IP Library › Granted Patent US 12,364,684
Granted Patent B2
US 12,364,684 · App. 18/823,274 · Granted Jul 22, 2025

Pharmaceutical composition

Inventors: Nicola Frances Bateman (Macclesfield, GB); Paul Richard Gellert (Macclesfield, GB); Kathryn Jane Hill (Macclesfield, GB)
Assignees: AstraZeneca AB; Array BioPharma, Inc.
A61K31/4184A61K9/0053A61K9/145A61K9/146A61K9/4858A61K9/4866A61K47/22A61K47/36C07D235/06
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Quick Facts
Patent No.
US 12,364,684
App. No.
18/823,274
Granted
Jul 22, 2025
Kind
B2
Abstract

The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament, and to processes for the preparation of said compositions.

Claims (52)

1. A method of inhibiting the proliferation of cancer cells in a human in need thereof, the method comprising orally administering to the human a pharmaceutical composition consisting of:

(i) from 5 to 10 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and

(ii) from 95 to 90 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS);

wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and

wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.

2. The method of claim 1 , wherein the cancer cells are MEK-sensitive cancer cells.

3. The method of claim 1 , wherein the cancer is malignant melanoma, or lung, squamous cell, bladder, gastric, pancreatic, breast, head, neck, renal, kidney, ovarian, prostate, colorectal, esophageal, testicular, gynecological, or thyroid cancer.

4. The method of claim 1 , wherein the cancer is brain cancer.

5. The method of claim 1 , wherein the composition contains 6.05+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

6. The method of claim 1 , wherein the composition contains 12.10+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

7. The method of claim 1 , wherein the composition contains 15.12+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

8. The method of claim 1 , wherein the composition contains 30.25+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

9. The method of claim 1 , wherein the composition contains 12.10 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

10. A method of inhibiting the proliferation of cancer cells in a human in need thereof, the method comprising orally administering to the human a pharmaceutical composition consisting of:

(i) approximately 10 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and

(ii) approximately 90 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS);

wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and

wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.

11. The method of claim 10 , wherein the cancer cells are MEK-sensitive cancer cells.

12. The method of claim 10 , wherein the cancer is malignant melanoma, or lung, squamous cell, bladder, gastric, pancreatic, breast, head, neck, renal, kidney, ovarian, prostate, colorectal, esophageal, testicular, gynecological, or thyroid cancer.

13. The method of claim 10 , wherein the cancer is brain cancer.

14. The method of claim 10 , wherein the composition contains 12.10+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

15. The method of claim 10 , wherein the composition contains 15.12+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

16. The method of claim 10 , wherein the composition contains 30.25+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

17. The method of claim 10 , wherein the composition contains 12.10 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

18. A method of inhibiting the proliferation of cancer cells in a human in need thereof, the method comprising orally administering to the human a pharmaceutical composition consisting of:

(i) from 15 to 25 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and

(ii) from 75 to 85 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS);

wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and

wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.

19. The method of claim 18 , wherein the cancer cells are MEK-sensitive cancer cells.

20. The method of claim 18 , wherein the cancer is malignant melanoma, or lung, squamous cell, bladder, gastric, pancreatic, breast, head, neck, renal, kidney, ovarian, prostate, colorectal, esophageal, testicular, gynecological, or thyroid cancer.

21. The method of claim 18 , wherein the cancer is brain cancer.

22. The method of claim 18 , wherein the pharmaceutical composition consists of:

(i) from 18 to 22 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and

(ii) from 78 to 82 parts of Vitamin E TPGS;

wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and

wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.

23. The method of claim 19 , wherein the pharmaceutical composition consists of:

(i) from 19 to 21 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and

(ii) from 79 to 81 parts of Vitamin E TPGS;

wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and

wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.

24. The method of claim 19 , wherein the pharmaceutical composition consists of:

(i) approximately 20 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and

(ii) approximately 80 parts of Vitamin E TPGS;

wherein both parts are by weight and the sum of the parts (i)+(ii)=100; and

wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.

25. The method of claim 18 , wherein the pharmaceutical composition contains 30.25+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

26. The method of claim 18 , wherein the composition contains 60.5+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

27. The method of claim 18 , wherein the composition contains 90.75+/−2 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

28. The method of claim 18 , wherein the pharmaceutical composition contains 30.25 mg of a hydrogen sulphate salt of 6-(4-bromo-2-chlorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 13, 2025
From: ASTRAZENECA AB
To: ALEXION PHARMA INTERNATIONAL OPERATIONS LIMITED
Reel/Frame 072888/0633 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 3, 2024
From: BATEMAN, NICOLA FRANCES; GELLERT, PAUL RICHARD; HILL, KATHRYN JANE
To: ASTRAZENECA AB; ARRAY BIOPHARMA, INC.
Reel/Frame 069473/0153 →
Continuity (11)
Continuation 18484334 · Oct 10, 2023
Continuation 17313312 · May 6, 2021
Continuation 16597237 · Oct 9, 2019
Continuation 16023102 · Jun 29, 2018
Continuation 15348053 · Nov 10, 2016
Continuation 14884343 · Oct 15, 2015
Continuation 13747853 · Jan 23, 2013
Continuation 13293368 · Nov 10, 2011
Continuation 12411865 · Mar 26, 2009
Provisional Application 61040372 · Mar 28, 2008
Related Publication 20250000848A1 · Jan 2, 2025
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