Nucleic acid ligand complexes

Abstract

This invention discloses a method for preparing a therapeutic or diagnostic complex comprised of a nucleic acid ligand and a lipophilic compound or non-immunogenic, high molecular weight compound by identifying a nucleic acid ligand by SELEX methodology and associating the nucleic acid ligand with a lipophilic compound or a non-immunogenic, high molecular weight compound. The invention further discloses complexes comprising one or more nucleic acid ligands in association with a lipophilic compound or non-immunogenic, high molecular weight compound.

1 . A therapeutic complex comprising a nucleic acid ligand and a polyethylene glycol (PEG) wherein said nucleic acid ligand is covalently linked to said PEG and wherein said nucleic acid ligand has a specific binding affinity for vascular endothelial growth factor (VEGF), wherein said PEG is at least about 1000 Daltons.  
     
     
         2 . The complex of  claim 1  wherein said PEG is about 10,000 Daltons.  
     
     
         3 . The complex of  claim 1  wherein said PEG is about 20,000 Daltons.  
     
     
         4 . The complex of  claim 1  wherein said PEG is about 40,000 Daltons.  
     
     
         5 . The complex of  claim 4  wherein said nucleic acid ligand comprises a 2′-O methyl pyrimidine nucleotide.  
     
     
         6 . A method of improving the pharmacokinetic properties of a nucleic acid ligand comprising covalently linking said nucleic acid ligand to a PEG, wherein said nucleic acid ligand has a specific binding affinity for VEGF, wherein said PEG is at least about 1000 Daltons.  
     
     
         7 . The method of  claim 6  wherein said PEG is about 10,000 Daltons.  
     
     
         8 . The method of  claim 6  wherein said PEG is about 20,000 Daltons.  
     
     
         9 . The method of  claim 6  wherein said PEG is about 40,000 Daltons.  
     
     
         10 . The method of  claim 9  wherein said nucleic acid ligand comprises a 2′-O methyl pyrimidine nucleotide.