Solid forms of a toll-like receptor modulator

Patent metadata

Field	Value
Publication number	US-12486271-B2
Application number	US-202318451611-A
Country	US
Kind code	B2
Filing date	Aug 17, 2023
Priority date	Sep 16, 2014
Publication date	Dec 2, 2025
Grant date	Dec 2, 2025

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 method of treating HIV in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a crystalline form of Compound I having the structure:

characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 11.6, and 22.3 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

2 . The method of claim 1 , wherein the crystalline form is characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 22.3, and 23.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

3 . The method of claim 1 , wherein the crystalline form is characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

4 . The method of claim 1 , wherein the crystalline form is characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 17.7, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

5 . The method of claim 1 , wherein the crystalline form is characterized by DSC endotherms at about 133° C. and about 170° C.

6 . The method of claim 1 , further comprising administering at least one additional therapeutic agent that is an anti-HIV agent.

7 . The method of claim 1 , further comprising administering at least one additional therapeutic agent selected from the group consisting of HIV antibodies, bispecific antibodies, and “antibody-like” therapeutic proteins; HIV vaccines; and combinations thereof.

8 . The method of claim 7 , wherein the at least one additional therapeutic agent is an HIV antibody, bispecific antibody, or “antibody-like” therapeutic protein.

9 . The method of claim 7 , wherein the at least one additional therapeutic agent is an HIV vaccine.

10 . The method of claim 1 , further comprising administering at least one additional therapeutic agent selected from the group consisting of:
(1) HIV vaccines selected from the group consisting of peptide vaccines, recombinant subunit protein vaccines, live vector vaccines, DNA vaccines, virus-like particle vaccines (pseudovirion vaccine), CD4-derived peptide vaccines, vaccine combinations, rgp120 (AIDSVAX), ALVAC HIV (vCP1521)/AIDSVAX B/E (gp120) (RV144), monomeric gp120 HIV-1 subtype C vaccine (Novartis), Remune, ITV-1, Contre Vir, Ad5-ENVA-48, DCVax-001 (CDX-2401), PEP-6409, Vacc-4x, Vacc-C5, VAC-3S, multiclade DNA recombinant adenovirus-5 (rAd5), Pennvax-G, VRC-HIV MAB060-00-AB, AVX-101, HIV-TriMix-mRNA vaccine, AVX-201, HIV-LAMP-vax, Ad35, Ad35-GRIN, NAcGM3/VSSP ISA-51, poly-ICLC adjuvanted vaccines, TatImmune, GTU-multiHIV (FIT-06), AGS-004, gp140[delta]V2.TV1+MF-59, rVSVIN HIV-1 gag vaccine, SeV-Gag vaccine, AT-20, DNK-4, Ad35-GRIN/ENV, TBC-M4, HIVAX, HIVAX-2, NYVAC-HIV-PT1, NYVAC-HIV-PT4, DNA-HIV-PT123, rAAV1-PG9DP, GOVX-B11, GOVX-B21, ThV-01, TUTI-16, VGX-3300, TVI-HIV-1, Ad-4 (Ad4-env Clade C+Ad4-mGag), EN41-UGR7C, EN41-FPA2, PreVaxTat, TL-01, SAV-001, AE-H, MYM-V101, CombiHIVvac, ADVAX, MYM-V201, MVA-CMDR, MVATG-17401, ETV-01, CDX-1401, rcAd26.MOS1.HIV-Env and DNA-Ad5 gag/pol/nef/nev (HVTN505); (2) HIV antibodies, bispecific antibodies and “antibody-like” therapeutic proteins selected from the group consisting of BMS-936559 and TMB-360; and (3) HIV antibodies targeting HIV gp120 or gp41 selected from the group consisting of bavituximab, UB-421, C2F5, C2G12, C4E10, C2F5+C2G12+C4E10, 3-BNC-117, PGT145, PGT121, MDX010 (ipilimumab), VRC01, A32, 7B2, 10E8, VRC-07-523 and VRC07.

