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 . (Currently Modified) A pharmaceutical composition comprising: (a) a pharmaceutically acceptable carrier, excipient or diluent; and (b) a modified L-nucleic acid, comprising an L-nucleic acid and a non-L-nucleic acid, wherein the L-nucleic acid is conjugated with the non-L-nucleic acid, wherein said modified L-nucleic acid comprises increased retention time in an organism as compared to a retention time in said organism of said L-nucleic acid, and wherein said L-nucleic acid is a spiegelmer. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid has a molecular weight of more than about 300 Da. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the modified L-nucleic acid has a molecular weight of about 600 to 500,000 Da. 
     
     
         5 . The pharmaceutical composition of  claim 2 , wherein the L-nucleic acid has a molecular weight of 300 to 50,000 Da. 
     
     
         6 . The pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid is linked to the L-nucleic acid via a functional group of the L-nucleic acid, 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 pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid is linked to the L-nucleic acid is via a 2′-OH-, 3′-OH-, 5′-OH-group or a derivative therefrom, or one or more sugars of the L-nucleic acid. 
     
     
         8 . The pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid is linked to the L-nucleic acid via at least one of the positions 5 or 6 of a pyrimidine base. 
     
     
         9 . The pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid is linked to the L-nucleic acid via a purine base. 
     
     
         10 . The pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid is linked to the L-nucleic acid at one or more of exocyclic amine groups, endocyclic amine groups or keto groups of a purine or pyrimidine base or a basic position. 
     
     
         11 . The pharmaceutical composition of  claim 2 , wherein the non-L-nucleic acid 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 pharmaceutical composition of  claim 2 , wherein a linker is arranged between the L-nucleic acid and the non-L-nucleic acid. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein said linker is a 6-aminohexylphosphate at a 5′-OH end. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein polyethylene glycol is coupled to the a free amine of the aminohexylphosphate linker. 
     
     
         15 . The pharmaceutical composition of  claim 2 , wherein molecular weight of said modified L-nucleic acid is more than about 20,000 Da. 
     
     
         16 . The pharmaceutical composition of  claim 2 , wherein molecular weight of said modified L-nucleic acid is more than 40,000 Da. 
     
     
         17 . The pharmaceutical composition of  claim 9 , wherein said linkage occurs at the purine 8 position. 
     
     
         18 . The pharmaceutical composition of  claim 2 , wherein said spiegelmer binds to a virus, a viroid, a bacterium, a cell, an organelle, a protein, a peptide, a nucleic acid, a pharmaceutical agent or a metabolite thereof. 
     
     
         19 .- 21 . (canceled)