C-MYC ANTISENSE OLIGONUCLEOTIDES AND METHODS FOR USING THE SAME TO TREAT CELL-PROLIFERATIVE DISORDERS
First Claim
1. An oligonucleotide comprising a sequence complementary to an mRNA from a c-myc gene, wherein the nucleoside subunits of the oligonucleotide are joined by intersubunit linkages, wherein at least one of the intersubunit linkages is a thiophosphoramidate linkage, wherein the oligonucleotide is about 6 to about 30 nucleotides in length, and wherein the oligonucleotide prevents translation of the mRNA by steric hindrance.
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Accused Products
Abstract
Provided herein are antisense oligonucleotides that can effectively prevent or decrease c-myc protein expression as well as decrease overall rates of cell proliferation in in vitro and mammalian in vivo models of cell proliferative disorders as well as methods for using the same.
9 Citations
38 Claims
- 1. An oligonucleotide comprising a sequence complementary to an mRNA from a c-myc gene, wherein the nucleoside subunits of the oligonucleotide are joined by intersubunit linkages, wherein at least one of the intersubunit linkages is a thiophosphoramidate linkage, wherein the oligonucleotide is about 6 to about 30 nucleotides in length, and wherein the oligonucleotide prevents translation of the mRNA by steric hindrance.
- 8. An oligonucleotide comprising a sequence complementary to an mRNA from a c-myc gene, wherein the nucleoside subunits of the oligonucleotide are joined by intersubunit linkages, wherein the oligonucleotide comprises alternating thiophosphoramidate or phosphoramidate and thiophosphate or phosphate intersubunit linkages, wherein the oligonucleotide is about 6 to about 30 nucleotides in length, and wherein the oligonucleotide is a substrate for RNase-H-mediated degradation of the mRNA from a c-myc gene or wherein the oligonucleotide prevents translation of the mRNA by steric hindrance.
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16. An oligonucleotide comprising a sequence complementary to an mRNA from a c-myc gene, wherein the nucleoside subunits of the oligonucleotide are joined by intersubunit linkages, wherein the oligonucleotide comprises two or more contiguous thiophosphoramidate or phosphoramidate linkages independently located on both the 5′
- and 3′
ends of the oligonucleotide, wherein the oligonucleotide is about 6 to about 30 nucleotides in length, and wherein the oligonucleotide is a substrate for RNase-H-mediated degradation of the mRNA from a c-myc gene and/or prevents translation of the mRNA by steric hindrance. - View Dependent Claims (17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 38)
- and 3′
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22. An oligonucleotide comprising a sequence complementary to an mRNA from a c-myc gene, wherein the nucleoside subunits of the oligonucleotide are joined by intersubunit linkages, wherein the oligonucleotide is a substrate for RNase-H-mediated degradation of the mRNA from a c-myc gene, and
a. wherein the oligonucleotide comprises at least two contiguous phosphoramidate intersubunit linkages located on the 5′ - end of the oligonucleotide;
b. wherein the oligonucleotide comprises at least two contiguous phosphoramidate intersubunit linkages located on the 3′
end of the oligonucleotide;c. wherein the oligonucleotide comprises 2-11 contiguous thiophosphate or phosphate linkages located in between said at least two contiguous phosphoramidate linkages located on the 5′
end and said at least two contiguous phosphoramidate linkages located on the 3′
end of the oligonucleotide; andd. wherein the oligonucleotide comprises the sequence AACGTTGAGGGGCAT (SEQ ID NO;
1).
- end of the oligonucleotide;
Specification