Compositions and methods for modulation of SMN2 splicing in a subject
First Claim
Patent Images
1. A method comprising administering by a bolus injection into the intrathecal space of a human subject having type II spinal muscular atrophy (SMA) an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-MOE nucleoside, and wherein the administering of the antisense compound ameliorates at least one symptom of SMA in the human subject.
6 Assignments
0 Petitions
Accused Products
Abstract
Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.
-
Citations
42 Claims
-
1. A method comprising administering by a bolus injection into the intrathecal space of a human subject having type II spinal muscular atrophy (SMA) an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-MOE nucleoside, and wherein the administering of the antisense compound ameliorates at least one symptom of SMA in the human subject. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-
11. A method comprising administering by a bolus injection into the intrathecal space of a human subject having type III spinal muscular atrophy (SMA) an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-MOE nucleoside, and wherein the administering of the antisense compound ameliorates at least one symptom of SMA in the human subject. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20)
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-
21. A method of increasing inclusion of exon 7 in SMN2 messenger ribonucleic acid (mRNA) transcripts in a human subject having loss of both functional copies of the SMN1 gene, the method comprising administering by a bolus injection into the intrathecal space of the human subject an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-MOE nucleoside, and wherein the administering of the antisense compound increases inclusion of exon 7 in SMN2 mRNA transcripts in the human subject. - View Dependent Claims (22, 23, 24)
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-
25. A method of increasing exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts in a human subject having mutations in the SMN1 gene that lead to functional SMN protein deficiency, the method comprising administering by a bolus injection into the intrathecal space of the human subject an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-MOE nucleoside, and wherein the administering of the antisense compound increases exon 7 inclusion in SMN2 mRNA transcripts in the human subject. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33)
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-
34. A method of treating spinal muscular atrophy (SMA) in a human subject having SMA, the method comprising administering by a bolus injection into the intrathecal space of the human subject an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO:
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
-MOE nucleoside, and wherein the administering of the antisense compound increases inclusion of exon 7 in SMN2 messenger ribonucleic acid (mRNA) transcripts in the human subject. - View Dependent Claims (35, 36, 37, 38, 39, 40, 41, 42)
- 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′
Specification