Compositions for treating muscular dystrophy

• US 10,364,431 B2
• Filed: 05/24/2017
• Issued: 07/30/2019
• 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:
  US15/604,335
• Publication Number:
  US 20180105811A1
• Time in Patent Office: 797 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 for treating Duchenne muscular dystrophy (DMD) in a patient in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient a composition comprising eteplirsen, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein eteplirsen, or a pharmaceutically acceptable salt thereof, is administered at a dose of about 30 mg/kg once a week for more than 120 weeks, such that disease progression in the patient is delayed, thereby treating the patient.

2. The method according to claim 1, wherein the patient is a pediatric patient.

3. The method of claim 2, wherein the patient is 7 years of age or older.

4. The method according to claim 1, wherein the patient is administered an oral corticosteroid for at least 24 weeks prior to the first dose of eteplirsen, or a pharmaceutically acceptable salt thereof.

5. The method according to claim 4, wherein the patient is a pediatric patient.

6. The method of claim 1, further comprising administering to the patient a corticosteroid.

7. The method of claim 6, wherein the corticosteroid is Betamethasone, Budesonide, Cortisone, Dexamethasone, Hydrocortisone, Methylprednisolone, Prednisolone, or Prednisone.

8. The method according to claim 6, wherein the patient is a pediatric patient.

9. The method of claim 6, wherein the corticosteroid is administered prior to, in conjunction with, or subsequent to administration of eteplirsen, or a pharmaceutically acceptable salt thereof.

10. The method of claim 1, wherein the composition further comprises a phosphate-buffered saline.

11. A method for restoring an mRNA reading frame to induce dystrophin production in a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 51 skipping, comprising intravenously administering to the patient a composition comprising eteplirsen, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein eteplirsen, or a pharmaceutically acceptable salt thereof, is administered at a dose of about 30 mg/kg once a week for more than 120 weeks, such that disease progression in the patient is delayed.

12. The method according to claim 11, wherein the patient is a pediatric patient.

13. The method of claim 12, wherein the patient is 7 years of age or older.

14. The method according to claim 11, wherein the patient is administered an oral corticosteroid for at least 24 weeks prior to the first dose of eteplirsen, or a pharmaceutically acceptable salt thereof.

15. The method according to claim 14, wherein the patient is a pediatric patient.

16. The method of claim 11, further comprising administering to the patient a corticosteroid.

17. The method of claim 16, wherein the corticosteroid is Betamethasone, Budesonide, Cortisone, Dexamethasone, Hydrocortisone, Methylprednisolone, Prednisolone, or Prednisone.

18. The method according to claim 16, wherein the patient is a pediatric patient.

19. The method of claim 18, wherein the patient is 7 years of age or older.

20. The method of claim 17, wherein the corticosteroid is administered prior to, in conjunction with, or subsequent to administration of eteplirsen, or a pharmaceutically acceptable salt thereof.

21. The method of claim 11, wherein the pharmaceutically acceptable carrier is a pH buffered solution.

22. The method of claim 21, wherein the pH buffered solution is a phosphate-buffered saline.