IP Library › Patent Application 16973464
Patent Application
App. No. 16/973,464

EXON SKIPPING OLIGOMERS FOR MUSCULAR DYSTROPHY

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Patent No.
US None
App. No.
16/973,464
Abstract

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

Claims (716)

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 NO. 50 

H51A(+69+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA TTT C

SEQ ID NO. 51 

H51A(+70+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA TTT 

SEQ ID NO. 52 

H51A(+71+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA TT 

SEQ ID NO. 53 

H51A(+72+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA T 

SEQ ID NO. 54 

H51A(+73+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA 

SEQ ID NO. 55 

H51A(+77+99) 

GTA CCT CCA ACA TCA AGG AAG AT 

SEQ ID NO. 56 

H51A(+78+99) 

GTA CCT CCA ACA TCA AGG AAG A 

SEQ ID NO. 57 

H51A(+79+99) 

GTA CCT CCA ACA TCA AGG AAG 

SEQ ID NO. 58 

H51.SA.(−60−36) 

GAA GAA AAA GAA AAA TTA GAA ACA C 

SEQ ID NO. 59 

H51.SA.(−50−26) 

AAG GAA AAA AGA AGA AAA AGA AAA A 

SEQ ID NO. 60 

H51.SA.(−45−21) 

GCA AAA AGG AAA AAA GAA GAA AAA G 

SEQ ID NO. 61 

H51.SA.(−40−16) 

TTT TTG CAA AAA GGA AAA AAG AAG A 

SEQ ID NO. 62 

H51.SA.(−35−11) 

TTG GGT TTT TGC AAA AAG GAA AAA A 

SEQ ID NO. 63 

H51.SA.(−30−6) 

ATA TTT TGG GTT TTT GCA AAA AGG A 

SEQ ID NO. 64 

H51.SA.(−25−1) 

CTA AAA TAT TTT GGG TTT TTG CAA A 

SEQ ID NO. 65 

H51.SA.(−20+5) 

AGG AGC TAA AAT ATT TTG GGT TTT T 

SEQ ID NO. 66 

H51.SA.(−15+10) 

TGA GTA GGA GCT AAA ATA TTT TGG G 

SEQ ID NO. 67 

H51.SA.(−10+15) 

CAG TCT GAG TAG GAG CTA AAA TAT T 

SEQ ID NO. 68 

H51.SA.(−5+20) 

AGT AAC AGT CTG AGT AGG AGC TAA A 

SEQ ID NO. 69 

H51.SA.(−1+24) 

CCA GAG TAA CAG TCT GAG TAG GAG C 

SEQ ID NO. 70 

H51.SA.(−65−41) 

AAA AGA AAA ATT AGA AAC ACA AGC T 

SEQ ID NO. 71 

H51.SA.(−70−46) 

AAA AAT TAG AAA CAC AAG CTA AAG A 

SEQ ID NO. 72 

H51.SA.(−75−51) 

TTA GAA ACA CAA GCT AAA GAG CCA A 

SEQ ID NO. 73 

H51.SA.(−80−56) 

AAC ACA AGC TAA AGA GCC AAT TTC A 

SEQ ID NO. 74 

H51.SA.(−85−61) 

AAG CTA AAG AGC CAA TTT CAA TAA C 

SEQ ID NO. 75 

H51.SA.(−90−66) 

AAA GAG CCA ATT TCA ATA ACA ATA A 

SEQ ID NO. 76 

H51.SA.(−95−71) 

GCC AAT TTC AAT AAC AAT AAG TCA A 

SEQ ID NO. 77 

H51.SA.(−100−76)

TTT CAA TAA CAA TAA GTC AAA TTT A 

SEQ ID NO. 78 

H51A(+1+30) 

GTG TCA CCA GAG TAA CAG TCT GAG TAG GAG

SEQ ID NO. 79 

H51A(+10+39) 

CCA CAG GTT GTG TCA CCA GAG TAA CAG TCT

SEQ ID NO. 80 

H51A(+6+35) 

