Tetrahedral Antibody Multi-Target Binding via 3D Arrangement
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Solution Overview
Problem
Conventional antibody configurations, such as the planar arrangement of binding domains, are not well-suited for engaging multiple targets simultaneously, limiting their ability to effectively bind to multiple antigens or targets.
Innovation Solution
A tetrahedral antibody configuration is introduced, comprising Fc and Fab domains arranged in a tetrahedral structure with non-covalent linkages via collectrin-like domain polypeptides, allowing for enhanced binding capabilities to multiple targets through specific domain attachments and linkages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a planar configuration of binding domains is used, then the antibody structure is simple and easy to manufacture, but the antibody cannot effectively engage multiple targets simultaneously
Solution Approach 1:
The patent transitions from a planar (2D) arrangement of binding domains to a three-dimensional tetrahedral configuration. This dimensional change allows the antibody to present multiple binding domains in spatial orientations that enable simultaneous engagement with multiple targets, thereby increasing adaptability without proportionally increasing structural complexity
Solution Approach 2:
The antibody is divided into distinct modular domains (Fc domains and Fab domains) that can be independently designed and assembled. The tetrahedral structure consists of multiple Fc domains connected through hinge regions, with Fab domains positioned at the vertices, allowing each domain to function independently while contributing to the overall multi-target binding capability
2Adaptability or versatility
If a tetrahedral antibody configuration is introduced, then the ability to bind multiple targets is improved, but the manufacturing complexity increases
Solution Approach 1:
The patent employs universal building blocks - standardized Fc domains and Fab domains - that can be reused and recombined to create different tetrahedral antibody variants. The Fc domains serve dual functions as both structural elements and binding units, while hinge regions provide universal connection points, simplifying the manufacturing process despite the complex three-dimensional architecture
3Reliability
If non-covalent linkages via collectrin-like domain polypeptides are used, then the stability and specificity of target binding is enhanced, but the structural complexity of the antibody increases
Solution Approach 1:
The patent introduces collectrin-like domain polypeptides as intermediary elements that mediate the connection between Fc domains. These intermediary structures provide specific interaction interfaces that enhance binding stability and specificity while maintaining a relatively organized and predictable structural arrangement, preventing excessive complexity
Data Source
AI summary
This invention provides a tetrahedral antibody comprising a first, second, third, fourth, fifth, and sixth domain, wherein each of the first and second domains are an Fc domain and comprise a first polypeptide chain comprising a first N-terminus and a first C-terminus of the domain, and a second polypeptide chain comprising a second N-terminus and a second C-terminus of the domain, wherein the third, fourth, fifth, and sixth domains are Fab domains.


