Solid forms of a toll-like receptor modulator

Inventors

Diaz, Krista Marie • Andres, Patricia • Smolenskaya, Valeriya N.

Assignees

Gilead Sciences Inc • Curia Global Inc

Abstract

The present invention provides crystalline forms, solvates and hydrates of 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one, and methods of making.

Core Innovation

The disclosure relates to Compound I, identified as 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one, and addresses solid-state forms of Compound I, focusing on crystalline forms as well as solvates and hydrates. The crystalline form of Compound I is defined by an X-ray powder diffraction (XRPD) pattern characterized by three or more peaks at specified 2θ values measured using CuKα1 radiation, and is further characterized by differential scanning calorimetry (DSC) endotherm(s) at about 142°C and/or about 274°C.

The invention provides crystalline Forms I-VI and additional Forms VII-XIV, together with various solvates and hydrates. For each form, the identity is characterized primarily by XRPD peak positions measured under CuKα1 radiation with an indicated tolerance, and for some forms, by DSC endotherms.

The document also describes solid-state forms of Compound I and interconversion between forms, including solvent crystallization, solvent/anti-solvent crystallization systems, thermal conversion, solvent removal, humidity-driven transformation, cooling below 0 °C, and drying/de-solvating to produce later forms. The solid-state characterization and interconversion approach are described in terms of achieving the defined crystalline forms and their defined XRPD/DSC signatures.

Claims Coverage

The partial content provided includes three independent claims, covering a crystalline form of Compound I defined by XRPD peak positions measured with CuKα1 radiation, a pharmaceutical composition comprising that crystalline form plus a pharmaceutically acceptable carrier or excipient, optionally combined with enumerated additional therapeutic agents, and a method of preparing the crystalline form using chloroform and forming a mixture that includes crystalline Form I defined by specific XRPD peaks.

Across the independent claims, the core coverage is directed to the crystalline form of Compound I as defined by an XRPD peak pattern measured with CuKα1 radiation, including XRPD-defined Form I and optionally characterized by DSC endotherm(s). The crystalline form is used in a pharmaceutical composition with a pharmaceutically acceptable carrier or excipient, and the document further includes compositions that can comprise additional therapeutic agents selected from explicitly enumerated hepatitis B-related and immunotherapy drug classes and named examples. The method claim covers preparing the XRPD-defined crystalline form using chloroform to form a mixture comprising crystalline Form I defined by specified XRPD peaks.

Stated Advantages

Documented Applications