Granted Patent
B2
US 12,551,447 · App. 18/070,341 · Granted Feb 17, 2026
Combination solid oral dosage forms of gonadotropin-releasing hormone antagonists
Inventors:
David E. Alonzo (Foster City, CA); Kathleen D. Ullmer (San Mateo, CA); Minli Xie (Belmont, CA)
Assignee:
Sumitomo Pharma Co., Ltd.
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Abstract
The present disclosure includes combination solid oral dosage forms having 40 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 hormone replacement medicaments. Also provided are processes for making and using the solid oral dosage forms.
Claims (30)
1 . A combination solid oral dosage form comprising:
about 18% to 22% w/w 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;
about 0.3% to 0.7% w/w of estradiol;
about 0.1% to 0.4% w/w of norethindrone acetate;
about 24% to 28% w/w of mannitol;
about 2% to 6% w/w of a starch selected from the group consisting of sodium starch glycolate, pregelatinized starch, and a combination of the foregoing;
about 0.5% to 3% w/w of hydroxypropyl cellulose;
about 0.5% to 3% w/w of magnesium stearate;
about 38% to 42% w/w of lactose monohydrate; and
about 1% to 5% w/w of a film coating.
2 . The combination solid oral dosage form of claim 1 comprising:
about 40 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;
about 1 mg of estradiol;
about 0.5 mg of norethindrone acetate;
about 51 mg of mannitol;
about 9 mg of sodium starch glycolate;
about 3 mg of hydroxypropyl cellulose;
about 2 mg of magnesium stearate;
about 78 mg of lactose monohydrate; and
about 7 mg of a film coating.
3 . The combination solid oral dosage form of claim 1 , wherein the starch is sodium starch glycolate.
4 . The combination solid oral dosage form of claim 3 , wherein the combination solid oral dosage form comprises about 9 mg of sodium starch glycolate.
5 . The combination solid oral dosage form of claim 1 , wherein the starch is pregelatinized starch.
6 . The combination solid oral dosage form of claim 1 , wherein the starch is a combination of sodium starch glycolate and pregelatinized starch.
7 . The combination solid oral dosage form of claim 6 comprising about 2% to 3% w/w sodium starch glycolate and about 2% to 3% w/w pregelatinized starch.
8 . The combination solid oral dosage form of claim 1 , wherein the amount of relugolix degradant present after storing said combination solid oral dosage form for 6 months, at 60° C. and ambient relative humidity, does not exceed 0.5% w/w.
9 . The combination solid oral dosage form of claim 1 , wherein the amount of estradiol degradant present after storing said combination solid oral dosage form for 6 months, at 60° C. and ambient relative humidity, does not exceed 1.4% w/w.
10 . The combination solid oral dosage form of claim 1 , wherein the amount of norethindrone acetate degradant present after storing said combination solid oral dosage form for 6 months, at 60° C. and ambient relative humidity, does not exceed 1.4% w/w.
11 . The combination solid oral dosage form of claim 1 , wherein when administered orally to a subject the mean maximum plasma concentration (C max ) 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, is in the range of 10 ng/ml to 30 ng/mL.
12 . The combination solid oral dosage form of claim 2 , wherein when administered orally to a subject the mean maximum plasma concentration (C max ) 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, is in the range of 10 ng/ml to 30 ng/mL.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 8, 2025
From: SUMITOMO PHARMA SWITZERLAND GMBH
To: SUMITOMO PHARMA CO., LTD.
Reel/Frame 071971/0600 →
CHANGE OF NAME
Recorded Sep 19, 2023
From: MYOVANT SCIENCES GMBH
To: SUMITOMO PHARMA SWITZERLAND GMBH
Reel/Frame 064954/0232 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 23, 2023
From: ALONZO, DAVID E.; XIE, MINLI; ULLMER, KATHLEEN D.
To: MYOVANT SCIENCES, INC.
Reel/Frame 063726/0229 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded May 23, 2023
From: MYOVANT SCIENCES, INC.
To: MYOVANT SCIENCES GMBH
Reel/Frame 063726/0333 →
Continuity (3)
Continuation
PCTEP2021064280
· May 27, 2021
Provisional Application
63032469
· May 29, 2020
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