Anti-CD3epsilon antibodies

Patent metadata

Field	Value
Publication number	US-12485298-B2
Application number	US-202217816732-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 . An isolated antibody or antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region, wherein the antibody or antigen-binding fragment selected from the group consisting of:
a) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:117, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 119; b) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:81, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 83; c) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:85, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 87; d) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:89, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 91; e) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:93, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 95; f) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:97, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 99; g) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:101, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 103; h) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:105, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 107; i) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:109, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 111; or j) a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains of SEQ ID NO:113, and a kappa light chain variable region that comprises CDR1, CDR2 and CDR3 domains of SEQ ID NO: 115.

2 . The antibody or an antigen-binding fragment thereof of claim 1 , comprising:
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.

3 . The 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.

4 . The antibody or an antigen-binding fragment thereof of claim 1 , which is a humanized antibody.

5 . The antibody or antigen-binding fragment thereof of claim 1 , which is a camelized single domain antibody, a diabody, a scFv, an scFv dimer, a BsFv, a dsFv, a (dsFv) 2 , a dsFv-dsFv′, an Fv fragment, a Fab, a Fab′, a F(ab′) 2 , a bispecific antibody, a ds diabody, a nanobody, a domain antibody, or a bivalent domain antibody.

6 . The antibody or an antigen-binding fragment thereof of claim 5 , wherein the antibody or an antigen-binding fragment thereof is bispecific and has a first specificity for CD3epsilon, and a second specificity.

7 . The antibody or an antigen-binding fragment thereof of claim 6 , wherein the second specificity is for a second antigen different from CD3epsilon 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.

8 . The 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.

9 . The antibody or an antigen-binding fragment thereof of claim 1 , 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.

10 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 , a

Assignees

• Wuxi Biologics Ireland Ltd

Inventors

• Li Jing
• Mei Qin

Classifications

• C07K2317/92

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

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/33

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