Antibodies against immunogenic glycopeptides, compositions comprising the same and use thereof

Abstract

Disclosed herein are antibodies which specifically bind to at least one epitope defined by the immunogenic glycopeptide. Other aspects of the present disclosure are pharmaceutical composition comprising the antibody; and method for preventing and/or treating Globo-H-positive cancer.

What is claimed is: 
     
         1 . An anti-Globo H antibody or an antigen-binding portion thereof comprising:
 (a) H-CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1, 2, 3 and 4 or a variant having amino acid sequence with at least 80% identity to any of SEQ ID NOs: 1 to 4;   (b) H-CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 5 and 6 or a variant having amino acid sequence with at least 80% identity to SEQ ID NOs: 5 or 6;   (c) H-CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 7, 8 and 9 or a variant having amino acid sequence with at least 80% identity to any of SEQ ID NOs: 7 to 9;   (d) L-CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 10, 11, 12 and 13 or a variant having amino acid sequence with at least 80% identity to any of SEQ ID NOs: 10 to 13;   (e) L-CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 14, 15 and 16 or a variant having amino acid sequence with at least 80% identity to any of SEQ ID NOs: 14 to 16; and   (f) L-CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 17, 18 and 19 or a variant having amino acid sequence with at least 80% identity to any of SEQ ID NOs: 17 to 19.   
     
     
         2 . The antibody or an antigen-binding portion thereof of  claim 1 , wherein the sequence identity is at least 90%. 
     
     
         3 . The antibody or an antigen-binding portion thereof of  claim 1 , which is a monoclonal antibody, chimeric antibody or humanized antibody. 
     
     
         4 . The antibody or an antigen-binding portion thereof of  claim 1  comprising
 (i) a heavy chain variable region comprising H-CDR1 selected from the group consisting of SEQ ID NOs: 1 to 4, H-CDR2 selected from the group consisting of SEQ ID NOs: 5 and 6, and H-CDR3 selected from the group consisting of SEQ ID NOs: 7 to 9, and 
 (ii) light chain variable regions comprising L-CDR1 selected from the group consisting of SEQ ID NOs: 10 to 13, L-CDR2 selected from the group consisting of SEQ ID NOs: 14 to 16, and L-CDR3 selected from the group consisting of SEQ ID NOs: 17 to 19. 
 
     
     
         5 . The antibody or an antigen-binding portion thereof of  claim 1 , wherein H-CDR1 comprises SEQ ID NO:3; H—CRD2 comprises SEQ ID NO:5; H-CDR3 comprises SEQ ID NO:8; L-CDR1 comprises SEQ ID NO:12; L-CDR2 comprises SEQ ID NO:16; and L-CDR3 comprises SEQ ID NO:18. 
     
     
         6 . The antibody or an antigen-binding portion thereof of  claim 1  comprising
 (i) a heavy chain variable region comprising an amino acid sequence at least 80% identity to any of the amino acid sequences of SEQ ID NOs: 140 to 163, and 
 (ii) a light chain variable region comprising an amino acid sequence at least 80% identity to any of the amino acid sequence of SEQ ID NO: 164 to 199. 
 
     
     
         7 . The antibody or an antigen-binding portion thereof of  claim 6 , wherein the sequence identity is at least 90%. 
     
     
         8 . The antibody or an antigen-binding portion thereof of  claim 6  comprising
 (i) a heavy chain variable region comprising an amino acid sequence at least 80% identical to the amino acid sequences of SEQ ID NO: 147, and 
 (ii) a light chain variable region comprising an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 195. 
 
     
     
         9 . The antibody or an antigen-binding portion thereof of  claim 6  comprising
 (i) a heavy chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 147, and 
 (ii) a light chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 195. 
 
     
     
         10 . The antibody or an antigen-binding portion thereof of  claim 1  comprising
 (i) a heavy chain variable region comprising an amino acid sequence at least 80% identical to any of the amino acid sequences of SEQ ID NOs: 20 to 43, and 
 (ii) a light chain variable region comprising an amino acid sequence at least 80% identical to any of the amino acid sequence of SEQ ID NO: 44 to 79 and 200 to 235. 
 
     
     
         11 . The antibody or an antigen-binding portion thereof of  claim 10 , wherein the sequence identity is at least 90%. 
     
     
         12 . The antibody or an antigen-binding portion thereof of  claim 10  comprising
 (i) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 20 to 43, and 
 (ii) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 44 to 79 and 200 to 235. 
 
     
     
         13 . The antibody or an antigen-binding portion thereof of  claim 10  comprising
 (i) a heavy chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 27, and a light chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 75; or 
 (ii) a heavy chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 27, and a light chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 231. 
 
     
     
         14 . The antibody or an antigen-binding portion thereof of  claim 1  comprising
 (i) a heavy chain variable region comprising an amino acid sequence at least 80% identical to any of the amino acid sequences of SEQ ID NOs: 80 to 103, and 
 (ii) a light chain variable region comprising an amino acid sequence at least 80% identical to any of the amino acid sequence of SEQ ID NOs: 104 to 139. 
 
     
     
         15 . The antibody or an antigen-binding portion thereof of  claim 14  comprising
 (i) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 80 to 103, and 
 (ii) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 104 to 139. 
 
     
     
         16 . The antibody or an antigen-binding portion thereof of  claim 14  comprising a heavy chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 90, and a light chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 135. 
     
     
         17 . The antibody or an antigen-binding portion thereof of  claim 1  comprising
 (i) a heavy chain variable region comprising an amino acid sequence at least 80% identical to any of the amino acid sequences of SEQ ID NOs: 140-163 wherein the last third sequence “V” of the amino acid sequences is changed to “I,” and 
 (ii) a light chain variable region comprising an amino acid sequence at least 80% identical to any of the amino acid sequence of SEQ ID NO:164-199. 
 
     
     
         18 . The antibody or an antigen-binding portion thereof of  claim 17 , comprising
 (i) a heavy chain variable region comprising an amino acid sequence at least 80% identical to the amino acid sequences of SEQ ID NO: 147 wherein the last third sequence “V” of the amino acid sequence is changed to “I,” and   (ii) a light chain variable region comprising an amino acid sequence at least 80% identical to the amino acid sequence of SEQ ID NO: 195.   
     
     
         19 . The antibody or an antigen-binding portion thereof of  claim 17 , comprising
 (i) a heavy chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 147 wherein the last third sequence “V” of the amino acid sequence is changed to “I”, and   (ii) a light chain variable region comprising an amino acid sequence consisting of SEQ ID NO: 195.   
     
     
         20 . A pharmaceutical composition comprising the antibody or an antigen-binding portion thereof  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         21 . The pharmaceutical composition of  claim 20 , further comprising an anti-tumor drug.