Crystalline forms of a CD73 inhibitor and uses thereof

Patent metadata

Field	Value
Publication number	US-11649261-B2
Application number	US-202117348833-A
Country	US
Kind code	B2
Filing date	Jun 16, 2021
Priority date	Jun 17, 2020
Publication date	May 16, 2023
Grant date	May 16, 2023

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 I of a compound of Formula (I):

characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.1, 13.8, 18.6, 20.1, 23.0, and 24.8 degrees 2θ (±0.2 degrees 2θ).

2. The crystalline Form I of claim 1 , wherein the XRPD pattern further comprises one or more peaks at 11.6, 14.7, 15.4, 16.6, 17.0, 19.3, 21.3, 22.1, 24.8, 26.6, 27.3, and 29.1 degrees 2θ (±0.2 degrees 2θ).

3. The crystalline Form I of claim 1 , characterized by an X-ray powder diffraction pattern that is substantially in accordance with FIG. 1 .

4. The crystalline Form I of claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 163.9° C.

5. The crystalline Form I of claim 1 , further characterized by a melting point onset of about 155.1° C. as determined by a differential scanning calorimetry thermogram (DSC).

6. The crystalline Form I of claim 4 , wherein the DSC thermogram is substantially in accordance with FIG. 2 .

7. Crystalline Form II of a compound of Formula (I):

characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 16.5, 22.8, and 24.6 degrees 2θ (±0.2 degrees 2θ).

8. The crystalline Form II of claim 7 , wherein the XRPD pattern further comprises one or more peaks at 10.1, 10.8, 12.8, 13.7, 17.7, and 19.0 degrees 2θ (±0.2 degrees 2θ).

9. The crystalline Form II of claim 7 , characterized by an X-ray powder diffraction pattern that is substantially in accordance with FIG. 3 .

10. The crystalline Form II of claim 7 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 166.5° C.

11. The crystalline Form II of claim 7 , further characterized by a melting point onset of about 157.4° C. as determined by a differential scanning calorimetry thermogram (DSC).

12. The crystalline Form II of claim 10 , wherein the DSC thermogram is substantially in accordance with FIG. 4 .

13. Crystalline Form V of a compound of Formula (I):

characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 15.8, 16.3, 16.8, 18.5, 19.1, 21.7, 22.1, and 23.0 degrees 2θ (±0.2 degrees 2θ).

14. The crystalline Form V of claim 13 , wherein the XRPD pattern further comprises one or more peaks at 10.4, 15.1, 19.7, and 23.6 degrees 2θ (±0.2 degrees 2θ).

15. The crystalline Form V of claim 13 , characterized by an X-ray powder diffraction pattern that is substantially in accordance with FIG. 8 .

16. The crystalline Form V of claim 13 , further characterized by a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak at about 150.4° C.

17. The crystalline Form V of claim 13 , further characterized by a melting point onset of about 135.8° C. as determined by a differential scanning calorimetry thermogram (DSC).

18. The crystalline Form V of claim 16 , wherein the DSC thermogram is substantially in accordance with FIG. 9 .

19. A pharmaceutical composition comprising a crystalline form of any one of claim 1 , 7 , or 13 , and a pharmaceutically acceptable excipient.

20. 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 claim 1 , 7 , or 13 , to a subject in need thereof.

21. The method of claim 20 , wherein the disease, disorder, or condition is cancer.

22. The method of claim 21 , 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.

23. 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 claim 1 , 7 , or 13 , 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

• C07H19/02

  sharing nitrogen · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61K45/06

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