IP Library › Granted Patent US 12,336,990
Granted Patent B2
US 12,336,990 · App. 18/937,891 · Granted Jun 24, 2025

Treatment of prostate cancer

Inventors: Vijaykumar Reddy Rajasekhar (Apple Valley, CA); Brendan Mark Johnson (Chapel Hill, NC); David B. Maclean (Cambridge, MA); Lynn Seely (San Mateo, CA); Paul N. Mudd, Jr. (Cary, NC); Hélène M. Faessel (Cambridge, MA)
Assignees: Sumitomo Pharma Switzerland GmbH; Takeda Pharmaceutical Company Limited
A61K31/501A61K9/0053A61K31/4166A61K31/513A61P35/00
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,336,990
App. No.
18/937,891
Granted
Jun 24, 2025
Kind
B2
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.

Claims (46)

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.

Assignments (14)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2025
From: SUMITOMO PHARMA SWITZERLAND GMBH
To: SUMITOMO PHARMA CO., LTD.
Reel/Frame 071971/0600 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: MUDD, PAUL N., JR.
To: ROIVANT SCIENCES, INC.
Reel/Frame 070082/0391 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: MACLEAN, DAVID
To: MILLENNIUM PHARMACEUTICALS, INC.
Reel/Frame 070082/0382 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: ROIVANT SCIENCES, INC.
To: MYOVANT SCIENCES GMBH
Reel/Frame 070082/0396 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: SEELY, LYNN; RAJASEKHAR, VIJAYKUMAR REDDY
To: MYOVANT SCIENCES, INC.
Reel/Frame 070082/0368 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: MILLENNIUM PHARMACEUTICALS, INC.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 070082/0387 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: MYOVANT SCIENCES, INC.
To: MYOVANT SCIENCES GMBH
Reel/Frame 070082/0601 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: TAKEDA DEVELOPMENT CENTER AMERICAS, INC.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 070082/0764 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: SEELY, LYNN; RAJASEKHAR, VIJAYKUMAR REDDY
To: MYOVANT SCIENCES, INC.
Reel/Frame 070082/0550 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: FAESSEL, HÉLÈNE M.
To: TAKEDA DEVELOPMENT CENTER AMERICAS, INC.
Reel/Frame 070082/0400 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: MYOVANT SCIENCES, INC.
To: MYOVANT SCIENCES GMBH
Reel/Frame 070082/0731 →
CHANGE OF NAME Recorded Feb 1, 2025
From: MYOVANT SCIENCES GMBH
To: SUMITOMO PHARMA SWITZERLAND GMBH
Reel/Frame 070082/0751 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: JOHNSON, BRENDAN MARK
To: ROIVANT SCIENCES, INC.
Reel/Frame 070082/0710 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 1, 2025
From: ROIVANT SCIENCES, INC.
To: MYOVANT SCIENCES GMBH
Reel/Frame 070082/0738 →
Continuity (9)
Continuation 18792752 · Aug 2, 2024
Continuation 17866203 · Jul 15, 2022
Continuation 16998900 · Aug 20, 2020
Continuation 16563161 · Sep 6, 2019
Continuation 16369729 · Mar 29, 2019
Continuation PCTEP2017074849 · Sep 29, 2017
Provisional Application 62402004 · Sep 30, 2016
Provisional Application 62402150 · Sep 30, 2016
Related Publication 20250057839A1 · Feb 20, 2025
References Cited (177)
US 5573777A · Serpelloni et al. · 1996 [cited by applicant]
US 6297379B1 · Furuya et al. · 2001 [cited by applicant]
US 6340686B1 · Furuya et al. · 2002 [cited by applicant]
US 6849738B2 · Fukuoka et al. · 2005 [cited by applicant]
US 7056927B2 · Guo et al. · 2006 [cited by applicant]
US 7176211B2 · Guo et al. · 2007 [cited by applicant]
US 7300935B2 · Cho et al. · 2007 [cited by applicant]
US 7419983B2 · Guo et al. · 2008 [cited by applicant]
US 7569570B2 · Furuya et al. · 2009 [cited by applicant]
US 8058280B2 · Cho et al. · 2011 [cited by applicant]
US 8735401B2 · Cho et al. · 2014 [cited by applicant]
