Humanized antibody against fibroblast growth factor-8 and antibody fragment thereof
The present invention relates to an antibody against FGF-8, particularly a humanized antibody against FGF-8 and the antibody fragment thereof, a DNA sequence encoding the above antibody or the antibody fragment, a vector comprising the DNA sequence and a host cell transformed by the vector, a production process of the above antibody or the antibody fragment using the host cell, and a therapeutic agent and a diagnostic agent for cancer using the antibody or the antibody fragment.
1. A human complementarity determining region (CDR)-grafted antibody which specifically reacts with fibroblast growth factor-8 (FGF-8) and inhibits biological function of FGF-8, or a FGF-8-binding antibody fragment thereof,
wherein a heavy chain variable region (VH) of the antibody comprises the amino acid sequence represented by SEQ ID NO:16, and
wherein a light chain variable region (VL) of the antibody comprises the amino acid sequence represented by SEQ ID NO:19.
2. A human complementarity determining region (CDR)-grafted antibody which specifically reacts with fibroblast growth factor-8 (FGF-8) and inhibits biological function of FGF-8, or a FGF-8-binding antibody fragment thereof,
wherein a heavy chain variable region (VH) of the antibody comprises the amino acid sequence represented by SEQ ID NO:16, and
wherein a light chain variable region (VL) of the antibody comprises the amino acid sequence represented by SEQ ID NO:38.
3. A human complementarity determining region (CDR)-grafted antibody which specifically reacts with fibroblast growth factor-8 (FGF-8) and inhibits biological function of FGF-8, or a FGF-8-binding antibody fragment thereof,
wherein a heavy chain variable region (VH) of the antibody comprises the amino acid sequence represented by SEQ ID NO:16, and
wherein a light chain variable region (VL) of the antibody comprises the amino acid sequence represented by SEQ ID NO:39.
4. An isolated DNA encoding the variable region of the human CDR-grafted antibody or the FGF-8-binding antibody fragment thereof according to any of claims 1 , 2 or 3 .
5. A recombinant vector comprising the DNA according to claim 4 .
6. An isolated transformed host cell comprising the recombinant vector according to claim 5 .
7. A process for producing an antibody or a FGF-8-binding antibody fragment thereof, which comprises culturing the transformed host cell according to claim 6 in a medium to prepare and accumulate the human CDR-grafted antibody or the FGF-8-binding antibody fragment in the culture, and recovering the human CDR-grafted antibody or the FGF-8-binding antibody fragment thereof from the culture.
8. A composition which comprises at least one selected from the human CDR-grafted antibody and the FGF-8-binding antibody fragment thereof according to any of claims 1 , 2 or 3 , and a pharmaceutically acceptable carrier.