Synergistic combinations of PI3K- and MEK-inhibitors

Patent metadata

Field	Value
Publication number	US-9675595-B2
Application number	US-201214240499-A
Country	US
Kind code	B2
Filing date	Aug 30, 2012
Priority date	Aug 31, 2011
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

A pharmaceutical combination comprising (a) the phosphatidylinositol 3-kinase (PI3K) inhibitor compound (S)-pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]thiazol-2-yl}-amide) or a pharmaceutically acceptable salt thereof, and (b) at least one mitogen activated protein kinase (MEK) inhibitor or a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

First claim

The invention claimed is:

1. A method for treating a proliferative disease selected from the group consisting of a colorectal cancer having at least one of a BRAF mutation, KRAS mutation, and PIK3CA mutation and not having a PTEN mutation; a pancreatic cancer having a KRAS mutation; a non-small cell lung cancer having a KRAS mutation; and a melanoma not having a PTEN mutation, comprising the simultaneous, separate or sequential administration of a therapeutically effective amount of the PI3K inhibitor compound (S)-pyrrolidine-1,2-dicarboxylic acid 2-amide 1-({4-methyl-5-[2-(2,2,2-trifluoro-1,1-dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl}-amide) or a pharmaceutically acceptable salt thereof, in combination with the MEK inhibitor compound 6 (4 bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethoxy)-amide or a pharmaceutically acceptable salt thereof, to a patient in need thereof having said proliferative disease.

2. A method according to claim 1 , wherein the proliferative disease is non-small-cell lung cancer (NSCLC).

Assignees

• Fritsch Christine
• Huang Xizhong
• Boehm Markus
• Di Tomaso Emmanuelle
• Cosaert Jan
• Novartis Ag

Inventors

• Fritsch Christine
• Huang Xizhong
• Boehm Markus
• Di Tomaso Emmanuelle
• Cosaert Jan

Classifications

• A61K47/00

  Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient · CPC title

• A61K45/06

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

• A61K31/4184 Primary

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title

• A61K31/4439 Primary

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61P35/02

  specific for leukemia · CPC title