US2023183696A1PendingUtilityA1
Compositions and Methods for Modulation of SMN2 Splicing in a Subject
Est. expiryApr 17, 2034(~7.7 yrs left)· nominal 20-yr term from priority
C12N 2310/343C12N 2310/346C12N 2320/33C12N 2310/11C12N 2310/3341C12N 2310/315C12N 15/113C12N 2310/322
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Claims
Abstract
Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject.
Claims
exact text as granted — not AI-modified1 . A compound comprising a modified oligonucleotide consisting of 16-20 linked nucleosides, wherein the modified oligonucleotide is complementary to SMN2; and wherein each internucleoside linkage is either phosphorothioate or phosphodiester and at least one internucleoside linkage is phosphorothioate and at least one internucleoside linkage is phosphodiester.
2 . The compound of claim 1 , wherein the modified oligonucleotide has a nucleobase sequence selected from any one of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, or 27, and having 6 or more phosphodiester internucleoside linkages, wherein each internucleoside linkage that is not a phosphodiester internucleoside linkage is a phosphorothioate internucleoside linkage.
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6 . The compound of claim 1 , having 7, 8, 9, 10, or more phosphodiester internucleoside linkages, wherein each internucleoside linkage that is not a phosphodiester internucleoside linkage is a phosphorothioate internucleoside linkage.
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44 . The compound of claim 1 , wherein each nucleoside of the modified oligonucleotide comprises a modified sugar moiety, and wherein each modified sugar moiety comprises a 2′-O-methoxyethyl modification.
45 . A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.
46 . A method of promoting inclusion of exon 7 in SMN2 transcripts in a cell, tissue or organ, comprising contacting said cell, tissue or organ with the compound of claim 1 .
47 . A method of treating Spinal Muscular Atrophy Type I, Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III, or Spinal Muscular Atrophy Type IV, comprising administering a therapeutically effective amount of the compound of claim 1 to a patient in need thereof.
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109 . An antisense oligonucleotide consisting of the nucleic acid sequence set forth in SEQ ID NO: 1, 2, or 7, wherein all cytosine residues of the nucleic acid sequence are 5-methylcytosines, and wherein each nucleoside of the nucleic acid sequence comprises a 2′-O-methoxyethyl sugar modification.
110 . The antisense oligonucleotide of claim 109 , wherein the nucleic acid sequence has any one of the following backbone chemistries:
(i) sossssossssossssoss; (ii) sosososososososooss; (iii) soosossossossosooss; (iv) sossossossossosooss; (v) sossossossossossoss; or (vi) sossosssosssosssoss, wherein “s” indicates a phosphorothioate linkage and “o” indicates a phosphodiester linkage.
111 . A pharmaceutical composition comprising the antisense oligonucleotide of claim 109 and a pharmaceutically acceptable carrier.
112 . A method of treating spinal muscular atrophy (SMA) in a human subject, the method comprising administering to the human subject a therapeutically effective amount of the antisense oligonucleotide of claim 109 .
113 . The method of claim 112 , wherein the SMA is SMA Type I, SMA Type II, SMA Type III, or SMA Type IV.Join the waitlist — get patent alerts
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