CpG oligonucleotide analogs containing hydrophobic T analogs with enhanced immunostimulatory activity
View Patent ↗The invention relates to oligonucleotides including at least one lipophilic substituted nucleotide analog and a pyrimidine-purine dinucleotide. The invention also relates to pharmaceutical compositions and methods of use thereof.
1. An oligonucleotide comprising the sequence JU*C-G*JU*C*G*A*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C*G (SEQ ID NO: 33), wherein the JU is 5-iodo-2′-deoxyuridine, the * is phosphorothioate internucleotide linkage, and the—is phosphodiester internucleotide linkage.
2. An oligonucleotide comprising the sequence JU*C-G*T*C*G*A*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C*G (SEQ ID NO: 31), wherein the JU is 5-iodo-2′-deoxyuridine, the * is phosphorothioate internucleotide linkage, and the—is phosphodiester internucleotide linkage.
3. An oligonucleotide comprising the sequence T*C-G*JU*C*G*A*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C*G (SEQ ID NO: 32), wherein the JU is 5-iodo-2′-deoxyuridine, the * is phosphorothioate internucleotide linkage, and the—is phosphodiester internucleotide linkage.
4. An oligonucleotide comprising the sequence JU*C-G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C*G (SEQ ID NO: 58), or the sequence JU*C*G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C*G (SEQ ID NO: 59), wherein the JU is 5-iodo-2′-deoxyuridine, the * is phosphorothioate internucleotide linkage, and the—is phosphodiester internucleotide linkage.
5. An oligonucleotide comprising the sequence EU*C-G*A*C*G*T*C*G*A*T*C*G*G*C*G*C*G*C*G*C*C*G (SEQ ID NO: 62), wherein the EU is 5-iodo-2′-deoxyuridine, the * is phosphorothioate internucleotide linkage, and the—is phosphodiester internucleotide linkage.
6. A pharmaceutical composition comprising the oligonucleotide of any one of claims 1 to 5 , said composition further comprising an antigen.
7. A pharmaceutical composition comprising the oligonucleotide of any one of claims 1 to 5 , said composition further comprising a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising the oligonucleotide of any one of claims 1 to 5 , said composition further comprising an antigen and a pharmaceutically acceptable carrier.