CCR4 Fc-Binding Constructs With Controlled Fc Dimerization

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing CCR4-targeted therapeutics, such as Poteligeo (mogamulizumab), face limitations in achieving uniform biological activity and efficacy due to variations in homodimerization and heterodimerization of Fc domains, which affect safety, efficacy, and reliability.

Innovation Solution

Combining a CCR4 binding domain with at least two Fc domains through linkers to create constructs that enhance effector functions like ADCC, ADCP, and CDC, ensuring a homogeneous population of Fc-antigen binding domains with controlled dimerization, thereby improving therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a single Fc domain is used in CCR4-targeted therapeutics, then the construct is simpler to manufacture, but the effector function and biological activity are limited

Engineering Contradiction:

Improveconstruct simplicityVSAvoideffector function

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent combines multiple Fc domains (at least two) with the CCR4 binding domain to create multi-Fc domain constructs. This merging approach enhances effector functions including ADCC, ADCP, and CDC activities while maintaining controlled dimerization through engineered interfaces, thereby improving biological activity without sacrificing manufacturability

Inventive Principle:

Principle #5Merging (Combining)

2Adaptability or versatility

If Fc domains are allowed to homodimerize and heterodimerize freely, then more biological activities may be achieved, but the composition becomes heterogeneous affecting safety and efficacy

Engineering Contradiction:

Improvebiological activityVSAvoidcomposition homogeneity

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent applies local quality by engineering specific dimerization interfaces at particular locations within the Fc domains. This allows controlled homodimerization and heterodimerization at defined sites while preventing uncontrolled dimerization elsewhere, achieving both desired biological activity and composition homogeneity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent introduces engineered dimerization interfaces as intermediaries that mediate controlled dimerization between Fc domains. These engineered interfaces act as selective mediators that enable specific homodimer and heterodimer formation while preventing formation of unwanted dimer combinations, ensuring composition uniformity

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If multiple Fc domains are combined to enhance effector function, then ADCC, ADCP, and CDC activities are improved, but the construct complexity increases

Engineering Contradiction:

Improveeffector functionVSAvoidconstruct complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the therapeutic construct into distinct functional modules: CCR4 binding domains for antigen recognition and multiple Fc domains for effector functions. This segmentation allows independent optimization of each module and facilitates controlled assembly through engineered dimerization interfaces, managing complexity while enhancing functionality

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250346676A1COMPOSITIONS AND METHODS RELATED TO ENGINEERED Fc-ANTIGEN BINDING DOMAIN CONSTRUCTS TARGETED TO CCR4

Publication Date: 2025.11.13 MOMENTA PHARMACEUTICALS INC

AI summary

Fc-antigen binding constructs having a CCR4 binding domain and two or more Fc domains are described as are methods for using such constructs. Also described are polypeptides making up such constructs. Fc domain monomers that are included in the constructs can include amino acid substitutions that promote homodimerization or heterodimerization.