Methods and compositions involving immunostimulatory oligodeoxynucleotides
View Patent ↗Described is an immunostimulatory oligodeoxynucleic acid molecule (ODN) having the structure according to formula (I) wherein any NMP is a 2′ deoxynucleoside monophosphate or monothiophosphate, selected from the group consisting of deoxyadenosine-, deoxyguanosine-, deoxyinosine-, deoxycytosine-, deoxyuridine-, deoxythymidine-, 2-methyl-deoxyinosine-, 5-methyl-deoxycytosine-, deoxypseudouridine-, deoxyribosepurine-, 2-amino-deoxyribosepurine-, -6-S-deoxyguanine-, 2-dimethyl-deoxyguanosine- or N-isopentenyl-deoxyadenosine-monophosphate or -monothiophosphate, NUC is a 2′ deoxynucleoside, selected from the group consisting of deoxyadenosine-, deoxyguanosine-, deoxyinosine-, deoxycytosine-, deoxyuridine-, deoxythymidine-, 2-methyl-deoxyinosine-, 5-methyl-deoxycytosine-, deoxypseudouridine-, deoxyribosepurine-, 2-amino-deoxyribosepurine-, 6-S-deoxyguanine-, 2-dimethyl-deoxyguanosine- or N-isopentenyl-deoxyadenosine, any X is O or S, a and b are integers from 0 to 100 with the proviso that a+b is between 4 and 150, B and E are common groups for 5′ or 3′ ends of nucleic acid molecules, as well as a pharmaceutical composition containing such ODNs.
1. A method of stimulating an immune system comprising administering to a patient at least one antigen and at least one immunostimulatory oligodeoxynucleotide molecule (ODN) consisting of the sequence oligo-dIC 26-mer (SEQ ID NO:30).
2. The method of claim 1 , further comprising placing the ODN in a pharmaceutical composition prior to administering the ODN to the patient.
3. The method of claim 2 , wherein the pharmaceutical composition further comprises at least one of a polycationic polymer, an antimicrobial peptide, a growth hormone, a cytokine, an anti-inflammatory substance, a pharmaceutically acceptable carrier, a buffer substance, or a stabilizer.
4. The method of claim 1 , wherein 1 ng to 1 g of the ODN is administered to the patient.
5. The method of claim 4 , wherein 100 ng to 10 mg of the ODN is administered to the patient.
6. The method of claim 4 , wherein 10 ng to 1 mg of the ODN is administered to the patient.
7. A method of vaccinating a patient comprising administering to the patient at least one antigen and at least one immunostimulatory oligodeoxynucleotide molecule (ODN) consisting of the sequence oligo-dIC 26-mer (SEQ ID NO: 30).
8. A pharmaceutical composition comprising at least one antigen and at least one immunostimulatory oligodeoxynucleotide molecule (ODN) consisting of the sequence oligo-dIC 26-mer (SEQ ID NO:30).
9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition further comprises at least one of a polycationic polymer, an antimicrobial peptide, a growth hormone, a cytokine, an anti-inflammatory substance, a pharmaceutically acceptable carrier, a buffer substance, or a stabilizer.
10. The pharmaceutical composition of claim 8 , further defined as comprising 1 ng to 1 g of the ODN.
11. The pharmaceutical composition of claim 10 , further defined as comprising 100 ng to 10 mg of the ODN.
12. The pharmaceutical composition of claim 10 , further defined as comprising 10 ng to 1 mg of the ODN.
13. The pharmaceutical composition of claim 9 , wherein the polycationic polymer is a synthetic peptide comprising two KLK-motifs separated by a linker of 3 to 7 hydrophobic amino acids.