Antisense oligomer compounds
A modified antisense oligonucleotide of about 10 to about 40 nucleobases is disclosed. The oligonucleotide comprises a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.
1. A modified antisense oligonucleotide, or a pharmaceutically acceptable salt thereof, of about 10 to about 40 nucleobases comprising a targeting sequence consisting of any one of SEQ ID NOs: 9-25.
2. The modified antisense oligonucleotide or pharmaceutically acceptable salt thereof of claim 1 , wherein the modified antisense oligonucleotide is conjugated to a peptide.
3. The modified antisense oligonucleotide or pharmaceutically acceptable salt thereof of claim 1 , wherein the modified antisense oligonucleotide enhances exon 7 inclusion in the processing of human SMN2 pre-processed mRNA.
4. A modified antisense oligonucleotide, or pharmaceutically acceptable salt thereof, of about 10 to about 40 nucleobases comprising a deletion sequence wherein the deletion sequence consists of at least one base sequence according to any one of SEQ ID NOs: 9-25.
5. The modified antisense oligonucleotide or pharmaceutically acceptable salt thereof of claim 4 , wherein the modified antisense oligonucleotide enhances exon 7 inclusion in the processing of human SMN2 pre-processed mRNA.
6. A pharmaceutical composition, comprising a modified antisense oligonucleotide of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition, comprising a modified antisense oligomer of claim 4 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
8. A method for treating spinal muscular atrophy in a patient in need thereof, comprising administering to the patient a modified antisense antisense oligonucleotide, or a pharmaceutically acceptable salt thereof, of claim 1 .
9. A method for treating spinal muscular atrophy in a patient in need thereof, comprising administering to the patient a modified antisense antisense oligonucleotide, or a pharmaceutically acceptable salt thereof, of claim 4 .