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.

1 - 37 . (canceled)  
     
     
         38 . A method of increasing by at least 2-fold the pharmaceutically acceptable dosage of a protein conjugate for therapeutic or diagnostic purposes, said method comprising: 
 administering to a patient one or more compounds selected from the group consisting of D-lysine, poly-lysine having a molecular weight in the range of 1-60 kD, pharmaceutically acceptable salts thereof and carboxyl derivatives thereof, wherein said protein conjugate has a molecular weight that is not greater than about 60 kD,    wherein the pharmaceutically acceptable salt and carboxyl derivative of poly-lysine has a molecular weight in the range of 1-60 kD,    wherein said 2-fold increase is relative to administration of said protein conjugate in the absence of administering said one or more compounds selected from the group consisting of D-lysine, poly-lysine having a molecular weight in the range of 1-60 kD, pharmaceutically acceptable salts thereof or carboxyl derivatives thereof.    
     
     
         39 . The method of  claim 38 , which increases by 2-3 fold the pharmaceutically acceptable dosage of said protein conjugates.  
     
     
         40 . The method of  claim 38 , wherein said protein conjugate is selected from the group consisting of peptide conjugates, polypeptide conjugates, glycoprotein conjugates, lipoprotein conjugates, antibody conjugates, and antibody fragment conjugates.  
     
     
         41 . The method of  claim 38 , wherein said protein conjugate is a radiolabeled conjugate.  
     
     
         42 . The method of  claim 41 , wherein the radiolabel in said radiolabeled conjugate is an imaging isotope.  
     
     
         43 . The method of  claim 41 , wherein the radiolabel in said radiolabeled conjugate is a therapeutic isotope.  
     
     
         44 . The method of  claim 38 , wherein said protein conjugate is selected from the group consisting of radiolabeled hapten conjugates and haptens conjugated to a cytotoxic agent.  
     
     
         45 . The method of  claim 38 , wherein said protein conjugate comprises a cytotoxic agent.  
     
     
         46 . The method of  claim 38 , wherein D-lysine is administered to said patient.  
     
     
         47 . The method of  claim 38 , wherein poly-D-lysine is administered to said patient.  
     
     
         48 . The method of  claim 38 , wherein a mixture of at least two of said compounds is administered to said patient.  
     
     
         49 . The method of  claim 38 , wherein said poly-lysine has a molecular weight of 15-30 kD.  
     
     
         50 . The method of  claim 38 , wherein said compound is parenterally administered to said patient in a physiologically acceptable aqueous solution.  
     
     
         51 . The method of  claim 50 , wherein said physiologically acceptable aqueous solution is administered to said patient by continuous infusion.  
     
     
         52 . The method of  claim 50 , wherein said physiologically acceptable aqueous solution is administered to said patient by means of at least one injection of a bolus of said solution.  
     
     
         53 . The method of  claim 50 , 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.  
     
     
         54 . The method of  claim 38 , wherein said compound is orally administered to said patient in a physiologically acceptable carrier.