Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/70
A61K-038/00
A61K-037/18
A61K-039/00
A61K-039/35
A61K-039/36
A01N-043/04
C07H-021/02
C07H-021/04
출원번호
UP-0268714
(2005-11-07)
등록번호
US-7776834
(2010-09-06)
발명자
/ 주소
Agrawal, Sudhir
Yu, Dong
Kandimalla, Ekambar
출원인 / 주소
Idera Pharmaceuticals, Inc.
대리인 / 주소
Keown, Wayne A.
인용정보
피인용 횟수 :
3인용 특허 :
12
초록▼
The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immuno
The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunostimulatory oligonucleotides according to the invention further comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5′ end.
대표청구항▼
What is claimed is: 1. An immunostimulatory oligonucleotide having a structure from the group of 5′-TCTGTR′GTTC1U1-X-U1C1TTGR′TGTCT-5′ (5′-SEQ ID NO: 3-3′-X-3′-SEQ ID NO: 3-5′); 5′-CTGTR′GTTCU1C1-X-C1U1CTTGR′TGTC-5′
What is claimed is: 1. An immunostimulatory oligonucleotide having a structure from the group of 5′-TCTGTR′GTTC1U1-X-U1C1TTGR′TGTCT-5′ (5′-SEQ ID NO: 3-3′-X-3′-SEQ ID NO: 3-5′); 5′-CTGTR′GTTCU1C1-X-C1U1CTTGR′TGTC-5′ (5′-SEQ ID NO: 5-3′-X-3′-SEQ ID NO: 5-5′); 5′-CTGTR′GTTC1U1C1-X-C1U1C1TTGR′TGTC-5′ (5′-SEQ ID NO: 6-3′-X-3′-SEQ ID NO: 6-5′); 5′-TCTGTR′GTTCT-X-CGTTCGAACGT-5′ (5′-SEQ ID NO: 7-3′-X-3′-SEQ ID NO: 17-5′); 5′-TCTGTR′GACAG-X-GACAGR′TGTCT-5′ (5′-SEQ ID NO: 8-3′-X-3′-SEQ ID NO: 8-5′); 5′-TCTGTR′GACA1G1-X-G1A1CAGR′TGTCT-5′ (5′-SEQ ID NO: 9-3′-X-3′-SEQ ID NO: 9-5′); 5′-TCAGTR′GTTAG-X-GATTGR′TGACT-5′ (5′-SEQ ID NO: 10-3′-X-3′-SEQ ID NO: 10-5′); 5′-TCAGTR′GACTG-X-GTCAGR′TGACT-5′ (5′-SEQ ID NO: 11-3′-X-3′-SEQ ID NO: 11-5′); 5′-TR′GTR′GAR′GAT-X-TAGR′AGR′TGR′T-5′(5′-SEQ ID NO: 12-3′-X-3′-SEQ ID NO: 12-5′); 5′-TR′GTR′GTAGTA-X-ATGATGR′TGR′T-5′ (5′-SEQ ID NO: 13-3′-X-3′-SEQ ID NO: 13-5′); 5′-TR′GAAR′GTTCT-X-TCTTGR′AAGR′T-5′ (5′-SEQ ID NO: 14-3′-X-3′-SEQ ID NO: 14-5′); and 5′-TR′GTAR′GTACT-X-TCATGR′ATGR′T-5′ (5′-SEQ ID NO: 15-3′-X-3′-SEQ ID NO: 15-5′), wherein R′=1-(2′-deoxy-β-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine; A1/C1/G1/U1=2′-O-methyl-ribonucleotides; R=2′-deoxy-7-deazaguanosine and X=glycerol linker. 2. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TCTGTR′GTTC1U1-X-U1C1TTGR′TGTCT-5′ (5′-SEQ ID NO: 3-3′-X-3′-SEQ ID NO: 3-5′). 3. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-CTGTR′GTTCU1C1-X-C1U1CTTGR′TGTC-5′ (5′-SEQ ID NO: 5-3′-X-3′-SEQ ID NO: 5-5′). 4. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-CTGTR′GTTC1U1C1-X-C1U1C1TTGR′TGTC-5′ (5′-SEQ ID NO: 6-3′-X-3′-SEQ ID NO: 6-5′). 5. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TCTGTR′GTTCT-X-CGTTCGAACGT-5′ (5′-SEQ ID NO: 7-3′-X-3′-SEQ ID NO: 17-5′). 6. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TCTGTR′GACAG-X-GACAGR′TGTCT-5′ (5′-SEQ ID NO: 8-3′-X-3′-SEQ ID NO: 8-5′). 7. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TCTGTR′GACA1U1-X-G1A1CAGR′TGTCT-5′ (5′-SEQ ID NO: 9-3′-X-3′-SEQ ID NO: 9-5′). 8. An inimunostimulatory oligonucleotide according to claim 1 having the structure 5′-TCAGTR′GTTAG-X-GATTGR′TGACT-5′ (5′-SEQ ID NO: 10-3′-X-3′-SEQ ID NO: 10-5′). 9. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TCAGTR′GACTG-X-GTCAGR′TGACT-5′ (5′-SEQ ID NO: 11-3′-X-3′-SEQ ID NO: 11-5′). 10. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TR′GTR′GAR′GAT-X-TAGR′AGR′TGR′T-5′ (5′-SEQ ID NO: 12-3′-X-3′-SEQ ID NO: 12-5′). 11. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TR′GTR′GTAGTA-X-ATGATGR′TGR′T-5′ (5′-SEQ ID NO: 13-3′-X-3′-SEQ ID NO: 13-5′). 12. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TR′GAAR′GTTCT-X-TCTTGR′AAGR′T-5′ (5′-SEQ ID NO: 14-3′-X-3′-SEQ ID NO: 14-5′). 13. An immunostimulatory oligonucleotide according to claim 1 having the structure 5′-TR′GTAR′GTACT-X-TCATGR′ATGR′T-5′ (5′-SEQ ID NO: 15-3′-X-3′-SEQ ID NO: 15-5′). 14. A pharmaceutical formulation comprising the oligonucleotide according to claim 1 and a physiologically acceptable carrier. 15. A method for generating an inmune response in a vertebrate, the method comprising administering to the vertebrate an immunostimulatory oligonucleotide having a structure from the group of 5′-TCTGTR′GTTC1U1-X-U1C1TTGR′TGTCT-5′ (5′-SEQ ID NO: 3-3′-X-3′-SEQ ID NO: 3-5′); 5′-CTGTR′GTTCU1C1-X-C1U1CTTGR′TGTC-5′ (5′-SEQ ID NO: 5-3′-X-3′-SEQ ID NO: 5-5′); 5′-CTGTR′GTTC1U1C1-X-C1U1C1TTGR′TGTC-5′ (5′-SEQ ID NO: 6-3′-X-3′-SEQ ID NO: 6-5′); 5′-TCTGTR′GTTCT-X-CGTTCGAACGT-5′ (5′-SEQ ID NO: 7-3′-X-3′-SEQ ID NO: 17-5′); 5′-TCTGTR′GACAG-X-GACAGR′TGTCT-5′ (5′-SEQ ID NO: 8-3′-X-3′-SEQ ID NO: 8-5′); 5′-TCTGTR′GACA1G1-X-G1A1CAGR′TGTCT-5′ (5′-SEQ ID NO: 9-3′-X-3′-SEQ ID NO: 9-5′); 5′-TCAGTR′GTTAG-X-GATTGR′TGACT-5′ (5′-SEQ ID NO: 10-3′-X-3′-SEQ ID NO: 10-5′); 5′-TCAGTR′GACTG-X-GTCAGR′TGACT-5′ (5′-SEQ ID NO: 11-3′-X-3′-SEQ ID NO: 11-5′); 5′-TR′GTR′GAR′GAT-X-TAGR′AGR′TGR′T-5′ (5′-SEQ ID NO: 12-3′-X-3′-SEQ ID NO: 12-5′); 5′-TR′GTR′GTAGTA-X-ATGATGR′TGR′T-5′ (5′-SEQ ID NO: 13-3′-X-3′-SEQ ID NO: 13-5′); 5′-TR′GAAR′GTTCT-X-TCTTGR′AAGR′T-5′ (5′-SEQ ID NO: 14-3′-X-3′-SEQ ID NO: 14-5′); and 5′-TR′GTAR′GTACT-X-TCATGR′ATGR′T-5′ (5′-SEQ ID NO: 15-3′-X-3′-SEQ ID NO: 15-5′), wherein R′=1-(2′-deoxy-β-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine; A1/C1/G1/U1=2′-O-methyl-ribonucleotides; R=2′-deoxy-7-deazaguanosine and X=glycerol linker. 16. The method according to claim 15, wherein the route of administration is selected from parenteral, oral, sublingual, transdermal, topical, intranasal, aerosol, intraocular, intratracheal, intrarectal, vaginal, gene gun, dermal patch, eye drop and mouthwash. 17. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TCTGTR′GTTC1U1-X-U1C1TTGR′TGTCT-5′ (5′-SEQ ID NO: 3-3′-X-3′-SEQ ID NO: 3-5′). 18. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-CTGTR′GTTCU1C1-X-C1U1CTTGR′TGTC-5′ (5′-SEQ ID NO: 5-3′-X-3′-SEQ ID NO: 5-5′). 19. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-CTGTR′GTTC1U1C1-X-C1U1C1TTGR′TGTC-5′ (5′-SEQ ID NO: 6-3′-X-3′-SEQ ID NO: 6-5′). 20. The method according to claim 15 comprising administering an inimunostimulatory oligonucleotide having the structure 5′-TCTGTR′GTTCT-X-GTTCGAACGT-5′ (5′-SEQ ID NO: 7-3′-X-3′-SEQ ID NO: 17-5′). 21. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TCTGTR′GACAG-X-GACAGR′TGTCT-5′ (5′-SEQ ID NO: 8-3′-X-3′-SEQ ID NO: 8-5′). 22. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TCTGTR′GACA1G1-X-G1A1CAGR′TGTCT-5′ (5′-SEQ ID NO: 9-3′-X-3′-SEQ ID NO: 9-5′). 23. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TCAGTR′GTTAG-X-GATTGR′TGACT-5′ (5′-SEQ ID NO: 10-3′-X-3′-SEQ ID NO: 10-5′). 24. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TCAGTR′GACTG-X-GTCAGR′TGACT-5′ (5′-SEQ ID NO: 11-3′-X-3′-SEQ ID NO: 11-5′). 25. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TR′GTR′GAR′GAT-X-TAGR′AGR′TGR′T-5′ (5′-SEQ ID NO: 12-3′-X-3′-SEQ ID NO: 12-5′). 26. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TR′GTR′GTAGTA-X-ATGATGR′TGR′T-5′(5′-SEQ ID NO: 13-3′-X-3′-SEQ ID NO: 13-5′). 27. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TR′GAAR′GTTCT-X-TCTTGR′AAGR′T-5′ (5′-SEQ ID NO: 14-3′-X-3′-SEQ ID NO: 14-5′). 28. The method according to claim 15 comprising administering an immunostimulatory oligonucleotide having the structure 5′-TR′GTAR′GTACT-X-TCATGR′ATGR′T-5′ (5′-SEQ ID NO: 15-3′-X-3′-SEQ ID NO: 15-5′). 29. The oligonucleotide according to claim 1, further comprising an antibody, antisense oligonucleotide, protein, antigen, allergen, chemotherapeutic agent or adjuvant. 30. The pharmaceutical composition according to claim 14, further comprising an antibody, antisense oligonucleotide, protein, antigen, allergen, chemotherapeutic agent or adjuvant. 31. The method according to claim 15, further comprising administering an antibody, antisense oligonucleotide, protein, antigen, allergen, chemotherapeutic agent or adjuvant.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (12)
Agrawal Sudhir ; Habus Ivan ; Kandimalla Ekambar R., Affinity-based purification of oligonucleotides using soluble multimeric oligonucleotides.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Kandimalla,Ekambar R.; Zhao,Qiuyan; Yu,Dong; Agrawal,Sudhir, Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes.
Agrawal Sudhir (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.