Antibody-drug conjugates

Abstract

Disclosed are anti-5T4 antibody drug conjugates and methods for preparing and using the same.

We Claim: 
     
         1 . An antibody-drug conjugate of the formula:
   Ab-(LU-D)p   
       or a pharmaceutically acceptable salt thereof wherein;
 (a) Ab is an anti-5T4 antibody or antigen binding portion thereof, comprising:
 (i) a VH CDR1 region as shown in SEQ ID NO: 5, 
 (ii) a VH CDR2 region as shown in SEQ ID NO: 6, 
 (iii) a VH CDR3 region as shown in SEQ ID NO: 7; 
 (iv) a VL CDR1 region as shown in SEQ ID NO: 8, 
 (v) a VL CDR2 region as shown in SEQ ID NO: 9, and 
 (vi) a VL CDR3 region as shown in SEQ ID NO: 10, 
 
 (b) LU is a linker unit selected from the group consisting of maleimidocaproyl and maleim idocaproyl-Val-Cit, 
 (c) p is an integer from about 1 to about 8, and 
 (d) D is a Drug unit selected from the group consisting of MMAE, MMAD, and MMAF. 
 
     
     
         2 . The antibody-drug conjugate of  claim 1  wherein said anti-5T4 antibody or antigen binding portion thereof, comprises the VH region of SEQ ID NO: 3 and the VL region of SEQ ID NO: 4. 
     
     
         3 . The antibody-drug conjugate of  claim 2  wherein said anti-5T4 antibody or antigen binding portion thereof, consists of a heavy chain having SEQ ID NO:1 and a light chain having SEQ ID NO: 2. 
     
     
         4 . The antibody-drug conjugate of  claim 3 , wherein said antibody or antigen binding portion thereof, recognizes an epitope on human 5T4 antigen, wherein said epitope comprises amino acid residues 173-258 and 282-361 of the amino acid sequence of SEQ ID NO:11. 
     
     
         5 . The antibody-drug conjugate of  claim 1  wherein:
 (a) said anti-5T4 antibody consists of a heavy chain having SEQ ID NO:1 and a light chain having SEQ ID NO: 2, 
 (b) said LU is maleimidocaproyl, 
 (c) said Drug is MMAF, and 
 (d) p is 4. 
 
     
     
         6 . A pharmaceutical composition comprising the antibody-drug conjugate of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         7 . A method of treating 5T4-positive cancer in a patient in need thereof, comprising administering to said patient the antibody-drug conjugate according to  claim 1 . 
     
     
         8 . The method of  claim 7  wherein said cancer is selected from the group consisting of colorectal, breast, pancreatic, and non-small cell lung carcinomas.