Anti-CD3epsilon antibodies

Patent metadata

Field	Value
Publication number	US-12486325-B2
Application number	US-202217816731-A
Country	US
Kind code	B2
Filing date	Aug 2, 2022
Priority date	Sep 21, 2017
Publication date	Dec 2, 2025
Grant date	Dec 2, 2025

Abstract

The present disclosure provides isolated monoclonal anti-CD3epsilon antibodies or antigen-binding fragments thereof comprising one or more heavy chain CDR sequences selected from the group consisting of: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, and 47, and/or one or more kappa light chain CDR sequences selected from the group consisting of: SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46 and 48, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the use thereof.

First claim

What is claimed is:

1 . A bispecific antibody or an antigen-binding fragment thereof, which has a first antigen binding domain specific for CD3, and a second antigen binding domain, wherein the first antigen binding domain comprises:
a) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 7, CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and CDR3 comprising the amino acid sequence of SEQ ID NO: 11; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 8, CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and CDR3 comprising the amino acid sequence of SEQ ID NO: 12; b) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 1, CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 2, CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and CDR3 comprising the amino acid sequence of SEQ ID NO: 6; c) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 13, CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 14, CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and CDR3 comprising the amino acid sequence of SEQ ID NO: 18; d) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 19, CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and CDR3 comprising the amino acid sequence of SEQ ID NO: 23; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 20, CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and CDR3 comprising the amino acid sequence of SEQ ID NO: 24; e) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 25, CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 26, CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and CDR3 comprising the amino acid sequence of SEQ ID NO: 30; f) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 31, CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 32, CDR2 comprising the amino acid sequence of SEQ ID NO: 34, and CDR3 comprising the amino acid sequence of SEQ ID NO: 36; g) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 37, CDR2 comprising the amino acid sequence of SEQ ID NO: 39, and CDR3 comprising the amino acid sequence of SEQ ID NO: 41; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 38, CDR2 comprising the amino acid sequence of SEQ ID NO: 40, and CDR3 comprising the amino acid sequence of SEQ ID NO: 42; or h) a heavy chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 43, CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and CDR3 comprising the amino acid sequence of SEQ ID NO: 47; and a kappa light chain variable region comprising CDR1 comprising the amino acid sequence of SEQ ID NO: 44, CDR2 comprising the amino acid sequence of SEQ ID NO: 46, and CDR3 comprising the amino acid sequence of SEQ ID NO: 48.

2 . The bispecific antibody or antigen-binding fragment thereof of claim 1 , wherein the first antigen binding domain comprises:
a) a heavy chain variable region comprising SEQ ID NO: 117 and a kappa light chain variable region comprising SEQ ID NO: 119; b) a heavy chain variable region comprising SEQ ID NO: 81 and a kappa light chain variable region comprising SEQ ID NO: 83; c) a heavy chain variable region comprising SEQ ID NO: 85 and a kappa light chain variable region comprising SEQ ID NO: 87; d) a heavy chain variable region comprising SEQ ID NO: 89 and a kappa light chain variable region comprising SEQ ID NO: 91; e) a heavy chain variable region comprising SEQ ID NO: 93 and a kappa light chain variable region comprising SEQ ID NO: 95; f) a heavy chain variable region comprising SEQ ID NO: 97 and a kappa light chain variable region comprising SEQ ID NO: 99; g) a heavy chain variable region comprising SEQ ID NO: 101 and a kappa light chain variable region comprising SEQ ID NO: 103; h) a heavy chain variable region comprising SEQ ID NO: 105 and a kappa light chain variable region comprising SEQ ID NO: 107; i) a heavy chain variable region comprising SEQ ID NO: 109 and a kappa light chain variable region comprising SEQ ID NO: 111; or j) a heavy chain variable region comprising SEQ ID NO: 113 and a kappa light chain variable region comprising SEQ ID NO: 115.

3 . The bispecific antibody or antigen-binding fragment thereof of claim 1 , wherein the first antigen binding domain further comprises one or more amino acid residue substitutions yet retains specific binding affinity to CD3, wherein the substitution is in one or more framework region (FR) sequences.

4 . The bispecific antibody or antigen-binding fragment thereof of claim 1 , further comprising an immunoglobulin constant region, optionally a constant region of IgG, optionally a constant region of human IgG1.

5 . The bispecific antibody or an antigen-binding fragment thereof of claim 1 , wherein the first antigen binding domain is capable of specifically binding to CD3epsilon, and optionally wherein the CD3epsilon are derived from mouse, rat, monkey or human, and optionally wherein the CD3epsilon is a recombinant CD3epsilon or a CD3epsilon expressed on a cell surface.

6 . The bispecific antibody or antigen-binding fragment thereof of claim 1 , wherein the second antigen is different from CD3, wherein presence of the second antigen in proximity to a CD3epsilon-expressing T cells is desirable for the second antigen to be recognized by immune system.

7 . The bispecific antibody or antigen-binding fragment of claim 1 , which is engineered at the interface so that a knob-into-hole association can be formed to promote heterodimerization of two different antigen-binding sites.

8 . The bispecific antibody or antigen-binding fragment thereof of claim 1 , wherein the second antigen is a tumor associated antigen or an epitope thereof.

9 . The bispecific antibody or antigen-binding fragment thereof of claim 1 linked to one or more conjugates, wherein the conjugate comprises a chemotherapeutic agent, a toxin, a radioactive isotope, a lanthanide, a luminescent label, a fluorescent label, or an enzyme-substrate label.

10 . A pharmaceutical composition comprising the bispecific antibody or antigen-binding fragment thereof of claim 1 , and a pharmaceutically acceptable carrier.

11 . An isolated polynucleotide encoding the bispecific antibody or an antigen-binding fragment thereof of claim 1 .

12 . A vector comprising the isolated polynucleotide of claim 11 .

13 . A host cell comprising the vector of claim 12 .

14 . A method of expressing the bispecific antibody or antigen-binding fragment thereof of claim 1 , comprising culturing a host cell comprising a vector comprising an isolated polynucleotide enc

Assignees

• Wuxi Biologics Ireland Ltd

Inventors

• Li Jing
• Mei Qin

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/33

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

• C07K2317/31

  multispecific · CPC title