Conjugated antisense compounds and their use

1. A compound comprising an oligomer and a conjugate group having Formula II:

wherein:

R 1 is selected from CH 2 NJ 1 J 2 and CH 2 SJ 3 ;

R 2 is N(H)C(═O) Q 2 ;

Q 2 is methyl;

Y is O;

L is a connecting group comprising a linear alkylene group optionally including one or more groups independently selected from O, S, NJ 7 , C(═O), a phosphorus linking group and a cleavable bond or L is a single bond between Y and T 1 ;

J 1 , J 2 , J 3 and J 7 are each, independently, H or a substituent group;

T 1 is said oligomer; and

each substituent group is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, aryl, heterocyclic and heteroaryl wherein each substituent group can include a linear or branched alkylene group optionally including one or more groups independently selected from O, S, NH and C(═O), and wherein each substituent group may be further substituted with one or more groups independently selected from C 1 -C 6 alkyl, halogen and C 1 -C 6 alkoxy wherein each cyclic group is mono or polycyclic.

2. The compound of claim 1 wherein R 1 is selected from CH 2 NJ1J2 and CH 2 SJ 3 wherein J 1 , J 2 and J 3 are each independently selected from H and CH 3 .

3. The compound of claim 2 wherein J 1 , J 2 and J 3 are each H.

4. The compound of claim 1 wherein L optionally comprises one or more amides and wherein L attaches to T 1 through a group selected from among:

5. The compound of claim 1 wherein L comprises a phosphorus linking group, NH 2 , or N(CH 3 ) 2 .

6. The compound of claim 1 having the configuration:

7. The compound of claim 1 , wherein the oligomer comprises at least one modified nucleoside comprising a modified base and or a modified sugar.

8. The compound of claim 7 having at least one modified nucleoside comprising a modified sugar selected from a bicyclic nucleoside and a 2′-modified nucleoside.

9. The compound of claim 8 , 4′-C(CH 3 )H-O-2′ or 4′-CH 2 —O-2′bridged bicyclic nucleoside.

10. The compound of claim 8 , comprising at least one 2′-O(CH 2 ) 2 OCH 3 substituted 2′-modified nucleoside.

11. The compound of claim 1 , wherein the conjugate group is attached to the 5′-terminal nucleoside of the oligomer.

12. The compound of claim 1 , wherein the conjugate group is attached to the 3′-terminal nucleoside of the oligomer.

13. The compound of claim 1 , wherein the oligomer has a sugar motif comprising:

a 5′-region consisting of 2-8 linked 5′-region nucleosides, wherein at least two 5′-region nucleosides are modified nucleosides and wherein the 3′-most 5′-region nucleoside is a modified nucleoside;

a 3′-region consisting of 2-8 linked 3′-region nucleosides, wherein at least two 3′-region nucleosides are modified nucleosides and wherein the 5′-most 3′-region nucleoside is a modified nucleoside; and

a central region between the 5′-region and the 3′-region consisting of 5-10 linked central region nucleosides, each independently selected from among: a modified nucleoside and an unmodified deoxynucleoside, wherein the 5′-most central region nucleoside is an unmodified deoxynucleoside and the 3′-most central region nucleoside is an unmodified deoxynucleoside.

14. The compound of claim 1 , wherein the oligomer comprises at least one modified internucleoside linkage.

15. The compound of claim 1 , wherein each internucleoside linkage of the oligomer is independently a phosphodiester or a phosphorothioate internucleoside linkage.

16. The compound of claim 1 , wherein the oligomer has a nucleobase sequence comprising an at least 14 or 16 nucleobase portion complementary to an equal length portion of a target nucleic acid.

17. A pharmaceutical composition comprising a compound or oligomer according to claim 1 and a pharmaceutically acceptable carrier or diluent.

18. The compound of claim 1 comprising an oligomer and three conjugate groups having Formula II attached to said oligomer through a single connecting group.