Mice expressing humanized fc alpha receptors

Genetically modified mice expressing human or humanized FcaR in the LRC on chromosome 7 address the disparity in IgA therapeutic agent testing, offering accurate pharmacokinetic and pharmacodynamic predictions and reducing the reliance on larger animal models.

AU2021400584B2Pending Publication Date: 2026-07-23REGENERON PHARMACEUTICALS INC
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Patent Information

Application Number
AU2021400584
Authority / Receiving Office
AU · AU
Patent Type
Applications
Current Assignee / Owner
Priority Date
2020-12-16
Filing Date
2021-12-15
Publication Date
2026-07-23

AI Technical Summary

Technical Problem

Existing mouse models lack an Fc alpha receptor (FcaR) for IgA antibodies, leading to significant differences in pharmacokinetic and pharmacodynamic properties of human IgA-based therapeutic agents when tested in mice compared to humans, limiting their predictive value for clinical applications.

Method used

Genetically modify mice to express a human or humanized FcaR, positioning the receptor in the leukocyte receptor complex (LRC) on mouse chromosome 7, allowing for accurate testing of human IgA antibodies and Fc fusion proteins by mimicking human Fc receptor interactions and reducing immune response.

Benefits of technology

The modified mice provide a reliable in vivo system for predicting the safety, efficacy, and optimal dosing of human IgA-based therapeutic agents, mimicking human Fc receptor functions and reducing the need for costly and less amendable larger animal models.

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Abstract

Provided herein are methods and compositions related to mice that express human or humanized Foot receptors (FcaR) from an FcaR locus positioned in the mouse leukocyte receptor complex (LRC). In certain embodiments, such mice are useful for in vivo testing of therapeutic agents comprising a human IgA Fc (e.g., the testing of the pharmacokinetic and / or pharmacodynamic properties of such therapeutic agents and dosing regimens). Also provided herein are methods of using such mice, cells from such mice, methods of making such mice, and ES cells comprising the same genetic modifications as such mice. Provided herein are methods and compositions related to mice that express human or humanized Foot receptors (FcaR) from an FcaR locus positioned in the mouse leukocyte receptor complex (LRC). In certain embodiments, such mice are useful for in vivo testing of therapeutic agents comprising a human IgA Fc (e.g., the testing of the pharmacokinetic and / or pharmacodynamic properties of such therapeutic agents and dosing regimens). Also provided herein are methods of using such mice, cells from such mice, methods of making such mice, and ES cells comprising the same genetic modifications as such mice.
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