The present invention makes it possible to enhance steroid efficacy in a steroid refractory or dependent patient afflicted with an inflammatory condition not responding or responding poorly or inadequately to anti-inflammatory treatment, by administering an oligonucleotide having the sequence 5 5′-X
The present invention makes it possible to enhance steroid efficacy in a steroid refractory or dependent patient afflicted with an inflammatory condition not responding or responding poorly or inadequately to anti-inflammatory treatment, by administering an oligonucleotide having the sequence 5 5′-Xm-CG-Yn-3′ in an effective amount to said patient and wherein X is A, T, C or G, Y is A, T, C, or G, m=1-100, n=1-100 and wherein at least one CG dinucleotide is ummethylated. The invention also encompasses the use of said oligonucleotide for the manufacture of pharmaceuticals.
대표청구항▼
1. A method for enhancing steroid efficacy in a steroid refractory patient afflicted with ulcerative colitis or Crohn's disease and currently on steroid anti-inflammatory treatment but not responding or responding poorly or inadequately to the steroid anti-inflammatory treatment, comprising administ
1. A method for enhancing steroid efficacy in a steroid refractory patient afflicted with ulcerative colitis or Crohn's disease and currently on steroid anti-inflammatory treatment but not responding or responding poorly or inadequately to the steroid anti-inflammatory treatment, comprising administering to the patient an oligonucleotide having the sequence 5′-GGAACAGTTCGTCCATGGC-3′ (SEQ ID NO: 1), wherein at least one CG dinucleotide is unmethylated, wherein the oligonucleotide is administered in an amount effective to improve sensitivity of the patient to the steroid anti-inflammatory treatment and thereby induce a clinical response to the steroid anti-inflammatory treatment. 2. The method according to claim 1, wherein said patient is currently on corticosteroid anti-inflammatory treatment. 3. The method according to claim 1, wherein said oligonucleotide comprises at least one modified sugar moiety nucleobase. 4. The method according to claim 3, wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety. 5. The method according to claim 1, wherein the amount of oligonucleotide administered to the patient is about 0.01 μg to about 100 mg per kg body weight. 6. The method according to claim 1, wherein the amount of oligonucleotide administered to the patient is about 0.1 μg to about 10 mg per kg body weight. 7. The method according to claim 1, wherein the amount of oligonucleotide administered to the patient is about 1 μg to about 5 mg per kg body weight. 8. The method according to claim 1, wherein the oligonucleotide is administered via inhalation, or opthalmically, intranasally, parenterally, orally, intradermally, or rectally. 9. The method according to claim 1, wherein the patient is human. 10. The method according to claim 1, wherein the patient is afflicted with ulcerative colitis. 11. The method according to claim 1, wherein the patient is afflicted with Crohn's disease. 12. The method according to claim 1, wherein said oligonucleotide comprises at least one nucleotide having a backbone modification. 13. The method according to claim 12, wherein said oligonucleotide comprises at least one nucleotide having a phosphate backbone modification. 14. The method according to claim 13, wherein the phosphate backbone modification is a phosphorothioate or phosphorodithioate modification. 15. The method according to claim 13, wherein the phosphate backbone modification is on the 5′ inter-nucleotide linkages. 16. The method according to claim 13, wherein the phosphate backbone modification is on the 3′ inter-nucleotide linkages. 17. The method according to claim 13, wherein the phosphate backbone modification is on the 5′ inter-nucleotide linkages and the 3′ inter-nucleotide linkages. 18. The method according to claim 12, wherein the modification occurs at one or more nucleotides at any position along the entire length of said oligonucleotide. 19. The method according to claim 1, wherein the oligonucleotide has the sequence 5′-G*G*A*ACAGTTCGTCCAT*G*G*C-3′ (SEQ ID NO: 1), wherein at least one CG dinucleotide is unmethylated, and * indicates phosphorothioate linkage, with remaining linkages comprising phosphodiester linkages. 20. The method according to claim 2, wherein said patient is currently on corticosteroid anti-inflammatory treatment. 21. The method according to claim 2, wherein said oligonucleotide comprises at least one modified sugar moiety nucleobase. 22. The method according to claim 21, wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety. 23. The method according to claim 2, wherein the amount of oligonucleotide administered to the patient is about 0.01 μg to about 100 mg per kg body weight. 24. The method according to claim 2, wherein the amount of oligonucleotide administered to the patient is about 0.1 μg to about 10 mg per kg body weight. 25. The method according to claim 2, wherein the amount of oligonucleotide administered to the patient is about 1 μg to about 5 mg per kg body weight. 26. The method according to claim 2, wherein the oligonucleotide is administered via inhalation, or opthalmically, intranasally, parenterally, orally, intradermally, or rectally. 27. The method according to claim 2, wherein the patient is human. 28. The method according to claim 2, wherein the patient is afflicted with ulcerative colitis. 29. The method according to claim 2, wherein the patient is afflicted with Crohn's disease. 30. The method according to claim 2, wherein said oligonucleotide comprises at least one nucleotide having a backbone modification. 31. The method according to claim 30, wherein said oligonucleotide comprises at least one nucleotide having a phosphate backbone modification. 32. The method according to claim 31, wherein the phosphate backbone modification is a phosphorothioate or phosphorodithioate modification. 33. The method according to claim 31, wherein the phosphate backbone modification is on the 5′ inter-nucleotide linkages. 34. The method according to claim 31, wherein the phosphate backbone modification is on the 3′ inter-nucleotide linkages. 35. The method according to claim 31, wherein the phosphate backbone modification is on the 5′ inter-nucleotide linkages and the 3′ inter-nucleotide linkages. 36. The method according to claim 30, wherein the modification occurs at one or more nucleotides at any position along the entire length of said oligonucleotide. 37. The method according to claim 2, wherein the oligonucleotide has the sequence 5′-G*G*A*ACAGTTCGTCCAT*G*G*C-3′ (SEQ ID NO: 1), wherein at least one CG dinucleotide is unmethylated, and * indicates phosphorothioate linkage, with remaining linkages comprising phosphodiester linkages. 38. The method according to claim 1, wherein a single administration of the oligonucleotide is made. 39. The method according to claim 2, wherein a single administration of the oligonucleotide is made.
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