide
- Claim 18: solvent is acetone:water (3:1) by volume
- Claims 19-20: heating at 30-70°C, including 55°C specifically
This is a process claim tied to:
1) starting from the dihydrochloride,
2) using NaOH aqueous (at least 2 equivalents), and
3) using specific solvent and temperature conditions.
Conversion of Form B to Form A (antisolvent-seeding and thermal conversion)
Two conversion strategies are claimed.
(A) Seeding approach
- Claim 21: convert Form B to Form A by adding a small amount of Form A to a suspension of Form B in a solvent
- Claim 22: Form A amount ≤ 1.0% by weight
- Claim 23: solvent acetone:water (1:1) at 20-40°C
(B) Heating approach
- Claim 24: convert Form B to Form A by heating a suspension of Form B in a solvent
- Claim 25: solvent acetone:water 1:1 to 5:1 by volume; temperature 30-70°C
- Claim 26: solvent acetone:water 1:1 and temperature 50°C
Scope reading for conversion
If an accused manufacturer:
- uses Form B suspension media in acetone/water ratios overlapping the ranges, and
- either seeds with ≤1% Form A or heats in the claimed temperature bands,
it lands inside method claim territory even if the ultimate end product is Form A.
Claim-to-coverage map (what each claim adds)
| Claim(s) |
Subject |
What narrows/defines it |
Coverage impact |
| 1, 8 |
Form A / Form B crystalline forms |
XRPD peak maxima set (2θ list) with “one or more” peaks |
Broad product-by-structure via XRPD |
| 2-4 |
Form A specifications |
DSC melt 174°C; TGA specs; IR band set |
Strengthens proof for Form A; narrows dependent product definition |
| 5-7 |
Form A purity |
Total impurities <1.0%, <0.5%, <0.1% |
Phase and impurity control barrier |
| 9-11 |
Form B specifications |
DSC melt 162°C; TGA specs; IR band set |
Strengthens proof for Form B; narrows dependent product definition |
| 12-14 |
Form B purity |
Total impurities <1.0%, <0.5%, <0.1% |
Tightens phase/impurity barrier |
| 15-16 |
Pharmaceutical compositions |
Composition containing the claimed form + carrier |
Blocks formulation workarounds |
| 17-20 |
Preparation method |
NaOH aq at ≥2 eq, dihydrochloride starting material; acetone:water 3:1; 30-70°C (55°C) |
Process constraint on manufacturing route |
| 21-23 |
Conversion method (seed) |
Form A seeding ≤1% into Form B suspension; acetone:water 1:1; 20-40°C |
Direct method coverage for crystallization management |
| 24-26 |
Conversion method (heat) |
Heating Form B suspension; acetone:water 1:1 to 5:1; 30-70°C (incl 1:1 at 50°C) |
Captures alternative conversion workflows |
What does this imply for freedom-to-operate (FTO) decisions?
US 9,309,229 is built around solid-state identity plus manufacturing conditions.
High-risk technical touchpoints
- XRPD matching: If an accused solid form yields peaks at any of the listed maxima for Form A or Form B, risk rises under claims 1 and 8.
- Thermal and IR conformity: Meeting the dependent DSC/TGA/IR limitations supports infringement on those dependent claims.
- Impurities: If a manufacturer targets high purity that falls under the <1.0%, <0.5%, or <0.1% bands, it increases the chance of meeting dependent claim limitations.
- Conversion operations: Seeding and heating strategies overlap common polymorph control workflows. The patent captures conversion of Form B to Form A specifically.
Design-around levers that are not “safe” by default
The claim design is such that typical “avoid the exact polymorph” strategies can fail if:
- the company’s alternative process unintentionally produces a crystalline form containing XRPD maxima from the claim set, or
- a conversion step is used near the specified solvent/temperature conditions.
Patent landscape: what other filings likely matter (based on the claim structure)
The patent is a crystalline form patent that likely belongs to a family where other jurisdictions also include:
- crystalline form definitions via XRPD peak lists, and
- conversion and crystallization/process claims (seeding, solvent systems, and temperature bands),
- plus form-specific pharmaceutical compositions.
Within the broader landscape, this patent usually competes with three categories:
- Base-molecule patents (the active compound per se)
- Intermediate and salt patents (dihydrochloride and other forms)
- Other polymorph patents (Form C, solvates, hydrates, etc., if they exist)
Given the claim text here, the litigation-relevant contested issue is typically whether the competitor’s solid is:
- the same polymorph (by XRPD maxima),
- the same or overlapping impurity profile,
- and produced or converted using overlapping solvent and temperature conditions.
Key Takeaways
- US 9,309,229 protects two crystalline forms (Form A and Form B) of the same API using XRPD peak maxima lists tied to claims 1 and 8, with “one or more” peak language driving broad XRPD-based scope.
- Dependent claims lock in DSC melting points (174°C for Form A; 162°C for Form B), TGA behavior (decomposition >250°C; very low weight loss at 200°C), IR band sets, and tight impurity limits (<1.0%, <0.5%, <0.1%).
- The patent extends to pharmaceutical compositions containing either form and to manufacturing and conversion methods, including Form B to Form A via ≤1.0% Form A seeding and via heating in acetone/water solvent systems across defined ratios and temperature ranges.
- For FTO, the most actionable risk points are XRPD peak selection, phase purity/impurities, and whether any polymorph conversion step uses the captured solvent and temperature windows.
FAQs
1) Does the XRPD claim require matching every peak in the list?
No. Claims 1 and 8 require the crystalline form to exhibit “one or more” XRPD peaks with maxima at angles selected from the listed 2θ values, which creates a subset-matching infringement pathway.
2) Are Form A and Form B protected only as raw crystalline powders?
No. The patent includes pharmaceutical composition claims for both forms (claims 15 and 16), so formulation use can fall within scope if the formulation contains the claimed solid form.
3) What are the key thermal identifiers for Form A and Form B?
Form A: DSC melting point 174°C (claim 2). Form B: DSC melting point 162°C (claim 9). Both require decomposition >250°C with low TGA weight loss at 200°C (claims 3 and 10).
4) What are the two main method routes for converting Form B to Form A?
A seeding route (claim 21 with ≤1.0% Form A; claim 22) and a heating route (claim 24 with acetone:water 1:1 to 5:1; claim 25, including 1:1 at 50°C in claim 26).
5) Does the process claim require the dihydrochloride starting material?
Yes. Claim 17 specifies reacting the dihydrochloride with aqueous sodium hydroxide at at least two equivalents, in a solvent (with dependent claims specifying acetone:water 3:1 and temperature conditions).
References
- US Patent 9,309,229, claims as provided by user (XRPD, DSC, TGA, IR, impurity limits, composition, preparation and conversion methods).
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