Modified Antibody Fc Regions for Stronger Fc Receptor Binding

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Solution Overview

Problem

Existing monoclonal antibodies lack optimal binding to Fc receptors and antibody-dependent cellular cytotoxicity (ADCC), necessitating improved Fc regions for enhanced therapeutic efficacy.

Innovation Solution

Modification of the Fc region with specific amino acid substitutions, such as T260L and T260N, to enhance binding to Fc receptors and increase ADCC activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If wild-type Fc region is used, then antibody production is simple, but binding to Fc receptors and ADCC activity are insufficient

Engineering Contradiction:

Improvebinding to Fc receptorsVSAvoidFc region modification

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by introducing specific amino acid substitutions (T260L and T260N) at position 260 of the Fc region. These molecular parameter modifications alter the binding affinity and pH-dependent characteristics of the Fc region, enabling enhanced Fc receptor binding and ADCC activity while maintaining a relatively simple modification approach.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If Fc region is modified to increase ADCC, then cancer cell destruction efficacy improves, but manufacturing complexity increases

Engineering Contradiction:

ImproveADCC activityVSAvoidantibody production

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The invention modifies the Fc region through specific amino acid substitutions (T260L, T260N) that enhance ADCC activity. These targeted parameter changes in the Fc region enable improved cancer cell destruction efficacy while maintaining compatibility with standard antibody production workflows, thus balancing performance enhancement with manufacturing feasibility.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If Fc region mutations are introduced, then binding affinity under different pH conditions is modified, but protein stability may be affected

Engineering Contradiction:

Improvebinding under different pH conditionsVSAvoidFc region stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces specific amino acid substitutions (T260L and T260N) at position 260 of the Fc region to modify pH-dependent binding characteristics. These targeted parameter changes enable enhanced binding affinity under different pH conditions while maintaining Fc region structural stability through the localized nature of the modifications.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP3470433B1Modified antibody regions and uses thereof

Publication Date: 2025.12.03 BIOATLA LLC

AI summary

The present invention relates to modified Fc regions of antibodies, and uses thereof, such as in antibodies that contain an Fc region of the present invention.