ANTISENSE OLIGONUCLEOTIDES FOR INDUCING EXON SKIPPING AND METHODS OF USE THEREOF

• US 20150057330A1
• Filed: 03/24/2014
• Published: 02/26/2015
• Est. Priority Date: 06/28/2004
• Status: Abandoned Application

• Current Assignee: University of Western Australia
• Original Assignee: University of Western Australia
• Inventors: Wilton, Stephen Donald, Fletcher, Sue, McClorey, Graham
• Application Number:
  US14/223,634
• Publication Number:
  US 20150057330A1
• 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. 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.

2. An antisense molecule according to claim 1 capable of inducing exon skipping in exons 3, 4, 8, 10 to 16, 19 to 40, 42 to 44, 46, 47 and 50 to 53 of the dystrophin gene.

3. A combination of two or more antisense molecules according to claim 1 or 2 capable of binding to a selected target to induce exon skipping in the dystrophin gene.

4. A combination or two or more antisense molecules according to claim 3 selected from Table 1B.

5. A combination of two or more antisense molecules according to claim 1 or 2 joined together to form a “

weasel”

, wherein said weasel is capable of binding to a selected target to induce exon skipping in the dystrophin gene.

6. A combination of two or more antisense molecules according to claim 5 selected from Table 1C.

7. The antisense molecule according to any one of claims 1 to 6, capable of binding to a selected target site, wherein the target site is an rnRNA splicing site selected from a splicer donor site, splice acceptor sites or exonic splicing enhancer elements.

8. A method of treating muscular dystrophy in a patient comprising administering to the patient a composition comprising an antisense molecule according to anyone of claims 1 to 6.

9. A pharmaceutical or therapeutic composition for the treatment of muscular dystrophy in a patient comprising (a) at least an antisense molecule according to any one of claims 1 to 6, and (b) one or more pharmaceutically acceptable carriers and/or diluents.

10. The composition according to claim 9, comprising about 20 nM to 600 nM of the antisense molecule.

11. The use of an antisense molecule according to any one of claims 1 to 6 for the manufacture of a medicament for modulation of muscular dystrophy.

12. An antisense molecule according to any one of claims 1 to 6 for use in antisense molecule based therapy.

13. An antisense molecule according to any one of claims 1 to 6 as herein before described with reference to the examples.

14. A kit comprising at least one antisense molecule according to any one of claims 1 to 6, a suitable carrier and instructions for its use.