Compositions and methods for modulating hbv expression

Abstract

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

1 . A compound comprising a modified oligonucleotide and a conjugate group,
 wherein the modified oligonucleotide consists of 10 to 30 linked nucleosides and has a nucleobase sequence at least 95% complementary to SEQ ID NO: 1 encoding hepatitis B virus (HBV), wherein the modified oligonucleotide consists of 10 to 30 linked nucleosides and has a nucleobase sequence comprising the sequence recited in SEQ ID NO: 10,   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;   wherein each nucleoside of the 5′ wing segment comprises a 2′-O-methoxyethyl sugar or a constrained ethyl sugar; wherein each nucleoside of the 3′ wing segment comprises a 2′-O-methoxyethyl sugar or a constrained ethyl sugar; wherein each internucleoside linkage of the modified oligonucleotide is selected from a phosphodiester internucleoside linkage and a phosphorothioate internucleoside linkage; and wherein each cytosine is a 5-methylcytosine.   
     
     
         2 . A compound consisting of ISIS 552925 and a conjugate group (original PCT claim  229 ). 
     
     
         3 . The compound of  claim 2 , wherein the conjugate group comprises: 
       
         
           
           
               
               
           
         
         wherein n is 1 or 2.