US 8765948B2 · Gallagher et al. · 2014 [cited by applicant]
US 9346822B2 · Cho et al. · 2016 [cited by applicant]
US 9382214B2 · Gallagher et al. · 2016 [cited by applicant]
US 9422310B2 · Beaton et al. · 2016 [cited by applicant]
US 9758528B2 · Fukuoka et al. · 2017 [cited by applicant]
US 10150778B2 · Miwa · 2018 [cited by applicant]
US 10350170B2 · Yamane et al. · 2019 [cited by applicant]
US 10449191B2 · Rajasekhar et al. · 2019 [cited by applicant]
US 10464945B2 · Miwa · 2019 [cited by applicant]
US 10544160B2 · Miwa · 2020 [cited by applicant]
US 10786501B2 · Rajasekhar et al. · 2020 [cited by applicant]
US 11053257B2 · Miwa · 2021 [cited by applicant]
US 11583526B2 · Rajasekhar et al. · 2023 [cited by applicant]
US 11731983B2 · Miwa · 2023 [cited by applicant]
US 11795178B2 · Fukuoka et al. · 2023 [cited by applicant]
US 12097198B2 · Rajasekhar et al. · 2024 [cited by applicant]
US 12144809B1 · Rajasekhar et al. · 2024 [cited by applicant]
US 12180224B2 · Fukuoka et al. · 2024 [cited by applicant]
US 20030055269A1 · Fukuoka et al. · 2003 [cited by applicant]
US 20050043315A1 · Tsutsumi et al. · 2005 [cited by applicant]
US 20060160829A1 · Cho et al. · 2006 [cited by applicant]
US 20090048273A1 · Furuya et al. · 2009 [cited by applicant]
US 20090186890A1 · Gellert et al. · 2009 [cited by applicant]
US 20090203622A1 · Persson · 2009 [cited by applicant]
US 20110172249A1 · Kamikawa et al. · 2011 [cited by applicant]
US 20170210753A1 · Fukuoka et al. · 2017 [cited by applicant]
US 20190262346A1 · Johnson et al. · 2019 [cited by applicant]
US 20200000730A1 · Yamane et al. · 2020 [cited by applicant]
US 20230212184A1 · Fukuoka et al. · 2023 [cited by applicant]
US 20240358700A1 · Rajasekhar et al. · 2024 [cited by applicant]
US 20250051353A1 · Miwa · 2025 [cited by applicant]
US 20250082632A1 · Rajasekhar et al. · 2025 [cited by applicant]
CA 2978223A1 · 2016 [cited by applicant]
EP 2329823A1 · 2011 [cited by applicant]
WO WO0056739A1 · 2000 [cited by applicant]
WO WO2010026993A1 · 2010 [cited by applicant]
WO WO2014051164A2 · 2014 [cited by applicant]
WO WO2014051164A3 · 2014 [cited by applicant]
WO WO2016030334A2 · 2016 [cited by applicant]
WO WO2016136849A1 · 2016 [cited by applicant]
WO WO2017040841A1 · 2017 [cited by applicant]
WO WO2018060501A2 · 2018 [cited by applicant]
WO WO2018060501A3 · 2018 [cited by applicant]
Albertsen, P.C et al. (2014). “Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist,” Europ. Urology 65:565-573. [cited by applicant]
Amory, J.K. et al. (2002). “Preoperative Supraphysiological Testosterone in Older Men Undergoing Knee Replacement Surgery,” J Am Geriatr Soc. 50(10):1698-1701. [cited by applicant]
Maurice Ahsman, Hélène M. Faessel, Nelleke Snelder, David MacLean, and Peter Vis, [cited by applicant]
Cancer.Org (2018). “Hormone therapy for prostate cancer,” located at https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html, 8 total pages. [cited by applicant]
ClinicalTrials.gov (2016). Bioavailability and Effect of Food on TAK-385 Tablet Formulations in Healthy Participants—Study Results—ClinicalTrials.gov, located at https://www.clinicaltrials.gov/ct2/show/results/NCT023961… [cited by applicant]
ClinicalTrials.gov (2016). NCT02135445, located at https://clinicaltrials.gov/archive/NCT02135445/2016_06_02, 6 pages. [cited by applicant]
ClinicalTrials.gov (2017). NCT02135445, History of Changes for Study, Safety and Efficacy of TAK-385 for Patients with Localized Prostate Cancer, 20 total pages. [cited by applicant]
ClinicalTrials.gov (2016). NCT02083185, located at https://clinicaltrials.gov/archive/NCT02083185/2016_06_02, 4 pages. [cited by applicant]
[cited by applicant]
