Immunostimulatory nucleic acids
View Patent ↗The invention relates to a class of soft or semi-soft CpG immunostimulatory oligonucleotides that are useful for stimulating an immune response.
1. An oligonucleotide having the following structure:
(SEQ ID NO: 313)
5′ T*C_G*T*C_G*T*T*T*T*G*A*C_G*T*T*T*T*G*T*C_G*T*
T 3′,
wherein * refers to the presence of a phosphorothioate internucleotide linkage, and wherein _ refers to the presence of a phosphodiester internucleotide linkage and wherein the oligonucleotide has a length of 24-40 nucleotides.
2. The oligonucleotide of claim 1 , wherein the oligonucleotide consists essentially of 5′
(SEQ ID NO: 313)
5′ T*C_G*T*C_G*T*T*T*T*G*A*C_G*T*T*T*T*G*T*C_G*T*
T 3′.
3. The oligonucleotide of claim 1 , wherein the oligonucleotide consists of
(SEQ ID NO: 313)
5′ T*C_G*T*C_G*T*T*T*T*G*A*C_G*T*T*T*T*G*T*C_G*T*
T 3′.
4. An oligonucleotide having the following structure:
(SEQ ID NO: 313)
5′ T*C_G*T*C_G*T*T*T*T*G*A*C_G*T*T*T*T*G*T*C_G*T*
T 3′
wherein each * refers to a phosphorothioate internucleotide linkage and each _ refers to a phosphodiester internucleotide linkage, and wherein the oligonucleotide is 24 nucleotides in length.
5. A pharmaceutical composition comprising an oligonucleotide as defined in claim 1 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising an oligonucleotide as defined in claim 4 and a pharmaceutically acceptable carrier.
7. An immunostimulatory oligonucleotide having at least two internal cytosine-guanine (CG) dinucleotides, wherein C is unmethylated cytidine, and G is guanosine, wherein the at least two internal CG dinucleotides have phosphodiester internucleotide linkages, wherein optionally each additional internal CG dinucleotide has a phosphodiester or stabilized internucleotide linkage, wherein all other internucleotide linkages are stabilized with a phosphorothioate internucleotide linkage, and wherein the immunostimulatory oligonucleotide is 6-100 nucleotides long.
8. The oligonucleotide of claim 7 , wherein the immunostimulatory oligonucleotide comprises a plurality of internal CG dinucleotides having a phosphodiester internucleotide linkage.
9. The oligonucleotide of claim 7 , wherein the immunostimulatory oligonucleotide is a B-Class immunostimulatory oligonucleotide.
10. The oligonucleotide of claim 7 , wherein the immunostimulatory oligonucleotide is not an antisense oligonucleotide, triple-helix-forming oligonucleotide, or ribozyme.
11. The oligonucleotide of claim 7 , wherein the oligonucleotide has a backbone comprising deoxyribose or ribose.