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Title:
TRISPECIFIC ANTIBODY TARGETING HER2, PD-L1 AND VEGF
Document Type and Number:
WIPO Patent Application WO/2023/236991
Kind Code:
A1
Abstract:
The present invention relates to a trispecific antibody targeting HER2, PD-L1 and VEGF. The trispecific antibody comprises two identical first polypeptides and two identical second polypeptides, wherein 1) each first polypeptide comprises VHH1-(X)n-VH-CH1-Hinge-Fc-(Y)m-VHH2 from the N-terminus to the C-terminus and each second polypeptide comprises VL-CL from the N-terminus to the C-terminus, or 2) each first polypeptide comprises VHH1-(X)n-VH-CH1-Hinge-Fc from the N-terminus to the C-terminus and each second polypeptide comprises VHH2-(Y)m-VL-CL from the N-terminus to the C-terminus; VHH1 represents a first VHH domain that binds to a first epitope, VHH2 represents a second VHH domain that binds to a second epitope, and VH and VL are combined to bind to a third epitope; x and y represent linkers, n = 0 or 1, and m = 0 or 1; Fc represents the Fc domain of an immunoglobulin heavy chain, CH1 represents the CH1 domain of the immunoglobulin heavy chain, and CL represents the CL domain of the immunoglobulin light chain; the Fc domains of the two first polypeptides are paired with each other and homodimerized, and VH-CH1 and VL-CL are paired with each other to form Fab, thereby forming a tetramer structure similar to that of natural IgG immunoglobulin; and VHH1 and VHH2 respectively bind to different targets selected from PD-L1 or VEGF, and VH and VL are paired to bind to HER2. In addition, the present invention further relates to the therapeutic use of the trispecific antibody. In addition, the present invention further relates to the therapeutic use of the trispecific antibody.

Inventors:
FU ZHIXIANG (CN)
LIU CHANJUAN (CN)
LANG GUOJUN (CN)
Application Number:
PCT/CN2023/098849
Publication Date:
December 14, 2023
Filing Date:
June 07, 2023
Export Citation:
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Assignee:
SANYOU BIOPHARMACEUTICALS CO LTD (CN)
International Classes:
C07K16/46; A61K39/395; A61K47/68; A61P35/00; C12N5/10; C12N15/85
Foreign References:
US20170043035A12017-02-16
Other References:
BOGEN JAN P., CARRARA STEFANIA C., FIEBIG DAVID, GRZESCHIK JULIUS, HOCK BJÖRN, KOLMAR HARALD: "Design of a Trispecific Checkpoint Inhibitor and Natural Killer Cell Engager Based on a 2 + 1 Common Light Chain Antibody Architecture", FRONTIERS IN IMMUNOLOGY, vol. 12, XP093021289, DOI: 10.3389/fimmu.2021.669496
CHEN, YILI ET AL.: "A Bispecific Antibody Targeting HER2 and PD-L1 Inhibits Tumor Growth with Superior Efficacy", J. BIOL. CHEM., vol. 297, no. 6, 31 December 2021 (2021-12-31), XP093060634, DOI: 10.1016/j.jbc.2021.101420
Attorney, Agent or Firm:
ZHONGZI LAW OFFICE (CN)
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