Antisense design

Abstract

A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.

1 .- 42 . (canceled) 
     
     
         43 . An oligonucleotide which comprises a sequence of nucleotides of formula, from 5′ to 3′: A-B-C or A-B-C-D, wherein,
 A represents a sequence of 2 to 6 locked nucleotide units; 
 B represents a sequence of 4 to 12 non-locked nucleotide units; 
 C represents a sequence of 1 to 5 locked nucleotide units; 
 D, when present, represents a non-locked nucleotide unit or a sequence of 1 to 3 non-locked nucleotide units; 
 wherein region A or region C comprise at least one alpha-L-oxy LNA unit located adjacent to region B. 
 
     
     
         44 . The oligonucleotide according to  claim 43 , wherein B represents a sequence of 2′-deoxy pentofuranose sugar moiety units. 
     
     
         45 . The oligonucleotide according to  claim 43 , wherein B represents a sequence of 6 to 12 2′-deoxy pentofuranose sugar moiety units. 
     
     
         46 . The oligonucleotide according to  claim 45 , wherein region A and region C comprise, independently, 2 to 4 consecutive locked nucleotide units. 
     
     
         47 . The oligonucleotide according to  claim 45 , wherein both region A and region C comprise an alpha-L-oxy-LNA nucleoside located adjacent to region B. 
     
     
         48 . The oligonucleotide according to  claim 46 , wherein both region A and region C comprise an alpha-L-oxy-LNA nucleoside located adjacent to region B. 
     
     
         49 . The oligonucleotide according to  claim 43 , wherein the remaining nucleosides of regions A and C are beta-D-oxy-LNA nucleosides. 
     
     
         50 . The oligonucleotide according to  claim 45 , wherein the remaining nucleosides of regions A and C are beta-D-oxy-LNA nucleosides. 
     
     
         51 . The oligonucleotide according to  claim 46 , wherein the remaining nucleosides of regions A and C are beta-D-oxy-LNA nucleosides. 
     
     
         52 . The oligonucleotide according to  claim 47 , wherein the remaining nucleosides of regions A and C are beta-D-oxy-LNA nucleosides. 
     
     
         53 . The oligonucleotide according to  claim 48 , wherein the remaining nucleosides of regions A and C are beta-D-oxy-LNA nucleosides. 
     
     
         54 . The oligonucleotide according to  claim 43 , wherein the remaining nucleosides of regions A and C are alpha-D-oxy-LNA nucleosides. 
     
     
         55 . The oligonucleotide according to  claim 45 , wherein the remaining nucleosides of regions A and C are alpha-D-oxy-LNA nucleosides. 
     
     
         56 . The oligonucleotide according to  claim 46 , wherein the remaining nucleosides of regions A and C are alpha-D-oxy-LNA nucleosides. 
     
     
         57 . The oligonucleotide according to  claim 47 , wherein the remaining nucleosides of regions A and C are alpha-D-oxy-LNA nucleosides. 
     
     
         58 . The oligonucleotide according to  claim 48 , wherein the remaining nucleosides of regions A and C are alpha-D-oxy-LNA nucleosides. 
     
     
         59 . The oligonucleotide according to  claim 45 , wherein the region A-B-C comprises at least one phosphorothioate internucleoside linkages 
     
     
         60 . The oligonucleotide according to  claim 45 , wherein all the internucleoside linkages within the region A-B-C are phosphorothioate internucleoside linkages.