Claims
- 1. An immunomodulatory composition, comprising a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) three to six nucleotides in length, wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′.
- 2. The composition of claim 1, wherein said IMO has a sequence according to the formula 5′-X1CGX2-3′, where X1 is zero to four nucleotides, X2 is zero to four nucleotides.
- 3. The composition according to claim 2, wherein said IMO has a sequence according to the formula 5′-X1TCGX2-3′ or 5′-X1UCGX2-3′, where X1 is zero to two nucleotides and X2 is zero to three nucleotides.
- 4. The composition of claim 3, wherein said IMO is six nucleotides in length.
- 5. The composition of claim 3, wherein said IMO is five nucleotides in length.
- 6. The composition of claim 3, wherein said IMO is four nucleotides in length.
- 7. The composition of claim 3, wherein said IMO is three nucleotides in length.
- 8. The composition of claim 1, wherein said IMO comprises at least one phosphorothioate linkage.
- 9. The composition of claim 1, wherein said IMO comprises at least one modified cytosine.
- 10. The composition of claim 1, wherein said microcarrier is a solid phase microcarrier.
- 11. The composition of claim 10, wherein the microcarrier is a biodegradable polymeric particle.
- 12. The composition of claim 10, wherein the microcarrier is a biodegradable polyester particle.
- 13. The composition of claim 12, wherein the microcarrier comprises a a polymer selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), poly(caprolactone), and polymethylidene malonate.
- 14. The composition of claim 12, wherein said microcarrier comprises a cationic moiety.
- 15. The composition of claim 10, wherein said microcarrier comprises an inorganic particle.
- 16. The composition of claim 15, wherein said microcarrier comprises an inorganic crystalline material.
- 17. The composition of claim 16, wherein said microcarrier comprises a material selected from the group consisting of hydroxyapatite and calcium phosphate.
- 18. The composition of claim 1, wherein said microcarrier is 10 nm to 10 μm in size.
- 19. The composition of claim 1, wherein said microcarrier is 25 nm to 5 μm in size.
- 20. The composition of claim 1, further comprising an antigen.
- 21. The composition of claim 20, wherein said antigen is linked to said MC and IMO complex.
- 22. The composition of claim 21, wherein said antigen is non-covalently linked to said MC and IMO complex.
- 23. The composition of claim 21, wherein said antigen is covalently linked to said MC and IMO complex.
- 24. The composition of claim 23, wherein said antigen is covalently linked to the MC of the MC and IMO complex.
- 25. The composition of claim 23, wherein said antigen is covalently linked to the IMO of the MC and IMO complex.
- 26. The composition of claim 20, wherein said antigen is not linked to said MC and IMO complex.
- 27. The composition of claim 1, wherein said composition does not comprise an antigen.
- 28. The composition of claim 1, wherein said complex does not comprise an oligonucleotide greater than 6 nucleotides in length.
- 29. A pharmaceutical composition, comprising:
a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) three to six nucleotides in length, wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-340 ; and a pharmaceutically acceptable excipient.
- 30. A method of modulating an immune response in an individual, comprising administering to said individual an amount of a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) effective to modulate an immune response in said individual, wherein the IMO is three to six nucleotides in length, wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′.
- 31. The method of claim 30, wherein said individual suffers from a disorder associated with a Th2-type immune response
- 32. The method of claim 31, wherein said disorder associated with a Th2-type immune response is selected from the group consisting of allergies and allergy-induced asthma.
- 33. The method of claim 30, wherein said individual is receiving a vaccine.
- 34. The method of claim 33, wherein said individual is receiving a therapeutic vaccine.
- 35. The method of claim 34, wherein said therapeutic vaccine comprises an epitope selected from the group consisting of an allergy epitope, a mycobacterial epitope, and a tumor-associated epitope.
- 36. The method of claim 33, wherein said individual is receiving a prophylactic vaccine.
- 37. The method of claim 36, wherein said individual is at risk of exposure to an infectious agent.
- 38. The method of claim 36, wherein said individual is at risk of developing cancer.
- 39. The method of claim 30, wherein said individual suffers from cancer.
