Preparation of and formulation comprising a MEK inhibitor

Patent metadata

Field	Value
Publication number	US-10398683-B2
Application number	US-201715842715-A
Country	US
Kind code	B2
Filing date	Dec 14, 2017
Priority date	Oct 19, 2012
Publication date	Sep 3, 2019
Grant date	Sep 3, 2019

Abstract

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound.

First claim

What is claimed is:

1. A method of treating colon cancer in a patient in need thereof, the method comprising:
administering to said patient an effective amount of:
(i) a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and a pharmaceutically acceptable carrier or excipient; and
(ii) an additional therapeutic agent which is a chemotherapeutic agent or anti-tumor agent.

2. The method according to claim 1 , wherein the pharmaceutical composition is formulated as a tablet.

3. The method according to claim 2 , wherein the pharmaceutical composition comprises approximately 15 mg of crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.

4. The method according to claim 1 , wherein the pharmaceutical composition is administered daily.

5. The method according to claim 1 , wherein the additional therapeutic agent is selected from mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzyme inhibitors, topoisomerase inhibitors, biological response modifiers, anti-hormones, angiogenesis inhibitors, and anti-androgens.

6. The method according to claim 4 , wherein the additional therapeutic agent is a growth factor inhibitor.

7. The method according to claim 6 , wherein the pharmaceutical composition is administered daily.

8. The method according to claim 1 , wherein the pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and the additional therapeutic agent are administered separately.

9. The method according to claim 1 , wherein the pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and the additional therapeutic agent are administered simultaneously.

10. The method according to claim 3 , wherein the additional therapeutic agent is selected from mitotic inhibitors, alkylating agents, anti-metabolites, intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzyme inhibitors, topoisomerase inhibitors, biological response modifiers, anti-hormones, angiogenesis inhibitors, and anti-androgens.

11. The method according to claim 10 , wherein the additional therapeutic agent is a growth factor inhibitor.

12. The method according to claim 9 , wherein the pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and the additional therapeutic agent are administered separately.

13. The method according to claim 9 , wherein the pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H- benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and the additional therapeutic agent are administered simultaneously.

14. The method according to claim 1 , wherein said effective amount is an amount that reduces the size of a tumor in said patient.

15. The method according to claim 1 , wherein said effective amount is an amount that decreases the growth rate of a tumor in said patient.

16. The method according to claim 5 , wherein said effective amount is an amount that reduces the size of a tumor in said patient.

17. The method according to claim 5 , wherein said effective amount is an amount that decreases the growth rate of a tumor in said patient.

18. The method according to claim 6 , wherein said effective amount is an amount that reduces the size of a tumor in said patient.

19. The method according to claim 6 , wherein said effective amount is an amount that decreases the growth rate of a tumor in said patient.

20. The method according to claim 10 , wherein said effective amount an amount that reduces the size of a tumor in said patient.

21. The method according to claim 10 , wherein said effective amount is an amount that decreases the growth rate of a tumor in said patient.

22. The method according to claim 11 , wherein said effective amount an amount that reduces the size of a tumor in said patient.

23. The method according to claim 11 , wherein said effective amount is an amount that decreases the growth rate of a tumor in said patient.

Assignees

• Array Biopharma Inc

Inventors

• Krell Christoph Max
• Misun Marian
• Niederer Daniel Andreas
• Pachinger Werner Heinz
• Wolf Marie-Christine
• Zimmermann Daniel
• Liu Weidong
• Stengel Peter J
• Nichols Paul

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C30B29/54

  Organic compounds · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title