A Study of TAK-385 in Hormone Treatment-naïve Participants with Prostate Cancer, Nat'l Inst. of Health, Dec. 15, 2015, https://clinicaltrials.gov/study/NCT02141659?term=NCT02141659%20&rank=1&tab=history&a=9; ClinicalTri… [cited by applicant]
Crawford (2011). “A Phase III Extension Trial With a 1-Arm Crossover from Leuprolide to Degarelix: Comparison of Gonadotropin-Releasing Hormone Agonist and Antagonist Effect on Prostate Cancer,” J Urol. 186(3):889-897. [cited by applicant]
Crawford et al. (2014). “The Role of the FSH System in the Development and Progression of Prostate Cancer,” The American Journal of Hematology/Oncology 10:5-13. [cited by applicant]
Crawford et al. (2017). “The potential role of follicle-stimulating hormone in the cardiovascular, metabolic, skeletal, and cognitive effects associated with androgen deprivation therapy,” Urologic Oncology: Seminars an… [cited by applicant]
Dandona, P. et al. (2010). “A practical guide to male hypogonadism in the primary care setting,” Int. J. Clin. Pract. 64:682-696. [cited by applicant]
D. Dearnaley, D.R. Saltzstein, J.E. Sylvester, L. Karsh, B.A. Mehlhaff, C. Pieczonka, J.L. Bailen, D.B. MacLean, H. Shi, H.M. Faessel, and N.D. Shore, [cited by applicant]
H.M. Faessel, N. Snelder, M. Ahsman, D.B. MacLean, F. Saad, N.D. Shore, H. Shi, K. Venkatakrishnan, and P. Vis, [cited by applicant]
Final Office Action mailed on Sep. 8, 2022, for U.S. Appl. No. 16/998,900, filed Aug. 20, 2020, 5 pages. [cited by applicant]
Hoare, D. et al. (2015). “Serum follicle-stimulating hormone levels predict time to development of castration-resistant prostate cancer,” Can Urol Assoc J. 9:122-171. [cited by applicant]
International Search Report mailed on Mar. 28, 2018, for PCT Application No. PCT/EP2017/074849, filed on Sep. 29, 2017, 5 pages. [cited by applicant]
David Burton MacLean, Hongliang Shi, Ajit Suri, Hélène Faessel, and Fred Saad, [cited by applicant]
Maclean, D.B et al. (2015). “Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males,” Journal of Clinical Endocrinology and Metabolism 100:4579-4587. [cited by applicant]
Maggio, M. et al. (2012). “Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG,” Conte. Clin. Trials 33:730-738. [cited by applicant]
Magnan, S. et al. (2015). “Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis,” JAMA Oncol. 1:1261-1269. [cited by applicant]
Matrana, M.R. (2017). “Latitude and Stampede trials presented at ASCO 2017 offer refreshing, practicing-changing alternatives to upfront docetaxel for men with high-risk metastatic prostate cancer, but questions remain,… [cited by applicant]
Miranda, E.P. et al. (2017). “MP91-10 testosterone recovery profiles after cessation of androgen deprivation therapy,” J. Urol. 197(4S):e1221-e1222, 2 total pages. [cited by applicant]
Miwa, K. et al. (2011). “Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a poten… [cited by applicant]
Moul, J.W. (2015). “Hormone naïve prostate cancer: predicting and maximizing response intervals,” Asian J Androl. 17:929-935. [cited by applicant]
Nakata, D. et al. (2014). “Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies… [cited by applicant]
Non-Final Office Action mailed on Feb. 12, 2020, for U.S. Appl. No. 16/563,161, filed Sep. 6, 2019, 6 pages. [cited by applicant]
Non-Final Office Action mailed on Apr. 8, 2022, for U.S. Appl. No. 16/998,900, filed Aug. 20, 2020, 6 pages. [cited by applicant]
Non-Final Office Action mailed on May 29, 2024, for U.S. Appl. No. 17/866,203, filed Jul. 15, 2022, 7 pages. [cited by applicant]
Notice of Allowance mailed on Jun. 18, 2019, for U.S. Appl. No. 16/369,729, filed Mar. 29, 2019, 7 pages. [cited by applicant]
Notice of Allowance Action mailed on May 21, 2020, for U.S. Appl. No. 16/563,161, filed Sep. 6, 2019, 5 pages. [cited by applicant]
