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Fully human antibody against ox40 and its preparation method and use

An antibody, fully human technology, applied in the fields of botanical equipment and methods, biochemical equipment and methods, antibodies, etc., can solve problems such as toxicity, high immunogenicity reduction, and limited clinical application.

Active Publication Date: 2022-05-31
CURON MACAO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As an agonist against co-stimulatory receptors, toxicity may be the most concern, such as cytokine storm, which limits clinical application
In addition, anti-OX40 antibodies currently tested in clinical trials are human-mouse chimeric or humanized antibodies, which reduce efficacy due to high immunogenicity due to protein sequences of mouse origin

Method used

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  • Fully human antibody against ox40 and its preparation method and use
  • Fully human antibody against ox40 and its preparation method and use
  • Fully human antibody against ox40 and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0431] Four benchmark antibodies, BMK1, BMK5, BMK7, and BMK10, were used as positive controls in the examples. According to beauty

[0433] To obtain tools for antibody screening and validation, we generated an OX40 transfected cell line. In short, the root

Embodiment 2

under cultivation, and regularly

monitor. When clones are large enough, transfer 100 uL of supernatant from the tissue culture plate to a 96-well assay plate for antibody screening.

2.2 High-throughput screening of hybridoma supernatants

[0439] Hybridoma supernatants were tested for binding to human and monkey OX40 protein using ELISA as a first screening method. simple

In brief, plates (Nunc) were coated with 1 ug / mL of soluble protein of human or cynomolgus OX40 ECD overnight at 4°C. in seal

After blocking and washing, hybridoma supernatants were transferred to coated plates and incubated at room temperature for 2 hours. Plates are then washed, followed by

It was then incubated with secondary antibody (goat anti-rat IgG HRP(Bethyl)) for 1 hour. After washing, TMB substrate was added and quenched with 2M HCl

stop interaction. Absorbance at 450 nm was read using a microplate reader (Molecular Device).

Embodiment 3

[0448]

[0450]

[0451] The resulting cDNA was used as a template for subsequent PCR amplification using primers specific for the gene of interest. PCR reaction is as follows

[0453]

[0455]

[0457] Hybridoma clones 1.7.10, 1.62.3, 1.134.9, 1.186.19 and 1.214.23 were selected for sequence optimization and

[0459] Antibody sequence optimization is performed by introducing appropriate modifications at specific sites into the nucleotide sequence encoding the antibody.

[0461] Figure 1 shows a comparison between variants after PTM mutation. The variants were named antibody "1.62.3‑u1‑1‑IgG1K",

[0463] The VH and VL of the OX40 hybridoma antibody were amplified as described above. Recloning of synthetic genes into modified human IgG1

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PUM

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Abstract

The present application provides fully human monoclonal antibodies directed against member 4 of the tumor necrosis factor receptor superfamily (TNFRSF4), also known as OX40 and CD134. The present application also provides a method for producing hybridomas using humanized transgenic rats, nucleic acid molecules encoding anti-OX40 antibodies, expression vectors and host cells for expressing anti-OX40 antibodies. The invention also provides methods for validating antibody function in vitro and antibody efficacy in vivo. The antibodies of the present invention provide very effective agents for the treatment of various cancers by modulating human immune function.

Description

Anti-OX40 fully human antibody and preparation method and use thereof [0001] Priority Information This application requires PCT application number PCT / CN2018 / 086574 submitted on May 11, 2018 and May 29, 2018 The priority of the Chinese application number 201810529840.5 filed on 201810529840.5. [0003] Sequence Listing [0004] This application contains a Sequence Listing, the entire contents of which are incorporated herein by reference. technical field [0005] The present application relates generally to antibodies. More specifically, the present application relates to a fully human monoclonal antibody against OX40, its preparation Preparation methods and their uses. Background of the Invention [0007] Growing evidence from preclinical and clinical results suggests that targeting immune checkpoints is emerging as a treatment option for cancer the most promising approach for patients with schizophrenia. Tumor necrosis factor receptor superfamily member 4 (TNFRSF4,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/28C12N15/13C12N15/85C12N5/10A61K39/395A61P35/00A61P37/02A61P29/00A61P31/00
CPCC07K16/2878C07K2317/565C07K2317/56A61P29/00A61P31/00A61P35/00A61P37/02A61P37/00C07K2317/21C07K2317/92C07K2317/33C07K2317/732C07K2317/734A61K2039/505C07K2317/34C12N5/163A01K2227/105A01K2267/0331C07K2317/75C07K16/2875C07K2317/76A61P35/04C07K2317/52
Inventor 郑勇杨宝田李竞
Owner CURON MACAO LTD
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