Antibody constructs for DLL3 and CD3

Patent metadata

Field	Value
Publication number	US-12435139-B2
Application number	US-202218069704-A
Country	US
Kind code	B2
Filing date	Dec 21, 2022
Priority date	Jul 31, 2015
Publication date	Oct 7, 2025
Grant date	Oct 7, 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 an epitope of human Delta-like Ligand 3 (DLL3) on the surface of a target cell within the amino acid sequence of SEQ ID NO: 269 and a second binding domain which binds 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: 171, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 172, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 173, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 174, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 175 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 176;
b) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 181, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 182, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 183, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 184, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 185 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 186;
c) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 191, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 192, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 193, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 194, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 195 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 196; and
d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 201, CDR-H2 comprising the amino acid sequence of SEQ ID NO: 202, CDR-H3 comprising the amino acid sequence of SEQ ID NO: 203, CDR-L1 comprising the amino acid sequence of SEQ ID NO: 204, CDR-L2 comprising the amino acid sequence of SEQ ID NO: 205 and CDR-L3 comprising the amino acid sequence of SEQ ID NO: 206.

2. The antibody construct of claim 1 , wherein the first binding domain comprises a VH region comprising an amino acid sequence comprising:
a) at least 85% identity to an amino acid sequence of SEQ ID NO: 177, SEQ ID NO: 187, SEQ ID NO: 197, or SEQ ID NO: 207; or
b) the amino acid sequence of SEQ ID NO: 177, SEQ ID NO: 187, SEQ ID NO: 197, or SEQ ID NO: 207.

3. The antibody construct of claim 1 , wherein the first binding domain comprises a VL region comprising an amino acid sequence comprising:
a) at least 85% identity to an amino acid sequence of SEQ ID NO: 178, SEQ ID NO: 188, SEQ ID NO: 198, or SEQ ID NO: 208; or
b) the amino acid sequence of SEQ ID NO: 178, SEQ ID NO: 188, SEQ ID NO: 198, or SEQ ID NO: 208.

4. The antibody construct of claim 1 , wherein the first binding domain comprises a VH region and VL region comprising a pair of amino acid sequences, respectively, comprising:
a) at least 85% identity to the amino acid sequences of SEQ ID NOs: 177 and 178, SEQ ID NOs: 187 and 188, SEQ ID NOs: 197 and 198, or SEQ ID NOs: 207 and 208; or
b) the amino acid sequences of SEQ ID NOs: 177 and 178, SEQ ID NOs: 178 and 188, SEQ ID NOs: 197 and 198, or SEQ ID NOs: 207 and 208.

5. The antibody construct of claim 1 , wherein the first binding domain comprises an amino acid sequence comprising:
a) at least 85% identity to an amino acid sequence of SEQ ID NO: 179, SEQ ID NO: 189, SEQ ID NO: 199, or SEQ ID NO: 209; or
b) the amino acid sequence of SEQ ID NO: 179, SEQ ID NO: 189, SEQ ID NO:199, or SEQ ID NO: 209.

6. The antibody construct of claim 1 , wherein the antibody construct comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 180, SEQ ID NO: 190, SEQ ID NO: 200, or SEQ ID NO: 210.

7. The antibody construct of claim 1 , wherein antibody construct is in a format of (scFv) 2 .

8. The antibody construct of claim 1 , wherein antibody construct is in a format of scFv-single domain monoclonal antibody (mAb).

9. The antibody construct of claim 1 , wherein the first binding domain, the second binding domain, or both is in a Fab format.

10. A composition comprising the antibody construct of claim 1 and an excipient or a combination of excipients.

11. A kit comprising the composition of claim 10 .

12. The kit of claim 11 further comprising instructions for use in treating or ameliorating a tumor or cancer disease expressing Delta-like Ligand 3 (DLL3).

Assignees

• Amgen Res Munich Gmbh

Inventors

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

Classifications

• 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

• C07K16/18 Primary

  against material from animals or humans · CPC title