Common Light-Chain Polypeptide for Bispecific Antibody Assembly
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Solution Overview
Problem
Conventional methods for preparing bispecific antibodies require simultaneous transfection of four plasmids, leading to heavy-light chain mispairing issues during assembly.
Innovation Solution
A polypeptide is designed as a common light chain that can pair with different heavy chains to construct antibodies, either homodimers or heterodimers, with specific amino acid sequences provided for various binding affinities and specificities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If four plasmids are simultaneously transfected to express two different heavy chains and two different light chains, then bispecific antibodies can be constructed, but heavy-light chain mispairing occurs during assembly
Solution Approach 1:
The patent applies universality by designing a common light chain that can pair with multiple different heavy chains (e.g., heavy chain A and heavy chain B) to form functional antibody complexes. This single light chain serves multiple functions: it pairs with HA to form Fab(A) and with HB to form Fab(B), enabling bispecific antibody construction without requiring separate light chains for each heavy chain, thereby preventing mispairing issues
Solution Approach 2:
The patent modifies specific local regions of the light chain, particularly the CDR3 region, to enhance its pairing capability with different heavy chains. By optimizing the local sequence characteristics of the light chain CDR3, the invention ensures high-affinity and specific pairing with various heavy chains while maintaining the ability to avoid mispairing during antibody assembly
2Adaptability or versatility
If conventional methods are used to prepare bispecific antibodies, then two different heavy chains and two different light chains can be expressed, but the assembly process becomes complex and error-prone
Solution Approach 1:
The common light chain design reduces the number of required plasmids from four to three (one light chain plasmid plus two heavy chain plasmids). This light chain serves universally for both heavy chains, simplifying the transfection process and reducing assembly complexity while still achieving bispecific functionality
Solution Approach 2:
The patent merges the function of two separate light chains into a single common light chain that performs the role of both light chains in conventional bispecific antibody construction. This consolidation reduces the number of components to be transfected and assembled, thereby simplifying the overall process
Data Source
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AI summary
Provided is a polypeptide, which is used as a light-chain or light-chain variable region of an antibody. The polypeptide is used to construct an antibody together with an antibody heavy-chain or antibody heavy-chain variable region having binding affinity to different targets (antigens), and the antibody retains binding affinity to targets (antigens) and biological activity. Further provided is an antibody containing the polypeptide.