C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders
First Claim
Patent Images
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 the oligonucleotide comprises two or more N3′
- →
P5′
thiophosphoramidate linkages independently located on both the 5′ and
3′
ends of the oligonucleotide, wherein the oligonucleotide further comprises two or more contiguous thiophosphate or phosphate linkages located in between the two or more N3′
→
P5′
thiophosphoramidate 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.
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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.
35 Citations
39 Claims
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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 the oligonucleotide comprises two or more N3′
- →
P5′
thiophosphoramidate linkages independently located on both the 5′ and
3′
ends of the oligonucleotide, wherein the oligonucleotide further comprises two or more contiguous thiophosphate or phosphate linkages located in between the two or more N3′
→
P5′
thiophosphoramidate 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. - View Dependent Claims (2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 39)
- →
-
6. 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 N3′ - →
P5′
thiophosphoramidate intersubunit linkages located on the 5′
end of the oligonucleotide;b. wherein the oligonucleotide comprises at least two contiguous N3′
→
P5′
thiophosphoramidate 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 N3′
→
P5′
thiophosphoramidate linkages located on the 5′
end and said at least two contiguous N3′
→
P5′
thiophosphoramidate linkages located on the 3′
end of the oligonucleotide; andd. wherein the oligonucleotide comprises the sequence AACGTTGAGGGGCAT (SEQ ID NO;
1).
- →
-
24. 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 N3′
- →
P5′
thiophosphoramidate or N3′
→
P5′
phosphoramidate linkages independently located on both the 5′ and
3′
ends of the oligonucleotide, wherein the oligonucleotide comprises two or more contiguous thiophosphate or phosphate linkages located in between the two or more N3′
→
P5′
thiophosphoramidate or N3′
→
P5′
phosphoramidate linkages, wherein the oligonucleotide is about 6 to about 30 nucleotides in length, wherein the oligonucleotide is a substrate for RNase-H-mediated degradation of the mRNA from a c-myc gene, and wherein the oligonucleotide comprises a sequence selected from the group consisting of CTGCTGTCGTTGAGAGGGTA (SEQ ID NO;
9), GGCATCGTCGCGGGAGGCTGCTGGAGCG (SEQ ID NO;
10), GGCATCGTCGCGGGAGGCTG (SEQ ID NO;
11), TCGTCGCGGGAGGCTGCTGG (SEQ ID NO;
12), CCGCCCGCTCGCTCCCTCTG (SEQ ID NO;
13), GTTCTCCTCCTCGTCGCAGT (SEQ ID NO;
14), and TCGTCGCGGGAGGCTG (SEQ ID NO;
16). - View Dependent Claims (25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38)
- →
Specification