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Mutated nonactivating IgG2 domains and anti-cd3 antibodies incorporating same

An antibody, variable technology, applied in the direction of antibody mimetics/scaffolds, medical formulations containing active ingredients, anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, etc. The role of anti-CD3 monoclonal antibodies and other issues

Inactive Publication Date: 2009-10-14
ABBVIE BIOTHERAPEUTICS +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the naturally occurring form of Fc is not suitable for the generation of non-activating anti-CD3 mAbs

Method used

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  • Mutated nonactivating IgG2 domains and anti-cd3 antibodies incorporating same
  • Mutated nonactivating IgG2 domains and anti-cd3 antibodies incorporating same
  • Mutated nonactivating IgG2 domains and anti-cd3 antibodies incorporating same

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Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0074] 1. Materials and methods

[0075] a. Cloning of V region cDNA

[0076] According to the anchored PCR (polymerase chain reaction) method described by Co et al. (Journal of Immunology, 148, 1149 (1992)), the V of OKT3 heavy and light chains were cloned from hybridoma cells expressing OKT3 (ATCC CRL 8001) Region cDNA. The cDNA was amplified with a 3'primer that can anneal to the C region of the mouse γ chain and κ chain and a 5'primer that can anneal to the additional G tail of the cDNA. Will V H And V L The cDNA was subcloned into the vector pUC19 for sequence determination. Their sequences are the same as those published by Woodle et al. (see Woodle et al., Journal of Immunology, 148, 2756 (1992)).

[0077] b. Expression of chimeric anti-CD3 antibody

[0078] Put OKT3's V H And V L The cDNA is constructed as an exon containing a signal sequence, a J segment and a splice donor sequence, which contains XbaI sites on both sides (see Co et al., Journal of Immunology, 148, 114...

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Abstract

The invention provides mutated IgG2 constant regions and anti-CD3 antibodies incorporating the same. Such antibodies specifically bind to the CD3 antigen on T-cells but induce reduced mitogenic response compared with otherwise identical antibodies bearing natural IgG2 constant regions. The antibodies can be used for treating disorders requiring immune suppression with fewer side effects than result from treatment with prior anti-CD3 antibodies.

Description

Technical field [0001] The present invention uses immune and molecular genetic technology to design a mutant non-activating IgG2 structural domain and a humanized anti-CD3 antibody inserted into the structural domain. Background of the invention [0002] The CD3 complex on T cells is closely related to T cell receptor (TCR) heterodimers, and plays an important role in the process of antigen binding to activate T cells. Certain anti-CD3 antibodies can activate T cells in the absence of antigen. This activation relies on the interaction of the Fc part of the monoclonal antibody (mAb) and the Fc receptor on the accessory cell to cross-link the CD3 complex on the T cell. Soluble anti-CD3 monoclonal antibodies will not stimulate T cell proliferation in vitro unless they bind to plastic or cells containing Fc receptors. [0003] Although the administration of this antibody to human subjects or mice will produce immunosuppressive effects, its efficacy is often affected by two factors. O...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/46C12N15/09A61K38/00C07K16/00C07K16/28
CPCC07K2319/00C07K16/00C07K16/2809A61K38/00C07K2317/24
Inventor J·Y·特索M·S·科勒C·阿纳瑟迪
Owner ABBVIE BIOTHERAPEUTICS