Crystalline forms of a CD73 inhibitor and uses thereof

Patent metadata

Field	Value
Publication number	US-12281136-B2
Application number	US-202318297398-A
Country	US
Kind code	B2
Filing date	Apr 7, 2023
Priority date	Jun 17, 2020
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

Crystalline forms of the compound of Formula (I), which modulates the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compound and methods for preparing the crystalline forms, are described herein. The use of such crystalline form of Formula (I) and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

First claim

What is claimed is:

1. Crystalline Form III of a compound of Formula (I):

characterized by an XRPD pattern comprising peaks at 6.6, 10.9, 14.2, 16.1, 18.4, and 19.3 degrees 20 (±0.2 degrees 2θ).

2. The crystalline Form III of claim 1 , wherein the XRPD pattern further comprises one or more peaks at 20.2, 22.0, 24.7, and 28.1 degrees 2θ (±0.2 degrees 2θ).

3. The crystalline Form III of claim 1 , wherein the XRPD pattern further comprises three or more peaks at 20.2, 22.0, 24.7, and 28.1 degrees 2θ (±0.2 degrees 2θ).

4. The crystalline Form III of claim 1 , wherein the X-ray powder diffraction pattern is substantially in accordance with FIG. 5 .

5. The crystalline Form III of claim 1 , which is substantially free of other crystalline or amorphous forms of a compound of Formula (I).

6. The crystalline Form III of claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 161.8° C.

7. The crystalline Form III of claim 1 , further characterized by a melting point onset of about 149.6° C. as determined by a differential scanning calorimetry thermogram (DSC).

8. The crystalline Form III of claim 6 , wherein the DSC thermogram is substantially in accordance with FIGS. 6 .

9. Crystalline Form VI of a compound of Formula (I):

characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 19.4, 21.3, 22.4, and 24.4 degrees 2θ (±0.2 degrees 2θ) and further comprising three or more peaks at 5.8, 10.4, 27.5, and 31.1 degrees 2θ (±0.2 degrees 2θ).

10. The crystalline Form VI of claim 9 , wherein the X-ray powder diffraction pattern is substantially in accordance with FIG. 10 .

11. The crystalline Form VI of claim 9 , which is substantially free of other crystalline or amorphous forms of a compound of Formula (I).

12. The crystalline Form VI of claim 9 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 142.9° C.

13. The crystalline Form VI of claim 12 , wherein the DSC thermogram is substantially in accordance with FIG. 11 .

14. The crystalline Form VI of claim 9 , further characterized by a melting point onset of about 116.6° C. as determined by a differential scanning calorimetry thermogram (DSC).

15. A pharmaceutical composition comprising a crystalline form of any one of claims 1 or 9 , and a pharmaceutically acceptable excipient.

16. A method of treating a disease, disorder, or condition, mediated at least in part by CD73, said method comprising administering an effective amount of a crystalline form of the compound of any one of claims 1 or 9 , to a subject in need thereof.

17. The method of claim 16 , wherein the disease, disorder, or condition is cancer.

18. The method of claim 17 , wherein the cancer is selected from the group consisting of melanoma, colon cancer, pancreatic cancer, breast cancer, prostate cancer, lung cancer, leukemia, a brain tumor, lymphoma, ovarian cancer, and Kaposi's sarcoma.

19. A method of treating cancer in a subject, said method comprising administering to said subject an effective amount of a crystalline form of the compound of any one of claims 1 or 9 , and at least one additional therapeutic agent.

Assignees

• Arcus Biosciences Inc

Inventors

• Pennell Andrew M K
• Connor Eric F
• Gottschling Stephen Edmund
• Colomvakos Jim Dimetrios
• Khan Mohammed Asadullah

Classifications

• C07K16/2827

  against B7 molecules, e.g. CD80, CD86 · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title