Antibody against human insulin-like growth factor
View Patent ↗For the effective treatment of diseases such as cancer in which hIGF participates, there have been desired to be developed antibodies which strongly bind to both factors hIGF-I and hIGF-II and inhibit their functions and fragments of these antibodies. The present invention provides antibodies which have the ability to specifically bind to human IGF-I and IGF-II to thereby inhibit the functions of human IGF-I and IGF-II and have binding activity with a binding constant of 5×10 9 M −1 or more measured with a biosensor BIACORE. In addition, the present invention provides diagnostics, preventives and remedies for an hIGF-mediated disease and a disease showing pathological progressing due to abnormally promoted hIGF production, which use said antibodies.
1. An antibody or an antibody fragment thereof, which (i) specifically binds to IGF-I and IGF-II to inhibit both human IGF-I and human IGF-II, and (ii) binds to both human IGF-I and human IGF-II with almost equivalent strength of affinity and with a binding constant of 5×10 9 M −1 or more measured with a biosensor BIACORE™, the CDR1, CDR2 and CDR3 of the VH chain of said antibody or said antibody fragment thereof comprising SEQ ID NOS:5, 6 and 7 respectively, and/or CDR1, CDR2 and CDR3 of the VL chain of said antibody or said antibody fragment comprising SEQ ID NOS: 8, 9 and 10 respectively.
2. The antibody or the antibody fragment thereof according to claim 1 , wherein the antibody is a non-human animal antibody or a recombinant antibody.
3. The antibody or the antibody fragment thereof according to claim 2 , which is a recombinant antibody selected from the group consisting of a human chimeric antibody, a human CDR-grafted antibody.
4. An isolated antibody or an antibody fragment thereof, which (i) specifically binds to IGF-I and IGF-II to inhibit both human IGF-I and human IGF-II, and (ii) binds to both human IGF-I and human IGF-II with almost equivalent strength of affinity and with a binding constant of 5×10 9 M −1 or more measured with a surface plasmon resonance biosensor, wherein the VH chain of the antibody or antibody fragment thereof comprises SEQ ID NO: 2 and/or the VL chain of the antibody or antibody fragment thereof comprises SEQ ID NO: 4.
5. The antibody or the antibody fragment thereof according to claim 4 , wherein the antibody of a non-human animal is produced by hybridoma KM1468 (FERM BP-7978).
6. The antibody or the antibody fragment thereof according to claim 3 , wherein the VH chain of the human chimeric antibody comprises SEQ ID NO: 2, and/or the VL chain of the human chimeric antibody comprises SEQ ID NO: 4.
7. The antibody or the antibody fragment thereof according to claim 6 , wherein the human chimeric antibody comprises the VH chain and/or the VL chain of the antibody produced by KM1468 (FERM BP-7978).
8. The antibody or the antibody fragment thereof according to claim 3 , wherein the human chimeric antibody comprises a constant region of a human antibody.
9. The antibody or the antibody fragment thereof according to claim 8 , wherein the constant region of a human antibody comprises the constant region of an IgG1 class and/or K class human antibody.
10. The antibody or the antibody fragment thereof according to claim 9 , wherein the human chimeric antibody is produced by transformant KM3002 (FERM BP-7996).
11. The antibody or the antibody fragment thereof according to claim 3 , wherein the human CDR-grafted antibody comprises a constant region of a human antibody.
12. The antibody fragment according to claim 11 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2 , single chain antibody (scFv), dimerized V region (diabody), disulfide-stabilized V region (dsFv) and a CDR-containing peptide.
13. A method for producing isolated an antibody or the antibody fragment thereof according to claim 2 , which comprises culturing a transformant obtained by introducing into a host cell a recombinant vector containing DNA encoding said antibody or antibody fragment thereof in a medium to produce and accumulate the antibody or the antibody fragment thereof, and recovering the antibody or the antibody fragment thereof from the culture.