Notice of Allowance mailed on Nov. 22, 2022, for U.S. Appl. No. 16/998,900, filed Aug. 20, 2020, 5 pages. [cited by applicant]
Notice of Allowance mailed on Jul. 18, 2024, for U.S. Appl. No. 17/866,203, filed Jul. 15, 2022, 5 pages. [cited by applicant]
Notice of Allowance mailed on Aug. 23, 2024, for U.S. Appl. No. 18/758,904, filed Jun. 28, 2024, 8 pages. [cited by applicant]
Paller, C.J. et al. (2013). “Management of biochemically recurrent prostate cancer after local therapy: Evolving standards of care and new directions,” Clin. Adv. Hematol. Oncol. 11:14-23. [cited by applicant]
Prostate Cancer UK (2018). Locally advanced prostate cancer, located at https://prostatecanceruk.org/media/2491080/locally_advanced_prostate_cancer-ifm.pdf, 12 total pages. [cited by applicant]
Request for Supplemental Examination of U.S. Pat. No. 10,449,191 (Terminated), Vijaykumar Reddy Rajasekhar et al., U.S. Appl. No. 96/050,044, filed Jun. 10, 2024, with Exhibits, 184 pages. [cited by applicant]
Request for Supplemental Examination of U.S. Pat. No. 10,786,501 (Terminated), Vijaykumar Reddy Rajashekhar et al., U.S. Appl. No. 96/050,045, filed Jun. 10, 2024, with Exhibits, 183 pages. [cited by applicant]
Request for Supplemental Examination of U.S. Pat. No. 11,583,526 (Terminated), Vijaykumar Reddy Rajasekhar et al., U.S. Appl. No. 96/050,046, filed Jun. 10, 2024, with Exhibits, 180 pages. [cited by applicant]
Saad, F. et al.: “Second interim analysis (IA2) results from a phase II trial of TAK-385, an oral GnRH antagonist, in prostate cancer patients (pts)”, Journal of Clinical Oncology, Jan. 10, 2016. [cited by applicant]
Fred Saad, James L. Bailen, Christopher Michael Pieczonka, Daniel R. Saltzstein, Paul R. Sieber, David B. MacLean, Hongliang Shi, Hélène M. Faessel, and Neal D. Shore, [cited by applicant]
Shahidi, M. et al. (2001). “Recovery of serum testosterone, LH and FSH levels following neoadjuvant hormone cytoreduction and radical radiotherapy in localized prostate cancer,” Clin. Oncol. 13:291-295. [cited by applicant]
Shore, N. et al. (2016). “PD28-01 testosterone lowering, PSA response and quality of life in patients with advanced hormone sensitive prostate cancer receiving TAK-385, an oral GNRH antagonist: phase 2 interim analysis,… [cited by applicant]
Shore, N. et al. (2015). “S474 Abstracts 2502: TAK-385, an oral GnRH antagonist: efficacy and safety results from a randomized phase 2 trial in prostate cancer patients (pts),” 8049:31324-7. [cited by applicant]
Neal D. Shore, James L. Bailen, Christopher Pieczonka, David B. MacLean, Hongliang Shi, Hélène M. Faessel, Fred Saad, [cited by applicant]
Neal D. Shore, James L. Bailen, Christopher Pieczonka, David B. Maclean, Hongliang Shi, Hélène M. Faessel, and Fred Saad, TAK-385, [cited by applicant]
Neal D. Shore, James L. Bailen, Christopher Pieczonka, Daniel R. Saltzstein, Paul R. Sieber, David B. MacLean, Hongliang Shi, Hélène M. Faessel, Huamao Mark Lin, Yanyan Zhu, and Fred Saad, [cited by applicant]
Takeda Press Release. (2016). Roivant Sciences and Takeda launch Myovant Sciences to develop innovative therapeutics for women's health and prostate cancer, located at https://www.takeda.com/newsroom/newsreleases/2016/r… [cited by applicant]
Tanaka, A. et al. (2009). “Pharmacological profile of TAK-385, an orally active gonadotropin releasing hormone (GNRH) antagonist,” [cited by applicant]
Texas Oncology (2019). Recurrent prostate cancer, located at https://www.texasoncology.com/types-of-cancer/prostate-cancer/recurrent-prostate-cancer, 5 total pages. [cited by applicant]
Tombal, B. et al. (2010). “Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by bas… [cited by applicant]
