Anti-glypican-3 antibody having improved kinetics in plasma
A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.
1. An isolated anti-glypican 3 antibody which comprises a heavy chain variable region shown in SEQ ID NO: 27 and a light chain variable region shown in SEQ ID NO: 29.
2. The antibody according to claim 1 , comprising a constant region of a human antibody.
3. The antibody according to claim 2 , wherein the constant region comprises a sequence shown in SEQ ID NO: 32 or SEQ ID NO: 33.
4. The antibody according to claim 1 , wherein the antibody has a reduced content of fucose attached to the Fc region of the antibody in comparison with the antibody which has a wild-type human Fc region.
5. A composition comprising the antibody according to any one of claims 2 - 4 and a pharmaceutically acceptable carrier.
6. An anticancer agent comprising as an active ingredient the antibody according to anyone of claims 2 - 4 , wherein the cancer expresses glypican-3.
7. The anticancer agent according to claim 6 , wherein the cancer is liver cancer.
8. An isolated nucleic acid that encodes a heavy or light chain variable region polypeptide of the antibody according to anyone of claims 2 - 4 .
9. An isolated host cell comprising the nucleic acid according to claim 8 .
10. The host cell according to claim 9 , wherein the host cell is a fucose transporter-deficient animal cell, a fucosyltransferase-deleted animal cell, or an animal cell in which a complex branched sugar chain modification is modified.
11. A method for preparing an antibody comprising culturing the host cell according to claim 9 and recovering the antibody from the cell culture.
12. A method for treating a cancer comprising administering to a subject in need of such treatment the antibody according to any one of claims 2 - 4 , wherein the cancer expresses glypican-3.
13. The method according to claim 12 , wherein the cancer is liver cancer.
14. A method for treating a cancer comprising administering to a subject in need of such treatment the composition according to claim 5 , wherein the cancer expresses glypican-3.
15. The method according to claim 14 , wherein the cancer is liver cancer.
16. A method for preparing an antibody comprising culturing the host cell according to claim 10 and recovering the antibody from the cell culture.