Bispecific, bivalent anti-vegf/anti-ang-2 antibodies

Abstract

The present invention relates to bispecific, bivalent antibodies against human vascular endothelial growth factor (VEGF/VEGF-A) and against human angiopoietin-2 (ANG-2), methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

1 .- 20 . (canceled) 
     
     
         21 . A bispecific, bivalent antibody comprising a first antigen-binding site that specifically binds to human VEGF, a second antigen-binding site that specifically binds to human ANG-2, and a modified constant variable domain of a human IgG1 subclass, wherein:
 i) said first antigen-binding site comprises a heavy chain variable domain (VH) of SEQ ID NO: 1, and a light chain variable domain (VL) of SEQ ID NO: 2;   ii) said second antigen-binding site comprises a VH of SEQ ID NO: 3, and a VL of SEQ ID NO: 4; and   iii) said modified constant variable domain comprises a heavy constant variable domain (CH1) and a light constant variable domain (CL), wherein:
 a) said CL of said second antigen-binding site is replaced by the CH1 of said second antigen-binding site; and 
 b) said CH1 of said second antigen-binding site is replaced by the CL of said second antigen-binding site. 
   
     
     
         22 . The bispecific antibody according to  claim 21 , wherein:
 i) the first antigen binding site comprises a heavy chain amino acid sequence of SEQ ID NO: 7, and a light chain amino acid sequence of SEQ ID NO: 5, and   ii) the second antigen binding site comprises a modified heavy chain amino acid sequence of SEQ ID NO: 8, and a modified light chain amino acid sequence of SEQ ID NO: 6.   
     
     
         23 . The bispecific antibody according to  claim 21 , wherein:
 i) the first antigen binding site comprises a heavy chain amino acid sequence of SEQ ID NO: 11, and a light chain amino acid sequence of SEQ ID NO: 9, and   ii) the second antigen binding site comprises a modified heavy chain amino acid sequence of SEQ ID NO: 12, and a modified light chain amino acid sequence of SEQ ID NO: 10.   
     
     
         24 . The bispecific antibody according to  claim 21 , wherein:
 i) the first antigen binding site comprises a heavy chain amino acid sequence of SEQ ID NO: 15, and a light chain amino acid sequence of SEQ ID NO: 13, and   ii) the second antigen binding site comprises a modified heavy chain amino acid sequence of SEQ ID NO: 16, and a modified light chain amino acid sequence of SEQ ID NO: 14.   
     
     
         25 . A method of treating a patient suffering from cancer, comprising administering to the patient an effective amount of the antibody of  claim 21 . 
     
     
         26 . A method of treating a patient suffering from cancer, comprising administering to the patient an effective amount of the antibody of  claim 22 . 
     
     
         27 . A method of treating a patient suffering from cancer, comprising administering to the patient an effective amount of the antibody of  claim 23 . 
     
     
         27 . A method of treating a patient suffering from cancer, comprising administering to the patient an effective amount of the antibody of  claim 24 . 
     
     
         28 . The method of  claim 25 , wherein the cancer is colorectal cancer, breast cancer, or gastric cancer. 
     
     
         29 . The method of  claim 26 , wherein the cancer is colorectal cancer, breast cancer, or gastric cancer. 
     
     
         30 . The method of  claim 27 , wherein the cancer is colorectal cancer, breast cancer, or gastric cancer. 
     
     
         31 . The method of  claim 28 , wherein the cancer is colorectal cancer, breast cancer, or gastric cancer.