Remedies for arthritis
The invention provides an agent for preventing or treating arthritis, a cartilage protecting agent, a joint destruction inhibitor and a synovial membrane growth inhibitor comprising an anti-FGF-8 neutralizing antibody as an active ingredient, as well as a diagnostic agent of arthritis comprising an anti-FGF-8 antibody as an active ingredient and a method for judging arthritis using the antibody.
1. A method of treating arthritis, comprising administering to a patient, as an active ingredient, an antibody which specifically binds to FGF-8 to inhibit activity of FGF-8,
wherein the antibody is a monoclonal antibody selected from an antibody produced by a hybridoma, a humanized antibody and an antigen-binding fragment thereof,
wherein the humanized antibody is a human chimeric antibody or a human complementarity determining region (CDR)-grafted antibody comprising CDRs of VH and VL of a monoclonal antibody which specifically binds to FGF-8 to inhibit activity of FGF-8 and CH and CL of a human antibody,
wherein CDR1, CDR2 and CDR3 of VH comprise the amino acid sequences of SEQ ID NOS: 7, 8 and 9 respectively and CDR1, CDR2 and CDR3 of VL comprise the amino acid sequences of SEQ ID NOS: 10, 11 and 12 respectively.
2. A method of treating arthritis, comprising administering to a patient, as an active ingredient, an antibody which specifically binds to FGF-8 to inhibit activity of FGF-8,
wherein the antibody is a monoclonal antibody selected from an antibody produced by a hybridoma, a humanized antibody and an antigen-binding fragment thereof,
wherein the humanized antibody is a human chimeric antibody or a human complementarity determining region (CDR)-grafted antibody comprising CDRs of VH and VL of a monoclonal antibody which specifically binds to FGF-8 to inhibit activity of FGF-8 and CH and CL of a human antibody,
wherein VH comprises the amino acid sequence of SEQ ID NO: 18 or 20 and VL comprises the amino acid sequence of SEQ ID NO: 19, 21, 42, 43, 44, 45, 46, 47, 50 or 51.
3. The method according to claim 2 , wherein the human CDR-grafted antibody is any of the following human CDR-grafted antibodies (a) to (c),
(a) a human CDR-grafted antibody in which VH comprises the amino acid sequence of SEQ ID NO: 18 and VL comprises the amino acid a sequence of SEQ ID NO: 21,
(b) a human CDR-grafted antibody in which VH comprises the amino acid sequence of SEQ ID NO: 18 and VL comprises the amino acid sequence of SEQ ID NO: 44, and
(c) a human CDR-grafted antibody in which VH comprises the amino acid sequence of SEQ ID NO: 18 and VL comprises an amino an the sequence of SEQ ID NO: 50.
4. A method of treating arthritis, comprising administering to a patient, as an active ingredient, an antibody which specifically binds to FGF-8 to inhibit activity of FGF-8,
wherein the antibody is a monoclonal antibody selected from an antibody produced by a hybridoma, a humanized antibody and an antigen-binding fragment thereof,
wherein the humanized antibody is a human chimeric antibody or a human complementarity determining region (CDR)-grafted antibody comprising CDRs of VH and VL of a monoclonal antibody which specifically binds to FGF-8 to inhibit activity of FGF-8 and CH and CL of a human antibody,
wherein the human CDR-grafted antibody is any of the following human CDR -grafted antibodies (a) to (c),
(a) a human CDR-grafted antibody produced by transformant KM8037 (FERM BP-8084),
(b) a human CDR-grafted antibody produced by transformant KM8035 (FERM BP-8082), and
(c) a human CDR-grafted antibody produced by transformant KM8036 (FERM BP-8083).