Preparation of and formulation comprising a MEK inhibitor

Patent metadata

Field	Value
Publication number	US-9980944-B2
Application number	US-201715445393-A
Country	US
Kind code	B2
Filing date	Feb 28, 2017
Priority date	Oct 19, 2012
Publication date	May 29, 2018
Grant date	May 29, 2018

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 melanoma in a patient in need thereof, the method comprising:
(a) detecting a melanoma in said patient that is a BRAF-mutant melanoma; and
(b) administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.

2. The method of claim 1 , wherein said BRAF-mutant melanoma is BRAFV600-mutant melanoma.

3. The method of claim 1 , further comprising treating said patient with at least one additional therapeutic agent selected from the group consisting of 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.

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

5. The method of claim 4 , wherein said BRAF-mutant melanoma is BRAFV600-mutant melanoma.

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

7. The method of claim 6 , wherein said BRAF-mutant melanoma is BRAFV600-mutant melanoma.

8. The method of claim 1 , wherein said pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide is formulated for oral administration.

9. The method of claim 8 , wherein said pharmaceutical composition is formulated as a tablet.

10. The method according to claim 9 , wherein said tablet further comprises lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, and magnesium stearate.

11. The method according to claim 9 , wherein said tablet comprises approximately 15 mg crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.

12. The method according to claim 10 , wherein said tablet comprises approximately 15 mg crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.

Assignees

• Array Biopharma Inc
• 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

• C30B7/08

  by cooling of the solution · CPC title

• A61K45/06

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

• C30B29/54

  Organic compounds · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title