ANTISENSE OLIGONUCLEOTIDES FOR INDUCING EXON SKIPPING AND METHODS OF USE THEREOF

• US 20140309285A1
• Filed: 06/27/2014
• Published: 10/16/2014
• Est. Priority Date: 06/28/2004
• Status: Active Grant

• Current Assignee: University of Western Australia
• Original Assignee: University of Western Australia
• Inventors: WILTON, Stephen Donald, FLETCHER, Sue, MCCLOREY, Graham
• Granted Patent: US 9,035,040 B2
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring
• CPC Class Codes: C12N 2310/33 of the base
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• CPC Class Codes: C12N 2310/3519 Fusion with another nucleic acid
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2320/33 Alteration of splicing

Abstract

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

Claims

1-3. -3. (canceled)

4. An antisense oligonucleotide of 25 nucleotides comprising at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO:

193), in which cytosine bases are 5-methylcytosine bases, wherein the antisense oligonucleotide is a 2′

-O-methyl phosphorothioate oligoribonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to an exon 53 target region of the human dystrophin gene to induce exon 53 skipping, and a pharmaceutically acceptable carrier.

5. A pharmaceutical composition comprising an antisense oligonucleotide of 25 nucleotides comprising at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO:

193), in which cytosine bases are 5-methylcytosine bases, wherein the antisense oligonucleotide is a 2′

-O-methyl phosphorothioate oligoribonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to an exon 53 target region of the human dystrophin gene to induce exon 53 skipping, and a pharmaceutically acceptable carrier.