Solid forms of a toll-like receptor modulator

Patent metadata

Field	Value
Publication number	US-10508117-B2
Application number	US-201816229460-A
Country	US
Kind code	B2
Filing date	Dec 21, 2018
Priority date	Sep 16, 2014
Publication date	Dec 17, 2019
Grant date	Dec 17, 2019

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.

First claim

What is claimed is:

1. A crystalline form of Compound I having the structure:

characterized by an X-ray powder diffraction (XRPD) pattern comprising three or more peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

2. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at 5.3, 9.8 and 15.6 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

3. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 and 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

4. The crystalline form of claim 1 , characterized by the XRPD pattern substantially in accordance with that of FIG. 20 .

5. The crystalline form of claim 1 , characterized by a differential scanning calorimetry (DSC) endotherm at about 141° C. or about 173° C.

6. The crystalline form of claim 1 , characterized by
an XRPD pattern comprising peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 and 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation; and
a DSC endotherm at about 173° C.

7. A method of preparing a crystalline form of claim 1 , comprising:
forming a mixture comprising a crystalline Form I of Compound I characterized by an XRPD pattern comprising three or more peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation, water and trifluoroethanol, under conditions suitable to prepare the crystalline form of claim 1 .

8. The method of claim 7 , wherein the ratio of trifluoroethanol to water is from about 10:1 to about 1:1 (volume/volume).

9. The method of claim 7 , wherein the ratio of trifluoroethanol to water is about 5:1 (volume/volume).

10. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound I of claim 1 , and a pharmaceutically acceptable carrier or excipient.

11. The pharmaceutical composition of claim 10 , further comprising at least one additional therapeutic agent.

12. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising four or more peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

13. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising five or more peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

14. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising one or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

15. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising two or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

16. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising three or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

17. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising four or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

18. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising five or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

Assignees

• Gilead Sciences Inc

Inventors

• Andres Patricia
• Diaz Krista Marie
• Smolenskaya Valeriya N

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P31/18

  for HIV · CPC title