Methods for reduced renal uptake of protein conjugates

Abstract

Kidney uptake of antibody fragment conjugates and protein conjugates in patients is reduced by administration to the patient of one or more compounds selected from the group consisting of D-lysine, poly-D-lysine, or poly-L-lysine, or pharmaceutically acceptable salts or carboxyl derivatives thereof.

What is claimed is:  
     
         1 . A method of reducing kidney retention of a protein conjugate in a patient, comprising administering to said patient one or more compounds selected from the group consisting of D-lysine, poly-D-lysine having a molecular weight in the range 1-60 kD, poly-L-lysine having a molecular weight in the range 1-60 kD, pharmaceutically acceptable salts thereof and carboxyl derivatives thereof, 
 wherein the pharmaceutically acceptable salts and carboxyl derivatives of poly-D-lysine or poly-L-lysine have a molecular weight in the range 1-60 kD,    whereby said compound or compounds reduce kidney retention of said conjugates.    
     
     
         2 . A method according to  claim 1 , wherein said protein conjugate is selected from the group consisting of protein conjugates, peptide conjugates, polypeptide conjugates, glycoprotein conjugates, lipoprotein conjugates, antibody conjugates, antibody fragment conjugates and the metabolic products thereof.  
     
     
         3 . A method according to  claim 1 , wherein said protein conjugate is a radiolabeled conjugate.  
     
     
         4 . A method according to  claim 3 , wherein the radiolabel in said radiolabeled conjugate is an imaging isotope.  
     
     
         5 . A method according to  claim 3 , wherein the radiolabel in said radiolabeled conjugate is an therapeutic isotope.  
     
     
         6 . A method according to  claim 1 , wherein said protein conjugate is selected from the group consisting of radiolabeled hapten conjugates and haptens conjugated to a cytotoxic agent.  
     
     
         7 . A method according to  claim 1 , wherein said protein conjugate comprises a cytotoxic agent.  
     
     
         8 . The method according to  claim 1 , wherein D-lysine is administered to said patient.  
     
     
         9 . The method according to  claim 1 , wherein poly-D-lysine is administered to said patient.  
     
     
         10 . The method according to  claim 1 , wherein poly-L-lysine is administered to said patient.  
     
     
         11 . The method according to  claim 1 , wherein a mixture of at least two of said compounds is administered to said patient.  
     
     
         12 . The method according to  claim 1 , wherein said poly-D-lysine and said poly-L-lysine each have a molecular weight of 15-30 kD.  
     
     
         13 . The method according to  claim 1 , wherein said compound is parenterally administered to said patient in a physiologically acceptable aqueous solution.  
     
     
         14 . The method according to  claim 13 , wherein said physiologically acceptable aqueous solution is administered to said patient by continuous infusion.  
     
     
         15 . The method according to  claim 13 , wherein said physiologically acceptable aqueous solution is administered to said patient by means of at least one injection of a bolus of said solution.  
     
     
         16 . The method according to  claim 15 , wherein said physiologically acceptable aqueous solution is administered to said patient by means of at least one injection of a bolus of said solution followed by oral administration in a physiologically acceptable carrier  
     
     
         17 . The method according to  claim 1 , wherein said compound is orally administered to said patient in a physiologically acceptable carrier.  
     
     
         18 . A method of r educing kidney retention of a protein conjugate in a patient undergoing treatment with a targeting protein conjugate comprising administering to said patient, one or more compounds selected from the group consisting of D-lysine, poly-D-lysine having a molecular weight in the range 1-60 kD, poly-L-lysine having a molecular weight in the range 1-60 kD, pharmaceutically acceptable salts thereof and carboxyl derivatives thereof, 
 wherein the pharmaceutically acceptable salts and carboxyl derivatives of poly-D-lysine or poly-L-lysine have a molecular weight in the range 1-60 kD,    whereby said compound or compounds reduce kidney retention of said conjugates.    
     
     
         19 . A method according to  claim 18 , wherein said protein conjugate is selected from the group consisting of protein conjugates, peptide conjugates, polypeptide conjugates, glycoprotein conjugates, lipoprotein conjugates, antibody conjugates, antibody fragment conjugates and the metabolic products thereof.  
     
     
         20 . A method according to  claim 18 , wherein said targeting protein conjugate comprises a ribonucleic acid binding protein.  
     
     
         21 . A method according to  claim 20 , wherein said ribonucleic acid binding protein is a ribonuclease.  
     
     
         22 . A method according to  claim 21 , wherein said ribonuclease is an onconase or recombinant form thereof.  
     
     
         23 . A method according to  claim 18 , wherein said protein conjugate is a radiolabeled conjugate.  
     
     
         24 . A method according to  claim 22 , wherein the radiolabel in said radiolabeled conjugates is an imaging isotope.  
     
     
         25 . A method according to  claim 22 , wherein the radiolabel in said radiolabeled conjugates is a therapeutic isotope.  
     
     
         26 . A method according to  claim 18 , wherein said protein conjugate is selected from the group consisting of radiolabeled hapten conjugates and haptens conjugated to a cytotoxic agent.  
     
     
         27 . A method according to  claim 18 , wherein said protein conjugate comprises a cytotoxic agent.  
     
     
         28 . The method according to  claim 18 , wherein D-lysine is administered to said patient.  
     
     
         29 . The method according to  claim 18 , wherein poly-D-lysine is administered to said patient.  
     
     
         30 . The method according to  claim 18 , wherein poly-L-lysine is administered to said patient.  
     
     
         31 . The method according to  claim 18 , wherein a mixture of at least two of said compounds is administered to said patient.  
     
     
         32 . The method according to  claim 18 , wherein said poly-D-lysine and said poly-L-lysine each have a molecular weight of 15-30 kD.  
     
     
         33 . The method according to  claim 18 , wherein said compound is parenterally administered to said patient in a physiologically acceptable aqueous solution.  
     
     
         34 . The method according to  claim 33 , wherein said physiologically acceptable aqueous solution is administered to said patient by continuous infusion.  
     
     
         35 . The method according to  claim 34 , wherein said physiologically acceptable aqueous solution is administered to said patient by means of at least one injection of a bolus of said solution.  
     
     
         36 . The method according to  claim 35 , wherein said physiologically acceptable aqueous solution is administered to said patient by means of at least one injection of a bolus of said solution followed by oral administration in a physiologically acceptable carrier .  
     
     
         37 . The method according to  claim 18 , wherein said compound is orally administered to said patient in a physiologically acceptable carrier.