Claims for Patent: 10,968,450

Summary for Patent: 10,968,450

Title:	Antisense oligonucleotides for inducing exon skipping and methods of use thereof
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 214.
Inventor(s):	Wilton; Stephen Donald (Applecross, AU), Fletcher; Sue (Bayswater, AU), McClorey; Graham (Bayswater, AU)
Assignee:	The University of Western Australia (Crawley, AU)
Application Number:	16/527,886
Patent Claims:	1. An antisense oligonucleotide comprising a base sequence 25 bases in length that is 100% complementary to 25 consecutive nucleotide bases of a target region of exon 53 of the human dystrophin pre-mRNA, wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the target region and induces exon 53 skipping, or a pharmaceutically acceptable salt thereof. 2. The antisense oligonucleotide of claim 1, wherein the antisense 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. The antisense oligonucleotide of claim 1, wherein the antisense oligonucleotide is in a free base form. 4. An injectable solution, comprising: an antisense oligonucleotide comprising a base sequence 25 bases in length that is 100% complementary to 25 consecutive nucleotide bases of a target region of exon 53 of the human dystrophin pre-mRNA, wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the target region and induces exon 53 skipping, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein the injectable solution is formulated for intravenous administration. 5. The injectable solution of claim 4, wherein the antisense 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. 6. The injectable solution of claim 4, wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution. 7. The injectable solution of claim 6, wherein the isotonic saline solution is phosphate-buffered saline. 8. The injectable solution of claim 4, wherein the antisense oligonucleotide is in a free base form. 9. An injectable solution, comprising an antisense oligonucleotide comprising a base sequence 25 bases in length that is 100% complementary to 25 consecutive nucleotide bases of a target region of exon 53 of the human dystrophin pre-mRNA, wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the target region and induces exon 53 skipping, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein the injectable solution is formulated for parenteral administration. 10. The injectable solution of claim 9, wherein the antisense 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. 11. The injectable solution of claim 9, wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution. 12. The injectable solution of claim 11, wherein the isotonic saline solution is phosphate-buffered saline. 13. The injectable solution of claim 9, wherein the antisense oligonucleotide is in a free base form. 14. The injectable solution of claim 9, wherein the injectable solution is formulated for intramuscular administration. 15. An injectable solution, comprising an antisense oligonucleotide comprising a base sequence 25 bases in length that is 100% complementary to 25 consecutive nucleotide bases of a target region of exon 53 of the human dystrophin pre-mRNA, wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the target region and induces exon 53 skipping, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein the injectable solution is formulated for subcutaneous administration. 16. The injectable solution of claim 15, wherein the antisense 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. 17. The injectable solution of claim 15, wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution. 18. The injectable solution of claim 17, wherein the isotonic saline solution is phosphate-buffered saline. 19. The injectable solution of claim 15, wherein the antisense oligonucleotide is in a free base form.