Methods and products related to treatment and prevention of hepatitis C virus infection

Abstract

The invention provides methods for identifying and treating subjects having hepatitis C infections. In some instances, the subjects are those that are non-responsive to non-CpG therapy. Preferably, the subjects are treated with C class CpG immunostimulatory nucleic acids having a semi-soft backbone.

1 - 71 . (canceled)  
     
     
         72 . A branched immunostimulatory CpG oligonucleotide comprising at least one unmethylated CpG dinucleotide (5′CG 3′) and one or more unusual linkages involving a sugar moiety (Su), a heterocyclic base (Ba) or a phosphate backbone (Ph), wherein the one or more unusual linkages are selected from the group consisting of Su-Su, Su-Ph, Su-Ba, Ba-Ba, Ba-Su, Ba-Ph, Ph-Ph, Ph-Su, Ph-Ba, and any combination thereof.  
     
     
         73 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , wherein the unusual linkages are selected from the group consisting of 2′5′-, 5′5′-, 3′3′-, 2′2′-, and 2′3′-linkages.  
     
     
         74 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , wherein one part of the oligonucleotide is connected at a 3′-end via a 3′3′-linkage to a second oligonucleotide part and at a 2′-end via a 2′3′-linkage to a third part of the molecule.  
     
     
         75 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , wherein the branched immunostimulatory CpG oligonucleotide has an activity selected from the group consisting of (i) an ability to stimulate IFN-γ production from human peripheral blood mononuclear cells, (ii) an ability to stimulate IFN-α production from human peripheral blood mononuclear cells, and (iii) an ability to stimulate B cell proliferation.  
     
     
         76 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , further comprising one or more non-nucleotidic linker selected from the group consisting of abasic linkers, triethylene glycol units, hexaethylene glycol units, C3, C6, C12 alkylamino linkers, linkers derived from ethanediol, linkers derived from propanediol, triethylene phosphate, and tetraethylene phosphate.  
     
     
         77 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , wherein the branched immunostimulatory CpG oligonucleotide comprises a sequence selected from the group consisting of TCG, TTCG, TTTCG, TTTTCGT, TTTTTCG, TCGT, TTCGT, TTCGT, TTTCGT, and TCGTCGT.  
     
     
         78 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , wherein the branched immunostimulatory CpG oligonucleotide has a length between 4 and 100 nucleotides.  
     
     
         79 . The branched immunostimulatory CpG oligonucleotide of  claim 72 , wherein the branched immunostimulatory CpG oligonucleotide has a length between 6 and 40 nucleotides.  
     
     
         80 . A pharmaceutical composition comprising the branched immunostimulatory CpG oligonucleotide of  claim 72  and a pharmaceutically acceptable excipient.  
     
     
         81 . A nucleic acid delivery complex comprising the branched immunostimulatory CpG oligonucleotide of  claim 72  associated with a cationic lipid.  
     
     
         82 . A pharmaceutical composition comprising the branched immunostimulatory CpG oligonucleotide of  claim 72  and a microsphere.  
     
     
         83 . A method of stimulating an immune response in an individual, the method comprising administering to an individual the branched immunostimulatory CpG oligonucleotide of  claim 72  in an amount sufficient to stimulate an immune response in the individual.  
     
     
         84 . The method of  claim 83 , wherein the individual suffers from a disorder associated with a Th2-type immune response.  
     
     
         85 . The method of  claim 84 , wherein the disorder associated with a Th2-type immune response is chronic HCV infection.  
     
     
         86 . A method of increasing the secretion of interferon-gamma (IFN-γ) by blood cells, comprising administering the branched immunostimulatory CpG oligonucleotide of  claim 72  in an amount sufficient to increase the secretion of IFN-γ by blood cells.  
     
     
         87 . A method of increasing the secretion of interferon-alpha (IFN-α) by blood cells, comprising administering the branched immunostimulatory CpG oligonucleotide of  claim 72  in an amount sufficient to increase the secretion of IFN-α by blood cells.