AG GTT GTG TCA CCA GA GTA ACA GTC TGA GT

SEQ ID NO. 81 

H51A(+49+78) 

ATG GCA TTT CTA GTT TGG AGA TGG CAG TTT

SEQ ID NO. 82 

H51A(+1+25) 

ACC AGA GTA ACA GTC TGA GTA GGA G 

SEQ ID NO. 83 

H51A(+4+28) 

GTC ACC AGA GTA ACA GTC TGA GTA G 

SEQ ID NO. 84 

H51A(+16+40) 

ACC ACA GGT TGT GTC ACC AGA GTA A 

SEQ ID NO. 85 

H51A(+21+45) 

TAG TAA CCA CAG GTT GTG TCA CCA G 

SEQ ID NO. 86 

H51A(+26+50) 

TTC CTT AGT AAC CAC AGG TTG TGT C 

SEQ ID NO. 87 

H51A(+31+55) 

GCA GTT TCC TTA GTA ACC ACA GGT T 

SEQ ID NO. 88 

H51A(+36+60) 

AGA TGG CAG TTT CCT TAG TAA CCA C 

SEQ ID NO. 89 

H51A(+41+65) 

TTT GGA GAT GGC AGT TTC CTT AGT A 

SEQ ID NO. 90 

H51A(+86+110) 

TGC CAG AGC AGG TAC CTC CAA CAT C 

SEQ ID NO. 91 

H51A(+91+115) 

AAA TCT GCC AGA GCA GGT ACC TCC A 

SEQ ID NO. 92 

H51A(+96+120) 

GGT TGA AAT CTG CCA GAG CAG GTA C 

SEQ ID NO. 93 

H51A(+101+125) 

AGC CCG GTT GAA ATC TGC CAG AGC A 

SEQ ID NO. 94 

H51A(+106+130) 

GTC CAA GCC CGG TTG AAA TCT GCC A 

SEQ ID NO. 95 

H51A(+111+135) 

GTT CTG TCC AAG CCC GGT TGA AAT C 

SEQ ID NO. 96 

H51A(+116+140) 

GGT AAG TTC TGT CCA AGC CCG GTT G 

SEQ ID NO. 97 

H51A(+121+145) 

CAG TCG GTA AGT TCT GTC CAA GCC C 

SEQ ID NO. 98 

H51A(+126+150) 

AAA GCC AGT CGG TAA GTT CTG TCC A 

SEQ ID NO. 99 

H51A(+131+155) 

CAG AGA AAG CCA GTC GGT AAG TTC T 

SEQ ID NO. 100 

H51A(+136+160) 

TCA AGC AGA GAA AGC CAG TCG GTA A 

SEQ ID NO. 101 

H51A(+141+165) 

CTT GAT CAA GCA GAG AAA GCC AGT C 

SEQ ID NO. 102 

H51A(+146+170) 

TAT AAC TTG ATC AAG CAG AGA AAG C 

SEQ ID NO. 103 

H51A(+151+175) 

GAT TTT ATA ACT TGA TCA AGC AGA G 

SEQ ID NO. 104 

H51A(+156+180) 

TCT GTG ATT TTA TAA CTT GAT CAA G 

SEQ ID NO. 105 

H51A(+161+185) 

CAC CCT CTG TGA TTT TAT AAC TTG A 

SEQ ID NO. 106 

H51A(+166+190) 

ACC ATC ACC CTC TGT GAT TTT ATA A 

SEQ ID NO. 107 

H51A(+171+195) 

CAC CCA CCA TCA CCC TCT GTG ATT T 

SEQ ID NO. 108 

H51A(+176+200) 

AAG GTC ACC CAC CAT CAC CCT CTG T 

SEQ ID NO. 109 

H51A(+181+205) 

TCC TCA AGG TCA CCC ACC ATC ACC C 

SEQ ID NO. 110 

H51A(+186+210) 

