Methods for inhibiting expression of connective tissue growth factor
AssigneesIsis Pharmaceuticals, Inc., Excaliard Pharmaceuticals, Inc.
InventorsNicholas M. Dean, J. Gordon Foulkes, Niall O'Donnell, C. Frank Bennett, Susan M. Frier
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Abstract
This invention provides compounds which comprise modified oligonucleotides capable of inhibitory expression of connective tissue factor and composition containing same as well as methods of treating hyperprolific disorders and fibrotic diseases, and of reducing scarring resulting from wound healing using such compounds.
Claims27
A method of treating hypertrophic scarring, comprising administering to a subject in need of treatment for hypertrophic scarring a therapeutically effective amount of a composition comprising a compound which comprises a modified oligonucleotide consisting of 12-30 linked nucleosides, at least a 12 nucleobase sequence portion of which is present within the nucleobase sequence set forth in SEQ ID NO:
- 39, wherein the modified oligonucleotide comprises:
- (a) a gap segment consisting of linked deoxynucleosides;
- (b) a 5′ wing segment consisting of linked modified nucleosides;
- and
- (c) a 3′ wing segment consisting of linked modified nucleosides;
- wherein the gap segment is positioned between the 5 wing segment and the 3′ wing segment, and wherein each modified nucleoside within each wing segment comprises a modified sugar.
A method of treating hypertrophic scarring, comprising administering to a subject in need of treatment for hypertrophic scarring a therapeutically effective amount of a composition comprising a compound which comprises a modified oligonucleotide consisting of 20 linked nucleosides having a nucleobase sequence as recited in SEQ ID NO 39, wherein the modified oligonucleotide comprises:
- (a) a gap segment consisting of thirteen linked deoxynucleosides;
- (b) a 5′ wing segment consisting of two linked modified nucleosides;
- and
- (c) a 3′ wing segment consisting of five linked modified nucleosides;
- wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment,
- wherein each modified nucleoside within each wing segment comprises a 2′-O-methoxyethyl sugar,
- wherein each internucleoside linkage is a phosphorothioate linkage, and
- wherein each cytosine nucleobase is a 5′-methylcytosine.
A method of treating hypertrophic scarring, comprising administering to a subject in need of treatment for hypertrophic scarring a therapeutically effective amount of a composition comprising an antisense oligonucleotide consisting of the nucleotide sequence of SEQ ID NO:39, said antisense oligonucleotide further characterized as having, from 5′ to 3′ direction,
- a 5′ wing segment consisting of two nucleotides, a gap segment consisting of 13 nucleotides, and a 3′ wing segment consisting of five nucleotides,
- wherein each nucleotide of said 5′ and 3′ wing segments comprises a 2′-O-methoxyethyl sugar,
- wherein each nucleotide of said gap segment comprises a deoxyribose sugar,
- wherein each cytosine base of said antisense oligonucleotide is a 5′-methylcytosine, and
- wherein the internucleotide linkages between each nucleotide of said antisense oligonucleotide are phosphorothioate linkages.
Dependencies are inferred from the claim text.