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US 8,476,416 B2Granted
Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes
AssigneeIdera Pharmaceuticals, Inc.
InventorsEkambar R. Kandimalla, Qiuyan Zhao, Dong Yu, Sudhir Agrawal
Life of this patent
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Abstract
The invention relates to the therapeutic use of oligonucleotides or oligonucleotide analogs as immunostimulatory agents in immunotherapy applications. The invention provides methods for enhancing the immune response caused by immunostimulatory oligonucleotide compounds.
Claims11
An immunostimulatory oligonucleotide compound comprising a sequence of formula (II):
- 5′-Um . . . U1-X1-X2-Y-Z-X3-X4-D1 . . . Dm-3′ (II)
- wherein Y is a non-natural pyrimidine nucleoside selected from 5-hydroxycytosine, 5-hydroxymethylcytosine, N4-alkylcytosine and 4-thiouracil;
- Z is guanosine, 2′-deoxyguanosine or a guanosine analog;
- each X independently is a naturally occurring deoxyribonucleoside or an immunostimulatory moiety;
- wherein Um . . . U1 represents an upstream potentiation domain, where each U independently is a naturally occurring deoxyribonucleoside or an immunostimulatory moiety;
- wherein D1 . . . Dm represents a downstream potentiation domain, where each D independently is a naturally occurring deoxyribonucleoside or an immunostimulatory moiety;
- wherein the terminal D is a C3 linker, and wherein the C3 linker may optionally be branched or unbranched, and optionally may be substituted or unsubstituted, and optionally a chirally pure or a racemic mixture;
- and
- wherein m, at each occurrence, represents a number from 0-30.
6 more elements
An immunostimulatory oligonucleotide compound comprising a sequence of formula (II):
- 5′-Um . . . U1-X1-X2-Y-Z-X3-X4-D1 . . . Dm-3′ (II)
- wherein Y is cytidine or 2′-deoxycytidine;
- Z is a guanosine analog;
- each X independently is a naturally occurring deoxyribonucleoside or an immunostimulatory moiety;
- wherein Um . . . U1 represents an upstream potentiation domain, where each U independently is a naturally occurring deoxyribonucleoside or an immunostimulatory moiety;
- wherein D1 . . . Dm represents a downstream potentiation domain, where each D independently is a naturally occurring deoxyribonucleoside or an immunostimulatory moiety;
- wherein the terminal D is a C3 linker, and wherein the C3 linker may optionally be branched or unbranched, and optionally may be substituted or unsubstituted, and optionally a chirally pure or a racemic mixture;
- and
- wherein m, at each occurrence, represents a number from 0-30.
6 more elements
Dependencies are inferred from the claim text.