IP Library › Granted Patent US 12,251,386
Granted Patent B2
US 12,251,386 · App. 17/936,555 · Granted Mar 18, 2025

Salt form of a human histone methyltransferase EZH2 inhibitor

Inventors: Kevin Wayne Kuntz (Woburn, MA); Kuan-Chun Huang (Andover, MA); Hyeong Wook Choi (Andover, MA); Kristen Sanders (Gilmanton, NH); Steven Mathieu (Andover, MA); Arani Chanda (Malden, MA); Francis Fang (Andover, MA)
Assignees: Epizyme, Inc.; Eisai R&D Management Co., Ltd.
A61K31/5377C07D405/12Y02A50/30
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Quick Facts
Patent No.
US 12,251,386
App. No.
17/936,555
Granted
Mar 18, 2025
Kind
B2
Abstract

Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

Claims (35)

1. A polymorph of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl) methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl) amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at 10.9±0.2 degrees, 20.9±0.2 degrees, and 25.7±0.2 degrees 2-theta.

2. The polymorph of claim 1 , wherein the polymorph is substantially free of impurities.

3. The polymorph of claim 1 , wherein the polymorph is a crystalline solid substantially free of amorphous N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl) methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl) amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide.

4. The polymorph of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having one or more of the following additional characteristic peaks expressed in degrees 2-theta: 8.5±0.2 degrees, 16.7±0.2 degrees, 17.4±0.2 degrees, and/or 22.1=0.2 degrees 2-theta.

5. The polymorph of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having the following additional characteristic peaks expressed in degrees 2-theta: 8.5±0.2 degrees, 16.7±0.2 degrees, 17.4±0.2 degrees, and 22.1±0.2 degrees 2-theta.

6. The polymorph of claim 5 , wherein the polymorph has an X-ray powder diffraction pattern substantially as shown in FIG. 10 .

7. A pharmaceutical composition comprising the polymorph of claim 1 , and a pharmaceutically acceptable carrier or diluent.

8. A pharmaceutical composition comprising the polymorph of claim 3 , and a pharmaceutically acceptable carrier or diluent.

9. A pharmaceutical composition comprising the polymorph of claim 4 , and a pharmaceutically acceptable carrier or diluent.

10. A pharmaceutical composition comprising the polymorph of claim 5 , and a pharmaceutically acceptable carrier or diluent.

11. A pharmaceutical composition comprising the polymorph of claim 6 , and a pharmaceutically acceptable carrier or diluent.

12. A method of treating cancer comprising oral administration to a human subject in need thereof the pharmaceutical composition of claim 7 , wherein the cancer is selected from a lymphoma and a sarcoma.

13. The method of claim 12 , wherein the cancer is follicular lymphoma (FL).

14. The method of claim 12 , wherein the cancer is a soft tissue sarcoma.

15. A method of treating cancer comprising oral administration to a human subject in need thereof the pharmaceutical composition of claim 8 , wherein the cancer is selected from a lymphoma and a sarcoma.

16. The method of claim 15 , wherein the cancer is follicular lymphoma (FL).

17. The method of claim 15 , wherein the cancer is a soft tissue sarcoma.

18. A method of treating cancer comprising oral administration to a human subject in need thereof the pharmaceutical composition of claim 9 , wherein the cancer is selected from a lymphoma and a sarcoma.

19. The method of claim 18 , wherein the cancer is follicular lymphoma (FL).

20. The method of claim 18 , wherein the cancer is a soft tissue sarcoma.

21. A method of treating cancer comprising oral administration to a human subject in need thereof the pharmaceutical composition of claim 10 , wherein the cancer is selected from a lymphoma and a sarcoma.

22. The method of claim 21 , wherein the cancer is follicular lymphoma (FL).

23. The method of claim 21 , wherein the cancer is a soft tissue sarcoma.

24. A method of inhibiting the histone methyltransferase activity of EZH2 in a human subject in need thereof comprising oral administration of the pharmaceutical composition of claim 7 to the human subject.

25. The method of claim 24 , wherein the human subject has follicular lymphoma (FL).

26. The method of claim 24 , wherein the human subject has a soft tissue sarcoma.

27. A method of inhibiting the histone methyltransferase activity of EZH2 in a human subject in need thereof comprising oral administration of the pharmaceutical composition of claim 8 to the human subject.

28. The method of claim 27 , wherein the human subject has follicular lymphoma (FL).

29. The method of claim 27 , wherein the human subject has a soft tissue sarcoma.

30. A method of inhibiting the histone methyltransferase activity of EZH2 in a human subject in need thereof comprising oral administration of the pharmaceutical composition of claim 9 to the human subject.

31. The method of claim 30 , wherein the human subject has follicular lymphoma (FL).

32. The method of claim 30 , wherein the human subject has a soft tissue sarcoma.

33. A method of inhibiting the histone methyltransferase activity of EZH2 in a human subject in need thereof comprising oral administration of the pharmaceutical composition of claim 10 to the human subject.

34. The method of claim 33 , wherein the human subject has follicular lymphoma (FL).

35. The method of claim 33 , wherein the human subject has a soft tissue sarcoma.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 4, 2022
From: KUNTZ, KEVIN WAYNE
To: EPIZYME, INC.
Reel/Frame 061297/0429 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 4, 2022
From: HUANG, KUAN-CHUN; CHOI, HYEONG WOOK; SANDERS, KRISTEN; MATHIEU, STEVEN; CHANDA, ARANI; FANG, FRANCIS
To: EISAI R&D MANAGEMENT CO., LTD.
Reel/Frame 061297/0432 →
Continuity (7)
Continuation 17032432 · Sep 25, 2020
Continuation 16270752 · Feb 8, 2019
Continuation 15837390 · Dec 11, 2017
Continuation 15199522 · Jun 30, 2016
Continuation 14394431
Provisional Application 61624215 · Apr 13, 2012
Related Publication 20230140327A1 · May 4, 2023
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