CD3 antibody and pharmaceutical use thereof

Patent metadata

Field	Value
Publication number	US-12258405-B2
Application number	US-201917298703-A
Country	US
Kind code	B2
Filing date	Dec 6, 2019
Priority date	Dec 7, 2018
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

The present disclosure relates to a CD3 antibody and a pharmaceutical use thereof. Specifically, the present disclosure relates to forming a multi-specificity antibody by using CD3 antibody and binding molecules of another target. The multi-specificity antibody may simultaneously bind to CD3 and another tumor-associated antigen, and bind and activate CD3-positive T cells while binding tumor-associated antigen-expressing cells, thereby promoting T cells specifically killing tumor cells that express tumor-associated antigens. In addition, the present disclosure also provides a preparation and application of a multi-specific antibody.

First claim

What is claimed is:

1. An antibody or antigen-binding fragment thereof specifically binding to human CD3, the antibody or antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, wherein:
the light chain variable region comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NOs: 48, 49 and 50, respectively, and
the heavy chain variable region is any one selected from the group consisting of the following i) to v):
i) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NOs: 37, 40 and 42, respectively;
ii) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NOs: 37, 47 and 45, respectively;
iii) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NOs: 37, 38 and 39, respectively;
iv) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NOs: 37, 40 and 43, respectively; and
v) a heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NOs: 37, 40 and 41, respectively.

2. The antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 1 , wherein the antibody or antigen-binding fragment thereof is a humanized antibody or antigen-binding fragment thereof.

3. The antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 2 , comprising a light chain variable region as shown in SEQ ID NO: 36, and/or a heavy chain variable region as shown in any one selected from the group consisting of SEQ ID NOs: 29, 30, 31, 32, and 35.

4. The antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 3 , further comprising an antibody light chain constant region and/or a heavy chain constant region;
optionally, the light chain constant region is a light chain constant region of a human kappa, lambda chain or variant thereof, and the heavy chain constant region is a heavy chain constant region of a human IgG1, IgG2, IgG3, IgG4 or variant thereof.

5. The antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 1 , wherein the antigen-binding fragment is selected from Fab, Fab′, F(ab′)2, dimerized V region (diabody) and disulfide-stabilized V region (dsFv).

6. A single-chain antibody, comprising the light chain variable region and the heavy chain variable region of the antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 1 .

7. The single-chain antibody according to claim 6 , wherein the sequence of the single-chain antibody is as shown in SEQ ID NO: 55, 56, 57, 58, 61, 62, 63, 64, 65 or 68.

8. A multispecific antibody specifically binding to human CD3 and tumor-associated antigen(s), the multispecific antibody comprising the single-chain antibody according to claim 6 .

9. The multispecific antibody according to claim 8 , wherein the tumor-associated antigen is selected from the group consisting of AFP, ALK, B7H3, BAGE protein, BCMA, BIRC5, BIRC7, β-catenin, brc-abl, BRCA1, BORIS, CA9, CA125, carbonic anhydrase IX, caspase-8, CALR, CCR5, CD19, CD20, CD22, CD30, CD33, CD38, CD40, CD123, CD133, CD138, CDK4, CEA, Claudin 18.2, cyclin-B1, CYP1B1, EGFR, EGFRvIII, ErbB2/Her2, ErbB3, ErbB4, ETV6-AML, EpCAM, EphA2, Fra-1, FOLR1, GAGE protein, GD2, GD3, GloboH, Glypican-3, GM3, gp100, Her2, HLA/B-raf, HLA/k-ras, HLA/MAGE-A3, hTERT, IL13Rα2, LMP2, κ-Light, LeY, MAGE protein, MART-1, Mesothelin, ML-IAP, MOv-γ, Muc1, Muc2, Muc3, Muc4, Muc5, CA-125, MUM1, NA17, NKG2D, NY-BR1, NY-BR62, NY-BR85, NY-ESO1, OX40, p15, p53, PAP, PAX3, PAX5, PCTA-1, PLAC1, PRLR, PRAME, PSMA, RAGE protein, Ras, RGS5, Rho, ROR1, SART-1, SART-3, STEAP1, STEAP2, TAG-72, TGF-β, TMPRSS2, Thompson-nouvelle antigen, TRP-1, TRP-2, tyrosinase, uroplakin-3 and 5T4.

10. A pharmaceutical composition, comprising a therapeutically effective amount of the antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 1 , and one or more pharmaceutically acceptable carriers, diluents, buffers or excipients.

11. An isolated nucleic acid molecule, encoding the antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 1 .

12. A recombinant vector, comprising the isolated nucleic acid molecule according to claim 11 .

13. A host cell transformed with the recombinant vector of claim 12 , wherein said host cell is a prokaryotic cell or a eukaryotic cell.

14. A method for producing the antibody or antigen-binding fragment thereof specifically binding to human CD3 according to claim 1 , the method comprising transforming the recombinant vector into a host cell and culturing a host cell in a culture medium to express and accumulate the antibody or antigen-binding fragment thereof specifically binding to human CD3, and recovering the antibody or antigen-binding fragment thereof.

Assignees

• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Ying Hua
• Zhang Ling
• Yang Xiaoying
• Ge Hu
• Tao Weikang

Classifications

• C07K2317/92

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

• C07K2317/622

  Single chain antibody (scFv) · 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

• C07K2317/31

  multispecific · CPC title