Immunostimulatory oligonucleotides and uses thereof
AssigneeImmunotech
InventorRicardo Agustin Lopez
Life of this patent
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Abstract
Oligonucleotides containing the non-palindromic sequence motif: X1X2X3X4X5X6X7X8, wherein X, is C,T,G or A (preferably T or C); wherein X2 is C,T,G or A; wherein X7 is C,T,G or A (preferably G); at least three, and preferably all, of X3, X4, X5, X6 and X8 are T; and with the proviso that, in the motif, a C does not precede a G (in other terms, the nucleic acid motif does not consist of a CpG oligonucleotide), that modulate the immune response of animals of the order Primate, including humans, are disclosed. This immune modulation is characterized by stimulation of proliferation, differentiation, cytokine production and antibody production on B-cells and cell differentiation on plasmacytoid dendritic cells.
Claims61
A immunostimulatory oligonucleotide having about 14 to 100 nucleotides, comprising a non palindromic nucleic acid sequence motif having the following formula:
- X1X2X3X4X5X6X7X8,
- wherein X1 is C,T,G or A;
- X2 is C,T,G or A;
- X7 is C,T,G or A;
- and at least three of X3, X4, X5, X6 and X8 are T;
- with the proviso that, in the motif, a C does not precede a G.
An immunostimulatory oligonucleotide which contains a nucleotide sequence selected from the group consisting of:
- TGCTGCTTTTGTGCTTTTGTGCTT (SEQ ID No 1);
- TCATCATTTTGTCATTTTGTCATT (SEQ ID No 2);
- TCCTCCTTTTGTCCTTTTGTCCTT (SEQ ID No 3);
- TCTTCTTTTTGTCTTTTTGTCTTT (SEQ ID No 4);
- TAGTAGTTTTGTAGTTTTGTAGTT (SEQ ID No 5);
- TGGTGGTTTTGTGGTTTTGTGGTT (SEQ ID No 6);
- TTGTTGTTTTGTTGTTTTGTTGTT (SEQ ID No 7);
- TCATTTTTTTGTTTTTTTGTCATT (SEQ ID No 10);
- TCATTGTTTTGTTGTTTTGTCATT (SEQ ID No 11);
- TCATTCTTTTGTTCTTTTGTCATT (SEQ ID No 12);
- TCATAATTTTGTAATTTTGTCATT (SEQ ID No 14);
- TCATTATTTTGTTATTTTGTCATT (SEQ ID No 15);
- TCATGATTTTGTGATTTTGTCATT (SEQ ID No 16);
- TCATCCTTTTGTCCTTTTGTCATT (SEQ ID No 17);
- TCATCTTTTTGTCTTTTTGTCATT (SEQ ID No 18);
- CATTTTGTTTTTTTTTTTTTTTTT (SEQ ID No 20);
- TTCATTTTGTTTTTTTTTTTTTTT (SEQ ID No 21);
- TTTTCATTTTGTTTTTTTTTTTTT (SEQ ID No 22);
- TTTTTTCATTTTGTTTTTTTTTTT (SEQ ID No 23);
- TTTTTTTTCATTTTGTTTTTTTTT (SEQ ID No 24);
- TTTTTTTTTTCATTTTGTTTTTTT (SEQ ID No 25);
- TTTTTTTTTTTTCATTTTGTTTTT (SEQ ID No 26);
- TTTTTTTTTTTTTTCATTTTGTTT (SEQ ID No 27);
- TTTTTTTTTTTTTTTTCATTTTGT (SEQ ID No 28);
- TTTTCATTTTGTCATTTTGTTTTT (SEQ ID No 29);
- TCATCAATTTGTCAATTTGTCATT (SEQ ID No 30);
- TCATCATATTGTCATATTGTCATT (SEQ ID No 31);
- TCATCATTATGTCATTATGTCATT (SEQ ID No 32);
- TCATCATTTAGTCATTTAGTCATT (SEQ ID No 33);
- TCATCATTTTATCATTTTATCATT (SEQ ID No 34);
- TCATCATTTTTTCATTTTTTCATT (SEQ ID No 35);
- TCATCATTTTCTCATTTTCTCATT (SEQ ID No 36);
- TCATCATTTTGACATTTTGACATT (SEQ ID No 37);
- TCATCATTTAGACATTTAGACATT (SEQ ID No 38);
- TCATCATTATGACATTATGACATT (SEQ ID No 39);
- TCATCATATTGACATATTGACATT (SEQ ID No 40);
- ACATCATTTTGTCATTTTGTCATT (SEQ ID No 46);
- CCATCATTTTGTCATTTTGTCATT (SEQ ID No 47);
- GCATCATTTTGTCATTTTGTCATT (SEQ ID No 48);
- TAATCATTTTGTCATTTTGTCATT (SEQ ID No 49);
- TTATCATTTTGTCATTTTGTCATT (SEQ ID No 50);
- TGATCATTTTGTCATTTTGTCATT (SEQ ID No 51);
- TCCTCATTTTGTCATTTTGTCATT (SEQ ID No 52);
- TCTTCATTTTGTCATTTTGTCATT (SEQ ID No 53);
- TCGTCATTTTGTCATTTTGTCATT (SEQ ID No 54);
- TCAACATTTTGTCATTTTGTCATT (SEQ ID No 55);
- TCACCATTTTGTCATTTTGTCATT (SEQ ID No 56);
- TCAGCATTTTGTCATTTTGTCATT (SEQ ID No 57);
- TCATCATTTTGTCATTTTGTAATT (SEQ ID No 58);
- TCATCATTTTGTCATTTTGTTATT (SEQ ID No 59);
- TCATCATTTTGTCATTTTGTGATT (SEQ ID No 60);
- TCATCATTTTGTCATTTTGTCCTT (SEQ ID No 61);
- TCATCATTTTGTCATTTTGTCTTT (SEQ ID No 62);
- TCATCATTTTGTCATTTTGTCGTT (SEQ ID No 63);
- TCATCATTTTGTCATTTTGTCAAT (SEQ ID No 64);
- TCATCATTTTGTCATTTTGTCACT (SEQ ID No 65);
- TCATCATTTTGTCATTTTGTCAGT (SEQ ID No 66);
- TCATCATTTTGTCATTTTGTCATA (SEQ ID No 67);
- TCATCATTTTGTCATTTTGTCATC (SEQ ID No 68);
- TCATCATTTTGTCATTTTGTCATG (SEQ ID No 69);
- TTTTCATTTTGTTTTT (SEQ ID No 71);
- TTTTCATTTTGTTTTTTTTT (SEQ ID No 72);
- TTTTTTTTTTTTCATTTTGTTTTT (SEQ ID No 73);
- TTTTCATTTTGTTTTTTTTTTTTTTTTT (SEQ ID No 74).
Dependencies are inferred from the claim text.