Salts and pharmaceutical compositions thereof for the treatment of inflammatory disorders

Inventors

SABOURAULT, Nicolas Luc • Wigerinck, Piet

Assignees

Alfasigma SpA

Abstract

The present invention discloses salts of a Compound 1: useful in the prophylaxis and/or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and/or disruption of cartilage homeostasis, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons.

Core Innovation

The document discloses salt forms and crystalline forms of Compound 1, defined as {5-[4-(1,1-dioxo-thiomorpholin-4-ylmethyl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl}-amide, in the form of pharmaceutically acceptable acid salts. The salts include hydrochloric acid, hydrobromic acid, maleic acid, sulfonic acids, oxalic acid, and L-tartaric acid, and include specific crystalline adducts such as Compound 1.HCl.3H2O and a 1:1 free base/maleic acid salt.

The salt and crystalline forms are stated to inhibit JAK, especially JAK1, and are linked to prophylaxis and treatment of chronic ulcerative colitis as well as a wide set of inflammatory, autoimmune, proliferative, allergic, and cytokine-driven conditions, including diseases associated with IL-6 or interferon hypersecretion. The document also describes crystalline forms characterized by X-ray powder diffraction, including XRPD-defined peaks at listed 2b8 positions (b10.2b0).

The document further reports extensive solid-state characterization of Compound 1 and its salts using XRPD, DSC, and TGA, including polymorphs, solvates, amorphous formation, solvent and thermal cycling, and single-crystal data for Compound 1.HCl.3H2O. It also states that selection of salt and crystal form is associated with improved solubility and exposure versus free base/amorphous forms.

Claims Coverage

Two independent claims are directed to treating chronic ulcerative colitis using a pharmaceutically acceptable salt of a compound according to Formula (I), either by administering the salt itself or a pharmaceutical composition comprising the salt. The inventive core across the claims is the 1:1 free base/maleic acid crystalline salt defined by multiple XRPD 2b8 peaks within b10.2b0; dependent claims optionally include another therapeutic agent from specified drug classes.

Both independent claims cover chronic ulcerative colitis treatment using a pharmaceutically acceptable 1:1 free base/maleic acid crystalline salt (Formula (I)) defined by XRPD peaks at the listed 2b8 positions (b10.2b0), with one claim directed to administering the salt and the other to administering a pharmaceutical composition comprising that salt. Dependent claims further permit administration of an additional therapeutic agent limited to specified drug categories.

Stated Advantages

Documented Applications