Antibody-drug conjugates

Abstract

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

1 . A process for producing an antibody-drug conjugate of the formula:
 Ab-(LU-D)p, wherein:
 (a) Ab is an anti-5T4 antibody comprising a VH CDR1 region as shown in SEQ ID NO: 5; a VH CDR2 region as shown in SEQ ID NO: 6; a VH CDR3 region as shown in SEQ ID NO: 7; a VL CDR1 region as shown in SEQ ID NO: 8; a VL CDR2 region as shown in SEQ ID NO: 9; and, 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 maleimidocaproyl-Val-Cit; 
 (c) D is a Drug unit selected from the group consisting of MMAE and MMAF; 
 (d) p is an integer from about 1 to about 8 said process further comprising: 
 (e) chemically linking LU to D to form LU-D; 
 (f) conjugating said LU-D to the Ab of (a); and, 
 (g) purifying the antibody-drug conjugate. 
   
     
     
         2 . The process of  claim 1  wherein LU is maleimidocaproyl, D is MMAF, and p is about 4. 
     
     
         3 . The process of  claim 1 , wherein said anti-5T4 antibody comprises a VH region of SEQ ID NO: 3 and a VL region of SEQ ID NO: 4. 
     
     
         4 . The process of  claim 3 , wherein said anti-5T4 antibody comprises a heavy chain having SEQ ID NO: 1 and a light chain having SEQ ID NO: 2.