Compounds and methods for modulating tmprss6 expression

Abstract

Disclosed herein are compositions and compounds comprising modified oligonucleotides for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and/or condition in an individual in need thereof. Iron accumulation diseases in an individual such as polycythemia, hemochromatosis or β-thalassemia can be treated, ameliorated, delayed or prevented with the administration of antisense compounds targeted to TMPRSS6.

1 - 36 . (canceled) 
     
     
         37 . An oligomeric compound according to the following chemical structure: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         38 . The oligomeric compound of  claim 37 , which is the sodium salt or the potassium salt. 
     
     
         39 . An oligomeric compound according to the following chemical structure: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         40 . An oligomeric compound, wherein the anion form of the oligomeric compound has the following chemical structure: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         41 . An oligomeric compound comprising a modified oligonucleotide according to the following formula: THA-C6 GalNAc 3  mCks Aes Gks mCds Tds Tds Tds Ads Tds Tds mCds mCds Aes Aes Aks Gk (SEQ ID NO: 77); wherein,
 A=an adenine nucleobase,   mC=a 5-methylcytosine nucleobase,   G=a guanine nucleobase,   T=a thymine nucleobase,   e=a 2′-MOE sugar moiety,   d=a 2′-β-D-deoxyribosyl sugar moiety,   s=a phosphorothioate internucleoside linkage,   o=a phosphodiester internucleoside linkage,   k=a cEt sugar moiety, and   THA-C6 GalNAc 3 =   
       
         
           
           
               
               
           
         
         wherein the cleavable moiety (CM) comprises a phosphodiester bond. 
       
     
     
         42 . A population of oligomeric compounds of  claim 37 , wherein all of the phosphorothioate internucleoside linkages of the modified oligonucleotides are stereorandom. 
     
     
         43 . A pharmaceutical composition comprising an oligomeric compound of  claim 37  and a pharmaceutically acceptable diluent. 
     
     
         44 . The pharmaceutical composition of  claim 43 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS) or water. 
     
     
         45 . A population of oligomeric compounds of  claim 38 , wherein all of the phosphorothioate internucleoside linkages of the modified oligonucleotides are stereorandom. 
     
     
         46 . A pharmaceutical composition comprising an oligomeric compound of  claim 38  and a pharmaceutically acceptable diluent. 
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS) or water. 
     
     
         48 . A population of oligomeric compounds of  claim 39 , wherein all of the phosphorothioate internucleoside linkages of the modified oligonucleotides are stereorandom. 
     
     
         49 . A pharmaceutical composition comprising an oligomeric compound of  claim 39  and a pharmaceutically acceptable diluent. 
     
     
         50 . The pharmaceutical composition of  claim 49 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS) or water. 
     
     
         51 . A population of oligomeric compounds of  claim 40 , wherein all of the phosphorothioate internucleoside linkages of the modified oligonucleotide are stereorandom. 
     
     
         52 . A pharmaceutical composition comprising the oligomeric compound of  claim 40  and a pharmaceutically acceptable diluent. 
     
     
         53 . The pharmaceutical composition of  claim 52 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS) or water. 
     
     
         54 . A population of oligomeric compounds of  claim 41 , wherein all of the phosphorothioate internucleoside linkages of the modified oligonucleotide are stereorandom. 
     
     
         55 . A pharmaceutical composition comprising the oligomeric compound of  claim 41  and a pharmaceutically acceptable diluent. 
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein the pharmaceutically acceptable diluent is phosphate-buffered saline (PBS) or water. 
     
     
         57 . A method of reducing expression of TMPRSS6 in a cell comprising contacting the cell with an oligomeric compound of  claim 37 . 
     
     
         58 . A method comprising administering the compound of  claim 37  to a subject in need thereof. 
     
     
         59 . The method of  claim 58 , wherein the subject has polycythemia, hemochromatosis or anemia. 
     
     
         60 . The method of  claim 59 , wherein the anemia is β-thalassemia. 
     
     
         61 . The method of  claim 59 , wherein the polycythemia is polycythemia vera. 
     
     
         62 . The method of  claim 58 , wherein the subject is human.