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Title:
BISPECIFIC ANTIBODY AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/121239
Kind Code:
A1
Abstract:
The present invention provides a bispecific antibody and an application thereof. IL15 and IL15Rα are respectively introduced into two chains of a first antibody of the bispecific antibody of the present invention (for example, IL15 and IL15Rα replace CL1 and CH1, respectively), and the high affinity of IL15 and IL15Rα is utilized to form an IL15/IL15Rα complex, thereby achieving the correct pairing of a light chain/heavy chain of the first antibody, and solving the problem of incorrectly matching light chains/heavy chains of bispecific antibodies. Meanwhile, the binding activity between the light chain/heavy chain of the first antibody may be further enhanced by adding one or more pairs of disulfide bonds between VH1 and VL1 and between IL15 and IL15Rα by mutating the amino acid sequences of variable domains VH1, VL1, IL15 and IL15Rα of the first antibody, to thereby effectively overcome challenges such as incorrectly matching light chains/heavy chains, high by-products and poor stability in the preparation process of a bispecific antibody, and finally prepare and obtain correctly paired bispecific multifunctional antibodies targeting cytokines. At the same time, the development period of bispecific antibodies is shortened and production costs are reduced.

Inventors:
QU XIANGDONG (CN)
Application Number:
PCT/CN2021/094672
Publication Date:
June 16, 2022
Filing Date:
May 19, 2021
Export Citation:
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Assignee:
QUREBIO LTD (CN)
International Classes:
C07K19/00; A61K39/395; A61P31/00; A61P35/00; A61P37/02
Domestic Patent References:
WO2019204665A12019-10-24
WO2019057122A12019-03-28
WO2019204655A12019-10-24
WO2019204646A12019-10-24
WO2014014796A12014-01-23
WO2019213517A12019-11-07
WO2019191100A12019-10-03
Foreign References:
CN108341884A2018-07-31
CN113135996A2021-07-20
CN106459219A2017-02-22
CN105189562A2015-12-23
CN109496217A2019-03-19
CN111518213A2020-08-11
CN110914296A2020-03-24
US20100286374A12010-11-11
CN201110459100A2011-12-31
Other References:
ULRICH BRINKMANN, ROLAND E. KONTERMANN: "The making of bispecific antibodies", MABS, vol. 9, no. 2, 17 February 2017 (2017-02-17), US , pages 182 - 212, XP055531122, ISSN: 1942-0862, DOI: 10.1080/19420862.2016.1268307
FRANKLIN, M .C. ET AL.: "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex", CANCER CELL, vol. 5, no. 4, 2004, pages 317 - 28, XP002372929, DOI: 10.1016/S1535-6108(04)00083-2
J.BOIL.CHEM., vol. 243, 1968, pages 3558
WARD ET AL., NATURE, vol. 341, 1989, pages 544 - 546
CATER ET AL., PROTEIN ENGINEERING, vol. 66, no. 7, 1996, pages 617 - 621
"UniProtKB", Database accession no. Q13261
JONATHAN H. DAVIS, PROTEIN ENGINEERING, DESIGN & SELECTIONPP, 2010, pages 1 - 8
SCIENCE, vol. 317, no. 5844, 2007
MABS, vol. 3, no. 6, November 2011 (2011-11-01), pages 546 - 557
"Molecular Cloning, Laboratory Manual", COLD SPRING HARBOR LABORATORY, article "Current Molecular Biology Methods, Cell Biology and so on"
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