IP Library › Granted Patent US 12,427,142
Granted Patent B2
US 12,427,142 · App. 17/802,223 · Granted Sep 30, 2025

Combination comprising alpelisib and 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl[oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid

Inventors: Monsif Bouaboula (Belmont, MA); Zhuyan Guo (Belmont, MA); Stéphane Poirier (Stoneham, MA); Maysoun Shomali (Belmont, MA); Fangxian Sun (Melrose, MA)
Assignee: Sanofi
A61K31/4439A61K31/40A61P35/00
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Quick Facts
Patent No.
US 12,427,142
App. No.
17/802,223
Granted
Sep 30, 2025
Kind
B2
Abstract

Herein are provided a combination of alpelisib and of 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing such a combination, and the therapeutic uses thereof, in particular for the treatment of cancer, including breast cancer.

Claims (22)

1. A combination comprising 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo [7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, and alpelisib.

2. The combination according to claim 1 , wherein the combination shows therapeutic synergy.

3. The combination according to claim 1 , for use in the treatment of cancer.

4. The combination according to claim 3 , wherein the cancer is breast cancer.

5. The combination according to claim 1 , wherein 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, and alpelisib are administered simultaneously or spaced out over a period of time.

6. A pharmaceutical composition comprising 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, and alpelisib, and at least one pharmaceutically acceptable excipient.

7. A kit comprising:

(i) a first pharmaceutical composition comprising 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient; and

(ii) a second pharmaceutical composition comprising alpelisib, and at least one pharmaceutically acceptable excipient;

wherein the first pharmaceutical composition and the second pharmaceutical composition are in separate compartments.

8. The kit of claim 7 , further comprising a label or package insert indicating that the first and second pharmaceutical compositions are administered for the treatment of cancer.

9. The kit of claim 8 , wherein the cancer is breast cancer.

10. The kit of claim 7 , further comprising a label or package insert indicating that the first and second pharmaceutical compositions are administered simultaneously or sequentially with respect to each other.

11. The kit of claim 7 , further comprising a label or package insert indicating that the first and second pharmaceutical compositions are administered simultaneously with respect to each other.

12. The kit of claim 7 , further comprising a label or package insert indicating that the first and second pharmaceutical compositions are administered sequentially with respect to each other.

13. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, and alpelisib.

14. The method of claim 13 , wherein the cancer is breast cancer.

15. The method of claim 13 , wherein the 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, and alpelisib are administered in amounts that exhibit therapeutic synergy.

16. The method of claim 13 , wherein the 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, is administered simultaneously or sequentially with alpelisib.

17. The method of claim 13 , wherein the 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, is administered simultaneously with alpelisib.

18. The method of claim 13 , wherein the 6-(2,4-dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid, or a pharmaceutically acceptable salt thereof, is administered sequentially with alpelisib.

19. The method of claim 13 , wherein the subject is a human.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 3, 2023
From: BOUABOULA, MONSIF; GUO, ZHUYAN; POIRIER, STÉPHANE; SHOMALI, MAYSOUN; SUN, FANGXIAN
To: SANOFI
Reel/Frame 062585/0969 →
Priority Claims (1)
EP 20305190 · Feb 27, 2020 · regional
Continuity (1)
Related Publication 20230089371A1 · Mar 23, 2023
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