Claims
- 1. An immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, comprising:
a polynucleotide linked to a biodegradable microcarrier (MC), wherein said polynucleotide comprises the sequence 5′-C, G-3′ and wherein said MC is less than 10 μm in size.
- 2. The IMP/MC complex of claim 1, wherein said polynucleotide is covalently linked to said microcarrier.
- 3. The IMP/MC complex of claim 1, wherein said polynucleotide is non-covalently linked to said microcarrier.
- 4. The IMP/MC complex of claim 1, wherein said microcarrier is a liquid phase microcarrier.
- 5. The IMP/MC complex of claim 1, wherein said microcarrier is a solid phase microcarrier.
- 6. The IMP/MC complex of claim 1, wherein said microcarrier is from 25 nm to 5 μm in size.
- 7. The IMP/MC complex of claim 6, wherein said microcarrier is from 1.0 μm to 2.0 μm in size.
- 8. The IMP/MC complex of claim 7, wherein said microcarrier is 1.4 μm in size.
- 9. The IMP/MC complex of claim 1, wherein said microcarrier is cationic.
- 10. The IMP/MC complex of claim 1, wherein said complex is antigen-free.
- 11. The IMP/MC complex of claim 1, wherein said polynucleotide comprises the sequence 5′-T, C, G-3′.
- 12. The IMP/MC complex of claim 11, wherein said polynucleotide comprises the sequence 5′-TCGX1X2X3X4-3′ or the sequence 5′-X1TCGX2X3X4-3′, wherein X1, X2, X3, X4 are nucleotides.
- 13. The IMP/MC complex of claim 12, wherein said polynucleotide comprises the sequence 5′-TCGTCGX1-3′, wherein X1 is a nucleotide.
- 14. The IMP/MC complex of claim 12, wherein said polynucleotide comprises a sequence selected from the group consisting of 5′-TCGTCGA-3′, 5′-TCGAAAA-3′, 5′-TCGCCCC-3′, 5′-TCGGGGG-3′ and 5′-TCGTTTT-3′.
- 15. The IMP/MC complex of claim 1, wherein said polynucleotide comprises the sequence 5′-C, G, pyrimidine, pyrimidine, C, G-3′.
- 16. The IMP/MC complex of claim 1, wherein said polynucleotide comprises the sequence 5′-purine, purine, C, G, pyrimidine, pyrimidine, C, G-3′.
- 17. The IMP/MC complex of claim 11, wherein said polynucleotide comprises the sequence SEQ ID NO:1.
- 18. The IMP/MC complex of claim 1, wherein said polynucleotide further comprises the sequence 5′-T, C, G-3′.
- 19. The IMP/MC complex of any of claims 1, 11, 12, 13, 14, or 18, wherein said polynucleotide is 7 nucleotides in length.
- 20. The IMP/MC complex of any of claims 1, 11, 12, 13, 14 or 18, wherein said complex further comprises an antigen.
- 21. The IMP/MC complex of claim 20, wherein said antigen is an allergen.
- 22. The IMP/MC complex of claim 1, wherein said polynucleotide comprises a phosphate backbone modification.
- 23. The IMP/MC complex of claim 22, wherein said phosphate backbone modification is a phosphorothioate.
- 24. A method of modulating an immune response in an individual comprising administering to an individual a composition comprising an immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, said complex comprising a polynucleotide linked to a biodegradable microcarrier (MC), wherein said polynucleotide comprises the sequence 5′-C, G-3′ and wherein said MC is less than 10 μm in size, in an amount sufficient to modulate an immune response in said individual.
- 25. The method of claim 24, wherein said microcarrier is a solid phase microcarrier.
- 26. The method of claim 24, wherein said microcarrier is a liquid phase microcarrier.
- 27. The method of claim 24, wherein said polynucleotide is covalently linked to said microcarrier.
- 28. The method of claim 24, wherein said polynucleotide is non-covalently linked to said microcarrier.
- 29. The method of claim 24, wherein said complex is antigen-free.
- 30. The method of claim 24, wherein a Th1-type immune response is stimulated.
- 31. The method of claim 24, wherein a Th2-type immune response is suppressed.
- 32. The method of claim 24, wherein interferon-gamma (IFN-γ) is increased in said individual.
- 33. The method of claim 24, wherein interferon-alpha (IFN-α) is increased in said individual.
- 34. The method of claim 24, wherein levels of IgE is reduced in said individual.
- 35. The method of claim 24, wherein said polynucleotide comprises the sequence 5′-T, C, G-3′.
- 36. The method of claim 35, wherein said polynucleotide comprises the sequence 5′-TCGX1X2X3X4-3′ or the sequence 5′-X1TCGX2X3X4-3′, wherein X1, X2, X3, X4 are nucleotides.
- 37. The method of claim 36, wherein the polynucleotide comprises the sequence 5′-TCGTCGX1-3′, wherein X1 is a nucleotide.
- 38. The method of claim 36, wherein said polynucleotide comprises a sequence selected from the group consisting of 5′-TCGTCGA-3′, 5′-TCGAAAA-3′, 5′-TCGCCCC-3′, 5′-TCGGGGG-3′ and 5′-TCGTTTT-3′.
- 39. The method of claim 24, wherein said polynucleotide comprises the sequence 5′-C, G, pyrimidine, pyrimidine, C, G-3′.
- 40. The method of claim 24, wherein said polynucleotide comprises the sequence 5′-purine, purine, C, G, pyrimidine, pyrimidine, C, G-3′.
- 41. The method of claim 35, wherein said polynucleotide comprises the sequence SEQ ID NO:1.
