Immunomodulatory oligonucleotides
AssigneesUniversity of Iowa Research Foundation, United States of America, Coley Pharmaceutical Group, Inc.
InventorsArthur M. Krieg, Dennis Klinman, Alfred D. Steinberg
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Abstract
Oligonucleotides containing unthylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response in a subject are disclosed. Also disclosed are therapies for treating diseases associated with immune system activation that are initiated by unthylated CpG dinucleotides in a subject comprising administering to the subject oligonucleotides that do not contain unmethylated CpG sequences (i.e. methylated CpG sequences or no CpG sequence) to outcompete unmethylated CpG nucleic acids for binding. Further disclosed are methylated CpG containing dinucleotides for use antisense therapies or as in vivo hybridization probes, and immunoinhibitory oligonucleotides for use as antiviral therapeutics.
Claims22
A composition comprising an oligonucleotide sequence which comprises 5′ TCAACGTT 3′ wherein C and G are unmethylated, and an antigen in a pharmaceutically acceptable carrier.
A composition comprising an oligonucleotide sequence which comprises 5′ GACGTT 3′ wherein C and G are unmethylated, and an antigen in a pharmaceutically acceptable carrier.
A composition comprising an oligonucleotide sequence which comprises 5′ AGCGTT 3′ wherein C and G are unmethylated, and an antigen in a pharmaceutically acceptable carrier.
A composition comprising an oligonucleotide sequence which comprises 5′ AACGCT 3′ wherein C and G are umnethylated, and an antigen in a pharmaceutically acceptable carrier.
A composition comprising an oligonucleotide sequence which comprises 5′ AACGAT 3′ wherein C and G are unmethylated, and an antigen in a pharmaceutically acceptable carrier.
A composition comprising:
- an immunostimulatory nucleic acid which comprises an oligonucleotide sequence including at least the following formula:
- 5′ X1X2CGX3X4 3′
- wherein C and G are unmethylated, wherein X1X2 are dinucleotides selected from the group consisting of:
- GpT, GpG, GpA, ApA, ApT, ApG, CpT, CpA, CpG, TpA, TpT, and TpG;
- and X3X4 are dinucleotides selected from the group consisting of:
- TpT, CpT, ApT, TpG, ApG, CpG, TpC, ApC, CpC, TpA, ApA, and CpA and wherein at least one nucleotide has a phosphate backbone modification, and
- an antigen in a pharmaceutically acceptable carrier.
A method for enhancing an immune response in a subject, comprising administering to the subject an immunostimulatory composition which enhances antigen specific B cell activation comprising an antigen and an immunostimulatory nucleic acid which comprises an oligonucleotide sequence having the following formula:
- 5′ X1X2CGX3X4 3′
- wherein C and G are unmethylated, wherein X1X2 are dinucleotides selected from the group consisting of:
- GpT, GpG, GpA ApA, ApT, ApG, CpT, CpA, CpG, TpA, TpT, and TpG;
- and X3X4 are dinucleotides selected from the group consisting of:
- TpT, CpT GpT, ApT, TpG, ApG, CpG, TpC, ApC, CpC, TpA, ApA, and CpA and wherein at least one nucleotide has a phosphate backbone modification.
Dependencies are inferred from the claim text.