IP Library Granted Patent US 12,281,120
Granted Patent B2
US 12,281,120 · App. 18/306,649 · Granted Apr 22, 2025

Crystalline forms of 2-[3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile

Inventors: Kolbot By (San Ramon, CA); Mohammad R. Masjedizadeh (San Jose, CA); Pasit Phiasivongsa (Hillsborough, CA); Jiang Zhu (San Ramon, CA)
Assignee: Principia Biopharma Inc.
C07D487/04C07B2200/13
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Quick Facts
Patent No.
US 12,281,120
App. No.
18/306,649
Granted
Apr 22, 2025
Kind
B2
Abstract

Crystalline forms of Compound (I): are disclosed. Pharmaceutical compositions comprising the same, methods of inhibiting BTK using the same, and methods for making crystalline forms of Compound (I) are also disclosed.

Claims (18)

1. Crystalline Form (II) of Compound (I):

wherein crystalline Form (II) is characterized by an X-ray powder diffractogram comprising at least one signal at a value (°2θ) chosen from 15.2°±0.2 °2θ, 16.0°±0.2 °2θ, 16.6°±0.2 °2θ, 17.7°±0.2 °2θ, 20.02+0.2 °2θ, 24.8°±0.2 °2θ, and 27.5°±0.2 °2θ.

2. The crystalline Form (II) according to claim 1 , wherein the crystalline Form (II) has at least one further characteristic chosen from (i), (ii), and (iii):

(i) a differential scanning calorimetry (DSC) thermogram having an endothermic peak at about 170.0° C. to about 170.2° C.;

(ii) a differential scanning calorimetry (DSC) thermogram showing an onset of melting at about 167.2° C. to about 167.6° C.; and

(iii) a mass loss of less than 1.5 wt. % between 35° C. and 220° C. by thermogravimetric analysis (TGA).

3. The crystalline Form (II) according to claim 1 , wherein at least 95% by weight of the crystalline Form (II) of Compound (I) is the (R) enantiomer.

4. The crystalline Form (II) according to claim 1 , wherein at least 95% by weight of the crystalline Form (II) of Compound (I) is the (E) diastereomer.

5. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the crystalline Form (II) according to claim 1 .

6. A process for preparing crystalline Form (II) of Compound (I):

wherein crystalline Form (II) is characterized by an X-ray powder diffractogram comprising at least one signal at a value (°2θ) chosen from 15.2°±0.2 °2θ, 16.0°±0.2 °2θ, 16.6°±0.2 °2θ, 17.7°±0.2 °2θ, 20.0°±0.2 °2θ, 24.8°±0.2 °2θ, and 27.5°±0.2 °2θ, and wherein the process comprises the following steps:

(1) dissolving amorphous (R)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl) piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile of the following formula:

in methyl tert-butyl ether to form a solution;

(2) stirring the solution formed in step (1) above, to form a precipitate; and

(3) isolating crystalline Form (II) of 2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl) piperidine-1-carbonyl)-4,4-dimethylpent-2-enenitrile (Compound (I)) above by filtration.

7. The Crystalline Form (II) of Compound (I):

wherein the crystalline Form (II) is further characterized by an X-ray powder diffractogram comprising at least two signals at values (°2θ) chosen from 6.3°±0.2 °2θ, 15.2°±0.2 °2θ, 16.0°±0.2 °2θ, 16.6°±0.2 °2θ, 17.7°±0.2 °2θ, 20.0°±0.2 °2θ, 24.8°±0.2 °2θ, and 27.5°±0.2 °2θ.

8. The crystalline Form (II) according to claim 7 , wherein the crystalline Form (II) is further characterized by an X-ray powder diffractogram comprising at least three signals at values (°2θ) chosen from 6.3°±0.2 °2θ, 15.2°±0.2 °2θ, 16.0°±0.2 °2θ, 16.6°±0.2 °2θ, 17.7°±0.2 °2θ, 20.0°±0.2 °2θ, 24.8°±0.2 °2θ, and 27.5°±0.2 °2θ.

Assignments (2)
ASSIGNEE CHANGE OF ADDRESS Recorded Sep 16, 2025
From: PRINCIPIA BIOPHARMA INC.
To: PRINCIPIA BIOPHARMA INC.
Reel/Frame 072881/0270 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 19, 2023
From: BY, KOLBOT; PHIASIVONGSA, PASIT; ZHU, JIANG; MASJEDIZADEH, MOHAMMAD
To: PRINCIPIA BIOPHARMA INC.
Reel/Frame 064309/0480 →
Continuity (3)
Division 17143355 · Jan 7, 2021
Provisional Application 62958389 · Jan 8, 2020
Related Publication 20240190882A1 · Jun 13, 2024
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