Travison, T.G. et al. (2017). “Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe,” J. Clin. Endocrinol. Metab. 102:1161-1173. [cited by applicant]
Tsumura, H. et al. (2015). “Recovery of serum testosterone following neoadjuvant and adjuvant androgen deprivation therapy in men treated with prostate brachytherapy,” World J. Radiol. 7:494-500. [cited by applicant]
Urology Care Foundation (2018). “What is advanced prostate cancer,” located at https://www.urologyhealth.org/urologic-conditions/advanced-prostate-cancer, 15 total pages. [cited by applicant]
Peter Vis, Nelleke Snelder, Maurice Ahsman, David Maclean, and Hélène Faessel, [cited by applicant]
WebMD (2019). “Advanced prostate cancer: Frequently asked questions,” 3 total pages. [cited by applicant]
Wessler, J.D. et al. (2013). “The P-glycoprotein transport system and cardiovascular drugs,” JACC 61:2495-2502. [cited by applicant]
Written Opinion of the International Searching Authority mailed on Mar. 28, 2018, for PCT Application No. PCT/EP2017/074849, filed on Sep. 29, 2017, 8 pages. [cited by applicant]
Supplemental Examination U.S. Appl. No. 96/050,044, Response to Notice of Non-Compliance with Exhibits 1-11, filed Jul. 10, 2024, 414 pages. [cited by applicant]
Supplemental Examination U.S. Appl. No. 96/050,045, Response to Notice of Non-Compliance with Exhibits 1-11, filed Jul. 10, 2024, 413 pages. [cited by applicant]
Supplemental Examination U.S. Appl. No. 96/050,046, Response to Notice of Non-Compliance with Exhibits 1-11, filed Jul. 10, 2024, 406 pages. [cited by applicant]
U.S. Appl. No. 18/392,110, filed Dec. 21, 2023, by Migoya et al. (Copy not attached). [cited by applicant]
U.S. Appl. No. 18/758,904, filed Jun. 28, 2024, by Rajasekhar et al. (Copy not attached). [cited by applicant]
U.S. Appl. No. 18/792,752, filed Aug. 2, 2024, by Rajasekhar et al. (Copy not attached). [cited by applicant]
U.S. Appl. No. 18/797,045, filed Aug. 7, 2024, by Migoya et al. (Copy not attached). [cited by applicant]
Amin, M.L. (Aug. 2013). “P-glycoprotein Inhibition for Optimal Drug Delivery,” Drug Target Insights 7:27-34. [cited by applicant]
Beckmann, W. (2000). “Seeding the desired polymorph: Background, possibilities, and case studies,” Organic Process Research and Development 4(5):372-383. [cited by applicant]
Beer, T.M. et al. (Jul. 2014). “Enzalutamide in metastatic prostate cancer before chemotherapy,” N. Engl. J. Med. 371(5):424-433. [cited by applicant]
Behre, H.M. et al. (May 1997). “High Loading and Low Maintenance Doses of a Gonadotropin-Releasing Hormone Antagonist Effectively Suppress Serum Luteinizing Hormone. Follicle-Stimulating Hormone, and Testosterone in Nor… [cited by applicant]
Bernstein, J. (2002). “Polymorphism in molecular crystals,” Clarendon Press, Oxford, p. 2 (11 total pages). [cited by applicant]
Brawer, M.K. et al. (2001). “Androgen deprivation and other treatments for advanced prostate cancer,” Reviews in Urology 3 Suppl. 2(Suppl 2):S59-S68. [cited by applicant]
Breier, A. et al. (Sep. 2005). “P-glycoprotein—Implications of metabolism of neoplastic cells and cancer therapy,” Curr. Cancer Drug Targets 5(6):457-468. [cited by applicant]
Brittain, H.G., ed. (1999). “Generation of polymorphs, hydrates, solvates, and amorphous solids,” Polymorphism in Pharmaceutical Solids, pp. 183-226. [cited by applicant]
Byrn, S. et al. (1995). “Pharmaceutical solids: A strategic approach to regulatory considerations,” Pharmaceutical Research 12(7):945-954. [cited by applicant]
ClinicalTrials.gov (2014). “Safety and Efficacy of TAK-385 for patients with localized prostate cancer,” ID No. NCT02135445, located at https://clinicaltrials.gov/study/NCT02135445?term=NCT02135445&rank=1&tab=history&a=… [cited by applicant]
