Modified L-Nucleic Acid

Abstract

A modified L-nucleic acid, containing an L-nucleic acid part conjugated to a non-L-nucleic acid part is described. The conjugate has extended retention time in and demonstrates a delayed elimination from an organism.

1 . (canceled) 
     
     
         2 . A modified L-nucleic acid, comprising a L-nucleic acid part and a non-L-nucleic acid part, wherein the L-nucleic acid part is conjugated with the non-L-nucleic acid part, and the conjugation of the L-nucleic acid part with the non-L-nucleic acid part leads to an increased retention time in an organism or a retarded excretion from an organism compared to a L-nucleic acid comprising only the L-nucleic acid part, and wherein said L-nucleic acid part is a spiegelmer. 
     
     
         3 . The modified L-nucleic acid of  claim 2 , wherein the non-L-nucleic acid part has a molecular weight of more than about 300 Da. 
     
     
         4 . The modified L-nucleic acid of  claim 2 , wherein the modified L-nucleic acid has a molecular weight of about 600 to 500,000 Da. 
     
     
         5 . The modified L-nucleic acid of  claim 2 , wherein the L-nucleic acid part has a molecular weight of 300 to 50,000 Da. 
     
     
         6 . The modified L-nucleic acid of  claim 2 , wherein the non-L-nucleic acid part is linked to the L-nucleic acid part via a functional group of the L-nucleic acid part, wherein the functional group is selected from the group consisting of terminal and non-terminal phosphates, terminal and non-terminal sugar portions, natural and non-natural purine bases, and natural and non-natural pyrimidine bases. 
     
     
         7 . The modified L-nucleic acid of  claim 6 , wherein the linkage of the non-L-nucleic acid part with the L-nucleic acid part is via the 2′-OH—, 3′-OH—, 5′-OH-group or a derivative therefrom, or one or more sugars of the L-nucleic acid part. 
     
     
         8 . The modified L-nucleic acid of  claim 6 , wherein the linkage is via at least one of the positions 5 or 6 of a pyrimidine base. 
     
     
         9 . The modified L-nucleic acid of  claim 6 , wherein the linkage is via a purine base. 
     
     
         10 . The modified L-nucleic acid of  claim 6 , wherein the linkage is at one or more of the exocyclic amine groups, endocyclic amine groups or keto groups of a purine or pyrimidine base or a basic position. 
     
     
         11 . The modified L-nucleic acid of  claim 2 , wherein the non-nucleic acid part is selected from the group consisting of linear poly (ethylene) glycol, branched poly (ethylene) glycol, hydroxyethyl starch, a peptide, a protein, a polysaccharide, a sterol, polyoxypropylene, polyoxyamidate, poly (2-hydroxyethyl)-L-glutamine and polyethylene glycol. 
     
     
         12 . The modified L-nucleic acid of  claim 2 , wherein a linker is arranged between the L-nucleic acid part and the non-L-nucleic acid part. 
     
     
         13 . The modified L-nucleic acid of  claim 2 , wherein said linker is a 6-aminohexylphosphate at the 5′-OH end. 
     
     
         14 . The modified L-nucleic acid of  claim 13 , wherein polyethylene glycol is coupled to the free amine of the aminohexylphosphate linker. 
     
     
         15 . The modified L-nucleic acid of  claim 2 , wherein the molecular weight is more than about 20,000 Da. 
     
     
         16 . The modified L-nucleic acid of  claim 2 , wherein the molecular weight is more than 40,000 Da. 
     
     
         17 . The modified L-nucleic acid of  claim 9 , wherein said linkage occurs at the 8 position. 
     
     
         18 . A pharmaceutical composition comprising the modified L-nucleic acid of  claim 2  and a pharmaceutically acceptable carrier, excipient or diluent. 
     
     
         19 . A method for preparing the modified L-nucleic acid of  claim 2 , comprising the steps:
 (a) providing an L-nucleic acid;   (b) providing a non-L-nucleic acid;   (c) reacting the L-nucleic acid from (a) and the non-L-nucleic acid from (b); and   (d) optionally isolating the modified L-nucleic acid obtained in step (c) wherein the L-nucleic acid part is a Spiegelmer.   
     
     
         20 . The method of  claim 19 , wherein the L-nucleic acid in step (a) comprises a linker. 
     
     
         21 . The method of  claim 19 , wherein after providing the L-nucleic acid in step (a), a linker is provided.