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-039/00
A61K-039/35
A61K-039/38
A61K-039/36
A61K-045/00
A61K-047/00
A01N-043/04
A01N-043/02
A01N-037/18
C07H-021/02
C07H-021/00
C07H-021/04
출원번호
US-0268683
(2005-11-07)
등록번호
US-7470674
(2008-12-30)
발명자
/ 주소
Agrawal,Sudhir
Yu,Dong
Kandimalla,Ekambar
출원인 / 주소
Idera Pharmaceuticals, Inc.
대리인 / 주소
Keown & Zucchero, LLP
인용정보
피인용 횟수 :
12인용 특허 :
17
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'-TCAGTCG2TTAG-X-GATTG2CTGACT-5' (SEQ ID NO: 2); 5'-TCG2TCG2TTAGA-X-AGATTG2CTG2CT-5' (SEQ ID NO: 3); 5'-CAGTCG2TTCAG-X-GACTTG2CTGAC-5' (SEQ ID NO: 4); 5'-TCAGTCG1TTAG-X-GATTG1CTGACT-5' (SEQ ID NO: 5);
What is claimed is: 1. An immunostimulatory oligonucleotide having a structure from the group of 5'-TCAGTCG2TTAG-X-GATTG2CTGACT-5' (SEQ ID NO: 2); 5'-TCG2TCG2TTAGA-X-AGATTG2CTG2CT-5' (SEQ ID NO: 3); 5'-CAGTCG2TTCAG-X-GACTTG2CTGAC-5' (SEQ ID NO: 4); 5'-TCAGTCG1TTAG-X-GATTG1CTGACT-5' (SEQ ID NO: 5); 5'-TCG1TCG1TTAGA-X-AGATTG1CTG1CT-5' (SEQ ID NO: 6) and 5'-CAGTCG1TTCAG-X-GACTTG1CTGAC-5' (SEQ ID NO: 7); wherein G1=2'-deoxy-7-deazaguanosine; G2=arabinoguanosine; and X=glycerol linker. 2. An immunostimulatory oligonucleotide according to claim 1 having the structure 5'-TCAGTCG2TTAG-X-GATTG2CTGACT-5' (SEQ ID NO: 2). 3. An immunostimulatory oligonucleotide according to claim 1 having the structure 5'-TCG2TCG2TTAGA-X-AGATTG2CTG2CT-5' (SEQ ID NO: 3). 4. An immunostimulatory oligonucleotide according to claim 1 having the structure 5'-CAGTCG2TTCAG-X-GACTTG2CTGAC-5' (SEQ ID NO: 4). 5. An immunostimulatory oligonucleotide according to claim 1 having the structure 5'-TCAGTCG1TTAG-X-GATTG1CTGACT-5' (SEQ ID NO: 5). 6. An immunostimulatory oligonucleotide according to claim 1 having the structure 5'-TCG1TCG1TTAGA-X-AGATTG1CTG1CT-5' (SEQ ID NO: 6). 7. An immunostimulatory oligonucleotide according to claim 1 having the structure 5'-CAGTCG1TTCAG-X-GACTTG1CTGAC-5' (SEQ ID NO: 7). 8. A pharmaceutical formulation comprising the oligonucleotide according to claim 1 and a physiologically acceptable carrier. 9. A method for generating an immune response in a vertebrate, the method comprising administering to the vertebrate an immunostimulatory oligonucleotide having a structure from the group of 5'-TCAGTCG2TTAG-X-GATTG2CTGACT-5' (SEQ ID NO: 2); 5'-TCG2TCG2TTAGA-X-AGATTG2CTG2CT-5' (SEQ ID NO: 3); 5'-CAGTCG2TTCAG-X-GACTTG2CTGAC-5' (SEQ ID NO: 4); 5'-TCAGTCG1TTAG-X-GATTG1CTGACT-5' (SEQ ID NO: 5); 5'-TCG1TCG1TTAGA-X-AGATTG1CTG1CT-5' (SEQ ID NO: 6) and 5'-CAGTCG1TTCAG-X-GACTTG1CTGAC-5' (SEQ ID NO: 7); wherein G1=2'-deoxy-7-deazaguanosine; G2=arabinoguanosine; and X=glycerol linker. 10. The method according to claim 9, 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. 11. The method according to claim 9 comprising administering an immunostimulatory oligonucleotide having the structure 5'-TCAGTCG2TTAG-X-GATTG2CTGACT-5' (SEQ ID NO: 2). 12. The method according to claim 9 comprising administering an immunostimulatory oligonucleotide having the structure 5'-TCG2TCG2TTAGA-X-AGATTG2CTG2CT-5' (SEQ ID NO: 3). 13. The method according to claim 9 comprising administering an immunostimulatory oligonucleotide having the structure 5'-CAGTCG2TTCAG-X-GACTTG2CTGAC-5' (SEQ ID NO: 4). 14. The method according to claim 9 comprising administering an immunostimulatory oligonucleotide having the structure 5'-TCAGTCG1TTAG-X-GATTG1CTGACT-5' (SEQ ID NO: 5). 15. The method according to claim 9 comprising administering an immunostimulatory oligonucleotide having the structure 5'-TCG1TCG1TTAGA-X-AGATTG1CTG1CT-5' (SEQ ID NO: 6). 16. The method according to claim 9 comprising administering an immunostimulatory oligonucleotide having the structure 5'-CAGTCG1TTCAG-X-GACTTG1CTGAC-5' (SEQ ID NO: 7). 17. The oligonucleotide according to claim 1, further comprising an antibody, antisense oligonucleotide, protein, antigen, allergen, chemotherapeutic agent or adjuvant. 18. The pharmaceutical composition according to claim 8, further comprising an antibody, antisense oligonucleotide, protein, antigen, allergen, chemotherapeutic agent or adjuvant. 19. The method according to claim 9, further comprising administering an antibody, antisense oligonucleotide, protein, antigen, allergen, chemotherapeutic agent or adjuvant.
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이 특허에 인용된 특허 (17)
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; Kandimalla,Ekambar R.; Yu,Dong; Bhagat,Lakshmi, Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends.
Agrawal,Sudhir; Kandimalla,Ekambar R.; Yu,Dong; Bhagat,Lakshmi, Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends.
Agrawal Sudhir (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses.
Baumhof, Patrick; Voss, Söhnke; Kramps, Thomas; Kallen, Karl-Josef, Complexation of nucleic acids with disulfide-crosslinked cationic components for transfection and immunostimulation.
Fotin-Mleczek, Mariola; Voss, Söhnke, Composition comprising a complexed (M)RNA and a naked mRNA for providing or enhancing an immunostimulatory response in a mammal and uses thereof.
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