Bispecific antibody construct directed to MUC17 and CD3

Patent metadata

Field	Value
Publication number	US-12258404-B2
Application number	US-201816956797-A
Country	US
Kind code	B2
Filing date	Dec 31, 2018
Priority date	Dec 29, 2017
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

The present invention provides bispecific antibody constructs characterized by comprising a first domain binding to MUC17, a second domain binding to an extracellular epitope of the human and the Macaca CD3ε chain and optionally a third domain, which is a specific Fc modality. Moreover, the invention provides a polynucleotide, encoding the antibody construct, a vector comprising this polynucleotide, host cells, expressing the construct and a pharmaceutical composition comprising the same.

First claim

The invention claimed is:

1. A bispecific antibody construct comprising:
a first domain comprising an antibody which binds to MUC17, wherein the antibody comprises a CDR-H1 as set forth in the amino acid sequence of SEQ ID NO: 176, a CDR-H2 as set forth in the amino acid sequence of SEQ ID NO: 177, a CDR-H3 as set forth in the amino acid sequence of SEQ ID NO: 178, a CDR-L1 as set forth in in the amino acid sequence of SEQ ID NO: 179, a CDR-L2 as set forth in the amino acid sequence of SEQ ID NO: 180, and a CDR-L3 as set forth in the amino acid sequence of SEQ ID NO: 181, and
a second domain comprising an antibody which binds to an extracellular epitope of the human CD3ε chain.

2. The bispecific antibody construct of claim 1 further comprising a third domain which comprises two polypeptide monomers, each monomer comprising a hinge, a CH2 domain and a CH3 domain, wherein the two polypeptide monomers are fused to each other via a peptide linker.

3. The bispecific antibody construct of claim 2 , wherein the third domain comprises in an amino to carboxyl order:
hinge-CH2-CH3-linker-hinge-CH2-CH3.

4. The bispecific antibody construct of claim 2 , wherein each of the polypeptide monomers of the third domain comprises an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of: SEQ ID NO: 17-24.

5. The bispecific antibody construct of claim 2 , wherein the first and second domains are fused to the third domain via a peptide linker.

6. The bispecific antibody construct of claim 1 , wherein the antibody construct is a bispecific single chain antibody construct.

7. The bispecific antibody construct of claim 1 , wherein
(i) the antibody which binds to MUC 17 comprises two antibody variable domains and the antibody which binds to the human CD3ε chain comprises two antibody variable domains; or
(ii) the antibody which binds to MUC 17 comprises two antibody variable domains and the antibody which binds to the human CD3ε chain comprises a single domain antibody.

8. The bispecific antibody construct of claim 1 , wherein the antibody construct comprises in an amino to carboxyl order:
(a) the first domain;
(b) a peptide linker comprising the amino acid sequence of SEQ ID NO: 1, 2, or 3; and
(c) the second domain.

9. The bispecific antibody construct of claim 8 , wherein the antibody construct further comprises in an amino to carboxyl order after the second domain:
(d) a peptide linker comprising the amino acid sequence of SEQ ID NO: 1, 2, 3, 9, 10, 11 or 12;
(e) a first polypeptide monomer of a third domain;
(f) a peptide linker comprising the amino acid sequence of SEQ ID NO: 5, 6, 7, or 8; and
(g) a second polypeptide monomer of the third domain.

10. 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: 183 and a VH region comprising the amino acid sequence of SEQ ID NO: 182.

11. The bispecific antibody construct of claim 1 , wherein the first domain comprises the amino acid sequence of SEQ ID NO: 184.

12. The bispecific antibody construct of claim 1 , wherein the antibody construct comprises in an amino to carboxyl order:
(a) the first domain comprising the antibody comprising the amino acid sequence of SEQ ID NO: 184;
(b) a peptide linker comprising the amino acid sequence of SEQ ID NO: 1, 2, or 3; and
(c) the second domain comprising the antibody comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 586-605 and 15.

13. The bispecific antibody construct of claim 12 , wherein the antibody construct further comprises in an amino to carboxyl order:
(d) a peptide linker which links the first and second domains to a third domain, the peptide linker comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 1, 2, 3, 9, 10, 11 and 12;
(e) a first polypeptide monomer of the third domain comprising an amino sequence selected from the group consisting of: SEQ ID NOs: 17-24;
(f) a peptide linker comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 5, 6, 7 and 8; and
(g) a second polypeptide monomer of the third domain comprising an amino sequence selected from the group consisting of: SEQ ID NOs: 17-24.

14. The bispecific antibody construct of claim 1 comprising
(a) the amino acid sequence of SEQ ID NO: 185 or 186; or
(b) an amino acid sequence comprising at least 90% identity to the amino acid sequence of SEQ ID NO: 185 or 186.

15. A pharmaceutical composition comprising the bispecific antibody construct of claim 1 , and a carrier, stabilizer, excipient, diluent, solubilizer, surfactant, emulsifier, preservative, and/or adjuvant.

16. A kit comprising the bispecific antibody construct of claim 1 and a means for reconstituting or diluting the antibody construct.

17. The bispecific antibody construct of claim 1 , wherein the second domain further binds to an extracellular epitope of the Macaca CD3ε chain.

18. The bispecific antibody construct of claim 1 , wherein the first binding domain comprises an antibody comprising a VL region comprising an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 183 and a VH region comprising an amino acid sequence having at least 90% identity to the sequence set forth in SEQ ID NO. 182.

19. The bispecific antibody construct of claim 1 , wherein the first domain comprises an antibody comprising an amino acid sequence having at least 90% identity to a sequence comprising the amino acid sequence of SEQ ID NO: 184.

Assignees

• Amgen Inc
• Amgen Res Munich Gmbh

Inventors

• Raum Tobias
• Arvedson Tara
• Bailis Julie
• Dahlhoff Christoph
• Ross Sandra
• Chen Irwin
• Blümel Claudia
• Nahrwold Elisabeth
• Pendzialek Jochen
• Wahl Joachim

Classifications

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/53

  Hinge · CPC title

• C07K2317/526

  CH3 domain · CPC title