IP Library › Granted Patent US 12,486,271
Granted Patent B2
US 12,486,271 · App. 18/451,611 · Granted Dec 2, 2025

Solid forms of a toll-like receptor modulator

Inventors: Brandon Heath Brown (Burlingame, CA); Paul A. Roethle (Berkeley, CA)
Assignee: Gilead Sciences, Inc.
C07D475/06A61K31/519A61K45/06C07D487/04
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Quick Facts
Patent No.
US 12,486,271
App. No.
18/451,611
Granted
Dec 2, 2025
Kind
B2
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.

Claims (29)

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.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 10, 2025
From: BROWN, BRANDON HEATH; ROETHLE, PAUL
To: GILEAD SCIENCES, INC.
Reel/Frame 072217/0070 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2023
From: DIAZ, KRISTA MARIE; ANDRES, PATRICIA; SMOLENSKAYA, VALERIYA N.
To: ALBANY MOLECULAR RESEARCH, INC.
Reel/Frame 064911/0415 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 14, 2023
From: ALBANY MOLECULAR RESEARCH, INC.
To: GILEAD SCIENCES, INC.
Reel/Frame 064911/0542 →
Continuity (7)
Continuation 17353462 · Jun 21, 2021
Continuation 16678788 · Nov 8, 2019
Continuation 16229460 · Dec 21, 2018
Continuation 15591711 · May 10, 2017
Continuation 14853855 · Sep 14, 2015
Provisional Application 62051063 · Sep 16, 2014
Related Publication 20240217975A1 · Jul 4, 2024
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