Cocrystals, pharmaceutical compositions thereof, and methods of treatment involving same
Inventors
Lane, Benjamin S. • Gu, Chong-Hui
Assignees
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Publication Number
US-12679820-B2
Publication Date
2026-07-14
Expiration Date
Abstract
Provided are solid forms of a compound useful for treating cancer, pharmaceutical compositions thereof, and methods of treating cancer comprising administering the solid forms described herein to a patient in need thereof.
Core Innovation
The disclosure describes multiple solid-state forms of compound (I), including crystalline free forms, solvates, hydrates, citric-acid and maleic-acid cocrystals, and an amorphous solid dispersion. Crystalline forms of compound (I) are defined by specified X-ray powder diffraction peak positions within ±0.2 degrees 2-theta. Characterization provides diffraction patterns, thermal behavior, and crystal-packing diagrams for Free Form Type A, an anhydrate Free Form B, a trihydrate Free Form C, and a dioxane solvate Free Form D.
The solid-state forms are directed to pharmaceutical compositions and methods of treating cancer characterized by an IDH1 or IDH2 mutation. In dissolution testing, the spray-dried HPMCAS amorphous solid dispersion maintains supersaturation. Citrate and maleate cocrystals demonstrate higher absolute bioavailability in rat pharmacokinetic evaluations than Free Forms A and C, while citric acid cocrystal Type A further exhibits high crystallinity, low hygroscopicity, and a sharp melting endotherm.
Claims Coverage
The claim coverage identifies one independent claim and four inventive features encompassing the crystalline form, further analytical characterizations, pharmaceutical compositions, and therapeutic treatments.
Crystalline form defined by diffraction peaks
The independent claim covers a crystalline form of a compound of formula (I) comprising at least one X-ray diffraction peak position selected from 11.7, 12.8, 14.2, 17.8, 19.8, 20.7, 21.8, 22.2, and 25.0 degrees 2-theta (±0.2 degrees 2-theta).
Further characterization of the crystalline form
Dependent claims further specify a reflection-mode X-ray powder diffraction pattern with at least two selected peak positions and a differential scanning calorimetry thermogram with an endothermic peak onset at a stated temperature.
Pharmaceutical composition
A dependent claim covers a pharmaceutical composition comprising a therapeutically effective amount of the crystalline form and one or more pharmaceutical excipients.
Treatment of IDH-mutated cancer
A dependent claim covers treating cancer characterized by an IDH1 or IDH2 mutation by administering a therapeutically effective amount of the crystalline form to a patient in need thereof.
The claims center on the specified crystalline form of compound (I), with dependent coverage extending to structural characterization, pharmaceutical compositions, and methods of treating IDH1- or IDH2-mutated cancer.
Stated Advantages
Citrate and maleate cocrystals demonstrate higher absolute bioavailability than Free Forms A and C in rat pharmacokinetic evaluations.
The spray-dried HPMCAS amorphous solid dispersion maintains supersaturation in dissolution testing.
Citric acid cocrystal Type A exhibits high crystallinity, a sharp melting endotherm, low hygroscopicity, and favorable bioavailability.
Documented Applications
A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form and one or more pharmaceutical excipients.
Treatment of cancer characterized by an IDH1 or IDH2 mutation by administering a therapeutically effective amount of the crystalline form to a patient in need thereof.
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