TLR agonists

Patent metadata

Field	Value
Publication number	US-9359360-B2
Application number	US-201213682208-A
Country	US
Kind code	B2
Filing date	Nov 20, 2012
Priority date	Aug 22, 2005
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

The present invention provides for TLR agonist conjugates (compounds) and compositions, as well as methods of using them. The compounds of the invention are broad-spectrum, long-lasting, and non-toxic combination of synthetic immunostimulatory agents, which are useful for activating the immune system of a mammal, preferably a human and can help direct the pharmacophore to the receptor within the endosomes of target cells and enhance the signal transduction induced by the pharmacophore.

First claim

What is claimed is:

1. A compound having formula (IA) and R 3 :

wherein X 1 is —O;
R 1 is (C 1 -C 10 )alkyl or substituted (C 1 -C 10 )alkyl, wherein the substituents are hydroxy, C 1-6 alkyl, hydroxyC 1-6 alkylene, or C 1-6 alkoxy;
wherein n=4 and each R 2 is —H;
X 2 is a bond or a linking group having up to about 24 atoms; wherein the atoms in the chain of the linking group are selected from the group consisting of carbon, nitrogen, sulfur, non-peroxide oxygen, and phosphorous; and R 3 is a protein that directs formula (IA) to receptors within endosomes of target cells;
or a pharmaceutically acceptable salt of the compound,
wherein the ratio of the compound having formula (IA) to R 3 is 5:1.

2. The compound of claim 1 , wherein R 1 is C 1-4 alkyl, or substituted C 1-4 alkyl.

3. The compound of claim 2 , wherein R 1 is CH 3 —, CH 3 —C 2 —, CH 3 CH 2 CH 2 —, hydroxyC 1-4 alkylene, or C 1-4 alkoxyC 1-4 alkylene.

4. The compound of claim 3 , wherein R 1 is CH 3 —, CH 3 —CH 2 —, CH 3 —O—CH 2 CH 2 — or CH 3 —CH 2 —O—CH 2 CH 2 —.

5. The compound of claim 1 , wherein X 2 is a bond or a chain having from about 4 to about 12 atoms.

6. The compound of claim 1 , wherein X 2 is a bond or a chain having from about 6 to about 9 atoms.

7. The compound of claim 1 , wherein X 2 is

8. The compound of claim 1 , wherein the protein is albumin.

9. The compound of claim 1 , wherein the protein is ovalbumin.

10. A compound having formula (IA) and R 3 :

wherein X 1 is —O—;
R 1 is (C 1 -C 10 )alkyl or substituted (C 1 -C 10 )alkyl, wherein the substituents are hydroxy, C 1-6 alkyl, hydroxyC 1-6 alkylene, or C 1-6 alkoxy;
each R 2 is —H and n=4;
X 2 is a bond or a linking group having up to about 24 atoms; wherein the atoms in the chain of the linking group are selected from the group consisting of carbon, nitrogen, sulfur, and non-peroxide oxygen; and R 3 is a protein that directs formula (IA) to receptors within endosomes of target cells;
or a pharmaceutically acceptable salt of the compound,
wherein the ratio of the compound having formula (IA) to R 3 is 5:1.

11. A pharmaceutical composition comprising the compound of claim 10 , and a pharmaceutically acceptable carrier.

12. The compound of claim 10 , wherein the protein is albumin.

13. The compound of claim 10 , wherein the protein is ovalbumin.

Assignees

• Grimshaw Suzanne
• Univ California

Inventors

• Carson Dennis A
• Takabayashi Kenji
• Cottam Howard B
• Chan Michael
• Wu Christina C N

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P43/00

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