Immunostimulatory nucleic acid molecules
Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.
1 - 18 . (canceled)
19 . An immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, comprising: a polynucleotide comprising an immunostimulatory sequence (ISS) linked to a nonbiodegradable microcarrier (MC), wherein the ISS comprises the sequence 5′-C, G-3′, with the proviso that if the MC is gold, latex or magnetic, the linkage is other than by biotin/avidin.
20 . The IMP/MC complex of claim 19 , wherein said polynucleotide is covalently linked to said microcarrier.
21 . The IMP/MC complex of claim 19 , wherein said polynucleotide is non-covalently linked to said microcarrier.
22 . The IMP/MC complex of claim 19 , wherein said microcarrier is a liquid phase microcarrier.
23 . The IMP/MC complex of claim 19 , wherein said complex is antigen-free.
24 . The IMP/MC complex of claim 19 , wherein the ISS comprises the sequence 5′-T, C, G-3′.
25 . The IMP/MC complex of claim 19 , wherein the ISS comprises the sequence 5′-purine, purine, C, G, pyrimidine, pyrimidine, C, G-3′.
26 - 56 . (canceled)
57 . An immunostimulatory nucleic acid/delivery complex comprising:
a nucleic acid comprising an immunostimulatory nucleic acid linked to a nucleic acid delivery complex, wherein the immunostimulatory nucleic acid comprises the sequence 5° C., G 3′.
58 . The complex of claim 57 , wherein the immunostimulatory nucleic acid is covalently linked to the nucleic acid delivery complex.
59 . The complex of claim 57 , wherein the immunostimulatory nucleic acid is non-covalently linked to the nucleic acid delivery complex.
60 - 78 . (canceled)
79 . The IMP/MC complex of claim 19 , wherein said polynucleotide comprises a phosphate backbone modification.
80 . The IMP/MC complex of claim 79 , wherein said phosphate backbone modification is a phosphorothioate.
81 - 88 . (canceled)
89 . An immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, comprising: a polynucleotide linked to a silica microcarrier (MC), wherein the polynucleotide is 2-100 nucleotides in length and comprises the sequence 5′-X 1 X 2 CGX 3 X 4 -3′, wherein X 1 , X 2 , X 3 and X 4 are nucleotides.
90 . The IMP/MC complex of claim 89 , wherein said polynucleotide comprises a phosphate backbone modification.
91 . The IMP/MC complex of claim 90 , wherein said phosphate backbone modification is a phosphorothioate.
92 . The IMP/MC complex of claim 89 , wherein said polynucleotide comprises the sequence 5′ purine, purine, C, G, pyrimidine, pyrimidine 3′.
93 . A composition comprising the IMP/MC complex of claim 19 and a pharmaceutically acceptable excipient.
94 . The composition of claim 93 wherein the composition is antigen free.
95 - 96 . (canceled)
95 - 96 . (canceled)