Modulators of complement factor b

Abstract

The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with dysregulation of the complement alternative pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.

1 - 10 . (canceled) 
     
     
         11 . A compound comprising a modified oligonucleotide consisting of 10 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs: 6-808. 
     
     
         12 - 23 . (canceled) 
     
     
         24 . The compound of  claim 11 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage, at least one modified sugar, or at least one modified nucleobase. 
     
     
         25 . The compound of  claim 24 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         26 . The compound of  claim 24 , wherein the modified sugar is a bicyclic sugar. 
     
     
         27 . The compound of  claim 26 , wherein the bicyclic sugar is selected from the group consisting of: 4′-(CH 2 )—O-2′ (LNA); 4′-(CH 2 ) 2 —O-2′ (ENA); and 4′-CH(CH 3 )—O-2′ (cEt). 
     
     
         28 . The compound of  claim 24 , wherein the modified sugar is 2′-O-methoxyethyl. 
     
     
         29 . The compound of  claim 24 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         30 . The compound of  claim 11 , wherein the modified oligonucleotide comprises:
 (a) a gap segment consisting of linked deoxynucleosides;   (b) a 5′ wing segment consisting of linked nucleosides; and   (c) a 3′ wing segment consisting of linked nucleosides;   wherein the gap segment is positioned immediately adjacent to and between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.   
     
     
         31 - 37 . (canceled) 
     
     
         38 . A composition comprising the compound of  claim 11  or salt thereof and a pharmaceutically acceptable carrier. 
     
     
         39 . A method of treating, preventing, or ameliorating a disease associated with dysregulation of the complement alternative pathway in a subject comprising administering to the subject a specific inhibitor of Complement Factor B (CFB), thereby treating, preventing, or ameliorating the disease. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 39 , wherein the inhibitor is the compound of  claim 11 . 
     
     
         42 - 94 . (canceled)