11 . A method of treating HIV in a human in need thereof, the method comprising administering to the human a pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound I having the structure:

characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 11.6, and 22.3 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation; and
a pharmaceutically acceptable excipient.

12 . The method of claim 11 , wherein the crystalline form is characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 22.3, and 23.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

13 . The method of claim 11 , wherein the crystalline form is characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

14 . The method of claim 11 , wherein the crystalline form is characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 17.7, 22.3, 23.9, 26.0 and 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.

15 . The method of claim 11 , wherein the crystalline form is characterized by DSC endotherms at about 133° C. and about 170° C.

16 . The method of claim 11 , further comprising administering at least one additional therapeutic agent that is an anti-HIV agent.

17 . The method of claim 11 , further comprising administering at least one additional therapeutic agent selected from the group consisting of HIV antibodies, bispecific antibodies, and “antibody-like” therapeutic proteins; HIV vaccines; and combinations thereof.

18 . The method of claim 17 , wherein the at least one additional therapeutic agent is an HIV antibody, bispecific antibody, or “antibody-like” therapeutic protein.

19 . The method of claim 17 , wherein the at least one additional therapeutic agent is an HIV vaccine.

20 . The method of claim 11 , further comprising administering at least one additional therapeutic agent selected from the group consisting of:
(1) HIV vaccines selected from the group consisting of peptide vaccines, recombinant subunit protein vaccines, live vector vaccines, DNA vaccines, virus-like particle vaccines (pseudovirion vaccine), CD4-derived peptide vaccines, vaccine combinations, rgp120 (AIDSVAX), ALVAC HIV (vCP1521)/AIDSVAX B/E (gp120) (RV144), monomeric gp120 HIV-1 subtype C vaccine (Novartis), Remune, ITV-1, Contre Vir, Ad5-ENVA-48, DCVax-001 (CDX-2401), PEP-6409, Vacc-4x, Vacc-C5, VAC-3S, multiclade DNA recombinant adenovirus-5 (rAd5), Pennvax-G, VRC-HIV MAB060-00-AB, AVX-101, HIV-TriMix-mRNA vaccine, AVX-201, HIV-LAMP-vax, Ad35, Ad35-GRIN, NAcGM3/VSSP ISA-51, poly-ICLC adjuvanted vaccines, TatImmune, GTU-multiHIV (FIT-06), AGS-004, gp140[delta]V2.TV1+MF-59, rVSVIN HIV-1 gag vaccine, SeV-Gag vaccine, AT-20, DNK-4, Ad35-GRIN/ENV, TBC-M4, HIVAX, HIVAX-2, NYVAC-HIV-PT1, NYVAC-HIV-PT4, DNA-HIV-PT123, rAAV1-PG9DP, GOVX-B11, GOVX-B21, ThV-01, TUTI-16, VGX-3300, TVI-HIV-1, Ad-4 (Ad4-env Clade C+Ad4-mGag), EN41-UGR7C, EN41-FPA2, PreVaxTat, TL-01, SAV-001, AE-H, MYM-V101, CombiHIVvac, ADVAX, MYM-V201, MVA-CMDR, MVATG-17401, ETV-01, CDX-1401, rcAd26.MOS1.HIV-Env and DNA-Ad5 gag/pol/nef/nev (HVTN505); (2) HIV antibodies, bispecific antibodies and “antibody-like” therapeutic proteins selected from the group consisting of BMS-936559 and TMB-360; and (3) HIV antibodies targeting HIV gp120 or gp41 selected from the group consisting of bavituximab, UB-421, C2F5, C2G12, C4E10, C2F5+C2G12+C4E10, 3-BNC-117, PGT145, PGT121, MDX010 (ipilimumab), VRC01, A32, 7B2, 10E8, VRC-07-523 and VRC07.

Assignees

• Gilead Sciences Inc

Inventors

• Brown Brandon Heath
• Roethle Paul A

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title