Methods and compositions for treating and diagnosing kidney disease

Abstract

The invention relates to a method for diagnosing a kidney disease state. The method comprises the steps of administering to a patient a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises a diagnostic marker, and diagnosing the kidney disease state. The invention also relates to a method for treating a kidney disease state. The method comprises the steps of administering to a patient suffering from the disease state an effective amount of a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises an antigen, a cytotoxin, or a cell growth inhibitor, and eliminating the disease state.

1 . A method for diagnosing a kidney disease state, said method comprising the steps of:
 administering to a patient a composition comprising a conjugate or complex of the general formula
   V-L-D 
   
     where the group V comprises a vitamin receptor binding ligand that binds to kidney cells and the group D comprises a diagnostic marker; and
 diagnosing the kidney disease state. 
 
   
   
       2 - 11 . (canceled) 
   
   
       12 . A method for treating a kidney disease state, said method comprising the steps of:
 administering to a patient suffering from the disease state an effective amount of a composition comprising a conjugate or complex of the general formula
   V-L-D 
   
     where the group V comprises a vitamin receptor binding ligand that binds to kidney cells and the group D comprises an antigen, a cytotoxin, or a cell growth inhibitor; and
 eliminating the disease state. 
 
   
   
       13 . The method of  claim 12  wherein V comprises a folate. 
   
   
       14 . (canceled) 
   
   
       15 . The method of  claim 12  wherein the group D comprises an antigen. 
   
   
       16 . The method of  claim 13  wherein the group D comprises an antigen. 
   
   
       17 . The method of  claim 12  wherein the group D comprises a cytotoxin. 
   
   
       18 . The method of  claim 17  wherein the group D further comprises a liposome. 
   
   
       19 . The method of  claim 13  wherein the group D comprises a cytotoxin. 
   
   
       20 . The method of  claim 19  wherein the group D further comprises a liposome. 
   
   
       21 . The method of  claim 12  wherein the group D comprises a cell growth inhibitor. 
   
   
       22 - 23 . (canceled) 
   
   
       24 . The method of  claim 13  wherein the group D comprises a cell growth inhibitor. 
   
   
       25 - 26 . (canceled) 
   
   
       27 . The method of  claim 21  wherein the cell growth inhibitor is rapamycin. 
   
   
       28 . The method of  claim 24  wherein the cell growth inhibitor is rapamycin. 
   
   
       29 . A compound of the formula V-L-D, wherein V is a folate receptor binding ligand, L is an optional linker, and D is a cell-growth inhibitor. 
   
   
       30 . The compound of  claim 29  wherein V-L-D has the following formula: 
     
       
         
         
             
             
         
       
       where L is as defined herein, and L is connected to the rapamycin or analog or derivative thereof at either of (O*), and the other of (O*) is substituted with R, wherein R is hydrogen or —CO(CR 3 R 4 ) b (CR 5 R 6 ) d CR 7 R 8 R 9 ; where 
       R 3  and R 4  are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, trifluoromethyl, or F; 
       R 5  and R 6  are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, (CR 3 R 4 ) f OH, CF 3 , F, or CO 2 R 11 ; 
       R 7  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, (CR 3 R 4 ) 10 H, CF 3 , F, or CO 2 R 11 ; 
       R 8  and R 9  are each, independently, hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, (CR 3 R 4 ) f OH, CF 3 , F, or CO 2 R 11 ; 
       R 11  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-7 carbon atoms, alkynyl of 2-7 carbon atoms, or phenylalkyl of 7-10 carbon atoms; 
       b=0-6; d=0-6; and f=0-6. 
     
   
   
       31 . (canceled) 
   
   
       32 . The compound of  claim 29  wherein the cell growth inhibitor is an epidermal growth factor receptor kinase inhibitor. 
   
   
       33 . The compound of  claim 29  wherein the cell growth inhibitor is an inhibitor of mTOR. 
   
   
       34 . The compound of  claim 29  wherein the cell growth inhibitor is a rapamycin. 
   
   
       35 . The compound of  claim 29  wherein the folate receptor binding ligand is a folate. 
   
   
       36 . The compound of  claim 29  wherein the linker is a peptide comprising one or more amino acids selected from the group consisting of cysteine, aspartic acid, and arginine, where the amino acid can be either the D or the L configuration in each instance.