ANTISENSE NUCLEIC ACIDS

• US 20200102343A1
• Filed: 12/12/2019
• Published: 04/02/2020
• Est. Priority Date: 09/01/2010
• Status: Active Grant

• Current Assignee: National Center of Neurology and Psychiatry, Nippon Shinyaku Company Limited
• Original Assignee: Nippon Shinyaku Company Limited
• Inventors: WATANABE, Naoki, SATOU, Youhei, TAKEDA, Shin'ichi, NAGATA, Tetsuya
• Granted Patent: US 10,662,217 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/4708 Duchenne dystrophy
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• 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 2310/11 Antisense
• CPC Class Codes: C12N 2310/3145 with the nitrogen in 3' or 5'-position
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy
• CPC Class Codes: C12N 2320/33 Alteration of splicing

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.

Claims

1-14. -14. (canceled)

15. A method of treating a DMD patient comprising intravenously administering to said patient an oligomer comprising:

a) a phosphorodiamidate morpholino oligomer (PMO) that is 100% complementary to the 36th to the 60th nucleotides from the 5′

end of the 53rd exon in a human dystrophin pre-mRNA, wherein the 53rd exon in said human dystrophin pre-mRNA consists of a nucleotide sequence corresponding to SEQ ID NO;

1, wherein said PMO hybridizes to said human dystrophin pre-mRNA with Watson-Crick base pairing, wherein the phosphorodiamidate morpholino monomers of said PMO have the formula;

16. A method of treating a DMD patient comprising intravenously administering to said patient an oligomer comprising:

a) a phosphorodiamidate morpholino oligomer (PMO) that is 100% complementary to the target sequence 5′

-GAACACCUUCAGAACCGGAGGCAAC-3′

(SEQ ID NO;

     124) of a human dystrophin pre-mRNA, wherein said PMO hybridizes to said human dystrophin pre-mRNA with Watson-Crick base pairing, wherein 25 of the phosphorodiamidate morpholino monomers of said PMO have the formula;

17. A method of treating a DMD patient comprising intravenously administering to said patient a phosphorodiamidate morpholino oligomer (PMO) that causes skipping of the 53rd exon in a human dystrophin pre-mRNA, consisting of a 25-mer oligomer that is 100% complementary to the 36th to the 60th nucleotides from the 5′

end of the 53rd exon in said human dystrophin pre-mRNA, wherein the 53rd exon in said human dystrophin pre-mRNA consists of a nucleotide sequence corresponding to SEQ ID NO;

1, wherein said morpholino oligomer hybridizes to said pre-mRNA with Watson-Crick base pairing, wherein each morpholino monomer has the formula;

18. A method of treating a DMD patient comprising intravenously administering to said patient a phosphorodiamidate morpholino oligomer (PMO) that causes skipping of the 53rd exon in a human dystrophin pre-mRNA, consisting of a 25-mer oligomer that is 100% complementary to the target pre-mRNA sequence 5′

-GAACACCUUCAGAACCGGAGGCAAC-3′

(add SEQ ID NO;

124), wherein said morpholino oligomer hybridizes to said pre-mRNA with Watson-Crick base pairing, wherein each morpholino monomer has the formula;