EXON SKIPPING COMPOSITIONS FOR TREATING MUSCULAR DYSTROPHY

• US 20190330624A1
• Filed: 12/07/2018
• Published: 10/31/2019
• Est. Priority Date: 03/14/2013
• Status: Abandoned Application

• Current Assignee: Sarepta Therapeutics, Inc.
• Original Assignee: Sarepta Therapeutics, Inc.
• Inventors: Bestwick, Richard K., Frank, Diane Elizabeth, Schnell, Fred Joseph
• Application Number:
  US16/213,428
• Publication Number:
  US 20190330624A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6455 Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 2310/3233 Morpholino-type ring
• CPC Class Codes: C12N 2310/33 of the base
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 2310/3535 Nitrogen
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2320/33 Alteration of splicing
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

Claims

1-20. -20. (canceled)

21. A morpholino antisense oligonucleotide of 20 to 25 bases comprising at least 20 consecutive nucleotides 100% complementary to a dystrophin exon 44 target region designated as annealing site H44A(+77+101), or pharmaceutically acceptable salt thereof.

22. A morpholino antisense oligonucleotide of 20 to 25 bases comprising at least 20 consecutive nucleotides of SEQ ID NO:

9, or pharmaceutically acceptable salt thereof.

23. The antisense oligonucleotide or pharmaceutically acceptable salt thereof of claim 22, wherein the antisense oligonucleotide is chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide.

24. The antisense oligonucleotide or pharmaceutically acceptable salt thereof of claim 22, wherein the oligonucleotide is chemically linked to a polyethylene glycol moiety.

25. A pharmaceutical composition comprising an antisense oligonucleotide of 25 bases comprising SEQ ID NO:

9, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and a pharmaceutically acceptable carrier, or pharmaceutically acceptable salt thereof.

26. The pharmaceutical composition or pharmaceutically acceptable salt thereof of claim 25, wherein the antisense oligonucleotide is chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide.

27. The pharmaceutical composition or pharmaceutically acceptable salt thereof of claim 25, wherein the oligonucleotide is chemically linked to a polyethylene glycol moiety.