Monoclonal antibody capable of binding to heparin-binding epidermal growth factor-like growth factor

Abstract

Medicaments for treating diseases related to HB-EGF escalation are in demand. The present invention provides a method for producing a monoclonal antibody or an antibody fragment thereof which binds to a cell membrane-bound HB-EGF, a membrane type HB-EGF and a secretory HB-EGF.

1 - 27 . (canceled) 
     
     
         28 . A process for producing an antibody or fragment thereof, wherein said antibody or said fragment comprises at least one heavy chain variable region and at least one light chain variable region,
 (a) wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:22, and wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:43; or   (b) wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:42, and wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:23; or   (c) wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:42, and wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:43; or   (d) wherein said heavy chain variable region comprises three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:12, 13 and 14; and wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:43; or   (e) wherein said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:42; and wherein said light chain variable region comprises at least three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:15, 16 and 17, comprising:   preparing a recombinant vector comprising a DNA encoding the antibody or the antibody fragment thereof according to any one of (a) to (e);   preparing a transformant comprising said recombinant vector;   culturing the transformant in a medium to form and accumulate the antibody or the antibody fragment thereof; and   recovering the antibody or the antibody fragment from the medium.   
     
     
         29 . The process of  claim 28 , wherein said antibody fragment binds HB-EGF and is selected from the group consisting of a Fab, Fab′, F(ab′)2, a single chain antibody (scFv), a diabody, a disulfide stabilized Fv(dsFv), and a peptide comprising six CDRs, wherein said peptide comprises at least one heavy chain variable region and at least one light chain variable region, wherein said heavy chain variable region comprises three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:12, 13 and 14; and wherein said light chain variable region comprises three complementarity-determining regions comprising the amino acid sequences of SEQ ID NOS:15, 16 and 17.