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Antigen-binding molecule for promoting loss of antigens

一种抗原结合分子、抗原的技术，应用在抗受体/细胞表面抗原/细胞表面决定因子免疫球蛋白、抗动物/人类的免疫球蛋白、抗体等方向，能够解决增强Fcγ受体结合活性没有进行尝试等问题

Pending Publication Date: 2019-12-13
CHUGAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, no attempt has been made so far to enhance Fcγ receptor binding activity among antibodies targeting soluble antigens, and there are no reports of this effect

Method used

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  • Antigen-binding molecule for promoting loss of antigens
  • Antigen-binding molecule for promoting loss of antigens
  • Antigen-binding molecule for promoting loss of antigens

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[1450] Method for preparing antigen binding molecules

[1451] In addition, the present invention provides a method for preparing an antigen-binding molecule, the antigen-binding molecule contains: an antigen-binding domain having human FcRn-binding activity under acidic pH range conditions and whose antigen-binding activity varies with ion concentration conditions; and, Fcγ receptor binding activity under the condition of neutral pH range. Compared with the Fcγ receptor binding activity of the natural Fcγ receptor binding domain containing fucose sugar chain, the sugar chain linked to EU number 297 is higher than the Fcγ receptor binding activity Structural domain.

[1452] That is, the present invention provides a method for preparing an antigen-binding molecule, which method includes the following steps (a) to (f):

[1453] (a) The step of obtaining the antigen binding activity of the antigen binding domain under the condition of high calcium ion concentration;

[1454] (b) The s...

Embodiment 1

[1652] (Example 1) Preparation of an antigen-binding molecule whose binding activity to mouse FcγR is higher than the binding activity to the Fc region of natural human IgG under the condition of a neutral pH range

[1653] (1-1) About pH-dependent human IL-6 receptor binding antibody

[1654] The H54 / L28-IgG1 containing H54-IgG1 (SEQ ID NO: 36) and L28-CK (SEQ ID NO: 37) described in WO2009 / 125825 is a humanized anti-IL-6 receptor antibody, including VH3-IgG1 (SEQ ID NO: 38) and VL3-CK (SEQ ID NO: 39) Fv4-IgG1 is a pH-dependent binding characteristic of H54 / L28-IgG1 with soluble human IL-6 receptor (at pH7 .4, and dissociate at pH 5.8) humanized anti-IL-6 receptor antibody. In the in vivo test of mice described in WO2009 / 125825, compared with the group administered with a mixture of H54 / L28-IgG1 and antigen-soluble human IL-6 receptor, it was compared with the group administered with Fv4-IgG1 and antigen-soluble human IL-6 receptor. In the group of the mixture of human IL-6 rec...

Embodiment 2

[1668] (Example 2) Effect of antigen-binding molecules with FcγR binding activity higher than that of the Fc region of natural human IgG to eliminate antigens from plasma

[1669] (2-1) The effect of H54 / L28-IgG1 and Fv4-IgG1 in eliminating antigens from plasma

[1670] Using the method of Reference Example 1, anti-human IL-6 receptor antibody H54 / L28-IgG1 and Fv4-IgG1, which have the property of binding to human IL-6 receptor in a pH-dependent manner, were produced. The in vivo infusion test using the prepared H54 / L28-IgG1 and Fv4-IgG1 was performed by the following method.

[1671] (2-1-1) In vivo injection test using human FcRn transgenic mice

[1672] Human FcRn transgenic mice (B6.mFcRn- / -.hFcRn Tg 32+ / + mice, Jackson Laboratories, Methods Mol Biol. (2010) 602, 93-104) were subcutaneously implanted with soluble human The IL-6 receptor infusion pump (MINI-OSMOTIC PUMP MODEL 2004, alzet) has created an animal model in which the concentration of soluble human IL-6 receptor in pla...

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Abstract

The present invention provides antigen-binding molecules comprising: antigen-binding domains which have binding affinity to human FcRn under acidic pH conditions, and with which the binding affinity of the antigen-binding molecules to antigens is altered according to ion concentration conditions; and Fc[gamma] receptor-binding domains which have a higher binding affinity to Fc[gamma] receptors under neutral pH conditions than the Fc[gamma] receptor-binding domains of the Fc regions of natural human IgG having a fucose-containing sugar chain as the sugar chain bound to position 297 (EU numbering).

Description

[0001] This application is the international application number PCT / JP2012 / 075092, the international filing date is September 28, 2012, the date of entering the Chinese national phase is May 29, 2014, the Chinese national application number is 201280058920.8, and the title of the invention is "Promoting Antigen Elimination The divisional application of “antigen-binding molecules”. Technical field [0002] The present invention provides: antigen-binding molecules that promote the uptake of bound antigens into cells, antigen-binding molecules that increase the number of antigens that can be bound per molecule, antigen-binding molecules that improve pharmacokinetics, and Antigen-binding molecules that promote the dissociation of extracellular antigens within the cell, antigen-binding molecules that promote the release of antigens outside the cell without being bound to the antigen, have the ability to increase the total antigen concentration or free antigen in the plasma Functional ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/00C07K16/08C07K16/18C07K16/28C07K16/30A61K39/395
CPCC07K16/2866A61K2039/505C07K2317/41C07K2317/72C07K2317/92C07K2317/94C07K2317/52A61P29/00A61P35/00A61P37/02C07K2317/22C07K16/283C07K16/468C07K2317/31
Inventor 井川智之前田敦彦原谷健太岩柳有起橘达彦
Owner CHUGAI PHARMA CO LTD