Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes
View Patent ↗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.
1. An immunostimulatory oligonucleotide compound, comprising:
an immunostimulatory dinucleotide of formula C*pG, C*pG* or CpG*, wherein C is cytosine G is guanosine or and G* is selected from 7-deazaguanosine and 6-thioguanosine, C* is selected from 5-hydroxycytosine, 5-hydroxymethylcytosine, N4-alkylcytosine and 4-thiouracil, and wherein p is an internucleotide linkage selected from the group consisting of phosphodiester, phosphorothioate and phosphorodithioate;
a 3′-3′ linkage; and
one or two accessible 5′ ends.
2. The immunostimulatory oligonucleotide compound of claim 1 , which oligonucleotide comprises two accessible 5′ ends.
3. The immunostimulatory oligonucleotide compound of claim 1 , wherein G* is 7-deazaguanosine.
4. The immunostimulatory oligonucleotide compound of claim 1 , wherein G* is 6-thioguanosine.