Claims
- 1. A branched immunomodulatory compound (BIC) comprising at least three nucleic acid moieties, at least one of which comprises the sequence 5′-CG-3′, and at least one branch-point nucleoside, wherein the BIC has immunomodulatory activity.
- 2. The BIC of claim 1, wherein said BIC has an immunomodulatory activity selected from the group consisting of (i) the ability to stimulate IFN-γ production from human peripheral blood mononuclear cells, (ii) the ability to stimulate IFN-α production from human peripheral blood mononuclear cells, and (iii) the ability to stimulate B cell proliferation.
- 3. The BIC of claim 1 that comprises three nucleic acid moieties covalently linked to a branch-point nucleoside either directly or through a non-nubleic acid spacer moiety.
- 4. The BIC of claim 1 that comprises at least two branch-point nucleosides and at least four nucleic acid moieties, wherein three moieties, each selected independently from the group consisting of the branchpoint point nucleosides and the nucleic acid moieties, are covalently linked directly or through a non-nucleic acid spacer moiety to each of the branch-point nucleosides.
- 5. The BIC of claim 3, comprising a non-nucleic acid spacer moiety that comprises a C4-C20 polyethylene glycol, C2-C8 alkyl, pentaerythritol, 2-(hydroxymethyl)ethyl, glycerol, a polysaccharide, 2-aminobutyl-1,3-propanediol, or 1,3-diamino-2-propanol.
- 6. The BIC of claim 4, comprising a non-nucleic acid spacer moiety that comprises a C4-C20 polyethylene glycol, C2-C8 alkyl, pentaerythritol, 2-(hydroxymethyl)ethyl, glycerol, a polysaccharide, 2-aminobutyl-1,3-propanediol, or 1,3-diamino-2-propanol.
- 7. The BIC of claim 1, wherein at least one of said three nucleic acid moieties comprises a sequence selected from the group consisting of
- 8. The BIC of claim 2, wherein all of said three nucleic acid moieties has a sequence comprising 5′-CG-3′.
- 9. The BIC of claim 2, wherein each of the nucleic acid moieties that comprises the sequence 5′-CG-3′ is less than 8 nucleotides in length.
- 10. The BIC of claim 1, wherein the branch-point nucleoside is a ribonucleoside or a 2′-deoxyribonucleoside.
- 11. The BIC of claim 1, wherein at least one 5′-CG-3′-containing nucleic acid moiety of the BIC (i) does not have isolated immunological activity or (ii) has inferior isolated immunological activity.
- 12. The BIC of claim 1 having a structure selected from the group consisting of a Y-type structure comprising only one branch-point nucleoside; a fork-type structure, an H-type structure, and a comb-type structure.
- 13. A self-assembling, hydrogen-bonded complex comprising a first BIC of according to claim 1 and a second BIC of claim 1, wherein a nucleic acid moiety of the first BIC is hydrogen-bonded to a nucleic acid moiety of the second BIC via Watson-Crick basepairing, and wherein the first BIC and second BIC are the same or different.
- 14. A pharmaceutical composition comprising the BIC of claim 1 and a pharmaceutically acceptable excipient.
- 15. The pharmaceutical composition of claim 14, further comprising an antigen or a cationic microsphere.
- 16. A method of modulating an immune response in an individual comprising administering to an individual the BIC of claim 1 in an amount sufficient to modulate an immune response in the individual.
- 17. The method of claim 16, wherein the individual suffers from a disorder associated with a Th2-type immune response.
- 18. The method of claim 17, wherein the disorder is an allergy, allergy-induced asthma, or an infectious disease.
- 19. A method of increasing the secretion of interferon-gamma (IFN-γ) by blood cells in an individual, comprising administering the BIC of claim 1 to the individual in an amount sufficient to increase the secretion of IFN-γ by blood cells in the individual.
- 20. A method of increasing the secretion of interferon-alpha (IFN-α) by blood cells in an individual, comprising administering the BIC of claim 1 to the individual in an amount sufficient to increase the secretion of IFN-α by blood cells in the individual.
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This application claims benefit of U.S. provisional patent application No. 60/436,406 filed Dec. 23, 2002, the entire disclosure of which is incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60436406 |
Dec 2002 |
US |