ANTISENSE MOLECULES AND METHODS FOR TREATING PATHOLOGIES
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Accused Products
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 59.
19 Citations
17 Claims
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1-3. -3. (canceled)
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4. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 45 skipping, comprising administering to the patient an antisense oligonucleotide selected from the group consisting of:
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(i) an antisense oligonucleotide of 34 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(ii) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(iii) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
06+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(iv) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
12+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(v) an antisense oligonucleotide of 22 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(vi) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(vii) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
12+16), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(viii) an antisense oligonucleotide of 32 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
14+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(ix) an antisense oligonucleotide of 27 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
08+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(x) an antisense oligonucleotide of 32 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
07+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xi) an antisense oligonucleotide of 34 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
12+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xii) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xiii) an antisense oligonucleotide of 39 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+30), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xiv) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
06+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xv) an antisense oligonucleotide of 34 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
06+28), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xvi) an antisense oligonucleotide of 25 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping; and(xvii) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+28), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;or a pharmaceutically acceptable salt thereof, thereby treating the patient. - View Dependent Claims (5, 6, 7)
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8. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 45 skipping, comprising administering to the patient an antisense oligonucleotide selected from the group consisting of:
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(i) an antisense oligonucleotide of 34 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA AGA U (SEQ ID NO;
11), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(ii) an antisense oligonucleotide of 28 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
55), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(iii) an antisense oligonucleotide of 31 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA A (SEQ ID NO;
61), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(iv) an antisense oligonucleotide of 31 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU GUA AGA UAC C (SEQ ID NO;
62), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base,(v) an antisense oligonucleotide of 22 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
63), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(vi) an antisense oligonucleotide of 28 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU GUA AGA U (SEQ ID NO;
64), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(vii) an antisense oligonucleotide of 28 bases comprising the base sequence UGC CAU CCU GGA GUU CCU GUA AGA UAC C (SEQ ID NO;
66), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(viii) an antisense oligonucleotide of 32 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA AG (SEQ ID NO;
227), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(ix) an antisense oligonucleotide of 27 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU GUA AGA (SEQ ID NO;
230), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(x) an antisense oligonucleotide of 34 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU GUA AGA UAC C (SEQ ID NO;
237), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(xi) an antisense oligonucleotide of 31 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU GUA AGA U (SEQ ID NO;
239), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(xii) an antisense oligonucleotide of 39 bases comprising the base sequence UUG CCG CUG CCC AAU GCC AUC CUG GAG UUC CUG UAA GAU (SEQ ID NO;
240), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(xiii) an antisense oligonucleotide of 32 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA AG (SEQ ID NO;
241), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(xiv) an antisense oligonucleotide of 28 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU GUA A (SEQ ID NO;
242), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(xv) an antisense oligonucleotide of 34 bases comprising the base sequence GCC GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA A (SEQ ID NO;
243), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;(xvi) an antisense oligonucleotide of 25 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
244), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base; and(xvii) an antisense oligonucleotide of 31 bases comprising the base sequence GCC GCU GCC CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
245), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide and is uniformly modified to comprise a 5-substituted pyrimidine base;or a pharmaceutically acceptable salt thereof, thereby treating the patient. - View Dependent Claims (9, 10, 11)
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12. A method for treating a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 45 skipping, comprising administering to the patient a pharmaceutical composition comprising:
- (i) antisense oligonucleotide selected from the group consisting of;
(i) an antisense oligonucleotide of 34 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA AGA U (SEQ ID NO;
11), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(ii) an antisense oligonucleotide of 28 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
55), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(iii) an antisense oligonucleotide of 31 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA A (SEQ ID NO;
61), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(iv) an antisense oligonucleotide of 31 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU GUA AGA UAC C (SEQ ID NO;
62), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(v) an antisense oligonucleotide of 22 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
63), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(vi) an antisense oligonucleotide of 28 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU GUA AGA U (SEQ ID NO;
64), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(vii) an antisense oligonucleotide of 28 bases comprising the base sequence UGC CAU CCU GGA GUU CCU GUA AGA UAC C (SEQ ID NO;
66), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(viii) an antisense oligonucleotide of 32 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA AG (SEQ ID NO;
227), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(ix) an antisense oligonucleotide of 27 bases comprising the base sequence CAA UGC CAU CCU GGA GUU CCU GUA AGA (SEQ ID NO;
230), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(x) an antisense oligonucleotide of 34 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU GUA AGA UAC C (SEQ ID NO;
237), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(xi) an antisense oligonucleotide of 31 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU GUA AGA U (SEQ ID NO;
239), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(xii) an antisense oligonucleotide of 39 bases comprising the base sequence UUG CCG CUG CCC AAU GCC AUC CUG GAG UUC CUG UAA GAU (SEQ ID NO;
240), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(xiii) an antisense oligonucleotide of 32 bases comprising the base sequence GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA AG (SEQ ID NO;
241), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(xiv) an antisense oligonucleotide of 28 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU GUA A (SEQ ID NO;
242), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(xv) an antisense oligonucleotide of 34 bases comprising the base sequence GCC GCU GCC CAA UGC CAU CCU GGA GUU CCU GUA A (SEQ ID NO;
243), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;(xvi) an antisense oligonucleotide of 25 bases comprising the base sequence GCC CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
244), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain; and(xvii) an antisense oligonucleotide of 31 bases comprising the base sequence GCC GCU GCC CAA UGC CAU CCU GGA GUU CCU G (SEQ ID NO;
245), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, wherein the antisense oligonucleotide is uniformly modified to comprise a 5-substituted pyrimidine base, and wherein the antisense oligonucleotide is chemically linked to a polyethylene glycol chain;or a pharmaceutically acceptable salt thereof; and (ii) a pharmaceutically acceptable carrier, thereby treating the patient. - View Dependent Claims (13)
- (i) antisense oligonucleotide selected from the group consisting of;
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14. A method for restoring an mRNA reading frame to induce dystrophin protein production in a patient with Duchenne muscular dystrophy (DMD) in need thereof who has a mutation of the DMD gene that is amenable to exon 45 skipping, comprising administering to the patient an antisense oligonucleotide selected from the group consisting of:
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(i) an antisense oligonucleotide of 34 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(ii) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(iii) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
06+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(iv) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
12+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(v) an antisense oligonucleotide of 22 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(vi) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(vii) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
12+16), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(viii) an antisense oligonucleotide of 32 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
14+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(ix) an antisense oligonucleotide of 27 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
08+19), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(x) an antisense oligonucleotide of 32 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
07+25), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xi) an antisense oligonucleotide of 34 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
12+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xii) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xiii) an antisense oligonucleotide of 39 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
09+30), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xiv) an antisense oligonucleotide of 28 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
06+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xv) an antisense oligonucleotide of 34 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
06+28), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;(xvi) an antisense oligonucleotide of 25 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+22), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping; and(xvii) an antisense oligonucleotide of 31 bases in length 100% complementary to a target region of exon 45 of the human dystrophin pre-mRNA, wherein the target region is annealing site H45A (−
03+28), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 45 skipping;or a pharmaceutically acceptable salt thereof, thereby restoring the mRNA reading frame to induce dystrophin protein production in the patient. - View Dependent Claims (15, 16, 17)
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Specification