Chimeric immunomodulatory compounds and methods of using the same - III

• US 20030225016A1
• Filed: 12/23/2002
• Published: 12/04/2003
• Est. Priority Date: 06/21/2001
• Status: Active Grant

• Current Assignee: Dynamax Technologies Limited
• Original Assignee: Dynamax Technologies Limited
• Inventors: Fearon, Karen L., Dina, Dino, Tuck, Stephen F.
• Granted Patent: US 7,785,610 B2
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: C07H 15/18 Acyclic radicals, substituted by carbocyclic rings
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.

Claims

1. A chimeric immunomodulatory compound (CIC) comprising two or more nucleic acid moieties and one or more non-nucleic acid spacer moieties,

wherein each nucleic acid moiety is covalently joined to at least one non-nucleic acid spacer moiety,

wherein at least one nucleic acid moiety comprises the sequence 5′

-CG-3′

, and

wherein said CIC has immunomodulatory activity.

2. The CIC of claim 1 comprising two nucleic acid moieties at least partially complementary to each other and able to form a duplex structure, wherein said CIC is not a branched CIC.

3. The CIC of claim 2 wherein at least one nucleic acid moiety comprises the sequence 5′

-TCG-3′

.

4. The CIC of claim 2 wherein at least one nucleic acid moiety comprises the sequence 5′

^F-TCG-3′

.

5. The CIC of claim 1 that is a branched CIC and wherein at least one nucleic acid moiety comprises the sequence 5′

-TCG-3′

.

6. The CIC of claim 5 wherein at least one nucleic acid moiety comprises the sequence 5′

^F-TCG-3′

.

7. The CIC of claim 5 having a fork structure, an H structure, a comb structure, or a central spacer structure.

8. The CIC of claim 7 wherein at least one non-nucleic acid spacer moiety comprises a glycerol component.

9. The CIC of claim 8 wherein the non-nucleic acid spacer moiety is a compound spacer comprising an oligoethylene glycol component.

10. The CIC of claim 9 wherein the oligoethylene glycol component is HEG.

11. The CIC of claim 7 wherein at least one nucleic acid moiety comprises the sequence 5′

-TCGA-3′

12. The CIC of claim 11 wherein at least one nucleic acid moiety has the sequence 5′

-TCGACGT-3′

or 5′

-TCGTCGA-3′

.

13. The CIC of claim 7 wherein every nucleic acid moiety that comprises the sequence 5′

-CG-3′

is less than 8 nucleotides in length.

14. The CIC of claim 7 wherein all of the nucleic acid moieties in the CIC have the same sequence.

15. A composition comprising a CIC of claim 7, an antigen, a pharmaceutically acceptable excipient, and, optionally a cationic microsphere.

16. The composition of claim 15 that is essentially endotoxin-free.

17. A method of modulating an immune response in an individual comprising administering to an individual a CIC of claim 7 in an amount sufficient to modulate an immune response in said individual.

19. A multimeric CIC comprising at least one, and optionally at least two, branched CICs according to claim 7.

20. The multimeric CIC of claim 19 that has a central axis structure or a cage structure.

21. The CIC of claim 20 wherein at least one nucleic acid moiety comprises the sequence 5′

^F-TCG-3′

.

22. The multimeric CIC of claim 20 wherein at least one nucleic acid moiety comprises the sequence 5′

-TCGA-3′

23. The multimeric CIC of claim 21 wherein at least one nucleic acid moiety has the sequence 5′

-TCGACGT-3′

or 5′

-TCGTCGA-3′

.

24. The multimeric CIC of claim 19 wherein every nucleic acid moiety that comprises the sequence 5′

-CG-3′

is less than 8 nucleotides in length.

25. The multimeric CIC of claim 19 wherein all of the nucleic acid moieties in the CIC have the same sequence.

26. A composition comprising a multimeric CIC of claim 19, an antigen, a pharmaceutically acceptable excipient, and, optionally a cationic microsphere.

27. The composition of claim 26 that is essentially endotoxin-free.

29. A method of modulating an immune response in an individual comprising administering to an individual a multimeric CIC of claim 19 in an amount sufficient to modulate an immune response in said individual.

30. A method of modulating an immune response of a population of cells, comprising contacting the population with a composition comprising a CIC of claim 1.

31. A method of modulating an immune response of a population of cells, comprising contacting the population with a composition comprising a CIC of claim 7.

33. A method of modulating an immune response of a population of cells, comprising contacting the population with a composition comprising a CIC of claim 19.

18. A multimeric CIC comprising a first CIC and a second CIC, wherein the first CIC is not a branched CIC, and wherein a nucleic acid moiety of the first CIC is at least partially complementary to a nucleic acid moiety of the second CIC, and the two nucleic acid moieties form a duplex structure.

28. A method of modulating an immune response in an individual comprising administering to an individual a multimeric CIC of claim 18 in an amount sufficient to modulate an immune response in said individual.

32. A method of modulating an immune response of a population of cells, comprising contacting the population with a composition comprising a multimeric CIC of claim 18.