Crystalline forms of N-[4-(chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide
Inventors
Dodd, Stephanie Kay • Grandeury, Arnaud • SUFFERT, Emmanuel • ROUSAKI, Evgenia
Assignees
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Publication Number
US-12252478-B2
Publication Date
2025-03-18
Expiration Date
Abstract
The present invention describes specific crystalline forms of N-[4-(Chlorodifluoromethoxy)phenyl]-6-[(3R)-3-hydroxypyrrolidin-1-yl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide. The present invention further relates to methods for preparing said crystalline forms, pharmaceutical compositions comprising said crystalline forms, and methods of using said crystalline forms and pharmaceutical compositions to treat disease.
Core Innovation
The disclosure describes crystalline forms of asciminib, including crystalline form A of asciminib hydrochloride and free base form A, together with multiple solvate forms S_A–S_D and additional hydrochloride crystalline forms. The described hydrochloride modifications include crystalline forms A and B and a trihydrate modification H_A. The crystalline form definitions are supported by XRPD together with thermal characterization.
The document characterizes the crystalline form A of asciminib hydrochloride using x-ray powder diffraction behavior, including a defined x-ray powder diffraction pattern comprising reflections at specified 2-Theta angles when measured at a specified temperature range using Cu-Kalpha1,2 radiation. Thermal behavior is characterized by DSC and TGA. Additional stability and transition behavior is described in relation to hydrochloride forms A and B.
The disclosure further describes pharmaceutical compositions that include therapeutically effective amounts of crystalline form A of asciminib hydrochloride in combination with pharmaceutically acceptable carriers, diluents, vehicles, or excipients. The document also describes pharmaceutical tablet formulations having an intra-granular phase, an extra-granular phase, and a film-coating with specified excipient sets. Characterization rationale for the solid forms and their physical properties is provided, including discussion of hygroscopic behavior and intrinsic dissolution behavior.
Claims Coverage
The provided material identifies one independent claim directed to a pharmaceutical composition comprising crystalline form A of asciminib hydrochloride defined by an XRPD reflection pattern, with multiple dependent claims refining characterization (XRPD/thermal), unit-cell characterization, and dosage-form and tablet-excipient constraints. The inventive features below summarize the main distinctions for the identified independent claim(s).
Pharmaceutical composition defined by crystalline form A XRPD reflections
A pharmaceutical composition comprising a therapeutically effective amount of a crystalline form A of asciminib hydrochloride and at least one pharmaceutically acceptable carrier, diluent, vehicle or excipient, wherein the crystalline form A is characterized by an x-ray powder diffraction pattern comprising reflections at 2-Theta angles of 12.6±0.2°, 18.9±0.2° and 20.9±0.2°, when measured at a temperature in the range of from 20 to 25° C. with Cu-Kalpha1,2 radiation having a wavelength of 0.1541 Å.
Across the provided claim set, protection centers on pharmaceutical compositions containing therapeutically effective amounts of asciminib hydrochloride in crystalline form A, where the form is defined by XRPD reflection criteria at specified 2-Theta values and measurement conditions. Dependent claims further refine the crystalline-form characterization and constrain formulation and tablet architecture, including intra-granular and extra-granular phases and film-coating.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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