Platelet derived growth factor (PDGF) nucleic acid ligand complexes

Abstract

This invention discloses a method for preparing a complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a PDGF Nucleic Acid Ligand by SELEX methodology and associating the PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more PDGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a PDGF Nucleic Acid Ligand or Complex and methods for making the same.

1 . A method for the preparation of a Complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound, said method comprising: 
 a) identifying a PDGF Nucleic Acid Ligand from a Candidate Mixture of Nucleic Acids by the method comprising:    b) contacting the Candidate Mixture with PDGF, wherein Nucleic Acids having an increased affinity to PDGF relative to the Candidate Mixture may be partitioned from the remainder of the Candidate Mixture;    c) partitioning the increased affinity PDGF Nucleic Acids from the remainder of the Candidate Mixture;    e) amplifying the increased affinity PDGF Nucleic Acids to yield a ligand-enriched mixture of Nucleic Acids; and    f) associating said identified PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound.    
     
     
         2 . The method of  claim 1  wherein said Complex is further associated with a Lipid Construct.  
     
     
         3 . The method of  claim 2  wherein said Lipid Construct is a Liposome.  
     
     
         4 . The method of  claim 3  wherein said Complex is comprised of a PDGF Nucleic Acid Ligand and a Lipophilic Compound and wherein said Complex is passively associated with the bilayer of said Liposomes by the method comprising the steps of: 
 a) forming a liposome; and    b) mixing said Complex comprised of a Nucleic Acid Ligand and a Lipophilic Compound with the Liposomes of step a) whereby the Nucleic Acid Ligand Component of said Complex becomes associated with the bilayer of the Liposome and projects from the exterior of the Lipid bilayer.    
     
     
         5 . The method of  claim 4  wherein said Complex further comprises a Linker between said Ligand and said Lipophilic Compound.  
     
     
         6 . The method of  claim 4  wherein said Ligand comprises a Linker.  
     
     
         7 . A method for improving the pharmacokinetic properties of a PDGF Nucleic Acid Ligand comprising: 
 covalently linking said PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound to form a Complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound; and administering said Complex to a patient.    
     
     
         8 . A method for targeting a therapeutic or diagnostic agent to a specific predetermined biological target that is expressing PDGF in a patient comprising: 
 covalently linking said therapeutic or diagnostic agent with a Complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound, and administering said Complex to a patient.