Humanized Anti-RAGE Antibody Engineering for Therapeutic Use

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Solution Overview

Problem

Current monoclonal antibodies targeting the receptor for advanced glycation end products (RAGE) are not humanized, limiting their therapeutic and diagnostic applications in humans, despite showing promise in animal models.

Innovation Solution

Development of a humanized anti-human RAGE monoclonal antibody with specific amino acid sequences for the heavy and light chains, designed to maintain binding activity with human RAGE, utilizing recombinant expression vectors and eukaryotic cells like CHO and human kidney 293 cells for production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If mouse monoclonal antibodies are used to target RAGE, then binding activity and diagnostic utility are achieved, but human therapeutic applications are limited due to non-humanization

Engineering Contradiction:

Improvetherapeutic applicabilityVSAvoidbinding activity

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequence parameters of the antibody to transform it from a mouse antibody to a humanized antibody. Specifically, the constant regions and framework regions are changed to human sequences while preserving the variable regions that confer RAGE-binding activity, thereby enabling human therapeutic use while maintaining binding reliability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses copying by creating a humanized version of the mouse antibody that replicates the essential binding function. The humanized antibody copies the antigen-binding capability of the original mouse antibody while adopting human antibody characteristics, allowing it to function both as a diagnostic tool and as a therapeutic agent in humans

Inventive Principle:

Principle #26Copying

2Adaptability or versatility

If humanized antibody sequences are developed, then therapeutic potential is improved, but development complexity and time increase

Engineering Contradiction:

Improvehuman therapeutic useVSAvoidantibody engineering complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the antibody into distinct functional modules: variable regions (VH and VL) that provide antigen binding, and constant regions (CH and CL) that provide human framework support. This segmentation allows independent optimization of binding activity and human compatibility, simplifying the overall engineering process while achieving therapeutic potential

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent achieves universality by designing a humanized antibody that can serve multiple functions: it maintains the diagnostic capability of the original mouse antibody while gaining therapeutic applicability in humans. The humanized format allows the same antibody structure to be used for both imaging/diagnosis and therapy, reducing overall development complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS10550184B2Humanized anti-rage antibody

Publication Date: 2020.02.04 THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK

AI summary

This invention provides a humanized, anti-human receptor for advance glycation end-products (RAGE) monoclonal antibody or a fragment of such antibody which binds human RAGE as well as compositions containing, and uses of, such antibody and fragments.