- 40. The method of claim 30, wherein said individual suffers from an infectious disease.
- 41. The method of claim 30, wherein said complex does not comprise an oligonucleotide greater than 6 nucleotides in length.
- 42. A method of increasing interferon-gamma (IFN-γ) in an individual, comprising administering to said individual an amount of a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) effective to increase IFN-γ in said individual, wherein the IMO is three to six nucleotides in length and wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′.
- 43. The method of claim 42, wherein said individual suffers from a disorder selected from the group consisting of idiopathic pulmonary fibrosis, scleroderma, cutaneous radiation-induced fibrosis, hepatic fibrosis, and renal fibrosis
- 44. A method of increasing interferon-alpha (IFN-α) in an individual, comprising administering to said individual an amount of a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) effective to increase IFN-α in said individual, wherein the IMO is three to six nucleotides in length and wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′.
- 45. The method of claim 44, wherein said individual suffers from a disorder selected from the group consisting of viral infections and cancer.
- 46. The method of claim 45, wherein said viral infection is an infection by a virus selected from the group consisting of influenza virus, respiratory syncytial virus (RSV), hepatitis virus B, hepatitis virus C, herpes virus, and papilloma virus.
- 47. A method of ameliorating one or more symptoms of an infectious disease in an individual, comprising administering to said individual an amount of a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) effective to ameliorate a symptom of said infectious disease in the individual, wherein the IMO is three to six nucleotides in length and wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′.
- 48. The method of claim 47, wherein said infectious disease is an infectious disease caused by a cellular pathogen.
- 49. The method of claim 48, wherein said infectious disease is selected from the group consisting of mycobacterial disease, malaria, leishmaniasis, toxoplasmosis, schistosomiasis and clonorchiasis.
- 50. A method of reducing levels of IgE in an individual having an IgE-related disorder, comprising administering to said individual an amount of a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) effective to reduce IgE levels in the individual, wherein the IMO is three to six nucleotides in length and wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′.
- 51. A kit for use in immunomodulation of an individual, comprising:
a complex of a microcarrier (MC) and an immunomodulatory oligonucleotide (IMO) three to six nucleotides in length and wherein said IMO does not have a sequence selected from the group consisting of 5′-GACGTT-3′, 5′-TCCGGA-3′, and 5′-GAGCTT-3′; and
- 52. The kit of claim 51, further comprising instructions for administration of said complex to immunomodulate an individual.
- 53. The kit of claim 52, wherein said instructions relate to immunomodulation of an individual suffering from a disorder associated with a Th2-type immune response.
- 54. The kit of claim 52, wherein said disorder is selected from the group consisting of allergies and allergy-induced asthma.
- 55. The kit of claim 52, wherein said instructions relate to immunomodulation of an individual receiving a vaccine.
- 56. The kit of claim 55, wherein said vaccine is a therapeutic vaccine.
- 57. The kit of claim 55, wherein said vaccine is a prophylactic vaccine.
- 58. The kit of claim 52, wherein said instructions relate to immunomodulation of an individual suffering from cancer.
- 59. The kit of claim 52, wherein said instructions relate to immunomodulation of an individual suffering from an infectious disease.
- 60. The kit of claim 52, wherein said instructions relate to immunomodulation of an individual at risk of exposure to an infectious agent.
- 61. The kit of claim 52, wherein said instructions relate to immunomodulation of an individual at risk of cancer.
- 62. An immunomodulatory composition, comprising an immunomodulatory oligonucleotide (IMO) three to six nucleotides in length encapsulated in a microcarrier (MC).
- 63. A method of modulating an immune response in an individual, comprising administering to said individual an amount of an immunomodulatory oligonucleotide (IMO) encapsulated in a microcarrier (MC) effective to modulate an immune response in said individual, wherein the IMO is three to six nucleotides in length.
REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Applications No. 60/310,743, filed Aug. 7, 2001, and No. 60/335,263, filed Oct. 25, 2001, each of which is incorporated by reference in its entirety.
Provisional Applications (2)
|
Number |
Date |
Country |
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60310743 |
Aug 2001 |
US |
|
60335263 |
Oct 2001 |
US |