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Bispecific antibody resistant to CD3 and CD123 and application of bispecific antibody

A bispecific antibody, LCDR2 technology, applied in the direction of antibodies, specific peptides, anti-tumor drugs, etc., can solve the problems of inconvenient clinical application and short half-life

Active Publication Date: 2020-05-19
BEIJING WISDOMAB BIOTECHNOLOGY CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The advantage of this type of bispecific antibody is that there is no mismatch between light and heavy chains, but the disadvantage is that the half-life is short and clinical application is inconvenient

Method used

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  • Bispecific antibody resistant to CD3 and CD123 and application of bispecific antibody
  • Bispecific antibody resistant to CD3 and CD123 and application of bispecific antibody
  • Bispecific antibody resistant to CD3 and CD123 and application of bispecific antibody

Examples

Experimental program
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Effect test

Embodiment 1

[0190] The preparation of embodiment 1 recombinant protein

[0191] The process of preparing and identifying CD3E×CD123 bispecific antibodies requires the use of a variety of different recombinant proteins, including human CD3E extracellular region (hCD3E, SEQ ID NO: 14), human CD3D extracellular region (hCD3D, SEQ ID NO : 15), monkey CD3E extracellular region (mfCD3E, SEQ ID NO: 16), monkey CD3D extracellular region (mfCD3D, SEQ ID NO: 17), mouse CD3E extracellular region (mCD3E, SEQ ID NO: 18), Mouse CD3D extracellular region (mCD3D, SEQ ID NO: 19) and human CD123 subtype 1 extracellular region (hCD123-SP1, SEQ ID NO: 20), monkey CD123 subtype 1 extracellular region (mfCD123-SP1, SEQ ID NO: 20) ID NO: 21), mouse CD123 subtype 1 extracellular region (mCD123-SP1, SEQ ID NO: 22). These recombinant proteins have a large number of post-translational modifications (such as glycosylation or disulfide bonds, etc.), so the use of mammalian cell expression systems will be more conduciv...

Embodiment 2

[0194] Example 2 Construction of CD123 mouse immune library based on immobilized light chain

[0195] In order to construct a CD3E×CD123 bispecific antibody based on the common light chain, the light chain variable region of a specific anti-CD3E monoclonal antibody was selected to cooperate with the mouse heavy chain variable region that had undergone in vivo affinity maturation for the CD123 antigen, and conventional molecular biology methods were used to A single-chain antibody (scFv) library was constructed for screening specific antibodies against CD123.

[0196] Splenocytes were collected after cross-immunization of 6-8 week-old BALB / c mice with hCD123-SP1-His and mfCD123-SP1-His recombinant proteins. Mouse spleen lymphocytes were isolated using mouse lymphocyte separation medium (Dakowei Biotechnology Co., Ltd., CAT#DKW33-R0100), and the total RNA extraction kit (Tiangen Biochemical Technology (Beijing) Co., Ltd., CAT#DP430), the isolated lymphocytes were subjected to e...

Embodiment 3

[0197] Example 3 Screening of CD123 mouse immune library with fixed light chain

[0198] 3.1 Screening of anti-human CD123 mouse single chain antibody

[0199] Using the recombinant hCD123-SP1-his prepared in Example 1 as an antigen, a solid-phase screening strategy (experimental scheme refers to Phage Display: General Experimental Guidelines / (US) Clarkson (Clackson, T.), (US) Loman (Lowman , H.B.) edited; Ma Lan et al. Translated. Chemical Industry Press, 2008.5) screened the phage library displaying mouse single-chain antibody constructed in Example 2, and carried out by binding, elution, neutralization, infection, and amplification. After three rounds of screening, a single-chain antibody S8F3 (SEQ ID NO: 36) specifically binding to human CD123 was finally obtained.

[0200] Using conventional molecular biology methods, the nucleotide sequences encoding the heavy chain variable region S8F3VH (SEQ ID NO: 37) and the light chain variable region WM03-C6VK (SEQ ID NO: 35) of S...

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Abstract

The invention provides a bispecific antibody. The bispecific antibody comprises an antigen binding part against human CD3E and / or an antigen binding part against human CD123. In addition, the invention also provides application of the bispecific antibody in medicine and biology.

Description

technical field [0001] The present application generally relates to the field of antibody medicines. Specifically, the present application provides a bispecific antibody comprising an antigen-binding portion against human CD3E and / or an antigen-binding portion against human CD123 and its medical and biological uses. Background technique [0002] Bispecific antibodies (BsAbs) are a class of artificial antibodies that contain two different antigen-binding sites. Bispecific antibodies are widely used in the field of biomedicine, especially in tumor immunotherapy. A bispecific antibody targeting CD3, one arm can bind to the CD3E subunit in the TCR receptor complex on the surface of T cells, and the other arm targets tumor antigens. In this way, bispecific antibodies can redirect T cells to specifically kill tumor cells in a non-histocompatibility complex (MHC)-dependent manner. [0003] There are many platforms and complex structures of bispecific antibodies. According to the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/46A61K39/395A61P35/00A61P35/02
CPCC07K16/2866A61P35/00C07K2317/31C07K2317/565C07K2317/622A61K2039/505C07K16/2809A61P35/02C07K2317/53C07K2317/52C07K2317/56C07K2317/24C07K2317/92C07K2317/73C07K2317/74A61K2039/545C07K2317/55
Inventor 刘志刚郝小勃张雪萍刘玉兰郭晶晶
Owner BEIJING WISDOMAB BIOTECHNOLOGY CO LTD
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