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Antibody targeting BCMA, bispecific antibody and uses of antibody targeting BCMA and bispecific antibody

A bispecific antibody and targeting technology, applied in the direction of antibodies, antibody medical components, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc., can solve light chain mismatch and heterodimerization and other issues to achieve the effect of optimizing activity, reducing toxicity and long half-life

Inactive Publication Date: 2021-03-30
NONA BIOSCIENCES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Half the size of traditional IgG antibodies, it can be used in the development of bispecific antibodies and solve the problems of light chain mismatch and heterodimerization

Method used

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  • Antibody targeting BCMA, bispecific antibody and uses of antibody targeting BCMA and bispecific antibody
  • Antibody targeting BCMA, bispecific antibody and uses of antibody targeting BCMA and bispecific antibody
  • Antibody targeting BCMA, bispecific antibody and uses of antibody targeting BCMA and bispecific antibody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1. The acquisition of mouse immunization and anti-BCMA antibody molecules

[0054]The BCMA antigen can be used to immunize experimental animals to obtain antibody molecules specifically binding to BCMA, and the experimental animals can be mice, rats, rabbits, sheep, camels and the like. Typically, the resulting antibody molecules are non-human. After obtaining non-human antibodies, these molecules need to be humanized using antibody engineering technology to reduce immunogenicity and improve druggability. However, the humanization process of antibodies has its own technical complexity, and molecules after humanization often reduce the affinity for antigens. On the other hand, advances in transgenic technology have made it possible to create genetically engineered mice that carry the human immunoglobulin immune repertoire and have their endogenous murine immune repertoire deleted. The antibody produced by this transgenic mouse has a fully human sequence, so the...

Embodiment 2

[0068] Embodiment 2.FACS detects the binding ability of the HCAb monoclonal antibody cell level of anti-human BCMA

[0069] This example is to study the activity of anti-human BCMA HCAb monoclonal antibody binding to human and cynomolgus monkey BCMA in vitro. The HEK293T cell line overexpressing human BCMA (HEK293T / huBCMA, Beijing Kangyuan), the HEK293T cell line overexpressing cyno BCMA (HEK293T / cynoBCMA, Beijing Kangyuan) and the cell line NCI-H929 overexpressing human BCMA ( CRL-9068 TM ) for antibody binding experiments at the cellular level. Briefly, HEK293T / huBCMA and HEK293T / cynoBCMA cells were digested and resuspended with DMEM complete medium to collect NCI-H929 cell suspension. Adjust the three cell densities to 1×10 6 cells / mL. 100 μL cells / well were inoculated in a 96-well V-bottom plate (Corning, Cat#: 3894), and then 100 μL / well, 3-fold dilutions of the antibody to be tested was added at 2 times the final concentration. Place the cells at 4°C and incubate f...

Embodiment 3

[0071] Example 3.ELISA detection of anti-human BCMA HCAb monoclonal antibody to the blocking of human BCMA and ligand BAFF protein binding

[0072] This example is to evaluate the blocking ability of anti-human BCMA HCAb monoclonal antibody on the binding of human BCMA (ACRO, BCA-H522y-100 μg) to the ligand BAFF protein (ACRO, BAF-H5248-50ug). Using a biotinylation kit (ThermoFisher, A39257, EZ-Link Sulfo-NHS-LC-Biotin), the BAFF protein was biotinylated according to the instructions. Use 1 μg / mL human BCMA protein, Fc Tag (ACRO, Cat#: BC7-H5254) to coat the plate (Corning, Cat#: 9018), overnight. After washing 3 times with PBST, add 2% BSA to block at room temperature for 1 hour. After washing with PBST for 3 times, add 100 μL / well of 3-fold concentration gradient dilution of the antibody to be tested, the initial concentration is 50 nM, and after incubation at room temperature for 1 hour, discard the supernatant, and add 100 μL / well of 0.5 μg / mL biotinylated human BAFF prot...

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Abstract

The invention discloses an antibody targeting BCMA, a bispecific antibody targeting BCMA and CD3, and applications of the antibody and the bispecific antibody. The antibody targeting the BCMA comprises two heavy chain variable regions, wherein the heavy chain variable regions comprise HCDR1, HCDR2 and HCDR3 which are respectively shown as amino acid sequences of SEQ ID NO: 22, SEQ ID NO: 33 and SEQ ID NO: 42, or HCDR1, HCDR2 and HCDR3 shown as amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 37 and SEQ ID NO: 41 respectively. The antibody provided by the invention effectively targets human BCMA and is combined with cynomolgus monkey BCMA; and the bispecific antibody effectively targets human BCMA and human CD3 at the same time, and can be combined with cynomolgus monkey BCMA and cynomolgus monkey CD3.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to an antibody targeting BCMA, a bispecific antibody and uses thereof. Background technique [0002] BCMA (B-cell maturation antigen, TNFRSF17, CD269) is a transmembrane protein belonging to the TNF receptor superfamily. BCMA is a non-glycosylated transmembrane protein involved in B cell maturation, growth and survival. BCMA is the receptor for two ligands of the TNF superfamily: the high-affinity ligand APRIL (proliferation-inducing ligand) and the low-affinity ligand BAFF (B-cell activating factor). BCMA is a highly differentiated plasma cell-selective protein whose expression is restricted to the B-cell lineage and is present primarily on plasma cells and plasmablasts and to some extent on memory B-cells, but not in the periphery on B-cells. BCMA is expressed in malignant plasma cells of multiple myeloma (MM) patients and supports the growth and survival of MM cells. [0003...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K16/46C12N15/13C12N15/85A61K47/68A61K39/395A61P35/00
CPCC07K16/2878C07K16/2809C12N15/85A61K47/6851A61P35/00C07K2317/52C07K2317/31A61K2039/505C07K2317/92C07K2317/94C07K2317/76C07K2317/73C07K2317/24C07K2317/33A61K2039/545C07K2317/21C07K2317/524C07K2317/569A61K47/6803A61K39/395A61K47/6849C07K2317/53C07K2317/565C07K2317/732C07K2317/734
Inventor 石磊张雪琨何云赵建勋周伟陈飞谭向阳戎一平
Owner NONA BIOSCIENCES CO LTD
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