Claims for Patent: 7,166,722

Summary for Patent: 7,166,722

Title:	N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-n′-(5-methyl-3-isoxazolyl)urea salt in crystalline form
Abstract:	The present invention provides a crystal of a pharmaceutically acceptable salt of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl) urea. This crystal of salt is usable for the therapy of a disease selected from the group consisting of tumors, diabetic retinopathy, chronic rheumatism, psoriasis, atherosclerosis, Kaposi's sarcoma, and exudation type age-related maculopathy, and has characteristics suitable for applications of oral pharmaceutical preparations.
Inventor(s):	Naoki Matsunaga, Satoshi Yoshida, Ayako Yoshino, Tatsuo Nakajima
Assignee:	KH Neochem Co Ltd, Kyowa Kirin Co Ltd
Application Number:	US10/532,104
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,166,722
Patent Claims:	1. Crystalline N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea monohydrochloric acid salt monohydrate. 2. The crystalline compound according to claim 1, wherein in powder X-ray diffractometry, the crystalline compound has peaks with not less than 10% relative intensity at least the following diffraction angles (2θ): TABLE A-1 Diffraction angle (2θ) 11.47 ± X 22.59 ± X 23.02 ± X 26.27 ± X 26.63 ± X wherein X is 0 to 0.20. 3. The crystalline compound according to claim 2, wherein the relative intensity in said diffraction angles (2θ) is not less than 15%. 4. The crystalline compound according to claim 2, wherein the relative intensity in said diffraction angles (2θ) is not less than 20%. 5. The crystalline compound according to claim 2, wherein the relative intensity in said diffraction angles (2θ) is not less than 25%. 6. The crystalline compound according to claim 2, wherein the relative intensity in said diffraction angles (2θ) is not less than 30%. 7. The crystalline compound according to any one of claims 2 to 6, wherein X is 0 to 0.10. 8. The crystalline compound according to claim 1, wherein in powder X-ray diffractometry, the crystalline compound has peaks with not less than 10% relative intensity at least the following diffraction angles (2θ): TABLE B-1 Diffraction angle (2θ) 8.76 ± X 11.47 ± X 15.28 ± X 17.16 ± X 17.53 ± X 18.80 ± X 20.02 ± X 22.59 ± X 23.02 ± X 25.32 ± X 25.43 ± X 26.27 ± X 26.63 ± X 27.00 ± X 28.57 ± X wherein X is 0 to 0.20. 9. The crystalline compound according to claim 8, wherein the relative intensity in said diffraction angles (2θ) is not less than 15%. 10. The crystalline compound according to claim 8, wherein the relative intensity in said diffraction angles (2θ) is not less than 20%. 11. The crystalline compound according to any one of claims 8 to 10, wherein X is 0 to 0.10. 12. The crystalline compound according to claim 1, wherein in powder X-ray diffractometry, the crystalline compound has the following diffraction angles (2θ) and relative intensities: TABLE 1 Diffraction angle (2θ) Relative intensity 8.76 22 11.47 100 15.28 21 17.16 21 17.53 23 18.80 21 20.02 25 22.59 35 23.02 37 25.32 29 25.43 23 26.27 36 26.63 32 27.00 29 28.57 28. 13. A process for producing a crystal N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea, monhydrochloric acid salt monohydrate, said process comprising the steps of: adding hydrochloric acid to a solution of N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(5-methyl-3-isoxazolyl)urea in an aprotic polar solvent selected from N,N-dimethylformamide and N,N-dimethylacetamide; adding ethanol and water to the above solution to precipitating crystals from the solution. 14. The process according to claim 13, wherein said hydrochloric acid has a concentration of 10 to 14 N. 15. The process according to claim 13, wherein in powder X-ray diffractometry, the crystal has peaks with not less than 10% relative intensity at least the following diffraction angles (2θ): TABLE A-1 Diffraction angle (2θ) 11.47 ± X 22.59 ± X 23.02 ± X 26.27 ± X 26.63 ± X wherein X is 0 to 0.20. 16. The process according to claim 14, wherein in powder X-ray diffractometry, the crystal has peaks with not less than 10% relative intensity at least the following diffraction angles (2θ): TABLE A-1 Diffraction angle (2θ) 11.47 ± X 22.59 ± X 23.02 ± X 26.27 ± X 26.63 ± X wherein X is 0 to 0.20.