Solid forms of a CDK4 inhibitor
Inventors
CLARK, Wesley Dewitt • Deal, Judith Gail • Samas, Brian Matthew
Assignees
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Publication Number
US-12570641-B2
Publication Date
2026-03-10
Expiration Date
Abstract
This invention relates to crystalline and amorphous forms of 1,5-anhydro-3-({5-chloro-4-[4-fluoro-2-(2-hydroxypropan-2-yl)-1-(propan-2-yl)-1H-benzimidazol-6-yl]pyrimidin-2-yl}amino)-2,3-dideoxy-D-threo-pentitol, to pharmaceutical compositions comprising such solid forms, and to use of such solid forms and pharmaceutical compositions for the treatment of cancer.
Core Innovation
The invention concerns solid forms of PF-07220060, including PF-07220060 monohydrate (Form 2), PF-07220060 hydrate (Form 1), PF-07220060 amorphous (Form 8), and anhydrous crystalline forms PF-07220060 (Form 6 and Form 11). The disclosed forms are characterized using powder X-ray diffraction (PXRD), Raman spectrum wavenumber peaks, and solid-state NMR resonance values, including 19F solid state NMR resonance values of −126.1 and −125.6 ppm ±0.2.
The document describes conversions and comparative characterization showing relationships among the forms, including Form 1 and Form 8 as compared with Form 2, using PXRD, Raman, and solid-state NMR fingerprints and related analytical assessments. The solid forms are defined by their analytical signatures rather than by synthesis details.
The invention further addresses solid-state performance for Form 2 under humidity/heat and light, and includes moisture sorption comparisons among Forms 1, 2, 6, and 8. Solid-state stability is evaluated using analytical profiles, and the document reports that no form change by PXRD is observed for Form 2 under the evaluated conditions.
Claims Coverage
The independent claims are directed to specific PF-07220060 solid forms (Form 2, Form 6, Form 11, and Form 8) defined by quantitative solid-state identification features using PXRD, Raman, and solid-state NMR (13C and/or 19F, with specified resonance or peak positions). Across the independent claims, the inventive features are the fingerprint-defined crystal or amorphous form identities and the defined NMR, PXRD, and Raman signature criteria for those identities.
19F solid state NMR-defined PF-07220060 monohydrate (Form 2)
A crystalline form of PF-07220060 monohydrate (Form 2) having a 19F solid state NMR spectrum comprising resonance (ppm) values of −126.1 and −125.6 (±0.2 ppm).
PXRD peaks-defined PF-07220060 monohydrate (Form 2)
A crystalline form of PF-07220060 monohydrate (Form 2) having a powder X-ray diffraction (PXRD) pattern comprising peaks at 2θ values of 9.6, 11.8 and 14.7 (each ±0.2).
Multi-signature-defined PF-07220060 monohydrate (Form 2)
A crystalline form of PF-07220060 monohydrate (Form 2), having PXRD peaks at 2θ values of 9.6, 11.8 and 14.7 (±0.2), Raman spectrum wavenumber values of 1484, 1555 and 1587 cm−1 (±2 cm−1), 13C solid state NMR resonance values of 22.8 and 163.0 ppm (±0.2 ppm), and/or 19F solid state NMR resonance values of −126.1 and −125.6 ppm (±0.2 ppm), or any combination of these characterization types.
PXRD, Raman, and solid-state NMR-defined anhydrous crystalline PF-07220060 (Form 6)
An anhydrous crystalline form of PF-07220060 (Form 6), having PXRD peaks at 2θ values of 8.5, 10.1 and 13.8 (±0.2), Raman spectrum wavenumber values of 1436, 1465 and 1566 cm−1 (±2 cm−1), 13C solid state NMR resonance values of 54.7, 112.6 and 132.8 ppm (±0.2 ppm), and/or 19F solid state NMR resonance values of −132.4 and −131.1 ppm (±0.2 ppm), or any combination of two or more of these characterization types.
PXRD-pattern defined anhydrous crystalline PF-07220060 (Form 11)
An anhydrous crystalline form of PF-07220060 (Form 11), having a powder X-ray diffraction (PXRD) pattern essentially the same as in FIG. 15.
NMR-defined amorphous PF-07220060 (Form 8)
An amorphous form of PF-07220060 (Form 8) having a 19F solid state NMR spectrum comprising a resonance (ppm) value of −127.5 (±0.5 ppm).
Overall, the claim set covers multiple PF-07220060 solid forms by defining each form through quantitative solid-state identification criteria. The independent claims use fingerprint-defined PXRD peak locations, Raman wavenumber peaks, and 13C/19F solid-state NMR resonance positions, including single-signature identification for Form 2, multi-signature identification for Form 2, combined fingerprint criteria for anhydrous Form 6, a PXRD similarity designation for Form 11, and a 19F NMR resonance criterion for amorphous Form 8.
Stated Advantages
No form change by PXRD is observed for Form 2 under the evaluated humidity/heat and light conditions.
Documented Applications
Breast cancer treatment by administering a therapeutically effective amount of either a crystalline form or an amorphous form of PF-07220060.
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