TGA TAT CCT CAA GGT CAC CCA CCA T 

SEQ ID NO. 111 

H51A(+191+215) 

CTC GTT GAT ATC CTC AAG GTC ACC C 

SEQ ID NO. 112 

H51A(+196+220) 

ATC ATC TCG TTG ATA TCC TCA AGG T 

SEQ ID NO. 113 

H51A(+201+225) 

TGA TGA TCA TCT CGT TGA TAT CCT C 

SEQ ID NO. 114 

H51A(+206+230) 

CTG CTT GAT GAT CAT CTC GTT GAT A 

SEQ ID NO. 115 

H51D(+211−02) 

ACC TTC TGC TTG ATG ATC ATC TCG T 

SEQ ID NO. 116 

H51D(+214−05) 

CAT ACC TTC TGC TTG ATG ATC ATC T 

SEQ ID NO. 117 

H51D(+217−08) 

TCT CAT ACC TTC TGC TTG ATG ATC A 

SEQ ID NO. 118 

H51D(+220−11) 

TTT TCT CAT ACC TTC TGC TTG ATG A 

SEQ ID NO. 119 

H51D(+223−14) 

ATT TTT TCT CAT ACC TTC TGC TTG A 

SEQ ID NO. 120 

H51D(+226−17) 

ATC ATT TTT TCT CAT ACC TTC TGC T 

SEQ ID NO. 121 

H51D(+229−20) 

TTT ATC ATT TTT TCT CAT ACC TTC T 

SEQ ID NO. 122 

H51D(+232−23) 

ACT TTT ATC ATT TTT TCT CAT ACC T 

SEQ ID NO. 123 

H51D(−02−26) 

CCA ACT TTT ATC ATT TTT TCT CAT A 

SEQ ID NO. 124 

H51A(+1+30) 

GTG TCA CCA GAG TAA CAG TCT GAG TAG GAG

SEQ ID NO. 125 

wherein A is

C is

G is

and T is

18 . The antisense oligomer, or a pharmaceutically acceptable salt thereof, of claim 17 , each Nu from 1 to (n+1) and 5′ to 3′ of Formula (I) corresponds to the following sequences: SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, SEQ ID NO. 26, SEQ ID NO. 34, SEQ ID NO. 45, SEQ ID NO. 47, SEQ ID NO. 51, SEQ ID NO. 52, SEQ ID NO. 53, SEQ ID NO. 54, SEQ ID NO. 55, SEQ ID NO. 59, SEQ ID NO. 60, SEQ ID NO. 61, SEQ ID NO. 62, SEQ ID NO. 63, SEQ ID NO. 64, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, and SEQ ID NO. 73.

19 . The antisense oligomer, or a pharmaceutically acceptable salt thereof, of claim 18 , wherein each Nu from 1 to (n+1) and 5′ to 3′ of Formula (I) corresponds to the nucleobases in one of the following sequences: SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, SEQ ID NO. 26, SEQ ID NO 45, SEQ ID NO. 47, SEQ ID NO. 51, SEQ ID NO. 52, SEQ ID NO. 54, SEQ ID NO. 55, SEQ ID NO. 61, and SEQ ID NO. 63.

20 . The antisense oligomer, or a pharmaceutically acceptable salt thereof, of claim 19 , wherein each Nu from 1 to (n+1) and 5′ to 3′ of Formula (I) corresponds to the nucleobases in one of the following sequences: SEQ ID NO. 47, SEQ ID NO. 52, and SEQ ID NO. 54.

