Multiple exon skipping compositions for DMD
First Claim
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1. An antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which thymine bases are uracil bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof.
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Abstract
Provided are antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping, and methods of use thereof to treat muscular dystrophy.
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Citations
8 Claims
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1. An antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which thymine bases are uracil bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof.
- 385), in which thymine bases are uracil bases, wherein the antisense oligonucleotide is a 2′
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2. An antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which;
(i) thymine bases are uracil bases and (ii) cytosine bases are 5-methylcytosine bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof.
- 385), in which;
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3. An antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which;
(i) thymine bases are uracil bases and (ii) one or more of the bases are hypoxanthine, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof.
- 385), in which;
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4. An antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which;
(i) thymine bases are uracil bases, (ii) one or more of the bases are hypoxanthine, and (iii) cytosine bases are 5-methylcytosine bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof.
- 385), in which;
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5. A pharmaceutical composition comprising an antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which thymine bases are uracil bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
- 385), in which thymine bases are uracil bases, wherein the antisense oligonucleotide is a 2′
-
6. A pharmaceutical composition comprising an antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which;
(i) thymine bases are uracil bases and (ii) cytosine bases are 5-methylcytosine bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
- 385), in which;
-
7. A pharmaceutical composition comprising an antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which;
(i) thymine bases are uracil bases and (ii) one or more of the bases are hypoxanthine, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
- 385), in which;
-
8. A pharmaceutical composition comprising an antisense oligonucleotide of 22 bases comprising a base sequence that is 100% complementary to 22 consecutive bases of exon 52 of the human dystrophin pre-mRNA, wherein the base sequence comprises 21 consecutive bases of CAGCGGTAATGAGTTCTTCCAACTG (SEQ ID NO:
- 385), in which;
(i) thymine bases are uracil bases, (ii) one or more of the bases are hypoxanthine, and (iii) cytosine bases are 5-methylcytosine bases, wherein the antisense oligonucleotide is a 2′
-O-methyl oligonucleotide, and wherein the antisense oligonucleotide induces exon 52 skipping;
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
- 385), in which;
Specification