Compositions for treating muscular dystrophy

• US 10,337,003 B2
• Filed: 11/22/2016
• Issued: 07/02/2019
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Sarepta Therapeutics, Inc.
• Original Assignee: Sarepta Therapeutics, Inc.
• Inventors: Kaye, Edward M.
• Primary Examiner(s): Poliakova-Georgantas, Ekaterina
• Application Number:
  US15/359,152
• Publication Number:
  US 20170283799A1
• Time in Patent Office: 952 Days
• Field of Search: None
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• 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 2310/33 of the base
• CPC Class Codes: C12N 2320/30 Special therapeutic applications

Abstract

Improved compositions and methods for treating muscular dystrophy by administering antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping are described.

Claims

1. A method of treating Duchenne muscular dystrophy (DMD) in a human subject who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising administering to the human subject a composition comprising eteplirsen and a phosphate-buffered saline at a dose of eteplirsen of about 30 mg/kg to about 50 mg/kg for a period of time sufficient to increase the number of dystrophin-positive fibers in a subject to at least 20% of normal.

2. The method of claim 1, wherein eteplirsen is administered for a period of time sufficient to increase the number of dystrophin positive fibers to about 50% of normal.

3. The method of claim 1, wherein the dose of eteplirsen is about 30 mg/kg.

4. The method of claim 1, wherein the composition is administered by systemic administration.

5. The method of claim 1, wherein the composition is administered once weekly by infusion.

6. The method of claim 1, further comprising administering a steroid to the human subject.

7. The method of claim 6, wherein the human subject is administered a stable dose of the steroid for at least 24 weeks prior to the first dose of eteplirsen.

8. The method of claim 7, wherein the steroid is a glucocorticoid.

9. The method of claim 1, wherein the human subject is 7 to 13 years of age.

10. The method of claim 9, wherein the human subject is a boy.

11. The method of claim 7, wherein the human subject is 7 to 13 years of age.

12. The method of claim 11, wherein the human subject is a boy.