ClinicalTrials.gov (2014). “A Phase 2 Study to Evaluate the Safety and Efficacy of TAK-385, Together with a Leuprorelin Observational Cohort, in Participants with Prostate Cancer,” ID No. NCT02083185, located at https:/… [cited by applicant]
Dailymed (Jul. 15, 2013). Nilandron—Nilutamide Tablet. Located at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ccf0e9a-8935-4c8c-b883-b4967281eb4a, retrieved on Feb. 10, 2025, 16 pages. [cited by applicant]
De La Rosette, J. et al. (May 2011). “Efficacy and safety of androgen deprivation therapy after switching from monthly leuprolide to monthly degarelix in patients with prostate cancer,” International Journal of Clinical… [cited by applicant]
Épshtein, N.A. (2004). “Structure of chemical compounds, methods, of analysis and process control—Validation of HPLC Techniques for Pharmaceutical Analysis,” Pharmaceutical Chemistry Journal 38(4):212-228. [cited by applicant]
Extended European Search Report mailed on Mar. 3, 2025, for EP Application No. 24 212 224.0, filed on Sep. 29, 2017, 17 pages. [cited by applicant]
FDA Guidance for Industry (Feb. 2012). Drug Interaction Studies—Study Design, Data Analysis, Implication for Dosing, and Labeling Recommendations, Clinical Pharmacology, 79 pages. [cited by applicant]
Finch, A. et al. (Aug. 2014). “P-glycoprotein and its role in drug-drug interactions” Aust. Prescr. 37(4):137-139. [cited by applicant]
Ganju, A. et al. (Apr. 2014). “Nanoways to overcome docetaxel resistance in prostate cancer,” Drug Resistance Updates 17(1-2):13-23. [cited by applicant]
GenTech Scientific (Jul. 26, 2023). How does high-performance liquid chromatography work? The General Knowledge of a POSA regarding HPLC Located at https://gentechscientific.com/how-does-high-performance-liquid-chromato… [cited by applicant]
Giacomini, K.M. et al. (Mar. 2010). “Membrane transporters in drug development,” Nat. Rev. Drug Discov. 9(3):215-236. [cited by applicant]
Gomella, L.G. (2009). “Effective Testosterone Suppression for Prostate Cancer: Is There a Best Castration Therapy?” Reviews in Urology 11(2):52-60. [cited by applicant]
Haleblian, J. et al. (Aug. 1969). “Pharmaceutical applications of polymorphism,” J. Pharm. Sci. 58(8):911-929. [cited by applicant]
Hawach Scientific (Dec. 12, 2024). “Why is the C18 column mostly used in HPLC?” Located at https://www.hawachhplccolumn.com/news/why-is-c18-column-mostly-used-in-hplc/#:˜:text=The%20C18%20column%20is%20popular,chemical%… [cited by applicant]
ICH Impurities in New Drug Substances Q3A(R2) (Oct. 25, 2006). International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland, EMEA, vol. 25, 1… [cited by applicant]
ICH Impurities in New Drug Substances Q3B(R2) (2006). International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Geneva, Switzerland, EMEA, vol. 25, 16 pages. [cited by applicant]
ICH Tripartite (Nov. 2005). “Q2(R1) Validation of analytical procedures: Text and methodology,” FDA, U.S. Department of Health and Human Services, 22 pages. [cited by applicant]
International Conference on Harmonisation (Dec. 2000). Guidance on Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Test Procedures and Accep… [cited by applicant]
Klotz, L. et al. (Dec. 2008). “The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer,” BJU Int. 102(11):1531-1538. [cited by applicant]
Kostanski, J.W. et al. (2001). “Return to fertility after extended chemical castration with a GnRH antagonist,” BMC Cancer 1:18, 7 pages. [cited by applicant]
Mccutcheon, S.B. (May 2013). “Enzalutamide: a new agent for the prostate cancer treatment armamentarium,” Journal of the Advanced Practitioner in Oncology 4(3):182-185. [cited by applicant]
