Immunostimulatory nucleic acids

Abstract

The invention relates to immunostimulatory nucleic acid compositions and methods of using the compositions. The T-rich nucleic acids contain poly T sequences and/or have greater than 25% T nucleotide residues. The TG nucleic acids have TG dinucleotides. The C-rich nucleic acids have at least one poly-C region and/ore greater than 50% c nucleotides. These immunostimulatory nucleic acids function in a similar manner to nucleic acids containing CpG motifs. The invention also encompasses preferred CpG nucleic acids.

1 . A method of stimulating an immune response comprising
 administering an immunostimulatory nucleic acid to a non-rodent subject in an amount effective to induce an immune response in the non-rodent subject, wherein the immunostimulatory nucleic acid is greater than 60% T, contains a CpG dinucleotide, and is 8-100 nucleotides in length.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the immunostimulatory nucleic acid is a poly T nucleic acid comprising
   5′TTTT3′.   
     
     
         4 . The method of  claim 3 , wherein the poly T nucleic acid comprises
   5′X 1 X 2 TTTTX 3 X 4 3′   wherein X 1 , X 2 , X 3  and X 4  are nucleotides.   
     
     
         5 . The method of  claim 3 , wherein the immunostimulatory nucleic acid comprises a plurality of poly T nucleic acid motifs. 
     
     
         6 . The method of  claim 4 , wherein X 1 X 2  is TT. 
     
     
         7 . The method of  claim 4 , wherein X 3 X 4  is TT. 
     
     
         8 - 14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the immunostimulatory nucleic acid comprises a nucleotide composition of greater than 80% T. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the immunostimulatory nucleic acid has a nucleotide backbone which includes at least one backbone modification. 
     
     
         19 . The method of  claim 18 , wherein the backbone modification is a phosphorothioate modification. 
     
     
         20 . The method of  claim 18 , wherein the nucleotide backbone is chimeric. 
     
     
         21 . The method of  claim 18 , wherein the nucleotide backbone is entirely modified. 
     
     
         22 - 33 . (canceled) 
     
     
         34 . The method of  claim 1 , wherein the immune response is a mucosal immune response. 
     
     
         35 . The method of  claim 1 , wherein the immune response is a systemic immune response. 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 1 , further comprising exposing the subject to an antigen and wherein the immune response is an antigen-specific immune response. 
     
     
         38 - 51 . (canceled) 
     
     
         52 . The method of  claim 1 , wherein the subject is a human. 
     
     
         53 . (canceled) 
     
     
         54 . The method of  claim 1 , further comprising administering an antibody specific for a cell surface antigen, and wherein the immune response results in antigen dependent cellular cytotoxicity (ADCC). 
     
     
         55 - 75 . (canceled) 
     
     
         76 . The method of  claim 1 , wherein the immunostimulatory nucleic acid is administered on a regular basis. 
     
     
         77 . The method of  claim 1 , wherein the immune response is an innate immune response. 
     
     
         78 . A composition comprising
 a sustained release device including an immunostimulatory nucleic acid, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.   
     
     
         79 . (canceled) 
     
     
         80 . A composition of a nutritional supplement comprising
 an immunostimulatory nucleic acid in a delivery device selected from the group consisting of a capsule, a pill, and a sublingual tablet, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.   
     
     
         81 . (canceled) 
     
     
         82 . A composition comprising
 an immunostimulatory nucleic acid and an antigen, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.   
     
     
         83 . A composition comprising
 an immunostimulatory nucleic acid and another therapeutic agent selected from the group consisting of: an anti-microbial agent, an anti-cancer agent, an asthma/allergy medicament, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.   
     
     
         84 - 94 . (canceled) 
     
     
         95 . A pharmaceutical composition comprising an effective amount for stimulating an immune response of an isolated the immunostimulatory nucleic acid of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         96 . A composition of matter, comprising the immunostimulatory nucleic acid of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         97 - 101 . (canceled) 
     
     
         102 . A composition comprising
 an immunostimulatory nucleic acid consisting essentially of:
   5′M 1 TCGTCGTTM 2 3′ 
   wherein at least one of the Cs is unmethylated, wherein M 1  is a nucleic acid having at least one nucleotide, wherein M 2  is a nucleic acid having between 0 and 50 nucleotides, and wherein the immunostimulatory nucleic acid has less than 100 nucleotides.   
     
     
         103 . A pharmaceutical composition comprising
 an immunostimulatory nucleic acid comprising:
   5′TCGTCGTT3′ 
   wherein at least one of the Cs is unmethylated, wherein the immunostimulatory nucleic acid has less than 100 nucleotides and a phosphodiester backbone,   and a sustained release device.   
     
     
         104 - 106 . (canceled)