Human CDR-grafted antibody and antibody fragment thereof
View Patent ↗A human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of human CC chemokine receptor 4 (CCR4) but does not react with a human blood platelet; a human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of CCR4 and has a cytotoxic activity against a CCR4-expressing cell; and a medicament, a therapeutic agent or a diagnostic agent comprising at least one of the antibodies and the antibody fragments thereof as an active ingredient.
1. A human CDR-grafted antibody or antibody fragment thereof which reacts with an extracellular region of human CC chemokine receptor 4 (CCR4) but does not specifically react with a human platelet, wherein said extracellular region is an epitope present in SEQ ID NO: 37, and
wherein the human CDR-grafted antibody or antibody fragment thereof comprises an antibody heavy chain (H chain) variable region (V region) comprising SEQ ID NO:4, 9, 10, 11, 38, 39, 40 or 41.
2. The human CDR-grafted antibody or antibody fragment thereof according to claim 1 , which further specifically reacts with a cell expressing said extracellular region of human CC chemokine receptor 4 (CCR4).
3. The human CDR-grafted antibody or antibody fragment according to claim 1 or 2 , which comprises an antibody heavy chain (H chain) variable region (V region) comprising SEQ ID NO:9 or 10; and an antibody light chain (L chain) V region comprising SEQ ID NO:14.
4. A process for producing a human CDR-grafted antibody or antibody fragment, comprising the steps of:
culturing a transformant which produces the human CDR-grafted antibody or antibody fragment thereof according to claim 3 in a medium to form and accumulate the human CDR-grafted antibody or antibody fragment in the culture; and
recovering the antibody or antibody fragment from the culture.
5. The human CDR-grafted antibody or the antibody fragment according to claim 3 and which has a cytotoxic activity against a cell expressing said extracellular region of human CC chemokine receptor 4 (CCR4).
6. A human CDR-grafted antibody or antibody fragment thereof in which the human CDR-grafted antibody or antibody fragment according to claim 3 is chemically conjugated to a radioisotope, protein or agent, or fused to a protein in the form of a fusion antibody.
7. A composition comprising at least one human CDR-grafted antibody or antibody fragment according to claim 3 as an active ingredient, together with a pharmaceutically acceptable carrier.
8. The human CDR-grafted antibody or antibody fragment according to claim 1 or 2 , further comprising an antibody light chain (L chain) V region comprising SEQ ID NO:8, 12, 13 or 14.
9. A process for producing a human CDR-grafted antibody or antibody fragment, comprising the steps of:
culturing a transformant which produces the human CDR-grafted antibody or antibody fragment thereof according to claim 8 in a medium to form and accumulate the human CDR-grafted antibody or antibody fragment in the culture; and
recovering the antibody or antibody fragment from the culture.
10. The human CDR-grafted antibody or the antibody fragment according to claim 8 and which has a cytotoxic activity against a cell expressing said extracellular region of human CC chemokine receptor 4 (CCR4).
11. A human CDR-grafted antibody or antibody fragment thereof in which the human CDR-grafted antibody or antibody fragment according to claim 8 is chemically conjugated to a radioisotope, protein or agent, or fused to a protein in the form of a fusion antibody.
12. A composition comprising at least one human CDR-grafted antibody or antibody fragment according to claim 8 as an active ingredient, together with a pharmaceutically acceptable carrier.
13. A human CDR-grafted antibody or antibody fragment thereof which reacts with an extracellular region of human CC chemokine receptor 4 (CCR4) but does not specifically react with a human platelet, wherein said extracellular region is an epitope present in SEQ ID NO: 37, and
wherein the human CDR-grafted antibody or antibody fragment thereof comprises an antibody light chain (L chain) variable region (V region) comprising SEQ ID NO:8, 12, 13 or 14.
14. The human CDR-grafted antibody or antibody fragment thereof according to claim 13 , which further specifically reacts with a cell expressing said extracellular region of human CC chemokine receptor 4 (CCR4).
15. A human CDR-grafted antibody or antibody fragment thereof, which is produced by a transformant KM8759 (FERM BP-8129) or KM8760 (FERM BP-8130).
16. A process for producing a human CDR-grafted antibody or antibody fragment, comprising the steps of:
culturing a transformant which produces the human CDR-grafted antibody or antibody fragment thereof according to any one of claims 1 , 13 or 15 , or KM8759 (FERM BP-8129) or KM8760 (FERM BP-8130) in a medium to form and accumulate the human CDR-grafted antibody or antibody fragment in the culture; and
recovering the antibody or antibody fragment from the culture.
17. A human CDR-grafted antibody or antibody fragment thereof in which the human CDR-grafted antibody or antibody fragment according to any one of claims 1 , 13 or 15 is chemically conjugated to a radioisotope, protein or agent, or fused to a protein in the form of a fusion antibody.
18. A composition comprising at least one human CDR-grafted antibody or antibody fragment according to any one of claims 1 , 13 or 15 as an active ingredient, together with a pharmaceutically acceptable carrier.
19. The human CDR-grafted antibody or the antibody fragment according to any one of claims 1 , 13 or 15 and which has a cytotoxic activity against a cell expressing said extracellular region of human CC chemokine receptor 4 (CCR4).