MODULATORS OF TOLL-LIKE RECEPTORS FOR THE TREATMENT OF HIV

• US 20170071944A1
• Filed: 09/13/2016
• Published: 03/16/2017
• Est. Priority Date: 09/15/2015
• Status: Abandoned Application

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: GELEZIUNAS, ROMAS, Kaur, Jasmine, Murry, Jeffrey Patrick, Sloan, Derek Dean, Hesselgesser, Joseph E.
• Application Number:
  US15/264,401
• Publication Number:
  US 20170071944A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/18 for HIV

Abstract

Provided are methods, uses, pharmaceutical regimens, pharmaceutical compositions, and kits comprising modulators of TLR8 and pharmaceutically acceptable salts thereof, useful in treating HIV infections.

Claims

1. A method of treating an HIV infection in a human, the method comprising administering to a human in need thereof a pharmaceutically effective amount of a TLR8 modulating compound, or a pharmaceutically acceptable salt thereof.

2. A method of treating an HIV infection in a human, the method comprising:

a) administering to a human in need thereof a pharmaceutically effective amount of a combination antiretroviral therapy regimen sufficient to lower the level of HIV detected in the human'"'"'s blood or plasma from a first level to a second level, the second level comprising a lower concentration of HIV in the human'"'"'s blood or plasma than the concentration of HIV in the human'"'"'s blood or plasma in the first level; and

b) administering to the human a pharmaceutically effective amount of a TLR8 modulating compound, or a pharmaceutically acceptable salt thereof.

3. The method of claim 2 wherein the first level of HIV in the human'"'"'s plasma is below 50 copies of HIV RNA/ml.

4. The method of claim 2 wherein the second level of HIV in the human'"'"'s plasma is below 30 copies of HIV RNA/ml.

5. The method of claim 2 wherein the first level of HIV in the human'"'"'s plasma is below 10 copies of HIV RNA/ml.

6. The method of claim 2 wherein the first level of HIV in the human'"'"'s plasma is below 1 copy of HIV RNA/ml.

7. The method of treating an HIV infection in a human of claim 2, the method further comprising the step of administering to the human a pharmaceutically effective amount of an HIV antibody.

8. The method of treating an HIV infection in a human of claim 2, the method further comprising the step of administering to the human in need thereof a pharmaceutically effective amount of an HIV vaccine.

9. The method of claim 2, wherein the TLR8 modulating compound is a compound of Formula (IV),

10. The method of claim 9, wherein the TLR8 modulating compound is a compound of Formula (IVa)

11. The method of claim 9, wherein the TLR8 modulating compound is a compound of Formula (IVb)

12. The method of claim 10, wherein the moiety

13. The method of claim 11, wherein the moiety

14. The method of claim 2, wherein the TLR8 modulating compound is selected from the group consisting of:

15. The method of claim 14, wherein the TLR8 modulating compound is selected from the group consisting of:

16. The method of claim 2 wherein the TLR8 modulating compound is

17. The method of claim 2 further comprising the step of administering to the human in need thereof a pharmaceutically effective amount of an immunomodulatory cytokine.

18. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and:

a) a pharmaceutically effective amount of an antiretroviral agent; and

b) a pharmaceutically effective amount of a TLR8 modulating compound.

19. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and:

a) a pharmaceutically effective amount of each of two or more antiretroviral agents; and

b) a pharmaceutically effective amount of a TLR8 modulating compound.