Heterodimeric antibodies that bind CD3 and tumor antigens

Patent metadata

Field	Value
Publication number	US-12359002-B2
Application number	US-202318308623-A
Country	US
Kind code	B2
Filing date	Apr 27, 2023
Priority date	Nov 26, 2014
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

The present invention is directed to novel heterodimeric antibodies.

First claim

What is claimed is:

1. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) a first variable heavy domain,
ii) a first constant heavy chain comprising a first Fc domain, and
iii) a scFv comprising a scFv variable light domain, a scFv linker and a scFv variable heavy domain; wherein said scFv is covalently attached to the C-terminus of said Fc domain using a domain linker;

b) a second monomer comprising a second variable heavy domain and a second constant heavy chain comprising a second Fc domain;
c) a first common light chain comprising a variable light domain and a constant light domain; and
d) a second common light chain comprising a variable light domain and a constant light domain,
wherein said first and said second Fc domains have a set of amino acid substitutions selected from the group consisting of S364K/E357Q:L368D/K370S; L368D/K370S:S364K; L368E/K370S:S364K; T411E/K360E/Q362E:D401K; L368D/K370S:S364K/E357L and K370S:S364K/E357Q,
wherein said first variable heavy domain and said variable light domain of said first common light chain bind a first antigen, said second variable heavy domain and said variable light domain of said second common light chain bind said first antigen, and said scFv binds a second antigen, and
wherein said heterodimeric antibody is a trivalent antibody.

2. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) a first variable heavy domain;
ii) a first constant heavy domain comprising a first CH1 domain and a first Fc domain; and
iii) a first variable light domain, wherein said first variable light domain is covalently attached between the C-terminus of the first CH1 domain of said first constant heavy domain and the N-terminus of said first Fc domain using domain linkers;

b) a second monomer comprising:
i) a second variable heavy domain,
ii) a second constant heavy domain comprising a second CH1 and a second Fc domain, and
iii) a third variable heavy domain, wherein said third variable heavy domain is covalently attached between the C-terminus of said second CH1 domain of said second constant heavy domain and the N-terminus of said second Fc domain using domain linkers;

c) a first common light chain comprising a second variable light domain and a constant light domain; and
d) a second common light chain comprising a second variable light domain and a constant light domain; and
wherein said first and said second Fc domains have a set of amino acid substitutions selected from the group consisting of S364K/E357Q:L368D/K370S; L368D/K370S:S364K; L368E/K370S:S364K; T411E/K360E/Q362E:D401K; L368D/K370S:S364K/E357L and K370S:S364K/E357Q,
and wherein said first variable heavy domain and said second variable light domain of said first common light chain bind a first antigen, said second variable heavy domain and said second variable light domain of said second common light chain bind said first antigen, and said first variable light domain and said third variable heavy domain binds a second antigen.

Assignees

• Xencor Inc

Inventors

• Bernett Matthew
• Moore Gregory
• Desjarlais John
• Chu Seung
• Rashid Rumana
• Muchhal Umesh
• Lee Sung-Hyung

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K2317/515

  Complete light chain, i.e. VL + CL · CPC title

• C07K16/3061

  Blood cells · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title