Anti-c-met tandem fc bispecific antibodies

Abstract

Provided herein are tandem Fcs and tandem Fc antibodies (“TFcAs”), e.g., tandem Fc bispecific antibodies (“TFcBAs”), which comprise one or at least two binding sites that specifically bind to one or more cell surface receptors. The binding sites are connected through a TFc, which TFc comprises a first Fc region and a second Fc region, wherein the first and the second Fc regions are linked through a TFc linker to form a contiguous polypeptide and dimerize to form an Fc dimer. Exemplary TFcBAs bind to the cell surface receptors c-Met and EpCam and inhibit signal transduction through the cell surface receptor(s) for which the binding sites of the TFcBA are specific.

1 - 21 . (canceled) 
     
     
         22 . A binding agent having a c-Met binding site comprising the CDR1, CDR2, and CDR3 of a heavy chain variable region comprising the amino acid sequence of positions 1-118 of SEQ ID NO: 410, and the CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence of positions 1-108 of SEQ ID NO: 400. 
     
     
         23 . A binding agent having a c-Met binding site, wherein the c-Met binding site comprises a heavy chain variable region comprising an amino acid sequence which is at least 90% identical to the amino acid sequence of positions 1-118 of SEQ ID NO: 410, and a light chain variable region comprising an amino acid sequence which is at least 90% identical to the amino acid sequence of positions 1-108 of SEQ ID NO: 400. 
     
     
         24 . The binding agent of  claim 22 , wherein the c-Met binding site comprises a heavy chain variable region comprising the amino acid sequence of positions 1-118 of SEQ ID NO: 410, and a light chain variable region comprising the amino acid sequence of positions 1-108 of SEQ ID NO: 400. 
     
     
         25 . The binding agent of  claim 22 , which is an antibody. 
     
     
         26 . The binding agent of  claim 25 , wherein the antibody is a monoclonal antibody. 
     
     
         27 . The binding agent of  claim 25 , wherein the antibody is an IgG antibody. 
     
     
         28 . An antibody which competes for binding to c-Met with the binding agent of  claim 24 . 
     
     
         29 . An antibody which binds to the same epitope on c-Met as the binding agent of  claim 24 . 
     
     
         30 . A nucleic acid encoding the heavy and/or light chain variable region of the binding agent of  claim 22 . 
     
     
         31 . A pharmaceutical formulation comprising the binding agent of  claim 22  and a pharmaceutically acceptable carrier. 
     
     
         32 . A method of treating cancer comprising administering to a subject in need thereof the binding agent of  claim 22 . 
     
     
         33 . A binding agent having a EpCAM binding site comprising the CDR1, CDR2, and CDR3 of a heavy chain variable region comprising the amino acid sequence of positions 135-250 of SEQ ID NO: 472, and the CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence of positions 1-113 of SEQ ID NO: 472. 
     
     
         34 . The binding agent of  claim 33 , wherein the EpCAM binding site comprises a heavy chain variable region comprising the amino acid sequence of positions 135-250 of SEQ ID NO: 472, and the CDR1, CDR2, and CDR3 of a light chain variable region comprising the amino acid sequence of positions 1-113 of SEQ ID NO: 472. 
     
     
         35 . The binding agent of  claim 33 , which is an antibody. 
     
     
         36 . The binding agent of  claim 35 , wherein the antibody is a monoclonal antibody. 
     
     
         37 . The binding agent of  claim 35 , wherein the antibody is an IgG antibody. 
     
     
         38 . A nucleic acid encoding the heavy and/or light chain variable region of the binding agent of  claim 33 . 
     
     
         39 . A pharmaceutical composition comprising the binding agent of  claim 33  and a pharmaceutically acceptable carrier. 
     
     
         40 . A method of treating cancer comprising administering to a subject in need thereof the binding agent of  claim 33 .