Crystalline and salt forms of an organic compound and pharmaceutical compositions thereof

Inventors

Sizemore, Jacob • Zhang, Shijie

Assignees

Servier Pharmaceuticals LLC

Abstract

Provided herein are various salts, including tris(hydroxymethyl)aminomethane salts and sodium salts, as well as various crystalline forms of the compound represented by the structural formula: Also provided are pharmaceutical compositions comprising these salts and crystalline forms, methods for their manufacture, and uses thereof for treating conditions, including but not limited to conditions that would benefit from inhibition of dihydroorotate dehydrogenase (DHODH).

Core Innovation

The invention relates to tris(hydroxymethyl)aminomethane salt forms of Compound 1, including Tris salt Form C, and to pharmaceutical compositions and formulations containing such Tris salts. The disclosure includes solid-state characterization and definition of particular crystalline forms, including identification using X-ray powder diffraction together with thermal characterization such as XRPD and DSC/TGA-type characterization described in the provided content.

The disclosed Tris salt forms are presented in the context of inhibiting dihydroorotate dehydrogenase (DHODH) and for therapeutic use in treating cancer. The described therapeutic uses include treatment of solid tumor cancers and hematological cancers, including myeloma, lymphoma, and leukemia.

The disclosure further identifies additional non-cancer conditions associated with the therapeutic area described in the provided content, including viral-mediated disease, transplant rejection, rheumatoid arthritis, psoriasis, autoimmune disease, and inflammatory disorder. Overall, the core of the invention is the provision of Tris salt forms of Compound 1, particularly defined crystalline forms, together with pharmaceutical compositions and therapeutic regimens for DHODH inhibition-associated indications.

Claims Coverage

The independent claim centers on a tris(hydroxymethyl)aminomethane salt of Compound 1, with dependent claim coverage refining the salt by specifying crystalline forms defined by X-ray powder diffraction and further extending coverage to pharmaceutical compositions and treatment methods for cancer and cancers responsive to DHODH inhibition. The inventive features indicated by the claims include crystalline form definitions and administration-based treatment with effective amounts, plus formulation with pharmaceutically acceptable excipients.

Claim coverage centers on Tris(hydroxymethyl)aminomethane salts of Compound 1, with specific crystalline forms defined by XRPD peak positions, and extends to pharmaceutical compositions containing pharmaceutically acceptable excipients and administration-based methods for treating cancer, including cancers responsive to inhibition of dihydroorotate dehydrogenase.

Stated Advantages

Documented Applications