Modulators of SMAD7 expression
AssigneeIonis Pharmaceuticals, Inc.
InventorsSusan M. Freier, Huynh-Hoa Bui
Life of this patent
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Abstract
The present embodiments provide methods, compounds, and compositions useful for inhibiting SMAD7 expression, which may be useful for treating, preventing, or ameliorating a disease associated with SMAD7.
Claims26
A compound comprising a modified oligonucleotide 16 to 30 linked nucleosides in length, wherein the modified oligonucleotide has a nucleobase sequence comprising any one of SEQ ID NOs:
- 2537, 1456, or 2109, wherein the modified oligonucleotide comprises:
- a gap segment consisting of linked deoxynucleosides;
- a 5′ wing segment consisting of linked nucleosides;
- and
- a 3′ wing segment consisting of linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.
A compound comprising a modified oligonucleotide 16 linked nucleosides in length having a nucleobase sequence consisting of any one of SEQ ID NOs:
- 2537, 1456, or 2109, wherein the modified oligonucleotide comprises:
- a gap segment consisting of ten linked deoxynucleosides;
- a 5′ wing segment consisting of three linked nucleosides;
- and
- a 3′ wing segment consisting of three linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment;
- wherein each nucleoside of the 5′ wing segment and the 3′ wing segment comprises a cEt sugar;
- wherein at least one internucleoside linkage is a phosphorothioate linkage;
- and wherein each cytosine is a 5-methylcytosine.
A compound comprising a modified oligonucleotide according to the following formula:
- Tks Tks Tks Gds Tds Ads Ads Ads Tds mCds Gds Ads Ads Aks Gks mCk (SEQ ID NO:
- 2537);
- wherein,
- A=an adenine,
- mC=a 5-methylcytosine
- G=a guanine,
- T=a thymine,
- k=a cEt modified sugar,
- d=a 2′-deoxynucleoside, and
- s=a phosphorothioate internucleoside linkage.
A compound according to the following formula:
- or a pharmaceutically acceptable salt thereof.
A modified oligonucleotide consisting of 16 linked nucleosides having the sequence of SEQ ID NO:
- 2537 and consisting of:
- a gap segment consisting of ten linked deoxynucleosides;
- a 5′ wing segment consisting of three linked nucleosides;
- and
- a 3′ wing segment consisting of three linked nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a cEt sugar;
- wherein each internucleoside linkage is a phosphorothioate linkage;
- wherein each cytosine is a 5-methylcytosine.
Dependencies are inferred from the claim text.