Antisense Oligonucleotides For Inducing Exon Skipping and Methods of Use Thereof

• US 20080200409A1
• Filed: 06/28/2005
• Published: 08/21/2008
• Est. Priority Date: 06/28/2004
• Status: Active Grant

• Current Assignee: University of Western Australia
• Original Assignee: University of Western Australia
• Inventors: McClorey, Graham, Fletcher, Sue, Wilson, Stephen Donald
• Granted Patent: US 7,807,816 B2
• Time in Patent Office: Days
• US Class Current: 514/44
• 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

Antisense molecules capable of binding to a selected target site in the dystrophin gene to induce exon skipping are described.

Claims

1. An antisense molecule that binds to the human dystrophin gene to induce exon skipping in the dystrophin gene, consisting of a sequence selected from SEQ ID NO:

1 to 202.

2. An antisense molecule according to claim 1 capable of inducing exon skipping in an exon or exons selected from 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 composition comprising at least two antisense molecules according to claim 1.

4. A composition according to claim 3, wherein said antisense molecules are selected from the following:

(a) SEQ ID Nos;

81 and 82;

(b) SEQ ID Nos;

79, 81, and 82;

(c) SEQ ID Nos;

194, 195, and 196.

5. A nucleotide molecule consisting essentially of two or more antisense molecules according to claim 1 joined together, wherein said nucleotide molecule binds to the human dystrophin gene to induce exon skipping.

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

9. A pharmaceutical or therapeutic composition comprising:

(a) at least an antisense molecule according to claim 1; 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.

6-7. -7. (canceled)

11-14. -14. (canceled)

15. An antisense molecule consisting of a sequence selected from the group: