Antisense oligonucleotides for inducing exon skipping and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10781451-B2
Application number	US-201916458929-A
Country	US
Kind code	B2
Filing date	Jul 1, 2019
Priority date	Jun 28, 2004
Publication date	Sep 22, 2020
Grant date	Sep 22, 2020

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 202.

First claim

We claim:

1. An antisense oligonucleotide of 30 bases comprising the base sequence CUCCAACAUC AAGGAAGAUG GCAUUUCUAG (SEQ ID NO: 181), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide.

2. The antisense oligonucleotide of claim 1 , wherein the oligonucleotide is chemically linked to a cholesterol moiety, cholic acid, a thioether, a thiocholesterol, an aliphatic chain, a phospholipid, a polyamine chain, a polyethylene glycol chain, adamantane acetic acid, a palmityl moiety, an octadecylamine moiety, or a hexylamino-carbonyl-oxycholesterol moiety.

3. An injectable solution, comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable carrier or diluent, wherein the injectable solution is formulated for intravenous administration.

4. The injectable solution of claim 3 , wherein the oligonucleotide is chemically linked to a cholesterol moiety, cholic acid, a thioether, a thiocholesterol, an aliphatic chain, a phospholipid, a polyamine chain, a polyethylene glycol chain, adamantane acetic acid, a palmityl moiety, an octadecylamine moiety, or a hexylamino-carbonyl-oxycholesterol moiety.

5. The injectable solution of claim 3 , wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution.

6. The injectable solution of claim 5 , wherein the isotonic saline solution is phosphate-buffered saline.

7. An injectable solution, comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable carrier or diluent, wherein the injectable solution is formulated for parenteral administration.

8. The injectable solution of claim 7 , wherein the oligonucleotide is chemically linked to a cholesterol moiety, cholic acid, a thioether, a thiocholesterol, an aliphatic chain, a phospholipid, a polyamine chain, a polyethylene glycol chain, adamantane acetic acid, a palmityl moiety, an octadecylamine moiety, or a hexylamino-carbonyl-oxycholesterol moiety.

9. The injectable solution of claim 7 , wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution.

10. The injectable solution of claim 9 , wherein the isotonic saline solution is phosphate-buffered saline.

11. An injectable solution, comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable carrier or diluent, wherein the injectable solution is formulated for intramuscular administration.

12. The injectable solution of claim 11 , wherein the oligonucleotide is chemically linked to a cholesterol moiety, cholic acid, a thioether, a thiocholesterol, an aliphatic chain, a phospholipid, a polyamine chain, a polyethylene glycol chain, adamantane acetic acid, a palmityl moiety, an octadecylamine moiety, or a hexylamino-carbonyl-oxycholesterol moiety.

13. The injectable solution of claim 11 , wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution.

14. The injectable solution of claim 13 , wherein the isotonic saline solution is phosphate-buffered saline.

Assignees

• Univ Western Australia

Inventors

• Wilton Stephen Donald
• Fletcher Sue
• Mcclorey Graham

Classifications

• C12N2310/3519

  Fusion with another nucleic acid · CPC title

• C12N2320/33

  Alteration of splicing · CPC title

• C12N2310/315

  Phosphorothioates · CPC title

• C12N2310/11

  Antisense · CPC title

• C12N2310/3233

  Morpholino-type ring · CPC title