BISPECIFIC ANTIBODIES SPECIFIC FOR T-CELL ACTIVATING ANTIGENS AND A TUMOR ANTIGEN AND METHODS OF USE
The present invention relates to bispecific antibodies that specifically bind a T-cell activating antigen and a Tumor Antigen (TA), comprising a first Fab fragment and a second Fab fragment, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody does not comprise a Fc domain; methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.
1 . A bispecific antibody that specifically binds a T-cell activating antigen and a Tumor Antigen (TA), comprising a first Fab fragment and a second Fab fragment, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody does not comprise a Fc domain.
2 . The bispecific antibody of claim 1 , wherein the first fragment comprises at least one antigen binding site specific for a Tumor Antigen; and the second Fab fragment comprises at least one antigen binding site specific for a T-cell activating antigen.
3 . The bispecific antibody of claim 1 , wherein the T-cell activating antigen is a CD3 T-Cell Co-Receptor (CD3) antigen.
4 . The bispecific antibody of claim 1 , wherein the N-terminus of the second Fab fragment is connected to the C-terminus of the first Fab fragment.
5 . The bispecific antibody of claim 1 , additionally comprising a third Fab fragment.
6 . The bispecific antibody of claim 5 , wherein the third Fab fragment comprises at least one antigen binding site specific for a Tumor Antigen.
7 . The bispecific antibody of claim 5 , wherein the third Fab fragment is connected to the first Fab fragment.
8 . The bispecific antibody of claim 7 , wherein the C-terminus of the third Fab fragment is connected to the N-terminus of the first Fab fragment.
9 . The bispecific antibody of claim 5 , wherein the third Fab fragment is connected to the second Fab fragment.
10 . The bispecific antibody of claim 9 , wherein the N-terminus of the third Fab fragment is connected to the C-terminus of the second Fab fragment.
11 . The bispecific antibody of claim 1 or claim 5 , wherein the Fab fragments are connected via a peptide linker.
12 . The bispecific antibody of claim 11 , wherein the peptide linker is a (G4S)2 linker.
13 . The bispecific antibody of claim 1 or claim 5 , wherein the Tumor Antigen is selected from the group consisting of Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP), Epidermal Growth Factor Receptor (EGFR), Carcinoembryonic Antigen (CEA), Fibroblast Activation Protein (FAP) and CD33.
14 . The bispecific antibody of claim 13 , wherein the Tumor Antigen is MCSP.
15 . A pharmaceutical composition comprising the bispecific antibody of claim 1 or claim 5 .
16 . (canceled)
17 . (canceled)
18 . A method of treating cancer comprising administering to a patient in need thereof an effective amount of the bispecific antibody of claim 1 or claim 5 .
19 . (canceled)
20 . A prokaryotic or eukaryotic host cell comprising vectors comprising nucleic acid molecules encoding the light chains and heavy chains of the bispecific antibody of claim 1 or claim 5 .
21 . A method of producing an antibody comprising culturing the host cell of claim 20 so that the antibody is produced.