Synthetic agonists of tlr9

Abstract

The invention provides novel oligonucleotide-based compounds that individually provide distinct immune response profiles through their interactions as agonists with TLR9. The TLR9 agonists according to the invention are characterized by specific and unique chemical modifications, which provide their distinctive immune response activation profiles.

1 . A TLR9 agonist comprising a structure selected from the group consisting of 5′-TAGTCG 1 TTCTC-X-CTCTTG 1 CTGAT-5′, 5′-TCG 1 TACG 1 TACG 1 -X-G 1 CATG 1 CATG 1 CT-5′, 5′-TCG 1 ATCG 1 ATCG 1 -X-G 1 CTAG 1 CTAG 1 CT-5′, 5′-TCTGTCG 2 TTTT-X-TTTTG 2 CTGTCT-5′, 5′-TCG 2 ATCG 2 ATCG 2 -X-G 2 CTAG 2 CTAG 2 CT-5′, 5′-TCG 1 AACG 1 TTCG 1 -M-TCTTG 1 CTGTCT-5′, 5′-TCG 1 AACG 1 TTCG 1 -L- GA CAG 1 CTGTCT-5′, 5′-TCG 1 AACG 1 TTCG 1 -L- GA CAG 1 CTGTCT-5′, 5′-TCG 1 TCG 1 ACG 1 AT-S-TAG 1 CAG 1 CTG 1 CT-5′, and 5′-TCAGToCG 2 TTAC-S-CATTG 2 CoTGACT-5′, wherein G 1  is 7-deaza-dG; G 2  is AraG;  G / A  is 2′-O-methylribonucleotides; o is phosphodiester linkage; X=Glycerol; L is 1,3-Propanediol; M is 1,5-Pentanediol; S is 3-Me-1,3,5-pentanetriol, wherein internucleoside linkages are selected from the group consisting of phosphodiester linkages, phosphorothioate linkages and mixtures thereof. 
     
     
         2 . A composition comprising the TLR9 agonist according to  claim 1 , and a physiologically acceptable carrier. 
     
     
         3 . A vaccine comprising the composition according to  claim 2 , and an antigen. 
     
     
         4 . A method for generating a TLR9-mediated immune response in a vertebrate, comprising administering to the vertebrate an effective amount of the TLR9 agonist according to  claim 1 . 
     
     
         5 . A method for generating a TLR9-mediated immune response in a vertebrate, comprising administering to the vertebrate an effective amount of the composition according to  claim 2 . 
     
     
         6 . A method for therapeutically treating a patient having a disease or disorder, comprising administering to the patient a therapeutically effective amount of the TLR9 agonist according to  claim 1 . 
     
     
         7 . A method for therapeutically treating a patient having a disease or disorder, comprising administering to the patient a therapeutically effective amount of the composition according to  claim 2 . 
     
     
         8 . A method for therapeutically treating a patient having a disease or disorder, comprising administering to the patient a therapeutically effective amount of the vaccine according to  claim 3 . 
     
     
         9 . A method for preventing a disease or disorder in a patient that is susceptible to the disease or disorder, comprising administering to the patient a prophylactically effective amount of the TLR9 agonist according to  claim 1 . 
     
     
         10 . A method for preventing a disease or disorder in a patient that is susceptible to the disease or disorder, comprising administering to the patient a prophylactically effective amount of the composition according to  claim 2 . 
     
     
         11 . A method for preventing a disease or disorder in a patient that is susceptible to the disease or disorder, comprising administering to the patient a prophylactically effective amount of the vaccine according to  claim 3 . 
     
     
         12 . The method according to any of  claims 4 - 11 , wherein the disease or disorder is selected from the group consisting of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, allergy, asthma and a disease caused by a pathogen.