Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof
OwnerEyal Raz, David Schwartz +2inventors
InventorsEyal Raz, David Schwartz, Mark Roman, Dino Dina
Life of this patent
Estimating the term…
Abstract
The invention relates to immunostimulatory oligonucleotide compositions. These oligonucleotides comprise an immunostimulatory octanucleotide sequence. These oligonucleotides can be administered in conjunction with an immunostimulatory peptide or antigen. Methods for modulating an immune response upon administration of the oligonucleotide are also disclosed. In addition, an in vitro screening method to identify oligonucleotides with immunostimulatory activity is provided.
Claims79
An immunomodulatory oligonucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises an octanucleotide sequence selected from the group consisting of GACTGCTCC;
- GACGCCC;
- AGCTGTTCC;
- AGCGCTCC;
- AGCGTCCC;
- AGCGCCCC;
- AACGTCCC;
- AACGCCCC;
- GGCGTTCC;
- GGCGCTCC;
- GGCGTCCC;
- GGCGCCCC;
- GACGCTCG;
- GACGTCCG;
- GACGCCCG;
- AGCGTTCG;
- AGCGTCCG;
- AGCGCCCG;
- AACGTCCG;
- AACGCCCG;
- GGCGTTCG;
- GGCGCTCG;
- GGCGTCCG;
- GGCGCCCG.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:2.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:4.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:6.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:7.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:12.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:15.
An immunomodulatory oligonucleotide comprising the sequence of SEQ ID NO:16.
An immunomodulatory comprising a polynucleotide comprising an immunostimulatory sequence (ISS) and an antigen, wherein the ISS comprises 5′-cytosine, guanine-3′, and wherein the ISS and the antigen are not conjugated and are proximately associated at a distance effective to enhance an immune response compared to co-administration of the ISS and antigen in solution.
A method of modulating an immune response in an individual comprising administering to the individual the immunomodulatory oligonucleotide of SEQ ID NO:2 in an amount sufficient to modulate the immune response.
A method to screen for human immunostimulatory activity of oligonucleotides comprising the steps of:
- (a) providing macrophage cells and an aliquot of an oligonucleotide to be tested;
- (b) incubating the cells and oligonucleotide of step a) for an appropriate length of time;
- (c) determining the relative amount of Th1-biased cytokines in the cell culture supernatant.
An immunomodulatory composition comprising a polynucleotide comprising (a) an immunostimulatory sequence (ISS);
- (b) an antigen;
- and (c) an adjuvant other than alum, wherein the ISS comprises 5′-cytosine, guanine-3′, wherein the ISS and antigen are not conjugated, and wherein the adjuvant is in an amount sufficient to enhance an immune response compared to co-administration of the ISS and antigen without adjuvant.
Dependencies are inferred from the claim text.