Antibody constructs for DLL3 and CD3

Patent metadata

Field	Value
Publication number	US-12304952-B2
Application number	US-202117236467-A
Country	US
Kind code	B2
Filing date	Apr 21, 2021
Priority date	Jul 31, 2015
Publication date	May 20, 2025
Grant date	May 20, 2025

Abstract

The present invention relates to a bispecific antibody construct comprising a first binding domain which binds to human DLL3 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising the polynucleotide and a host cell transformed or transfected with the polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of the antibody construct and a kit comprising the antibody construct.

First claim

The invention claimed is:

1. A bispecific antibody construct comprising a first binding domain which binds to human delta-like 3 (DLL3) on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from the group consisting of:
a) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 121, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 122, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 123, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 124, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 125 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 126;
b) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 132, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 134, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
c) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 141, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 142, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 143, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 144, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 145 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 146;
d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 161, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 162, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 163, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 164, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 165 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 166;
e) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 439, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 134, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
f) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 440, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 134, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
g) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 132, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 441, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
h) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 132, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 442, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 132, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 443, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
j) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 132, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 444, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136;
k) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 439, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 441, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136; and
l) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 131, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 440, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 133, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 442, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 135 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 136.

2. The bispecific antibody construct of claim 1 , wherein the first binding domain comprises a VH region comprising the amino acid sequence of SEQ ID NO: 127, SEQ ID NO: 137, SEQ ID NO: 147, SEQ ID NO: 167, SEQ ID NO: 445, SEQ ID NO: 446, SEQ ID NO: 447, SEQ ID NO: 448, SEQ ID NO: 449, SEQ ID NO: 450, SEQ ID NO: 451, SEQ ID NO: 452, SEQ ID NO: 453, SEQ ID NO: 454, or SEQ ID NO: 455.

3. The bispecific antibody construct of claim 1 , wherein the first binding domain comprises a VL region comprising the amino acid sequence of SEQ ID NO: 128, SEQ ID NO: 138, SEQ ID NO: 148, SEQ ID NO: 168, SEQ ID NO: 456, SEQ ID NO: 457, SEQ ID NO: 458, SEQ ID NO: 459, SEQ ID NO: 460, SEQ ID NO: 461, SEQ ID NO: 462, SEQ ID NO: 463, SEQ ID NO: 464, SEQ ID NO: 465, SEQ ID NO: 466, SEQ ID NO: 467, SEQ ID NO: 468, SEQ ID NO: 469, or SEQ ID NO: 470.

4. The bispecific antibody construct of claim 1 , wherein the first binding domain comprises a VH region and a VL region comprising the pair of amino acid sequences, respectively, of SEQ ID NOs: 127 and 128; SEQ ID NOs: 137 and 138; SEQ ID NOs: 147 and 148; SEQ ID NOs: 167 and 168; SEQ ID NOs: 137 and 456; SEQ ID NOs: 137 and 457; SEQ ID NOs: 137 and 458; SEQ ID NOs: 137 and 459; SEQ ID NOs: 137 and 460; SEQ ID NOs: 445 and 138; SEQ ID NOs: 446 and 138; SEQ ID NOs: 447 and 138; SEQ ID NOs: 445 and 460; SEQ ID NOs: 448 and 461; SEQ ID NOs: 449 and 462; SEQ ID NOs: 450 and 463; SEQ ID NOs: 450 and 464; SEQ ID NOs: 450 and 465; SEQ ID NOs: 450 and 466; SEQ ID NOs: 450 and 467; SEQ ID NOs: 450 and 468; SEQ ID NOs: 451 and 463; SEQ ID NOs: 452 and 463; SEQ ID NOs: 453 and 463; SEQ ID NOs: 451 and 468; SEQ ID NOs: 454 and 469; or SEQ ID NOS: 455 and 470.

5. The bispecific antibody construct of claim 1 , wherein the first binding domain comprises the amino acid sequence of SEQ ID NO: 129, SEQ ID NO: 139, SEQ ID NO: 149, SEQ ID NO: 169, SEQ ID NO: 471, SEQ ID NO: 472, SEQ ID NO: 473, SEQ ID NO: 474, SEQ ID NO: 475, SEQ ID NO: 476, SEQ ID NO: 477, SEQ ID NO: 478, SEQ ID NO: 479, SEQ ID NO: 480, SEQ ID NO: 481, SEQ ID NO: 482, SEQ ID NO: 483, SEQ ID NO: 484, SEQ ID NO: 485, SEQ ID NO: 486, SEQ ID NO: 487, SEQ ID NO: 488, SEQ ID NO: 489, SEQ ID NO: 490, SEQ ID NO: 491, SEQ ID NO: 492, or SEQ ID NO: 493.

6. The bispecific antibody construct of claim 1 comprising the amino acid sequence of SEQ ID NO: 130, SEQ ID NO: 140, SEQ ID NO: 150, SEQ ID NO: 170; SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 494, SEQ ID NO: 495, SEQ ID NO: 496, SEQ ID NO: 497, SEQ ID NO: 498, SEQ ID NO: 499, SEQ ID NO: 500, SEQ ID NO: 501, SEQ ID NO: 502, SEQ ID NO: 503, SEQ ID NO: 504, SEQ ID NO: 505, SEQ ID NO: 506, SEQ ID NO: 507, SEQ ID NO: 508, SEQ ID NO: 509, SEQ ID NO: 510, SEQ ID NO: 511, SEQ ID NO: 512, SEQ ID NO: 513, SEQ ID NO: 514, SEQ ID NO: 515, or SEQ ID NO: 516.

7. The bispecific antibody construct of claim 1 , wherein the second binding domain comprises a VL region compri

Assignees

• Amgen Res Munich Gmbh

Inventors

• Raum Tobias
• Blümel Claudia
• Dahlhoff Christoph
• Hoffmann Patrick
• Kufer Peter
• LUTTERBÜSE Ralf
• Nahrwold Elisabeth
• Pendzialek Jochen

Classifications

• A61K39/00113

  Growth factors · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title