21 .- 43 . (canceled)

44 . The antisense oligomer of claim 17 , wherein the antisense oligomer is according to Formula (II):

or a pharmaceutically acceptable salt thereof, where R 200 is hydrogen;

each Nu from 1 to (n+1) and 5′ to 3′ corresponds to the nucleobases in the following sequences:

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 NO. 50 

H51A(+69+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA TTT C

SEQ ID NO. 51 

H51A(+70+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA TTT

SEQ ID NO. 52 

H51A(+71+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA TT 

SEQ ID NO. 53 

H51A(+72+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA T 

SEQ ID NO. 54 

H51A(+73+99) 

GTA CCT CCA ACA TCA AGG AAG ATG GCA 

SEQ ID NO. 55 

H51A(+77+99) 

GTA CCT CCA ACA TCA AGG AAG AT 

SEQ ID NO. 56 

H51A(+78+99) 

GTA CCT CCA ACA TCA AGG AAG A 

SEQ ID NO. 57 

H51A(+79+99) 

GTA CCT CCA ACA TCA AGG AAG 

SEQ ID NO. 58 

H51.SA.(−60−36) 

GAA GAA AAA GAA AAA TTA GAA ACA C 

SEQ ID NO. 59 

H51.SA.(−50−26) 

AAG GAA AAA AGA AGA AAA AGA AAA A 

SEQ ID NO. 60 

H51.SA.(−45−21) 

GCA AAA AGG AAA AAA GAA GAA AAA G 

SEQ ID NO. 61 

H51.SA.(−40−16) 

TTT TTG CAA AAA GGA AAA AAG AAG A 

SEQ ID NO. 62 

H51.SA.(−35−11) 

TTG GGT TTT TGC AAA AAG GAA AAA A 

SEQ ID NO. 63 

H51.SA.(−30−6) 

ATA TTT TGG GTT TTT GCA AAA AGG A 

SEQ ID NO. 64 

H51.SA.(−25−1) 

CTA AAA TAT TTT GGG TTT TTG CAA A 

SEQ ID NO. 65 

H51.SA.(−20+5) 

AGG AGC TAA AAT ATT TTG GGT TTT T 

SEQ ID NO. 66 

H51.SA.(−15+10)

TGA GTA GGA GCT AAA ATA TTT TGG G 

SEQ ID NO. 67 

H51.SA.(−10+15) 

CAG TCT GAG TAG GAG CTA AAA TAT T 

SEQ ID NO. 68 

H51.SA.(−5+20) 

AGT AAC AGT CTG AGT AGG AGC TAA A 

SEQ ID NO. 69 

H51.SA.(−1+24) 

CCA GAG TAA CAG TCT GAG TAG GAG C 

SEQ ID NO. 70 

H51.SA.(−65−41) 

AAA AGA AAA ATT AGA AAC ACA AGC T 

SEQ ID NO. 71 

H51.SA.(−70−46) 

AAA AAT TAG AAA CAC AAG CTA AAG A 

SEQ ID NO. 72 

H51.SA.(−75−51) 

TTA GAA ACA CAA GCT AAA GAG CCA A 

SEQ ID NO. 73 

H51.SA.(−80−56) 

AAC ACA AGC TAA AGA GCC AAT TTC A 

SEQ ID NO. 74 

H51.SA.(−85−61) 

AAG CTA AAG AGC CAA TTT CAA TAA C 

SEQ ID NO. 75 

H51.SA.(−90−66) 

AAA GAG CCA ATT TCA ATA ACA ATA A 

SEQ ID NO. 76 

H51.SA.(−95−71) 

GCC AAT TTC AAT AAC AAT AAG TCA A 

SEQ ID NO. 77 

H51.SA.(−100−76)

TTT CAA TAA CAA TAA GTC AAA TTT A 

SEQ ID NO. 78 

H51A(+1+30) 

GTG TCA CCA GAG TAA CAG TCT GAG TAG GAG

SEQ ID NO. 79 

H51A(+10+39) 

CCA CAG GTT GTG TCA CCA GAG TAA CAG TCT

SEQ ID NO. 80 

H51A(+6+35) 

AG GTT GTG TCA CCA GA GTA ACA GTC TGA GT

SEQ ID NO. 81 

H51A(+49+78) 

ATG GCA TTT CTA GTT TGG AGA TGG CAG TTT

SEQ ID NO. 82 

H51A(+1+25) 

