Multifunctional Heteromultimeric Constructs with Defined Component Ratios

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Solution Overview

Problem

Current multimeric systems for targeted therapies face challenges in precisely controlling the number of functional components, leading to unpredictable binding specificity and affinity, which affects their therapeutic efficacy and reproducibility.

Innovation Solution

The development of methods to prepare multifunctional heteromultimeric protein complexes with a defined ratio of functional components through successive transfections and selections, allowing for the controlled assembly of bifunctional, trifunctional, or tetrafunctional multimers with specific ratios of tracking, targeting, and effector components.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If functional components are attached to a polymer scaffold to create multimeric systems, then therapeutic effectiveness and binding affinity are improved, but the chemical formulation becomes undefined and the number of functional components cannot be controlled

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidcontrol over number of functional components
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The invention divides the multimeric system into distinct modular components: a polymer scaffold and separately attached functional components. This segmentation allows independent control and characterization of each component while maintaining the overall therapeutic function, resolving the contradiction between therapeutic effectiveness and manufacturing precision.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs preliminary characterization and definition of the polymer scaffold's chemical formulation before attaching functional components. By establishing the scaffold's structure and properties in advance, the invention enables precise control over the final multimeric system's composition and stoichiometry, addressing the manufacturing precision issue.

Inventive Principle:
Principle #10Preliminary action

2Power

If multiple functional components are combined in one multimeric molecule, then synergistic therapeutic effect is achieved, but the binding specificity and affinity become unpredictable

Engineering Contradiction:
Improvesynergistic therapeutic effectVSAvoidbinding specificity and affinity
Core Design Contradiction:
PowerVSMeasurement precision

Solution Approach 1:

The invention implements feedback mechanisms through characterization techniques that measure and monitor the binding properties of multimeric systems. By analyzing the interaction between functional components and targets, the patent enables optimization of binding specificity and affinity while maintaining synergistic effects.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent systematically varies and optimizes parameters such as the number, type, and arrangement of functional components attached to the polymer scaffold. This parameter optimization allows tuning of binding affinity and specificity while preserving synergistic therapeutic effects.

Inventive Principle:
Principle #35Parameter changes

3Power

If the number of functional components is increased on a polymer molecule, then therapeutic potency is enhanced, but the reproducibility and control of the system deteriorate

Engineering Contradiction:
Improvetherapeutic potencyVSAvoidreproducibility
Core Design Contradiction:
PowerVSReliability

Solution Approach 1:

The invention develops a universal polymer scaffold platform that can accommodate varying numbers and types of functional components through standardized attachment mechanisms. This universality enables reproducible production of multimeric systems with different functional compositions while maintaining consistent manufacturing processes.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230130737A1Multifunctional Heteromultimeric Constructs
Publication Date: 2023.04.27 UNIV DE REIMS CHAMPAGNE ARDENNE
  • US20230130737A1 patent drawing
  • US20230130737A1 patent drawing
  • US20230130737A1 patent drawing

AI summary

The present invention is situated in the field of multimers used for targeted therapies. More particularly, the invention relates to methods for preparing multifunctional heteromultimeric protein complexes with a defined ratio of functional components and to multifunctional heteromultimeric protein complexes for directing complement-dependent cytolysis, optionally comprising a scaffold, which display three or more different functional components present in a defined relative ratio, of which one is a tracking component.