IP Library › Granted Patent US 12,552,810
Granted Patent B2
US 12,552,810 · App. 18/020,802 · Granted Feb 17, 2026

Crystalline forms of CFTR modulators

Inventors: Satish Kumar Iyemperumal (Reading, GB); Andrey Peresypkin (Newton, MA); Yi Shi (Natick, MA); Muna Shrestha (Belmont, MA)
Assignee: Vertex Pharmaceuticals Incorporated
C07D513/22A61P11/00C07B2200/13
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Quick Facts
Patent No.
US 12,552,810
App. No.
18/020,802
Granted
Feb 17, 2026
Kind
B2
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.

Claims (19)

1 . A substantially crystalline Compound I

wherein the 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, wherein less than 15% of Compound I is in amorphous form.

2 . The substantially crystalline Compound I according to claim 1 , wherein less than 10% of Compound I is in amorphous form.

3 . The substantially crystalline Compound I according to claim 1 , wherein less than 5% of Compound I is in amorphous form.

4 . The substantially crystalline Compound I according to claim 1 , wherein 100% of Compound I is crystalline.

5 . A pharmaceutical composition comprising the substantially crystalline Compound I according to claim 1 .

6 . The pharmaceutical composition according to claim 5 , further comprising one or more additional CFTR modulating compounds.

7 . The pharmaceutical composition according to claim 6 , wherein at least one additional CFTR modulating compound is a CFTR potentiator.

8 . The pharmaceutical composition according to claim 6 , wherein at least one additional CFTR modulating compound is a CFTR corrector.

9 . The pharmaceutical composition according to claim 6 , wherein the one or more additional CFTR modulating compounds are selected from

10 . A method of treating cystic fibrosis comprising administering an effective amount of the substantially crystalline Compound I according to claim 1 to a subject in need thereof.

11 . The method of treating cystic fibrosis according to claim 10 , wherein the substantially crystalline Compound I is administered with one or more additional CFTR modulating compounds.

12 . The method of treating cystic fibrosis according to claim 11 , wherein the one or more additional CFTR modulating compound are selected from

13 . A method of preparing a substantially crystalline Compound I according to claim 1 , comprising:

(a) bead milling Compound I free acid with benzenesulfonic acid in ethanol and drying under vacuum to provide crystalline Compound I benzenesulfonic acid Form A;

(b) bead milling Compound I free acid with benzenesulfonic acid in THF and drying under vacuum to provide crystalline Compound I benzenesulfonic acid Form B;

(c) bead milling Compound I free acid with benzenesulfonic acid in isopropyl acetate and drying under vacuum to provide crystalline Compound I benzenesulfonic acid Form C;

(d) bead milling Compound I free acid with p-toluenesulfonic acid in isopropyl acetate and drying under vacuum to provide crystalline Compound I p-toluenesulfonic acid Form A; or

(e) slurrying Compound I free acid with magnesium chloride and sodium hydroxide in a mixture of 1,4-dioxane and water, freeze drying the mixture, adding acetone and water, temperature cycling the mixture between ambient temperature and 40° C., filtering the solids, and drying under vacuum to provide substantially crystalline Compound I magnesium salt Form A.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 3, 2025
From: IYEMPERUMAL, SATISH KUMAR; PERESYPKIN, ANDREY; SHI, YI; SHRESTHA, MUNA
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 072757/0298 →
Continuity (2)
Provisional Application 63065057 · Aug 13, 2020
Related Publication 20230303589A1 · Sep 28, 2023
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