- 42. The method of claim 24, wherein said polynucleotide further comprises the sequence 5′-T, C, G-3′.
- 43. The method of any of claims 24, 35, 36, 37, 38 or 42, wherein said polynucleotide is 7 nucleotides in length.
- 44. The method of any of claims 24, 35, 36, 37, 38 or 42, wherein said composition further comprises an antigen.
- 45. The method of claim 44, wherein said antigen is an allergen.
- 46. The method of claim 24, wherein said polynucleotide comprises a phosphate backbone modification.
- 47. The method of claim 46, wherein said phosphate backbone modification is a phosphorothioate.
- 48. A kit, comprising:
an immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, said complex comprising a polynucleotide linked to a biodegradable microcarrier (MC), wherein said polynucleotide comprises the sequence 5′-C, G-3′ and wherein said MC is less than 10 μm in size.
- 49. The kit of claim 48, wherein said polynucleotide is covalently linked to said microcarrier.
- 50. The kit of claim 48, wherein said polynucleotide is non-covalently linked to said microcarrier.
- 51. The kit of claim 48, wherein said microcarrier is a liquid phase microcarrier.
- 52. The kit of claim 48, wherein said microcarrier is a solid phase microcarrier.
- 53. The kit of claim 48, wherein said microcarrier is from 25 nm to 5 μm in size.
- 54. The kit of claim 53, wherein said microcarrier is from 1.0 μm to 2.0 μm in size.
- 55. The kit of claim 54, wherein said microcarrier is 1.4 μm in size.
- 56. The kit of claim 48, wherein said microcarrier is cationic.
- 57. The kit of claim 48, wherein said complex is antigen-free.
- 58. The kit of claim 48, wherein said polynucleotide comprises the sequence 5′-T, C, G-3′.
- 59. The kit of claim 58, wherein said polynucleotide comprises the sequence 5′-TCGX1X2X3X4-3′ or the sequence 5′-X1TCGX2X3X4-3′, wherein X1, X2, X3, X4 are nucleotides.
- 60. The kit of claim 59, wherein said polynucleotide comprises the sequence 5′-TCGTCGX1-3′, wherein X1 is a nucleotide.
- 61. The kit of claim 59, wherein said polynucleotide comprises a sequence selected from the group consisting of 5′-TCGTCGA-3′, 5′-TCGAAAA-3′, 5′-TCGCCCC-3′, 5′-TCGGGGG-3′ and 5′-TCGTTTT-3′.
- 62. The kit of claim 48, wherein the polynucleotide comprises the sequence 5′-C, G, pyrimidine, pyrimidine, C, G-3′.
- 63. The kit of claim 48, wherein the polynucleotide comprises the sequence 5′-purine, purine, C, G, pyrimidine, pyrimidine, C, G-3′.
- 64. The kit of claim 58, wherein the polynucleotide comprises the sequence SEQ ID NO:1.
- 65. The kit of claim 48, wherein said polynucleotide further comprises the sequence 5′-T, C, G-3′.
- 66. The kit of any of claims 48, 58, 59, 60, 61 or 65, wherein said kit further comprises an antigen.
- 67. The kit of claim 66, wherein said antigen is an allergen.
- 68. The kit of claim 48, wherein said polynucleotide comprises a phosphate backbone modification.
- 69. The kit of claim 68, wherein said phosphate backbone modification is a phosphorothioate.
- 70. A kit, comprising:
an immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, said complex comprising a polynucleotide linked to a biodegradable microcarrier (MC), wherein said polynucleotide comprises the sequence 5′-C, G-3′ and wherein said polynucleotide is 7 nucleotides in length.
- 71. The kit of claim 70, wherein said polynucleotide comprises the sequence 5′-T, C, G-3′.
- 72. The kit of claim 71, wherein said polynucleotide consists of the sequence 5′-TCGX1X2X3X4-3′ or the sequence 5′-X1TCGX2X3X4-3′, wherein X1, X2, X3, X4 are nucleotides.
- 73. The kit of claim 72, wherein said polynucleotide consists of the sequence 5′-TCGTCGX1-3′, wherein X1 is a nucleotide.
- 74. The kit of claim 72, wherein said polynucleotide consists of a sequence selected from the group consisting of 5′-TCGTCGA-3′, 5′-TCGAAAA-3′, 5′-TCGCCCC-3′, 5′-TCGGGGG-3′ and 5′-TCGTTTT-3′.
- 75. The kit of claim 70, wherein said polynucleotide further comprises the sequence 5′-T, C, G-3′.
- 76. The kit of claim 70, wherein said complex is antigen-free.
- 77. The kit of claim 70, further comprising an antigen.
- 78. The kit of claim 77, wherein said antigen is an allergen.
- 79. The kit of claim 70, wherein said polynucleotide comprises a phosphate backbone modification.
- 80. The kit of claim 79, wherein said phosphate backbone modification is a phosphorothioate.
- 81. A composition comprising an IMP/MC complex of claim 1 and a pharmaceutically acceptable excipient.
- 82. A composition according to claim 81, wherein the composition is antigen-free.
- 83. A composition according to claim 81, wherein the composition further comprises an antigen.
- 84. A composition according to claim 83, wherein the antigen is an allergen.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of copending U.S. application Ser. No. 09/802,359, filed Mar. 9, 2001, which in turn claims the priority benefit of U.S. Provisional application 60/188,303, filed Mar. 10, 2000, each of which is hereby incorporated herein by reference in their entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60188303 |
Mar 2000 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09802359 |
Mar 2001 |
US |
Child |
09927422 |
Aug 2001 |
US |