Antibody Constant Region Antigen Binding Loops

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Solution Overview

Problem

Conventional antibodies have limited antigen binding capacity, primarily restricted to the VH and VL regions, which hinders their ability to bind to multiple antigens effectively, limiting their therapeutic potential.

Innovation Solution

Development of binding molecules with additional antigen binding sites in the CH1 and CL regions, specifically incorporating antigen binding loops in the AB, BC, CD, DE, EF, and FG loop regions, enhancing the antibodies' capacity to bind to multiple antigens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional antibody structure is used, then the structure is simple and well-understood, but the antigen binding capacity is limited to VH and VL regions only

Engineering Contradiction:

Improveantigen binding capacityVSAvoidantibody structure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention divides the antibody structure into functional segments by introducing separate antigen binding loops (AB, BC, CD, DE, EF, FG) in the constant region, allowing independent binding sites that can target different antigens while maintaining the overall antibody framework

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The constant region of the antibody is engineered to perform multiple functions: maintaining structural integrity and simultaneously providing additional antigen binding capability through incorporated antigen binding loops, making the antibody both structural and functional in binding multiple antigens

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If additional antigen binding sites are introduced in CH1 and CL regions, then the ability to bind multiple antigens is enhanced, but the structural complexity increases

Engineering Contradiction:

Improvemulti-antigen binding capabilityVSAvoidbinding molecule structure

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

Antigen binding loops are strategically positioned at specific locations (AB, BC, CD, DE, EF, FG regions) within the constant region, creating localized binding sites that preserve the global structural integrity while adding specific functional capabilities at targeted positions

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If antigen binding loops are incorporated in constant region loops, then binding capability is expanded, but the manufacturing complexity increases

Engineering Contradiction:

Improvetherapeutic application rangeVSAvoidproduction process complexity

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The invention modifies specific parameters of the constant region by incorporating antigen binding loops with defined amino acid sequences at specific positions, changing the binding properties while maintaining compatibility with standard antibody production and purification methodologies

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20240218083A1Molecules with engineered antibody constant region variants

Publication Date: 2024.07.04 JANSSEN BIOTECH INC

AI summary

A binding molecule comprising (i) a first polypeptide comprising a heavy chain variable region (VH) and a region derived from the first constant region of an antibody heavy chain (CH1), and (ii) a second polypeptide comprising a light chain variable region (VL) and a region derived from the constant region of an antibody light chain (CL), wherein the region derived from the CH1 region and/or the region derived from the CL region comprises one or more antigen binding loop(s).