Multimeric Fc Constructs for Serum Half-Life and Receptor Binding
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Solution Overview
Problem
Current therapeutic proteins for immunological and inflammatory diseases often have limitations in serum half-life and binding affinity to Fc receptors, leading to inadequate treatment of autoimmune and inflammatory conditions.
Innovation Solution
Development of biologically active Fc domain-containing therapeutic constructs with 2-10 Fc domains, designed to enhance serum half-life and binding affinity to Fc receptors, which can be used to reduce inflammation, promote autoantibody clearance, and suppress immune responses without stimulating immune cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If conventional therapeutic proteins are used, then treatment of immunological diseases is provided, but serum half-life is insufficient and binding affinity to Fc receptors is inadequate
Solution Approach 1:
The patent combines multiple Fc domains (2-10 Fc domains) into a single therapeutic construct to simultaneously achieve prolonged serum half-life and enhanced binding affinity to Fc receptors. The multimeric Fc construct merges the advantages of extended circulation time with improved receptor interaction, resolving the contradiction between duration of action and binding reliability.
Solution Approach 2:
The therapeutic construct uses composite Fc domain architecture where multiple Fc domains are assembled into a unified structure with optimized properties. This composite approach allows the construct to exhibit both prolonged serum half-life characteristics and enhanced Fc receptor binding affinity that individual Fc domains cannot achieve alone.
2Reliability
If Fc constructs with multiple Fc domains are created, then binding affinity and serum half-life are improved, but structural complexity increases
Solution Approach 1:
The Fc construct is segmented into multiple identical or similar Fc domain units (2-10 domains) that can be systematically assembled. This segmentation allows for modular design where each Fc domain contributes equally to the overall function, simplifying the design process despite the multimeric complexity. The repetitive structural unit approach makes the complex structure more manageable and predictable.
Solution Approach 2:
The Fc construct achieves multiple functions simultaneously: prolonged serum half-life, enhanced Fc receptor binding affinity, and reduced inflammation. By designing a universal multimeric Fc structure that performs these diverse functions, the patent reduces the need for separate therapeutic agents, effectively managing complexity through functional integration.
3Reliability
If conventional therapeutic proteins are used, then immune response is activated, but this may cause harmful immune cell stimulation in autoimmune diseases
Solution Approach 1:
The Fc construct is designed with specific local properties through controlled Fc domain assembly that modulates immune cell interaction. By optimizing the number and arrangement of Fc domains (2-10 domains), the construct achieves selective immune response activation that promotes beneficial immune functions while avoiding harmful immune cell stimulation in autoimmune conditions. The local structural configuration of Fc domains determines the quality of immune interaction.
Data Source
AI summary
The present invention relates to compositions and methods of engineered IgG Fc constructs, wherein said Fc constructs include one or more Fc domains.