Modulation of androgen receptor expression
AssigneeIsis Pharmaceuticals, Inc.
InventorsRobert A. Macleod, Youngsoo Kim, Tianyuan Zhou, Susan M. Freier, Brett Monia
Life of this patent
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Abstract
Certain embodiments are directed to compounds and compositions targeted to human androgen receptor (AR) for inhibiting androgen receptor levels in a cell, which can be useful for methods of treating cancer and inhibiting cancer cell growth or proliferation.
Claims20
A compound comprising a single-stranded modified oligonucleotide consisting of 16 linked nucleosides having a nucleobase sequence consisting of the sequence of SEQ ID NO:
- 35, or a pharmaceutically acceptable salt thereof, wherein the modified oligonucleotide comprises:
- a gap segment consisting of 9 linked deoxynucleosides;
- a 5′ wing segment consisting of three linked nucleosides;
- and
- a 3′ wing segment consisting of four linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment;
- the three linked nucleosides of the 5′ wing segment are each a constrained ethyl (cEt) sugar;
- the four linked nucleosides of the 3′ wing segment are a constrained ethyl (cEt) sugar, a constrained ethyl (cEt) sugar, a constrained ethyl (cEt) sugar, and a 2′-O-methoxyethyl sugar in the 5′ to 3′ direction;
- each internucleoside linkage is a phosphorothioate linkage;
- and each cytosine is a 5-methylcytosine.
A compound comprising a single-stranded modified oligonucleotide consisting of 16 linked nucleosides having a nucleobase sequence consisting of the sequence of SEQ ID NO:
- 39, or a pharmaceutically acceptable salt thereof, wherein the modified oligonucleotide comprises:
- a gap segment consisting of 7 linked deoxynucleosides;
- a 5′ wing segment consisting of four linked nucleosides;
- and
- a 3′ wing segment consisting of five linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment;
- the four linked nucleosides of the 5′ wing segment are a 2′-O-methoxyethyl sugar, a constrained ethyl (cEt) sugar, a constrained ethyl (cEt) sugar, and a constrained ethyl (cEt) sugar in the 5′ to 3′ direction;
- the five linked nucleosides of the 3′ wing segment are a constrained ethyl (cEt) sugar, a constrained ethyl (cEt) sugar, a constrained ethyl (cEt) sugar, a 2′-O-methoxyethyl sugar, and a 2′-O-methoxyethyl sugar in the 5′ to 3′ direction;
- each internucleoside linkage is a phosphorothioate linkage;
- and each cytosine is a 5-methylcytosine.
Dependencies are inferred from the claim text.