Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response
First Claim
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1. An immune regulatory oligonucleotide (IRO) compound comprising the sequence 5′
- -CTATCTGUYZTTCTCTGT-3′
(SEQ ID NO;
102), wherein G is 2′
-OMe-G and U is 2′
-OMe-U and wherein YZ is an oligonucleotide motif that is CpG, C*pG, C*pG* or CpG* wherein C is deoxycytosine, 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-5-hydroxycytidine, 2′
-deoxy-N4-alkyl-cytidine, 2′
-deoxy-4-thiouridine, or other pyrimidine nucleoside analogs;
G is deoxyguanosine, and G* is 2′
-deoxy-7-deazaguanosine, 2′
-deoxy-6-thioguanosine, arabinoguanosine, 2′
-deoxyinosine, or other purine nucleoside analogs.
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Abstract
The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.
20 Citations
24 Claims
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1. An immune regulatory oligonucleotide (IRO) compound comprising the sequence 5′
- -CTATCTGUYZTTCTCTGT-3′
(SEQ ID NO;
102), wherein G is 2′
-OMe-G and U is 2′
-OMe-U and wherein YZ is an oligonucleotide motif that is CpG, C*pG, C*pG* or CpG* wherein C is deoxycytosine, 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-5-hydroxycytidine, 2′
-deoxy-N4-alkyl-cytidine, 2′
-deoxy-4-thiouridine, or other pyrimidine nucleoside analogs;
G is deoxyguanosine, and G* is 2′
-deoxy-7-deazaguanosine, 2′
-deoxy-6-thioguanosine, arabinoguanosine, 2′
-deoxyinosine, or other purine nucleoside analogs. - View Dependent Claims (2, 3, 4, 16, 19, 20)
- -CTATCTGUYZTTCTCTGT-3′
-
5. A method for inhibiting a TLR7-, TLR8- and/or TLR9-mediated immune response in a vertebrate comprising administering to the vertebrate an immune regulatory oligonucleotide (IRO) compound comprising the sequence 5′
- -CTATCTGUYZTTCTCTGT-3′
(SEQ ID NO;
102), wherein G is 2′
-OMe-G and U is 2′
-OMe-U and wherein YZ is an oligonucleotide motif that is C*pG, C*pG* or CpG* wherein C is deoxycytosine, 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-5-hydroxycytidine, 2′
-deoxy-N4-alkyl-cytidine, 2′
-deoxy-4-thiouridine, or other pyrimidine nucleoside analogs;
G is deoxyguanosine, and G* is 2′
-deoxy-7-deazaguanosine, 2′
-deoxy-6-thioguanosine, arabinoguanosine, 2′
-deoxyinosine, or other purine nucleoside analogs. - View Dependent Claims (6, 7, 8, 14, 15, 21, 22)
- -CTATCTGUYZTTCTCTGT-3′
-
9. A method for treating a vertebrate having a disease comprising administering to the vertebrate an immune regulatory oligonucleotide (IRO) compound comprising the sequence 5′
- -CTATCTGUYZTTCTCTGT-3′
(SEQ ID NO;
102), wherein G is 2′
-OMe-G and U is 2′
-OMe-U and wherein YZ is an oligonucleotide motif that is C*pG, C*pG* or CpG* wherein C is deoxycytosine, 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-5-hydroxycytidine, 2′
-deoxy-N4-alkyl-cytidine, 2′
-deoxy-4-thiouridine, or other pyrimidine nucleoside analogs;
G is deoxyguanosine, and G* is 2′
-deoxy-7-deazaguanosine, 2′
-deoxy-6-thioguanosine, arabinoguanosine, 2′
-deoxyinosine, or other purine nucleoside analogs. - View Dependent Claims (10, 11, 12, 13, 17, 18, 23, 24)
- -CTATCTGUYZTTCTCTGT-3′
Specification