Claims for Patent: 12,336,990

Summary for Patent: 12,336,990

Title:	Treatment of prostate cancer
Abstract:	Methods for treating prostate cancer, including advanced prostate cancer, in a subject in need thereof, include administering once-daily to the subject, at least 80 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof. Another method includes: administering once-daily to the subject in need thereof, an oral load dose formulation having from 240 mg to 480 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof, and thereafter administering once-daily to the subject, an oral maintenance dose formulation having 80 mg to 160 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof.
Inventor(s):	Vijaykumar Reddy RAJASEKHAR, Brendan Mark JOHNSON, David B. MacLean, Lynn Seely, Paul N. MUDD, Jr., Hélène M. Faessel
Assignee:	Takeda Pharmaceutical Co Ltd , Sumitomo Pharma Co Ltd
Application Number:	US18/937,891
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,336,990
Patent Claims:	1. A method of treating prostate cancer in a subject in need thereof, the method comprising: (i) orally administering a loading dose of 360 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject; and (ii) about one day after administering the loading dose, orally administering a 120 mg dose of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject once a day; wherein the subject's prostate cancer is treated. 2. The method of claim 1, wherein profound castration is achieved. 3. The method of claim 2, wherein the profound castration is achieved within 24 to 48 hours after administration of the loading dose. 4. The method of claim 2, wherein the profound castration is achieved within about 4 consecutive weeks of treatment after administration of the loading dose. 5. The method of claim 4, wherein the profound castration is sustained through at least 24 consecutive weeks of treatment after administration of the loading dose. 6. The method of claim 4, wherein the profound castration is sustained through at least 36 consecutive weeks of treatment after administration of the loading dose. 7. The method of claim 1, wherein the prostate cancer is advanced prostate cancer. 8. The method of claim 1, wherein the once a day administration of the 120 mg dose is suspended. 9. The method of claim 8, wherein the once a day administration of the 120 mg dose is suspended for a period of at least 4 weeks. 10. The method of claim 8, wherein the once a day administration of the 120 mg dose is suspended for a period of at least 8 weeks. 11. The method of claim 8, wherein the suspension of the once a day 120 mg dose results in a return to baseline testosterone level of the patient prior to treatment. 12. The method of claim 8, wherein the suspension of the once a day 120 mg dose results in a testosterone level of at least about 280 ng/dL. 13. The method of claim 8, wherein administration of the once a day 120 mg dose is resumed after it has been suspended. 14. The method of 13, further comprising orally administering a loading dose of 360 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea about 1 day prior to resuming administration of the once a day 120 mg dose of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea. 15. A method of treating prostate cancer in a subject in need thereof, the method comprising: reducing FSH levels in the subject by (i) orally administering a loading dose of 360 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno [2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject; and (ii) about one day after administering the loading dose, orally administering a 120 mg dose of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject once a day; wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL by about 24 consecutive weeks of treatment after administration of the loading dose. 16. The method of claim 15, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL by about 12 consecutive weeks of treatment after administration of the loading dose. 17. The method of claim 16, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL by about 4 consecutive weeks of treatment after administration of the loading dose. 18. The method of claim 16, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL through at least 36 weeks after administration of the loading dose. 19. The method of claim 16, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL through at least 48 weeks after administration of the loading dose. 20. The method of claim 15, wherein the prostate cancer is advanced prostate cancer. 21. A method of treating prostate cancer in a subject in need thereof, the method comprising: reducing FSH and LH levels in the subject by (i) orally administering a loading dose of 360 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d] pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject; and (ii) about one day after administering the loading dose, orally administering a 120 mg dose of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject once a day; wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL and the subject's serum LH level is less than or equal to about 2.0 mIU/mL by about 24 consecutive weeks of treatment after administration of the loading dose. 22. The method of claim 21, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL by about 4 consecutive weeks of treatment after administration of the loading dose. 23. The method of claim 22, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL through at least 12 weeks after administration of the loading dose. 24. The method of claim 21, wherein the prostate cancer is advanced prostate cancer. 25. A method of treating prostate cancer in a subject in need thereof, the method comprising: reducing FSH, LH, and testosterone levels in the subject by (i) orally administering a loading dose of 360 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d] pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject; and (ii) about one day after administering the loading dose, orally administering a 120 mg dose of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N′-methoxyurea to the subject once a day; wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL and the subject's serum LH level is less than or equal to about 2.0 mIU/mL by about 24 consecutive weeks of treatment after administration of the loading dose; and wherein profound castration is achieved by about 4 consecutive weeks of treatment after administration of the loading dose. 26. The method of claim 25, wherein the prostate cancer is advanced prostate cancer. 27. The method of claim 25, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL by about 12 consecutive weeks of treatment after administration of the loading dose. 28. The method of claim 27, wherein the subject's serum FSH level is less than or equal to about 2.4 mIU/mL through at least 24 weeks after administration of the loading dose. 29. The method of claim 27, wherein the profound castration is sustained through at least 24 consecutive weeks of treatment after administration of the loading dose. 30. The method of claim 27, wherein the profound castration is sustained through at least 48 consecutive weeks of treatment after administration of the loading dose.