IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0865245
(2004-06-10)
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등록번호 |
US8008267
(2011-08-15)
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발명자
/ 주소 |
- Kandimalla, Ekambar R.
- Bhagat, Lakshmi
- Pandey, Rajendra K.
- Yu, Dong
- Agrawal, Sudhir
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출원인 / 주소 |
- Idera Pharmaceuticals, Inc.
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대리인 / 주소 |
Wood, Phillips, Katz, Clark & Mortimer
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인용정보 |
피인용 횟수 :
6 인용 특허 :
6 |
초록
▼
The invention provides immunostimulatory oligonucleotides having at least one CpG dinucleotide and a secondary structure at the 5′- or 3′-end. These oligonucleotides have either reduced or improved immunostimulatory properties. The invention establishes that 5′-terminal secondary structures affect i
The invention provides immunostimulatory oligonucleotides having at least one CpG dinucleotide and a secondary structure at the 5′- or 3′-end. These oligonucleotides have either reduced or improved immunostimulatory properties. The invention establishes that 5′-terminal secondary structures affect immunostimulatory activity significantly more than those at the 3′-end. The invention also provides methods for increasing or decreasing the immunostimulatory activity of a CpG-containing nucleic acid.
대표청구항
▼
What is claimed is: 1. An immunostimulatory nucleic acid, having secondary structure formed by intermolecular hydrogen bonding between two oligonucleotide compounds, wherein each of the oligonucleotide compounds comprise the general structure of:Domain A-Domain B-Domain C, (I)wherein Domain A is 5′
What is claimed is: 1. An immunostimulatory nucleic acid, having secondary structure formed by intermolecular hydrogen bonding between two oligonucleotide compounds, wherein each of the oligonucleotide compounds comprise the general structure of:Domain A-Domain B-Domain C, (I)wherein Domain A is 5′-3′ DNA not having a palindromic ornot having a palindromic or self-complementary domain and containing at least one dinucleotide selected from the group consisting of CpG, C*pG, C*pG*, and CpG*, wherein C is cytidine or 2′-deoxycitidine, G is guanosine or 2′-deoxyguanosine, C* is 2′-deoxythymidine, 1-(2′-deoxy-β-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine, 2′ dideoxy-5-halocytosine, 2′-dideoxy-5-nitrocytosine, arabinocytidine, 2′-deoxy-2′-substitutedarabinocytidine, 2′-O-substituted arabinocytidine, 2′-deoxy-5-hydroxycytidine, 2′-deoxy-N4-alkyl-cytidine, 2′-deoxy-4-thiouridine, or other non-natural pyrimidine nucleosides, G′ is 2′ deoxy-7-deazaguanosine, 2′-deoxy-6-thioguanosine, arabinoguanosine, 2′-deoxy-2′-substituted-arabinoguanosine, 2′-O-substituted-arabinoguanosine, 2′-deoxyinosine, or other non-natural purine nucleoside, and p is an internucleoside linkage selected from the group consisting of phosphodiester, phosphorothioate, and phosphorodithioate, wherein Domain B is a non-nucleoside linker joining Domain A and Domain C, wherein Domain C is 3′-5′ DNA or RNA having a palindromic or self-complementary domain allowing for intermolecular hydrogen bonding, and which can or cannot have a dinucleotide selected from the group consisting of CpG, C*pG, C*pG*, and CpG*, wherein C is cytidine or 2′ deoxycytidine, G is guanosine or 2′ deoxyguanosine, C* is 2′-deoxythymidine, 1-(2′-deoxy-β-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine, 2′-dideoxy-5-halocytosine, 2′-dideoxy-5-nitrocytosine, arabinocytidine, 2′-deoxy-2′-substituted arabinocytidine, 2′-O-substituted arabinocytidine, 2′-deoxy-5-hydroxycytidine, 2′-deoxy-N4-alkyl-cytidine, 2′-deoxy-4-thiouridine, or other non-natural pyrimidine nucleosides, G* is 2′deoxy-7-deazaguanosine, 2′-deoxy-6-thioguanosine, arabinoguanosine, 2′-deoxy-2′ substituted-arabinoguanosine, 2′-O-substituted-arabinoguanosine, 2′-deoxyinosine, or other non-natural purine nucleoside, p is an internucleoside linkage selected from the group consisting of phosphodiester, and phosphorothioate, wherein each oligonucleotide compound comprises from about 12 to about 50 nucleotides in length.
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