Antidotes to antisense compounds

Abstract

The present invention relates to antisense antidote compounds and uses thereof. Such antidote compounds reduce the magnitude and/or duration of the antisense activity of an antisense compound.

1 . An antidote compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to an antisense compound. 
     
     
         2 . The antidote compound of  claim 1 , wherein the modified oligonucleotide is a single-stranded oligonucleotide. 
     
     
         3 . The antidote compound of  claim 1 , wherein the antidote compound is at least 90% complementary to the antisense compound. 
     
     
         4 . The antidote compound of  claim 1 , wherein the antidote compound is fully complementary to the antisense compound. 
     
     
         5 . The antidote compound of  claim 1 , wherein at least one internucleoside linkage is a modified internucleoside linkage. 
     
     
         6 . (canceled) 
     
     
         7 . The antidote compound of  claim 1 , wherein at least one nucleoside comprises a modified sugar. 
     
     
         8 . The antidote compound of  claim 7 , wherein at least one modified sugar is a bicyclic sugar. 
     
     
         9 . The antidote compound of  claim 7 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl. 
     
     
         10 . The antidote compound of  claim 1 , wherein at least one nucleoside comprises a modified nucleobase. 
     
     
         11 . (canceled) 
     
     
         12 . The antidote compound of  claim 1 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides;   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 modified sugar.   
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The antidote compound of  claim 1 , wherein each nucleoside is modified. 
     
     
         16 . The antidote compound of  claim 1 , wherein the antisense compound is targeted to an mRNA. 
     
     
         17 . The antidote compound of  claim 1 , wherein the antisense compound is targeted to an mRNA encoding a blood factor. 
     
     
         18 - 25 . (canceled) 
     
     
         26 . The antidote compound of  claim 1 , wherein the antisense compound is targeted to a pre-mRNA. 
     
     
         27 . The antidote compound of  claim 1 , wherein the antisense compound is targeted to a micro-RNA. 
     
     
         28 . The antidote compound of  claim 1 , wherein the antisense compound is an RNase H dependent antisense compound. 
     
     
         29 . The antidote compound of  claim 1 , wherein the antisense compound alters splicing of a target nucleic acid. 
     
     
         30 . The antidote compound of  claim 1 , wherein the antisense compound activates the RISC pathway. 
     
     
         31 . The antidote compound of  claim 1 , wherein the antidote compound activates RNase H. 
     
     
         32 . The antidote compound of  claim 1 , wherein the antidote compound activates the RISC pathway. 
     
     
         33 - 59 . (canceled) 
     
     
         60 . A kit comprising an antisense compound and an antidote compound. 
     
     
         61 . A kit comprising an antidote compound and a non-oligomeric antidote. 
     
     
         62 . The kit of  claim 61  wherein the non-oligomeric antidote is a target protein.