EP3333167A1 — Solid forms of venetoclax

USPTO Abstract

The present invention relates to novel forms of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1 -en- 1 -yl]methyl}piperazin-1 -yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (also known as venetoclax) as well as to the preparation thereof. One novel polymorph is an anhydrous crystalline form of venetoclax (referred to herein as "Form S"). Another novel polymorph is a crystalline hydrate of venetoclax (referred to herein as "Form HyD"). The present invention also discloses a novel amorphous form of venetoclax having a low solvent content, and refers to a pharmaceutical composition comprising said novel forms of venetoclax. Moreover, the present invention relates to the use of Form HyD as an intermediate for the preparation of crystalline Form S. Finally, the present invention refers to the novel polymorphs, or the pharmaceutical composition comprising the novel polymorphs of venetoclax or amorphous form of venetoclax, for use in a method of preventing or treating a disease that is characterized by apoptotic dysfunction and/or overexpression of an anti-apoptotic Bcl-2 family protein.