ANTISENSE MOLECULES AND METHODS FOR TREATING PATHOLOGIES

• US 20120270925A1
• Filed: 11/12/2010
• Published: 10/25/2012
• Est. Priority Date: 11/12/2009
• Status: Active Grant

• Current Assignee: University of Western Australia
• Original Assignee: University of Western Australia
• Inventors: Wilton, Stephen Donald, Fletcher, Sue, Adams, Abbie, Meloni, Penny
• Granted Patent: US 8,637,483 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: A61P 21/04 for myasthenia gravis
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• 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 2310/3181 Peptide nucleic acid, PNA
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2310/3521 Methyl
• 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 59.

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 a sequence selected from the following:

SEQ ID NOs;

1, 3 to 6, 9 to 18, 20 to 24, 26 to 28, 30 to 32, 34 to 36, 40, 42, 44 to 46, and 48 to 59.

2. An antisense molecule according to claim 1 capable of inducing exon skipping in exons 5, 11, 12, 17, 21, 22, 24, 43-47, 49-64, 66 and 67 of the dystrophin gene.

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

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

14. An antisense molecule according to claim 1 in combination with an antisense molecule selected from the following:

SEQ ID NOs;

2, 4, 7, 8, 19, 25, 29, 33, 37 to 39, 41, 43 and 47 wherein the combination is capable of binding to a selected target to induce exon skipping in the dystrophin gene.

16. The antisense molecule according to claim 1, 2, 3, 13, 14 or 15, capable of binding to a selected target site, wherein the target site is an mRNA splicing site selected from a splicer donor site, splice acceptor sites or exonic splicing enhancer elements.

17. A method of treating muscular dystrophy in a patient comprising administering to the patient a composition comprising an antisense molecule according to claim 1, 2, 3, 13, 14 or 15.

18. A pharmaceutical or therapeutic composition for the treatment of muscular dystrophy in a patient comprising (a) at least an antisense molecule according to claim 1, 2, 3, 13, 14 or 15, and (b) one or more pharmaceutically acceptable carriers and/or diluents.

19. The composition according to claim 17, comprising about 20 nM to 600 nM of the antisense molecule.

20. An antisense molecule according to claim 1, 2, 3, 13, 14 or 15 for use in antisense molecule based therapy.

21. A kit comprising at least one antisense molecule according to claim 1, 2, 3, 13, 14 or 15, a suitable carrier and instructions for its use.

4-12. -12. (canceled)

15. A combination of two or more antisense molecules selected from the following combinations:

SEQ ID NO;

31 and 32;

SEQ ID NO;

33 and 34;

SEQ ID NO;

35 and 36;

SEQ ID NO;

39, 40 and 41;

SEQ ID NO;

42 and 43;

SEQ ID NO;

44 and 45;

SEQ ID NO;

46 and 47;

SEQ ID NO;

48 and 49;

SEQ ID NO;

50 and 51;

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