Claims
- 1. A method for ameliorating an IL-15-associated disorder in a subject, comprising administering to the subject having an IL-15-associated disorder, a therapeutically effective amount of a composition containing an antisense oligonucleotide, wherein said oligonucleotide interacts with a polynucleotide encoding IL-15 thereby inhibiting IL-15 production.
- 2. The method of claim 1, wherein the antisense oligonucleotide is expressed from an expression vector.
- 3. The method of claim 2, wherein the vector is a plasmid.
- 4. The method of claim 2, wherein the vector is a viral vector.
- 5. The method of claim 1, wherein the IL-15-associated disorder is selected from the group consisting of inflammatory bowel disease, arthritis, cirrhosis, multiple sclerosis, chronic liver disease, ulcerative colitis and cell proliferative disorders.
- 6. The method of claim 1, wherein the antisense oligonucleotide is from about 8 to 40 nucleic acids in length.
- 7. The method of claim 1, wherein the antisense oligonucleotide is chemically modified.
- 8. The method of claim 7, wherein the chemical modification is by substitution in a non-bridging oxygen atom of the antisense nucleic acid back bone with a moiety selected from the group consisting of methane phosphate, methyl phosphate, phosphoramidite, and phosphorthioate.
- 9. The method of claim 8, wherein the substitution is at the 5′ terminal region or the 3′ terminal region.
- 10. The method of claim 1, wherein the antisense oligonucleotide is DNA.
- 11. The method of claim 1, wherein the antisense oligonucleotide is RNA.
- 12. The method of claim 1, wherein the antisense oligonucleotide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO. 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 and any combination thereof.
- 13. The method of claim 1, wherein the subject is a mammal.
- 14. The method of claim 13, wherein the mammal is a human.
- 15. The method of claim 1, wherein the polynucleotide encoding IL-15 is DNA.
- 16. The method of claim 1, wherein the polynucleotide encoding IL-15 is RNA.
- 17. The method of claim 16, wherein the RNA is mRNA.
- 18. A method of inhibiting production of IL-15 in vivo, comprising administering to a subject having an IL-15-associated disorder, a therapeutically effective amount of a composition containing an antisense oligonucleotide, wherein said oligonucleotide interacts with a polynucleotide encoding IL-15 thereby inhibiting IL-15 production.
- 19. The method of claim 18, wherein the antisense oligonucleotide is expressed from an expression vector.
- 20. The method of claim 19, wherein the vector is a plasmid.
- 21. The method of claim 19, wherein the vector is a viral vector.
- 22. The method of claim 18, wherein the IL-15-associated disorder is selected from the group consisting of inflammatory bowel disease, arthritis, cirrhosis, multiple sclerosis, chronic liver disease, ulcerative colitis and cell proliferative disorders.
- 23. The method of claim 18, wherein the antisense oligonucleotide is from about 8 to 40 nucleic acids in length.
- 24. The method of claim 18, wherein the antisense oligonucleotide is chemically modified.
- 25. The method of claim 24, wherein the chemical modification is by substitution in a non-bridging oxygen atom of the antisense nucleic acid back bone with a moiety selected from the group consisting of methane phosphate, methyl phosphate, phosphoramidite, and phosphorthioate.
- 26. The method of claim 25, wherein the substitution is at the 5′ terminal region or the 3′ terminal region.
- 27. The method of claim 18, wherein the antisense oligonucleotide is DNA.
- 28. The method of claim 18, wherein the antisense oligonucleotide is RNA.
- 29. The method of claim 18, wherein the antisense oligonucleotide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO. 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and any combination thereof.
- 30. The method of claim 18, wherein the subject is a mammal.
- 31. The method of claim 30, wherein the mammal is a human.
- 32. A method of inhibiting production of IL-15, comprising contacting a sample containing a polynucleotide encoding IL-15 with an inhibiting effective amount of IL-15 antisense oligonucleotide.
- 33. The method of claim 32, wherein the antisense oligonucleotide is in an expression vector.
- 34. The method of claim 33, wherein the vector is a plasmid.
- 35. The method of claim 33, wherein the vector is a viral vector.
- 36. The method of claim 32, wherein the antisense oligonucleotide is from about 8 to 40 nucleic acids in length.
- 37. The method of claim 32, wherein the antisense oligonucleotide is chemically modified.
- 38. The method of claim 37, wherein the chemical modification is by substitution in a non-bridging oxygen atom of the antisense nucleic acid back bone with a moiety selected from the group consisting of methane phosphate, methyl phosphate, phosphoramidite, and phosphorthioate.
- 39. The method of claim 38, wherein the substitution is at the 5′ terminal region or the 3′ terminal region.
- 40. The method of claim 32, wherein the antisense oligonucleotide is DNA.
- 41. The method of claim 32, wherein the antisense oligonucleotide is RNA.
- 42. The method of claim 32, wherein the antisense oligonucleotide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO. 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and any combination thereof.
- 43. The method of claim 32, wherein the sample contains cells.
- 44. The method of claim 32, wherein the sample is a tissue.
- 45. An antisense oligonucleotide about 8 to 40 nucleic acids in length comprising a contiguous nucleic acid sequence which selectively binds to an IL-15 polynucleotide.
- 46. The antisense oligonucleotide of claim 45, wherein said antisense oligonucleotide is chemically modified by a substitution in a non-bridging oxygen atom of the antisense nucleic acid back bone with a moiety selected from the group consisting of methane phosphate, methyl phosphate, phosphoramidite, and phosphorthioate.
- 47. The antisense oligonucleotide of claim 45, wherein the substitution is at the 5′ terminal region or the 3′ terminal region.
- 48. The antisense oligonucleotide of claim 45, wherein the antisense oligonucleotide is DNA.
- 49. The antisense oligonucleotide of claim 45, wherein the antisense oligonucleotide is RNA.
- 50. The antisense oligonucleotide of claim 45, wherein the antisense oligonucleotide is contained in a vector.
- 51. The antisense oligonucleotide of claim 50, wherein the vector is an expression vector.
- 52. The antisense oligonucleotide of claim 50, wherein the vector is a plasmid.
- 53. The antisense oligonucleotide of claim 50, wherein the vector is a viral vector.
- 54. The antisense oligonucleotide of claim 45, wherein the antisense oligonucleotide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO. 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and any combination thereof.
- 55. An antisense oligonucleotide complementary to a polynucleotide encoding IL-15 and which hybridizes to a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO. 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15.
- 56. A recombinant nucleic acid sequence which, upon transcription, provides an antisense oligonucleotide, wherein the oligonucleotide modulates expression of IL-15 by interacting with a polynucleotide encoding IL-15.
- 57. The recombinant nucleic acid sequence of claim 56, wherein the polynucleotide encoding IL-15 is DNA.
- 58. The recombinant nucleic acid sequence of claim 56, wherein the polynucleotide encoding IL-15 is RNA.
- 59. The recombinant nucleic acid sequence of claim 56, wherein the modulating of IL-15 expression is by inhibition.
- 60. A pharmaceutical composition comprising an antisense oligonucleotide selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO. 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, and any combination thereof.
- 61. A method of monitoring the effectiveness of suppressing IL-15 production after administering a therapeutically effective amount of the antisense oligonucleotide of claim 43, comprising detecting the level of IL-15 production in a sample before and after the antisense therapy.
Parent Case Info
[0001] This application claims priority from U.S. Provisional Application Ser. No. 60/091,873 filed Jul. 7, 1998, the disclosure of which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60091873 |
Jul 1998 |
US |