Claims for Patent: 10,821,113

Summary for Patent: 10,821,113

Title:	Salt form of a human histone methyltransferase EZH2 inhibitor
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'-bip- henyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.
Inventor(s):	Kuntz; Kevin Wayne (Woburn, MA), Huang; Kuan-Chun (Andover, MA), Choi; Hyeong Wook (Andover, MA), Sanders; Kristen (Gilmanton, NH), Mathieu; Steven (Andover, MA), Chanda; Arani (Malden, MA), Fang; Francis (Andover, MA)
Assignee:	Epizyme, Inc. (Cambridge, MA) Eisai R&D Management Co., Ltd. (Tokyo, JP)
Application Number:	16/270,752
Patent Claims:	1. A polymorph of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydr- o-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-ca- rboxamide hydrobromide, wherein the polymorph exhibits an X-ray powder diffraction pattern having one or more characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 17.5+/-0.3 degrees, and about 22.0+/-0.3 degrees 2-theta. 2. The polymorph of to claim 1, wherein the polymorph exhibits an X-ray powder diffraction pattern having one or more characteristic peaks expressed in degrees 2-theta at about 14.3+/-0.3 degrees, about 18.7+/-0.3 degrees, about 23.3+/-0.3 degrees, and about 23.6+/-0.3 degrees 2-theta. 3. The polymorph of claim 1, wherein the polymorph exhibits an X-ray powder diffraction pattern having at least 5 characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 4. The polymorph of claim 1, wherein the polymorph exhibits an X-ray powder diffraction pattern having at least 6 characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 5. The polymorph of claim 1, wherein the polymorph exhibits an X-ray powder diffraction pattern having at least 7 characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 6. The polymorph of claim 1, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 7. The polymorph of claim 1, wherein the polymorph exhibits a differential scanning calorimetry thermogram having a characteristic peak expressed in units of .degree. C. at a temperature of 255+/-5.degree. C. 8. A pharmaceutical composition comprising the polymorph of claim 1, and a pharmaceutically acceptable carrier or diluent. 9. The pharmaceutical composition of claim 8, wherein the polymorph exhibits an X-ray powder diffraction pattern having one or more characteristic peaks expressed in degrees 2-theta at about 14.3+/-0.3 degrees, about 18.7+/-0.3 degrees, about 23.3+/-0.3 degrees, and about 23.6+/-0.3 degrees 2-theta. 10. The pharmaceutical composition of claim 8, wherein the polymorph exhibits an X-ray powder diffraction pattern having at least 5 characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 11. The pharmaceutical composition of claim 8, wherein the polymorph exhibits an X-ray powder diffraction pattern having at least 6 characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 12. The pharmaceutical composition of claim 8, wherein the polymorph exhibits an X-ray powder diffraction pattern having at least 7 characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 13. The pharmaceutical composition of claim 8, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at about 10.1+/-0.3 degrees, about 14.3+/-0.3 degrees, about 17.5+/-0.3 degrees, about 18.7+/-0.3 degrees, about 20.6+/-0.3 degrees, about 20.9+/-0.3 degrees, about 21.8+/-0.3 degrees, about 22.0+/-0.3 degrees, about 23.3+/-0.3 degrees and about 23.6+/-0.3 degrees 2-theta. 14. The pharmaceutical composition of claim 8, wherein the polymorph exhibits a differential scanning calorimetry thermogram having a characteristic peak expressed in units of .degree. C. at a temperature of 255+/-5.degree. C. 15. The polymorph of claim 1, wherein the polymorph is substantially free of impurities. 16. The polymorph of claim 1, wherein the polymorph contains less than 5% by weight total impurities. 17. 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'-bip- henyl]-3-carboxamide hydrobromide. 18. The pharmaceutical composition of claim 8, wherein the polymorph is substantially free of impurities. 19. The pharmaceutical composition of claim 8, wherein the polymorph contains less than 5% by weight total impurities. 20. The pharmaceutical composition of claim 8, 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'-bip- henyl]-3-carboxamide hydrobromide.