ACC AGA GTA ACA GTC TGA GTA GGA G 

SEQ ID NO. 83 

H51A(+4+28) 

GTC ACC AGA GTA ACA GTC TGA GTA G 

SEQ ID NO. 84 

H51A(+16+40) 

ACC ACA GGT TGT GTC ACC AGA GTA A 

SEQ ID NO. 85 

H51A(+21+45) 

TAG TAA CCA CAG GTT GTG TCA CCA G 

SEQ ID NO. 86 

H51A(+26+50) 

TTC CTT AGT AAC CAC AGG TTG TGT C 

SEQ ID NO. 87 

H51A(+31+55) 

GCA GTT TCC TTA GTA ACC ACA GGT T 

SEQ ID NO. 88 

H51A(+36+60) 

AGA TGG CAG TTT CCT TAG TAA CCA C 

SEQ ID NO. 89 

H51A(+41+65) 

TTT GGA GAT GGC AGT TTC CTT AGT A 

SEQ ID NO. 90 

H51A(+86+110) 

TGC CAG AGC AGG TAC CTC CAA CAT C 

SEQ ID NO. 91 

H51A(+91+115) 

AAA TCT GCC AGA GCA GGT ACC TCC A 

SEQ ID NO. 92 

H51A(+96+120) 

GGT TGA AAT CTG CCA GAG CAG GTA C 

SEQ ID NO. 93 

H51A(+101+125)

AGC CCG GTT GAA ATC TGC CAG AGC A 

SEQ ID NO. 94 

H51A(+106+130)

GTC CAA GCC CGG TTG AAA TCT GCC A 

SEQ ID NO. 95 

H51A(+111+135)

GTT CTG TCC AAG CCC GGT TGA AAT C 

SEQ ID NO. 96 

H51A(+116+140)

GGT AAG TTC TGT CCA AGC CCG GTT G 

SEQ ID NO. 97 

H51A(+121+145)

CAG TCG GTA AGT TCT GTC CAA GCC C 

SEQ ID NO. 98 

H51A(+126+150)

AAA GCC AGT CGG TAA GTT CTG TCC A 

SEQ ID NO. 99 

H51A(+131+155)

CAG AGA AAG CCA GTC GGT AAG TTC T 

SEQ ID NO. 100 

H51A(+136+160)

TCA AGC AGA GAA AGC CAG TCG GTA A 

SEQ ID NO. 101 

H51A(+141+165)

CTT GAT CAA GCA GAG AAA GCC AGT C 

SEQ ID NO. 102 

H51A(+146+170)

TAT AAC TTG ATC AAG CAG AGA AAG C 

SEQ ID NO. 103 

H51A(+151+175)

GAT TTT ATA ACT TGA TCA AGC AGA G 

SEQ ID NO. 104 

H51A(+156+180)

TCT GTG ATT TTA TAA CTT GAT CAA G 

SEQ ID NO. 105 

H51A(+161+185)

CAC CCT CTG TGA TTT TAT AAC TTG A 

SEQ ID NO. 106 

H51A(+166+190)

ACC ATC ACC CTC TGT GAT TTT ATA A 

SEQ ID NO. 107 

H51A(+171+195)

CAC CCA CCA TCA CCC TCT GTG ATT T 

SEQ ID NO. 108 

H51A(+176+200) 

AAG GTC ACC CAC CAT CAC CCT CTG T 

SEQ ID NO. 109 

H51A(+181+205) 

TCC TCA AGG TCA CCC ACC ATC ACC C 

SEQ ID NO. 110 

H51A(+186+210) 

TGA TAT CCT CAA GGT CAC CCA CCA T 

SEQ ID NO. 111 

H51A(+191+215) 

CTC GTT GAT ATC CTC AAG GTC ACC C 

SEQ ID NO. 112 

H51A(+196+220) 

