Modulation of hepatitis B virus (HBV) expression
View Patent ↗Disclosed herein are antisense compounds and methods for decreasing HBV mRNA, DNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate HBV-related diseases, disorders or conditions.
1. An antisense compound comprising a modified oligonucleotide consisting of 18-20 linked nucleosides having a nucleobase sequence comprising an at least 18 contiguous nucleobase portion 100% complementary to nucleotides 1827-1846 of SEQ ID NO: 1, wherein the 5′ end of the nucleobase sequence has a non-complementary nucleobase with respect to SEQ ID NO: 1.
2. The antisense compound of claim 1 , wherein at least one internucleoside linkage of said modified oligonucleotide is a modified internucleoside linkage.
3. The antisense compound of claim 2 , wherein the modified internucleoside linkage is a phosphorothioate linkage.
4. The antisense compound of claim 2 , wherein at least one nucleoside of said modified oligonucleotide comprises a modified sugar.
5. The antisense compound of claim 4 , wherein the modified sugar comprises 2′-O—CH 3 .
6. The antisense compound of claim 5 , wherein the modified sugar comprises 2′-F.
7. The antisense compound of claim 1 , wherein the compound consists of a single-stranded modified oligonucleotide.
8. The antisense compound of claim 1 , wherein the compound comprises a double-stranded RNA oligonucleotide.
9. The antisense compound of claim 8 , wherein at least one internucleoside linkage of said modified oligonucleotide is a modified internucleoside linkage.
10. The antisense compound of claim 9 , wherein the modified internucleoside linkage is a phosphorothioate linkage.
11. The antisense compound of claim 8 , wherein at least one nucleoside of said modified oligonucleotide comprises a modified sugar.
12. The antisense compound of claim 11 , wherein the modified sugar comprises 2′-O—CH 3 .
13. The antisense compound of claim 11 , wherein the modified sugar comprises 2′-F.
14. The antisense compound of claim 8 , wherein the modified oligonucleotide comprises at least one phosphorothioate linkage and at least one modified sugar.
15. The antisense compound of claim 14 , wherein the modified sugar comprises 2′-O—CH 3 .
16. The antisense compound of claim 15 , wherein the modified sugar comprises 2′-F.
17. A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering to the animal the compound of claim 1 , thereby preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in the animal.
18. A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering to the animal the compound of claim 8 , thereby preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in the animal.
19. A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering to the animal the compound of claim 14 , thereby preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in the animal.
20. A method of preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in an animal comprising administering to the animal the compound of claim 15 or 16 , thereby preventing, treating, ameliorating, or slowing progression of a HBV-related disease, disorder or condition in the animal.