Cell engaging binding molecules
First Claim
Patent Images
1. A binding molecule, comprising:
- (a) a first polypeptide and a second polypeptide, each comprising an antibody light chain,(b) a third polypeptide comprising, in the order from N-terminus to C-terminus, a first variable heavy (VH) region and a first constant heavy 1 (CH1) region, and a second VH region; and
(c) a fourth polypeptide comprising, in the order from N-terminus to C-terminus, a third VH region and a second CH1 region, and a variable light (VL) region,wherein the first polypeptide and the first VH region and the first CH1 region of the third polypeptide form a first antigen binding Fab region;
wherein the second polypeptide and the third VH region and the second CH1 region of the fourth polypeptide form a second antigen binding Fab region;
wherein the second VH region of the third polypeptide and the VL region of the fourth polypeptide form an antigen binding Fv region;
wherein the first Fab region and the second Fab region bind to Programmed Death-Ligand 1 (PD-L1), and the Fv region binds to Cluster of Differentiation 3 (CD3);
wherein the antibody light chains of the first and the second polypepetides each comprise three Complementarity Determining Regions (CDRs) having amino acid sequences of SEQ ID NO.;
9, SEQ ID NO.;
10, and SEQ ID NO.;
11;
wherein in the third polypeptide, the first VH region comprises three CDRs having amino acid sequencies of SEQ ID NO.;
5, SEQ ID NO.;
6, and SEQ ID NO.;
7, and the second VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
13, SEQ ID NO.;
14, and SEQ ID NO.;
15; and
wherein in the fourth polypeptide, the third VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
5, SEQ ID NO.;
6, and SEQ ID NO.;
7, and the VL region comprises three CDRs having amino acid sequences of SEQ ID NO.;
17, SEQ ID NO.;
18, and SEQ ID NO.;
19.
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Abstract
The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present disclosure generally related to a binding molecule comprising antibody variable light (VL) regions, variable heavy (VH) regions, constant heavy 1 (CH1) regions, and light chain constant (CL) regions that are configured to form two antigen binding Fab regions and an antigen binding Fv region so that the binding molecule binds to two different antigens.
61 Citations
30 Claims
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1. A binding molecule, comprising:
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(a) a first polypeptide and a second polypeptide, each comprising an antibody light chain, (b) a third polypeptide comprising, in the order from N-terminus to C-terminus, a first variable heavy (VH) region and a first constant heavy 1 (CH1) region, and a second VH region; and (c) a fourth polypeptide comprising, in the order from N-terminus to C-terminus, a third VH region and a second CH1 region, and a variable light (VL) region, wherein the first polypeptide and the first VH region and the first CH1 region of the third polypeptide form a first antigen binding Fab region; wherein the second polypeptide and the third VH region and the second CH1 region of the fourth polypeptide form a second antigen binding Fab region; wherein the second VH region of the third polypeptide and the VL region of the fourth polypeptide form an antigen binding Fv region; wherein the first Fab region and the second Fab region bind to Programmed Death-Ligand 1 (PD-L1), and the Fv region binds to Cluster of Differentiation 3 (CD3); wherein the antibody light chains of the first and the second polypepetides each comprise three Complementarity Determining Regions (CDRs) having amino acid sequences of SEQ ID NO.;
9, SEQ ID NO.;
10, and SEQ ID NO.;
11;wherein in the third polypeptide, the first VH region comprises three CDRs having amino acid sequencies of SEQ ID NO.;
5, SEQ ID NO.;
6, and SEQ ID NO.;
7, and the second VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
13, SEQ ID NO.;
14, and SEQ ID NO.;
15; andwherein in the fourth polypeptide, the third VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
5, SEQ ID NO.;
6, and SEQ ID NO.;
7, and the VL region comprises three CDRs having amino acid sequences of SEQ ID NO.;
17, SEQ ID NO.;
18, and SEQ ID NO.;
19. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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23. A binding molecule, comprising:
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(a) a first polypeptide and a second polypeptide, each comprising an antibody light chain, (b) a third polypeptide comprising, in the order from N-terminus to C-terminus, a first variable heavy (VH) region and a first constant heavy 1 (CH1) region, and a second VH region; and (c) a fourth polypeptide comprising, in the order from N-terminus to C-terminus, a third VH region and a second CH1 region, and a variable light (VL) region, wherein the first polypeptide and the first VH region and the first CH1 region of the third polypeptide form a first antigen binding Fab region; wherein the second polypeptide and the third VH region and the second CH1 region of the fourth polypeptide form a second antigen binding Fab region; wherein the second VH region of the third polypeptide and the VL region of the fourth polypeptide form an antigen binding Fv region; wherein the first Fab region and the second Fab region binds to Programmed Death-Ligand 1 (PD-L1), and the Fv region binds to Cluster of Differentiation 3 (CD3); wherein the antibody light chains of the first and the second polypeptides each comprise three Complementarity Determining Regions (CDRs) having amino acid sequences of SEQ ID NO.;
9, SEQ ID NO.;
10, and SEQ ID NO.;
11;wherein in the third polypeptide, the first VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
5, SEQ ID NO.;
6, and SEQ ID NO.;
7, and the second VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
78, SEQ ID NO.;
79, and SEQ ID NO.;
80; andwherein in the fourth polypeptide, the third VH region comprises three CDRs having amino acid sequences of SEQ ID NO.;
5, SEQ ID NO.;
6, and SEQ ID NO.;
7, and the VL region comprises three CDRs having amino acid sequences of SEQ ID NO.;
82, SEQ ID NO.;
83, and SEQ ID NO.;
87. - View Dependent Claims (24, 25, 26, 27, 28, 29, 30)
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Specification