ATC ATC TCG TTG ATA TCC TCA AGG T 

SEQ ID NO. 113 

H51A(+201+225) 

TGA TGA TCA TCT CGT TGA TAT CCT C 

SEQ ID NO. 114 

H51A(+206+230) 

CTG CTT GAT GAT CAT CTC GTT GAT A 

SEQ ID NO. 115 

H51D(+211−02) 

ACC TTC TGC TTG ATG ATC ATC TCG T 

SEQ ID NO. 116 

H51D(+214−05) 

CAT ACC TTC TGC TTG ATG ATC ATC T 

SEQ ID NO. 117 

H51D(+217−08) 

TCT CAT ACC TTC TGC TTG ATG ATC A 

SEQ ID NO. 118 

H51D(+220−11) 

TTT TCT CAT ACC TTC TGC TTG ATG A 

SEQ ID NO. 119 

H51D(+223−14) 

ATT TTT TCT CAT ACC TTC TGC TTG A 

SEQ ID NO. 120 

H51D(+226−17) 

ATC ATT TTT TCT CAT ACC TTC TGC T 

SEQ ID NO. 121 

H51D(+229−20) 

TTT ATC ATT TTT TCT CAT ACC TTC T 

SEQ ID NO. 122 

H51D(+232−23) 

ACT TTT ATC ATT TTT TCT CAT ACC T 

SEQ ID NO. 123 

H51D(−02−26) 

CCA ACT TTT ATC ATT TTT TCT CAT A 

SEQ ID NO. 124 

H51A(+1+30) 

GTG TCA CCA GAG TAA CAG TCT GAG TAG GAG

SEQ ID NO. 125 

wherein A is

C is

G is

and T is

45 . The antisense oligomer, or a pharmaceutically acceptable salt thereof, of claim 44 , wherein each Nu from 1 to (n+1) and 5′ to 3′ of Formula (II) corresponds to the following sequences: SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, SEQ ID NO. 26, SEQ ID NO. 34, SEQ ID NO. 45, SEQ ID NO. 46, SEQ ID NO. 47, SEQ ID NO. 51, SEQ ID NO. 52, SEQ ID NO. 53, SEQ ID NO. 54, SEQ ID NO. 55, SEQ ID NO. 59, SEQ ID NO. 60, SEQ ID NO. 61, SEQ ID NO. 62, SEQ ID NO. 63, SEQ ID NO. 64, SEQ ID NO. 70, SEQ ID NO. 71, SEQ ID NO. 72, and SEQ ID NO. 73.

46 . The antisense oligomer, or a pharmaceutically acceptable salt thereof, of claim 45 , wherein each Nu from 1 to (n+1) and 5′ to 3′ of Formula (II) corresponds to the nucleobases in one of the following sequences: SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, SEQ ID NO. 26, SEQ ID NO 45, SEQ ID NO. 47, SEQ ID NO. 51, SEQ ID NO. 52, SEQ ID NO. 54, SEQ ID NO. 55, SEQ ID NO. 61, and SEQ ID NO. 63.

47 . The antisense oligomer, or a pharmaceutically acceptable salt thereof, of claim 46 , wherein each Nu from 1 to (n+1) and 5′ to 3′ of Formula (II) corresponds to the nucleobases in one of the following sequences: SEQ ID NO. 47, SEQ ID NO. 52, and SEQ ID NO. 54.

48 - 83 . (canceled)

Assignments (2)
SECURITY INTEREST Recorded May 7, 2025
From: SAREPTA THERAPEUTICS, INC.
To: JPMORGAN CHASE BANK, N.A. AS ADMINISTRATIVE AGENT
Reel/Frame 071218/0445 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 13, 2025
From: SCHNELL, FREDERICK JOSEPH; PASSINI, MARCO; ESTRELLA, NELSA; HANSON, GUNNAR; ZHOU, MING; BESTWICK, RICHARD
To: SAREPTA THERAPEUTICS, INC.
Reel/Frame 070206/0340 →