Crystalline forms of CFTR modulators
Inventors
IYEMPERUMAL, Satish Kumar • Peresypkin, Andrey • Shi, Yi • Shrestha, Muna
Assignees
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Publication Number
US-12552810-B2
Publication Date
2026-02-17
Expiration Date
Abstract
Crystalline forms of salts of Compound I are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.
Core Innovation
The invention concerns substantially crystalline Compound I selected from substantially pure Compound I benzenesulfonic acid Forms A, B, and C, Compound I p-toluenesulfonic acid Form A, and Compound I magnesium salt Form A. The claimed crystalline Compound I contains less than 15% of Compound I in amorphous form. The crystalline forms are distinguished by characteristic X-ray powder diffraction peak patterns and characterized by thermogravimetric analysis and differential scanning calorimetry data.
The crystalline forms may provide improved purity, chemical or physical stability, and lower hygroscopicity compared with previously disclosed amorphous forms. Compound I increases CFTR-mediated chloride transport alone and demonstrates greater effects in combination with Compound II or Compound III, showing synergy in combinations with Compound III. The disclosure further describes pharmaceutical compositions and cystic fibrosis treatment.
Claims Coverage
The claims identify one independent claim comprising two inventive features directed to substantially crystalline Compound I in specified salt forms and with a limit on amorphous content.
Specified crystalline Compound I forms
Substantially crystalline Compound I is selected from substantially pure Compound I benzenesulfonic acid Form A, Compound I benzenesulfonic acid Form B, Compound I benzenesulfonic acid Form C, Compound I p-toluenesulfonic acid Form A, and Compound I magnesium salt Form A.
Limit on amorphous Compound I
Less than 15% of Compound I is in amorphous form.
The independent claim covers five specified crystalline forms of Compound I and limits the amorphous content to less than 15%.
Stated Advantages
The crystalline forms may provide improved purity compared with previously disclosed amorphous forms.
The crystalline forms may provide improved chemical or physical stability compared with previously disclosed amorphous forms.
The crystalline forms may provide lower hygroscopicity compared with previously disclosed amorphous forms.
Compound I modestly increases CFTR-mediated chloride transport alone, with greater effects when combined with Compound II and/or Compound III; combinations involving Compound III show synergy.
Documented Applications
Use in a pharmaceutical composition comprising substantially crystalline Compound I.
Treatment of cystic fibrosis with substantially crystalline Compound I, including treatment in combination with one or more additional CFTR modulators selected from Compound II, Compound III, or Compound III-d.
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