Granted Patent B2

US 12,545,686 · App. 18/614,458 · Granted Feb 10, 2026

Inventors: Jean-Michel Vernier (San Diego, CA); Fritz Blatter (Reinach, CH); Axel Rainer Maier (Baden-Württemberg, DE); Nicolino Tufilli (Moehlin, CH)

Assignee: KATMAI PHARMACEUTICALS, INC.

C07D491/056A61K31/517

Abstract

Claims (43)

1 . A polymorph of Compound (I):

wherein the polymorph is Form D; and

wherein the polymorph is characterized by an X-ray powder diffraction pattern comprising characteristic peaks expressed in values (°2θ) at 15.6°±0.2°2θ, 16.9°±0.2°±2θ, 19.1°±0.2°±2θ, 19.5°±0.2°±2θ, 22.5°±0.2°2θ, and 26.0°±0.2°2θ.

2 . The polymorph of claim 1 , wherein the polymorph is further characterized by an X-ray powder diffraction pattern comprising a characteristic peak expressed in a value (°2θ) at 15.2°±0.2°2θ.

3 . The polymorph of claim 1 , wherein the polymorph is further characterized by an X-ray powder diffraction pattern comprising characteristic peaks expressed in values (°2θ) at 10.2°±0.2°2θ, 13.5°±0.2°2θ, 15.9°±0.2°2θ, 23.3°±0.2°2θ, 24.3°±0.2°2θ, 24.7°±0.2°2θ, 24.9°±0.2°2θ, 27.9°±0.2°2θ, and 29.6°±0.2°2θ.

4 . The polymorph of claim 1 , wherein the polymorph is further characterized by a melting point of 153° C.

5 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the polymorph of Compound (I) of claim 1 .

6 . A method for treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the polymorph of Compound (I) of claim 1 .

7 . The method of claim 6 , wherein the cancer is characterized by aberrant epidermal growth factor receptor (EGFR) expression.

8 . The method of claim 6 , wherein the cancer is brain cancer.

9 . A process for preparing the polymorph of Compound (I) of claim 1 :

wherein the polymorph is Form D; and

wherein the polymorph is characterized by an X-ray powder diffraction pattern comprising characteristic peaks expressed in values (°2θ) at 15.6°±0.2°2θ, 16.9°±0.2°2θ, 19.1°±0.2°2θ, 19.5°±0.2°2θ, 22.50°±0.202θ, and 26.0°±0.2°2θ;

wherein the process comprises:

evaporating a solution of an amorphous form of Compound (I):

wherein a solvent of the solution is selected from the group consisting of (a), (b), and (c):

(a) acetone:heptane (1:3);

(b) n-butyl acetate; and

(c) methanol:diisopropyl ether (1:12).

10 . A process for preparing the polymorph of Compound (I) of claim 1 :

wherein the polymorph is Form D; and

wherein the polymorph is characterized by an X-ray powder diffraction pattern comprising characteristic peaks expressed in values (°2θ) at 15.6°±0.2°2θ, 16.9°±0.2°2θ, 19.1°±0.2°2θ, 19.5°±0.2°2θ, 22.5°±0.2°2θ, and 26.0°±0.2°2θ;

wherein the process comprises:

crystallizing an amorphous form of Compound (I):

in a nonaqueous solvent system via a technique selected from the group consisting of equilibrating, seeding, and slurrying, or a combination thereof, to convert the amorphous form of Compound (I) to polymorph Form D of Compound (I).

11 . The process of claim 10 , wherein the crystallizing further comprises an equilibrating, a seeding, or a slurrying technique selected from the group consisting of (a), (b), (c), (d), (e), and (f):

(a) equilibrating in isopropyl acetate:heptane (1:1);

(b) equilibrating in isopropyl acetate:heptane (2:3);

(c) equilibrating in methyl tetrahydrofuran (THF):methyl cyclohexane (1:2);

(d) seeding with Form D in ethyl acetate;

(e) slurrying in acetonitrile; and

(f) slurrying in ethyl acetate.

12 . The process of claim 10 , wherein the equilibrating is suspension equilibrating.

13 . The process of claim 12 , wherein the suspension equilibrating further comprises a suspension equilibrating technique selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), and (i):

(a) suspension equilibrating in n-butyl acetate:heptane (5:2);

(b) suspension equilibrating in tert-butyl methyl ether (TBME) with seeding with Form D;

(c) suspension equilibrating in heptane:methyl isobutyl ketone (MIBK) (4:1);

(d) suspension equilibrating in isopropyl acetate:cyclohexane (1:2);

(e) suspension equilibrating in diisopropyl ether;

(f) suspension equilibrating in methanol:methyl cyclohexane (1:4);

(g) suspension equilibrating in methyl ethyl ketone (MEK):diisopropyl ether;

(h) suspension equilibrating in methyl ethyl ketone (MVEK):p-xylene (1:2) and partial evaporation of solvent; and

(i) suspension equilibrating in trimethylamine.

Assignments (2)

Continuity (3)

References Cited (137)