Exon skipping oligomer conjugates for muscular dystrophy
Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.
1. A method for treating Duchenne muscular dystrophy (DMD) in a primate subject in need thereof, wherein the primate subject has a mutation of the dystrophin gene that is amenable to exon 51 skipping, the method comprising administering to the primate subject an antisense oligomer conjugate of Formula (IV):
(peptide is SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof.
2. A method of restoring an mRNA reading frame to induce dystrophin production in a primate subject having a mutation of the dystrophin gene that is amenable to exon 51 skipping, the method comprising administering to the primate subject an antisense oligomer conjugate of Formula (IV):
(peptide is SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof.
3. A method for treating Duchenne muscular dystrophy (DMD) in a primate subject in need thereof, wherein the primate subject has a mutation of the dystrophin gene that is amenable to exon 51 skipping, the method comprising administering to the primate subject a pharmaceutical composition comprising an antisense oligomer conjugate of Formula (IV):
(peptide is SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
4. A method of restoring an mRNA reading frame to induce dystrophin production in a primate subject having a mutation of the dystrophin gene that is amenable to exon 51 skipping, the method comprising administering to the primate subject a pharmaceutical composition comprising an antisense oligomer conjugate of Formula (IV):
(peptide is SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
5. A method of excluding exon 51 from dystrophin pre-mRNA during mRNA processing in a primate subject having a mutation of the dystrophin gene that is amenable to exon 51 skipping, the method comprising administering to the primate subject a pharmaceutical composition comprising antisense oligomer conjugate of Formula (IV):
(peptide is SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
6. A method of binding exon 51 of a dystrophin pre-mRNA in a primate subject having a mutation of the dystrophin gene that is amenable to exon 51 skipping, the method comprising administering to the primate subject a pharmaceutical composition comprising an antisense oligomer conjugate of Formula (IV):
(peptide is SEQ ID NO: 4), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
7. The method of claim 1 , wherein the subject is human.
8. The method of claim 2 , wherein the subject is human.
9. The method of claim 3 , wherein the subject is human.
10. The method of claim 6 , wherein the subject is human.
11. The method of claim 1 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt.
12. The method of claim 11 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt of Formula (IVA):
13. The method of claim 2 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt.
14. The method of claim 13 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt of Formula (IVA):
15. The method of claim 3 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt.
16. The method of claim 15 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt of Formula (IVA):
17. The method of claim 4 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt.
18. The method of claim 17 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt of Formula (IVA):
19. The method of claim 5 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt.
20. The method of claim 19 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt of Formula (IVA):
21. The method of claim 6 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt.
22. The method of claim 21 , wherein the antisense oligomer conjugate is in the form of a pharmaceutically acceptable salt of Formula (IVA):