Oligomeric compounds comprising bicyclic nucleotides and uses thereof

Abstract

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

We claim: 
     
         1 .- 238 . (canceled) 
     
     
         239 . A compound comprising:
 a modified oligonucleotide consisting of 10 to 20 linked nucleosides, wherein the modified oligonucleotide comprises:   a 5′-wing consisting of 2 to 5 linked nucleosides;   a 3′-wing consisting of 2 to 5 linked nucleosides; and   a gap between the 5′-wing and the 3′-wing consisting of 6 to 14 linked 2′-deoxynucleosides; and   wherein at least one of the 5′-wing and the 3′-wing comprises at least one bicyclic nucleoside selected from among LNA, α-L-LNA, or ENA; at least one of the 5′-wing and the 3′-wing comprises at least one 2′-substituted nucleoside; and at least one of the 5′-wing and the 3′-wing comprises at least one 2′-deoxynucleoside; and   wherein the nucleobase sequence of the modified oligonucleotide is complementary to the nucleobase sequence of a target nucleic acid.   
     
     
         240 . The compound of  claim 239 , wherein each of the 5′-wing and the 3′-wing comprises at least one 2′-deoxynucleoside. 
     
     
         241 . The compound of  claim 239 , wherein the 3′-wing comprises at least one 2′-deoxynucleoside. 
     
     
         242 . The compound of  claim 239 , wherein the 5′-wing comprises at least one 2′-deoxynucleoside. 
     
     
         243 . The compound of  claim 239 , wherein the 2′-substituent of the at least one 2′-substituted nucleoside is selected from among OCH 3 , F, OCH 2 F, OCHF 2 , OCF 3 , OCH 2 CH 3 , O(CH 2 ) 2 F, OCH 2 CHF 2 , OCH 2 CF 3 , OCH 2 —CH═CH 2 , O(CH 2 ) 2 —OCH 3 , O(CH 2 ) 2 —SCH 3 , O(CH 2 ) 2 —OCF 3 , O(CH 2 ) 3 —N(R 4 )(R 5 ), O(CH 2 ) 2 —ON(R 4 )(R 5 ), O(CH 2 ) 2 —O(CH 2 ) 2 —N(R 4 )(R 5 ), OCH 2 C(═O)—N(R 4 )(R 5 ), OCH 2 C(═O)—N(R 6 )—(CH 2 ) 2 —N(R 4 )(R 5 ) and O(CH 2 ) 2 —N(R 6 )—C(═NR 7 )[N(R 4 )(R 5 )] wherein R 4 , R 5 , R 6  and R 7  are each, independently, H or C 1 -C 6  alkyl. 
     
     
         244 . The compound of  claim 239 , wherein the 2′-substituent of the at least one 2′-substituted nucleoside is selected from among OCH 3 , F, and O(CH 2 ) 2 —OCH 3 . 
     
     
         245 . The compound of  claim 244 , wherein the 2′-substituent of the at least one 2′-substituted nucleoside is O(CH 2 ) 2 —OCH 3 . 
     
     
         246 . The compound of  claim 244 , wherein the 2′-substituent of the at least one 2′-substituted nucleoside is OCH 3 . 
     
     
         247 . The compound of  claim 239 , wherein the 5′-wing does not comprise a bicyclic nucleotide. 
     
     
         248 . The compound of  claim 239 , wherein the 3′-wing does not comprise a bicyclic nucleotide. 
     
     
         249 . The compound of  claim 239 , wherein the 5′-wing consists of 2 linked nucleosides. 
     
     
         250 . The compound of  claim 239 , wherein the 5′-wing consists of 3 linked nucleosides. 
     
     
         251 . The compound of  claim 239 , wherein the 5′-wing consists of 4 linked nucleosides. 
     
     
         252 . The compound of  claim 239 , wherein the 5′-wing consists of 5 linked nucleosides. 
     
     
         253 . The compound of  claim 239 , wherein the gap consists of 9 linked 2′-deoxynucleosides. 
     
     
         254 . The compound of  claim 239 , wherein the gap consists of 10 linked 2′-deoxynucleosides. 
     
     
         255 . The compound of  claim 239 , wherein the oligonucleotide consists of 18 linked nucleosides. 
     
     
         256 . The compound of  claim 239 , wherein the oligonucleotide consists of 20 linked nucleosides. 
     
     
         257 . The compound of  claim 239 , wherein each internucleoside linkage is a modified internucleoside linkage. 
     
     
         258 . The compound of  claim 239 , wherein the modified internucleoside linkage is a phosphorothioate linkage.