Anti-Glypican 3 Antibody

Abstract

An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.

1 . An isolated polynucleotide comprising a sequence that encodes an antibody heavy chain variable region of any one of (1)-(7):
 (1) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 84;   (2) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 85;   (3) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 86;   (4) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87;   (5) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 88;   (6) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 89; or   (7) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 90.   
     
     
         2 . The polynucleotide of  claim 1 , further comprising a sequence that encodes an antibody light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:92. 
     
     
         3 . An expression vector comprising the polynucleotide of  claim 1 . 
     
     
         4 . A host cell comprising the polynucleotide of  claim 1 . 
     
     
         5 . An isolated polynucleotide comprising a sequence that encodes an antibody heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively. 
     
     
         6 . The polynucleotide of  claim 5 , wherein the antibody heavy chain variable region is humanized. 
     
     
         7 . An expression vector comprising the polynucleotide of  claim 5 . 
     
     
         8 . A host cell comprising the polynucleotide of  claim 5 . 
     
     
         9 . An isolated polynucleotide comprising a sequence that encodes an antibody light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:92. 
     
     
         10 . An expression vector comprising the polynucleotide of  claim 9 . 
     
     
         11 . A host cell comprising the polynucleotide of  claim 9 . 
     
     
         12 . An isolated polynucleotide comprising a sequence that encodes an antibody light chain variable region of any one of (1)-(16) below:
 (1) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 143, 144 and 158, respectively   (2) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 174, 144 and 158, respectively;   (3) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 175, 144 and 158, respectively;   (4) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 176, 144 and 158, respectively;   (5) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 177, 144 and 158, respectively;   (6) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 178, 144 and 158, respectively;   (7) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 179, 144 and 158, respectively;   (8) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 180, 144 and 158, respectively;   (9) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 181, 144 and 158, respectively;   (10) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 182, 144 and 158, respectively;   (11) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 183, 144 and 158, respectively;   (12) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 184, 144 and 158, respectively;   (13) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 185, 144, and 158, respectively;   (14) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 186, 144 and 158, respectively;   (15) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 187, 144 and 158, respectively; and   (16) a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 188, 144 and 158, respectively.   
     
     
         13 . The polynucleotide of  claim 12 , wherein the antibody light chain variable region is humanized. 
     
     
         14 . An expression vector comprising the polynucleotide of  claim 12 . 
     
     
         15 . The expression vector of  claim 14 , wherein the vector further comprises a sequence that encodes an antibody heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively. 
     
     
         16 . A host cell comprising the polynucleotide of  claim 12 . 
     
     
         17 . The host cell of  claim 16 , wherein the host cell further comprises a polynucleotide comprising a sequence that encodes an antibody heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively.