Exon skipping oligomers for muscular dystrophy

Patent metadata

Field	Value
Publication number	US-2022251551-A1
Application number	US-201916973464-A
Country	US
Kind code	A1
Filing date	Jun 12, 2019
Priority date	Jun 13, 2018
Publication date	Aug 11, 2022
Grant date	—

Abstract

Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.

First claim

1 - 16 . (canceled)

17 . An antisense oligomer according to Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
each Nu is a nucleobase which taken together form a targeting sequence;
T′ is a moiety selected from:

R 100 and R 200 are each hydrogen and R 1 is C 1 -C 6 alkyl;
each Nu from 1 to (n+1) and 5′ to 3′ corresponds to the nucleobases in the following:

Annealing Site
Base Sequence [5′ to 3′]
SEQ ID NO.

H51A(+61+90) 
ACA TCA AGG AAG ATG GCA TTT CTA GTT TGG 
SEQ ID NO. 1 

H51D(+16−07) 
CTC ATA CCT TCT GCT TGA TGA TC 
SEQ ID NO. 2 

H50D(+103+127) 
GGG ATC CAG TAT ACT TAC AGG CTC C 
SEQ ID NO. 3 

H51A(+61+82) 
GAA GAT GGC ATT TCT AGT TTG G 
SEQ ID NO. 15 

H51A(+61+83) 
GGA AGA TGG CAT TTC TAG TTT GG 
SEQ ID NO. 16 

H51A(+61+89) 
CAT CAA GGA AGA TGG CAT TTC TAG TTT GG 
SEQ ID NO. 17 

H51A(+66+89) 
CAT CAA GGA AGA TGG CAT TTC TAG 
SEQ ID NO. 18 

H51A(+66+93) 
CCA ACA TCA AGG AAG ATG GCA TTT CTA G 
SEQ ID NO. 19 

H51A(+69+92) 
CAA CAT CAA GGA AGA TGG CAT TTC 
SEQ ID NO. 20 

H51A(+69+96) 
CCT CCA ACA TCA AGG AAG ATG GCA TTT C 
SEQ ID NO. 21 

H51A(+74+96) 
CCT CCA ACA TCA AGG AAG ATG GC 
SEQ ID NO. 22 

H51A(+74+99) 
GTA CCT CCA ACA TCA AGG AAG ATG GC 
SEQ ID NO. 23 

H51A(+74+100) 
GGT ACC TCC AAC ATC AAG GAA GAT GGC 
SEQ ID NO. 24 

H51A(+74+102) 
CAG GTA CCT CCA ACA TCA AGG AAG ATG GC 
SEQ ID NO. 25 

H51A(+74+103) 
GCA GGT ACC TCC AAC ATC AAG GAA GAT GGC 
SEQ ID NO. 26 

H51A(+75+96) 
CCT CCA ACA TCA AGG AAG ATG G 
SEQ ID NO. 27 

H51A(+75+99) 
GTA CCT CCA ACA TCA AGG AAG ATG G 
SEQ ID NO. 28 

H51A(+76+99) 
GTA CCT CCA ACA TCA AGG AAG ATG 
SEQ ID NO. 29 

H51A(+76+105) 
GAG CAG GTA CCT CCA ACA TCA AGG AAG ATG 
SEQ ID NO. 30 

H51A(+80+103) 
GCA GGT ACC TCC AAC ATC AAG GAA G 
SEQ ID NO. 31 

H51A(+80+105) 
GAG CAG GTA CCT CCA ACA TCA AGG AAG 
SEQ ID NO. 32 

H51A(+80+107) 
CAG AGC AGG TAC CTC CAA CAT CAA GGA AG 
SEQ ID NO. 33 

H51A(+80+108) 
CCA GAG CAG GTA CCT CCA ACA TCA AGG AAG 
SEQ ID NO. 34 

H51A(+83+103) 
GCA GGT ACC TCC AAC ATC AAG G 
SEQ ID NO. 35 

H51A(+83+105) 
GAG CAG GTA CCT CCA ACA TCA AGG 
SEQ ID NO. 36 

H51A(+83+107) 
CAG AGC AGG TAC CTC CAA CAT CAA GG 
SEQ ID NO. 37 

H51A(+83+109) 
GCC AGA GCA GGT ACC TCC AAC ATC AAG G 
SEQ ID NO. 38 

H51A(+84+107) 
CAG AGC AGG TAC CTC CAA CAT CAA G 
SEQ ID NO. 39 

H51A(+84+111) 
CTG CCA GAG CAG GTA CCT CCA ACA TCA AG
SEQ ID NO. 40 

H51A(+84+105) 
GAG CAG GTA CCT CCA ACA TCA AG 
SEQ ID NO. 41 

H51A(+87+109) 
GCC AGA GCA GGT ACC TCC AAC ATC 
SEQ ID NO. 42 

H51A(+93+116) 
GAA ATC TGC CAG AGC AGG TAC CTC 
SEQ ID NO. 43 

H51A(+75+100) 
GGT ACC TCC AAC ATC AAG GAA GAT GG 
SEQ ID NO. 44 

H51A(+74+101) 
AGG TAC CTC CAA CAT CAA GGA AGA TGG C
SEQ ID NO. 45 

H51A(+74+98) 
TAC CTC CAA CAT CAA GGA AGA TGG C 
SEQ ID NO. 46 

H51A(+74+97) 
ACC TCC AAC ATC AAG GAA GAT GGC 
SEQ ID NO. 47 

H51A(+74+94) 
TCC AAC ATC AAG GAA GAT GGC 
SEQ ID NO. 48 

H51A(+74+93) 
CCA ACA TCA AGG AAG ATG GC 
SEQ ID NO. 49 

H51A(+74+92) 
CAA CAT CAA GGA AGA TGG C 
SEQ ID

Assignees

• Sarepta Therapeutics Inc

Inventors

• Schnell Frederick Joseph
• Passini Marco
• Estrella Nelsa
• Hanson Gunnar
• Zhou Ming
• Bestwick Richard

Classifications

• C12N15/113 Primary

  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 title

• C12N2310/3513

  Protein; Peptide · CPC title

• C12N2310/3233

  Morpholino-type ring · CPC title

• C12N2320/33

  Alteration of splicing · CPC title

• C12N2310/11

  Antisense · CPC title