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Chimeric nucleic acid molecule and application thereof to humanized antibody preparation

A technology for humanized antibodies and nucleic acid molecules, applied to nucleic acid molecules and their applications in the preparation of humanized antibodies, to achieve the effect of high gene rearrangement efficiency

Active Publication Date: 2016-03-30
CHONGQING JINMAIBO BIOTEC CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that secondary transformation is required to obtain fully humanized antibodies

Method used

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  • Chimeric nucleic acid molecule and application thereof to humanized antibody preparation
  • Chimeric nucleic acid molecule and application thereof to humanized antibody preparation
  • Chimeric nucleic acid molecule and application thereof to humanized antibody preparation

Examples

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Effect test

Embodiment 1

[0045] Transfer the modified human immunoglobulin gene into mice, and then immunize mice containing human immunoglobulin genes to obtain fully humanized antibodies. The specific steps are as follows:

[0046] 1. Optimization and transformation of human immunoglobulin genes

[0047] 1) Transformation of human immunoglobulin heavy chain gene

[0048] The IgM constant region gene fragment of the host animal is transformed into the YAC or BAC vector containing human Ig through homologous recombination, and the gene cluster of the human immunoglobulin heavy chain gene is constructed as follows: figure 2 Shown (the position in the black box is the gene fragment of the introduced mouse IgM constant region). Including the V region, D region, J region of the human immunoglobulin heavy chain gene, hIgHCμ, hIgHCγ3, hIgHCγ1, hIgHCα1, hLCR; among them, hIgHCμ has been genetically modified, and the CH2 partial sequence, CH3, CH4, TM1 of mouse IgHCμ and TM2 sequence and the sequence betwe...

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Abstract

The invention provides a nucleic acid molecule. The nucleic acid molecule comprises human immunoglobulin genes or segments thereof and is characterized by also comprising gene segments in a host animal IgM (immunoglobulin M) constant region. The nucleic acid molecule can be used for efficiently preparing full humanized antibodies and has the effect of solving the problem of incompatibility of the interactions between BCRs (B cell receptors) of different species and Ig alpha and Ig beta. Meanwhile, the humanized antibodies expressed by the nucleic acid molecule are unnecessary to undergo second modification.

Description

technical field [0001] The invention belongs to the field of biotechnology, and mainly relates to a nucleic acid molecule and its application in the preparation of humanized antibodies. Background technique [0002] Antibodies are an important class of biomedical products, which play an important role in the prevention and treatment of human diseases. The development of therapeutic antibodies has gone through different development stages such as murine antibodies, chimeric antibodies, reshaped antibodies, resurfaced antibodies and fully humanized antibodies. [0003] Fully humanized antibody (Full Humanized Antibody) refers to an antibody that is completely identical to the protein sequence of a human antibody obtained through genetic modification or immunization of transgenic animals. Since fully humanized antibodies do not contain animal protein, they have lower side effects and better effects, and have become the main research and development direction of current and fut...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/13C07K16/46C12N15/85A01K67/027
CPCA01K67/027C07K16/46C12N15/85
Inventor 葛良鹏刘作华游小燕邹贤刚吴梦杨松全林保忠刘雪芹黄勇丁玉春
Owner CHONGQING JINMAIBO BIOTEC CO LTD
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