Modulation of hepatitis b virus (hbv) expression

Abstract

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 - 36 . (canceled) 
     
     
         37 . A compound comprising a modified oligonucleotide consisting of 10 to 30 linked nucleosides having a nucleobase sequence comprising a portion of at least 8 contiguous nucleobases 100% complementary to an equal length portion of nucleobases, 
       wherein the nucleobase sequence of the modified oligonucleotide is complementary to SEQ ID NO:1. 
     
     
         38 . The compound of  claim 37 , wherein at least one internucleoside linkage is a modified internucleoside linkage, at least one nucleoside of the modified oligonucleotide comprises at least one 2′-O-methoxyethyl sugar or constrained ethyl sugar, and at least one nucleoside comprises a modified nucleobase, wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage, and wherein the modified nucleobase is 5-methylcytosine. 
     
     
         39 . The compound of  claim 37  comprising a modified oligonucleotide consisting of 10 to 30 linked nucleosides and having a nucleobase sequence comprising a portion of at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 224, 226 and 807. 
     
     
         40 . The compound of  claim 37  comprising a modified oligonucleotide consisting of 10 to 30 linked nucleosides and having a nucleobase sequence comprising a portion of at least 8 contiguous nucleobases of SEQ ID NO: 226. 
     
     
         41 . The compound of  claim 40 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides; and   a 3′ wing segment consisting of linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl modified sugar.   
     
     
         42 . The compound of claim  2 Z, wherein said modified oligonucleotide consists of 18 to 22 linked nucleosides. 
     
     
         43 - 44 . (canceled) 
     
     
         45 . A composition comprising the compound of  claim 37  or salt thereof and at least one of a pharmaceutically acceptable carrier or diluent. 
     
     
         46 - 47 . (canceled) 
     
     
         48 . A method comprising administering to an animal the compound of  claim 37 . 
     
     
         49 . The method of  claim 48 , wherein the animal is a human. 
     
     
         50 . The method of  claim 49 , wherein administering the compound prevents, treats, ameliorates, or slows progression of a HBV-related disease, disorder or condition. 
     
     
         51 . The method of  claim 50 , wherein the disease, disorder or condition is liver disease. 
     
     
         52 . The method of  claim 50 , wherein the disease, disorder or condition is jaundice, liver inflammation, liver fibrosis, inflammation, liver cirrhosis, liver failure, diffuse hepatocellular inflammatory disease, hemophagocytic syndrome, serum hepatitis, HBV viremia, or liver disease-related transplantation. 
     
     
         53 . The method of  claim 50 , wherein the disease or condition is a hyperproliferative condition. 
     
     
         54 . The method of  claim 53 , wherein the hyperproliferative condition is liver cancer. 
     
     
         55 . A method of reducing antigen levels in an animal comprising administering to said animal the compound of  claim 37 . 
     
     
         56 . The method of  claim 55 , wherein HBsAG levels are reduced. 
     
     
         57 . The method of  claim 55 , wherein HBeAG levels are reduced. 
     
     
         58 . The method of  claim 55 , wherein the animal is human. 
     
     
         59 . The method of  claim 55 , comprising co-administering the compound or composition and a second agent. 
     
     
         60 . The method of  claim 59 , wherein the compound or composition and the second agent are administered concomitantly. 
     
     
         61 - 72 . (canceled)