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IgG heterozygous anti-TNFα and IL-17A bispecific antibody

A bispecific antibody, IL-17A technology, applied in the field of immunology, can solve the problems of poor antibody stability, immunogenicity, and poor specificity, and achieve good biocompatibility, broad application prospects, and good therapeutic effects. Effect

Active Publication Date: 2020-11-17
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

First of all, in terms of configuration, many configurations of existing bispecific antibodies are quite different from those of naturally occurring antibodies, resulting in poor stability and specificity of antibodies, prone to homodimers, and poor pharmacokinetics characteristic, even immunogenic

Method used

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  • IgG heterozygous anti-TNFα and IL-17A bispecific antibody
  • IgG heterozygous anti-TNFα and IL-17A bispecific antibody
  • IgG heterozygous anti-TNFα and IL-17A bispecific antibody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] (1) Construction of plasmid

[0048] (1.1) Recombinant vector construction of anti-TNFα antibody gene

[0049] (1.1.1) containing anti-TNFαV H Gene (SEQ ID NO: 11) recombinant vector pcDNA3.1(+)-GS-intron-IRES-V H -C H build

[0050] (1.1.1.1) Whole-gene synthesis of anti-TNFα V H (SEQ ID NO: 11) nucleotide sequence DNA molecule, the extracted plasmid was digested with BamHI and NheI restriction endonucleases respectively, digested overnight at 37°C respectively, and recovered a 450bp digested fragment by gel after digestion;

[0051] (1.1.1.2) Extraction of pcDNA3.1(+)-GS-intron-IRES-C H Plasmid (the structure of the plasmid is as follows figure 2 As shown, the CH in the plasmid is the C of TNFα H gene), the V recovered from step (1.1.1.1) H The gene and the pcDNA3.1(+)-GS-intron-IRES-CH plasmid were respectively digested with BamHI and NheI endonucleases, digested at 37°C overnight, and the digested fragments were recovered by gel. The gel recovery step See ...

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Abstract

The present invention provides an IgG hybrid bispecific antibody against TNFα and IL-17A. The hybrid antibody comprises a first heavy chain and a first light chain from a human IgG binding specifically to TNFα, and a second heavy chain and a second light chain of a human IgG binding specifically to IL-17A. A variable region of the second heavy chain is exchanged with a variable region of the second light chain, and / or a variable region of the first heavy chain is exchanged with a variable region of the first light chain; and constant regions of the first heavy chain and the second heavy chain interact with each other via enhanced electrostatic interaction or hydrophobic interaction.

Description

technical field [0001] The invention relates to the field of immunology, in particular to an IgG hybrid anti-TNFα and IL-17A bispecific antibody capable of simultaneously binding tumor necrosis factor alpha (TNFα) and interleukin 17A (IL-17A). Background technique [0002] At present, monoclonal antibodies produced by genetic engineering technology play an important role in the field of biomedicine, but because many major diseases are not caused by a single antigen, such as tumors and autoimmune diseases, they are often caused by a variety of cytokines ( Including those driven by tumor necrosis factor α (TNFα) and interleukin 17A (IL-17A), the use of monoclonal antibodies in the treatment of such diseases has certain limitations. Therefore, if it is possible to produce antibodies that can combine two or more Antibodies to antigens can greatly reduce the limitations of monoclonal antibodies in treating diseases, and are very beneficial to the treatment of tumors and autoimmun...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/46C12N15/13C12N5/10C12P21/02A61K39/395A61P19/02A61P29/00A61P1/00A61P17/06A61P35/00G01N33/68
CPCA61K39/00C07K16/468G01N33/6863G01N33/6869A61K39/395C07K16/24C07K16/46C12N15/63G01N33/53
Inventor 赵琦徐天殊
Owner SHENZHEN INST OF ADVANCED TECH
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