Claims for Patent: 10,870,676

Summary for Patent: 10,870,676

Title:	Antisense nucleic acids
Abstract:	The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene. Also provided is a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.
Inventor(s):	Watanabe; Naoki (Tsukuba, JP), Satou; Youhei (Tsukuba, JP), Takeda; Shin'ichi (Kodaira, JP), Nagata; Tetsuya (Kodaira, JP)
Assignee:	NIPPON SHINYAKU CO., LTD. (Kyoto, JP) NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY (Kodaira, JP)
Application Number:	16/408,529
Patent Claims:	1. A method of treating Duchenne muscular dystrophy (DMD) in a patient in need thereof comprising administering an antisense oligomer, or a pharmaceutically acceptable salt or hydrate thereof, wherein the antisense oligomer consists of a nucleotide sequence complementary to the sequence consisting of the 36th to the 56th nucleotides from the 5' end of the 53rd exon in a human dystrophin pre-mRNA, and wherein the 53rd exon in the human dystrophin pre-mRNA consists of a nucleotide sequence corresponding to SEQ ID NO: 1. 2. A method of treating Duchenne muscular dystrophy (DMD) in a patient in need thereof comprising administering a pharmaceutical composition comprising as an active ingredient an antisense oligomer, or a pharmaceutically acceptable salt or hydrate thereof, wherein the antisense oligomer consists of a nucleotide sequence complementary to the sequence consisting of the 36th to the 56th nucleotides from the 5' end of the 53rd exon in a human dystrophin pre-mRNA, and wherein the 53rd exon in the human dystrophin pre-mRNA consists of a nucleotide sequence corresponding to SEQ ID NO: 1. 3. The method according to claim 1, wherein the antisense oligomer is an oligonucleotide. 4. The method according to claim 3, wherein the oligonucleotide comprises at least one nucleotide having a modified sugar moiety or having a modified phosphate-binding region. 5. The method according to claim 4, wherein the modified sugar moiety is a ribose in which the 2'-OH group is replaced by any one selected from the group consisting of: OR, R, R'OR, SH, SR, NH.sub.2, NHR, NR.sub.2, N.sub.3, CN, F, Cl, Br, and I (wherein R is an alkyl or an aryl and R' is an alkylene). 6. The method according to claim 4, wherein the modified phosphate-binding region is any one selected from the group consisting of: a phosphorothioate bond, a phosphorodithioate bond, an alkylphosphonate bond, a phosphoramidate bond, and a boranophosphate bond. 7. The method according to claim 1, wherein the antisense oligomer is a morpholino oligomer. 8. The method according to claim 7, wherein the antisense oligomer is a phosphorodiamidate morpholino oligomer. 9. The method according to claim 8, wherein the 5' end of the antisense oligomer is any one of the groups of chemical formulae (1) to (3) below: ##STR00024## 10. The method according to claim 1, wherein the antisense oligomer, or the pharmaceutically acceptable salt or hydrate thereof, is administered intravenously. 11. The method according to claim 2, wherein the antisense oligomer is an oligonucleotide. 12. The method according to claim 11, wherein the oligonucleotide comprises at least one nucleotide having a modified sugar moiety or having a modified phosphate-binding region. 13. The method according to claim 12, wherein the modified sugar moiety is a ribose in which the 2'-OH group is replaced by any one selected from the group consisting of: OR, R, R'OR, SH, SR, NH.sub.2, NHR, NR.sub.2, N.sub.3, CN, F, Cl, Br, and I (wherein R is an alkyl or an aryl and R' is an alkylene). 14. The method according to claim 12, wherein the modified phosphate-binding region is any one selected from the group consisting of: a phosphorothioate bond, a phosphorodithioate bond, an alkylphosphonate bond, a phosphoramidate bond, and a boranophosphate bond. 15. The method according to claim 2, wherein the antisense oligomer is a morpholino oligomer. 16. The method according to claim 15, wherein the antisense oligomer is a phosphorodiamidate morpholino oligomer. 17. The method according to claim 16, wherein the 5' end of the antisense oligomer is any one of the groups of chemical formulae (1) to (3) below: ##STR00025## 18. The method according to claim 2, wherein the pharmaceutical composition is administered intravenously.