Mealey, K.L. et al. (Jan. 2015). “P-Glycoprotein Mediated Drug Interactions in Animals and Humans with Cancer,” J. Vet. Intern. Med. 29(1):1-6. [cited by applicant]
Mearini, L. et al. (Apr. 2011). “Intermittent Androgen Suppression in Prostate Cancer: Testosterone Levels and Its Implication,” J. Sex. Med. 8(4):1218-1227. [cited by applicant]
ORGOVYX (2023). Highlights and Prescribing Information, located at https://www.myovant.com/wp-content/uploads/2022/10/NDA-214621-USPlandPI.pdf, 18 total pages. [cited by applicant]
Pahwa, R. et al. (2011). “Superdisintegrants in the development of orally disintegrating tablets: A review,” IJPSR 2(11):2767-2780. [cited by applicant]
Papadasu, N. (Apr.-Jun. 2024). “A novel validated stability indicative UPLC method for Relugolix for the determination of process-related and degradation impurities,” Rasayan Journal of Chemistry 17(2):325-336. [cited by applicant]
Pearlitol® 50 C Mannitol (2016-2025). Product Profile, located at https://www.roquette.com/innovation-hub/pharma/product-profile-pages/pearlitol-50c-mannitol, retrieved on Feb. 7, 2025, 4 pages. [cited by applicant]
Pham, T. et al. (Jun. 2016). “Advances in hormonal therapies for hormone naive and castration resistant prostate cancers with or without previous chemotherapy,” Exp. Hematol. Oncol. 5:15, 11 pages. [cited by applicant]
Pilaniya, K. et al. (Jul. 2010). “Recent trends in the impurity profile of pharmaceuticals,” Journal of Advanced Pharmaceutical Technology and Research 1(3):302-310. [cited by applicant]
Pubchem (Feb. 23, 2016). Relugolix Impurity 17. PubChem CID 118378832. Located at https://pubchem.ncbi.nlm.nih.gov/compounds/118378832, retrieved on Feb. 10, 2025, 11 pages. [cited by applicant]
Rahman, N. et al. (Apr. 2006). “The importance of impurity analysis in pharmaceutical products: An integrated approach,” Accreditation and Quality Assurance 11:69-74. [cited by applicant]
Sharifi, N. et al. (Jul. 2005). “Androgen Deprivation Therapy for Prostate Cancer,” JAMA 294(2):238-244. [cited by applicant]
Shore, N.D. et al. (Feb. 2013). “Experience with degarelix in the treatment of prostate cancer,” Ther. Adv. Urol. 5(1):11-24. [cited by applicant]
Spry, N.A. et al. (May 2006). “Adverse Effects to Quality of Life Arising From Treatment Can Recover with Intermittent Androgen Suppression in Men with Prostate Cancer,” Eur. J. Cancer 42(8):1083-1092. [cited by applicant]
[cited by applicant]
[cited by applicant]
[cited by applicant]
[cited by applicant]
[cited by applicant]
[cited by applicant]
Takeda TAK-385 Clinical Study Report C27005 Synopsis (Nov. 25, 2014). “A Phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Effects of Multiple Oral Doses of Fluconazole and Atorvastatin on the Pharmacokin… [cited by applicant]
Takeda TAK-385 Clinical Study Report TAK-385/CPH-010 (Jun. 21, 2013). “TAK-385/CPH-010: A phase 1, Open-Label, Drug-Drug Interaction Study to Evaluate the Effects of Multiple Oral Doses of Erythromycin on the Pharmacoki… [cited by applicant]
Taylor, L.S. et al. (1999). “Amorphous solids,” in Chapter 16: Polymorphism in Pharmaceutical Solids, pp. 587-629. [cited by applicant]
Threlfall, T.L. (Oct. 1995). “Analysis of organic polymorphs, A review,” Analyst 120:2435-2460. [cited by applicant]
Tukun, F-L. et al. (Dec. 2017). “Recent Development of Non-Peptide GnRH Antagonists,” Molecules 22(12):2188, 25 pages. [cited by applicant]
Van Poppel, H. et al. (Oct. 2008). “Degarelix: A novel gonadotropin-releasing hormone (GnRH) receptor blocker—results from a 1-year, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate can… [cited by applicant]
U.S. Appl. No. 19/086,039, filed Mar. 20, 2025, by Migoya et al. (Copy not attached). [cited by applicant]
Cited By (4)
US 12,551,447 US 12,629,370 US 12,655,154 US 12,735,430