Antibody Binding scFv Linker Specificity
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Solution Overview
Problem
Current antibodies that bind to scFv fusion proteins have limited specificity due to their affinity for other immunoglobulins, making them unsuitable for in vivo applications where other immunoglobulins are present, and existing solutions like protein L have low specificity for scFv.
Innovation Solution
Development of an antibody that binds to the linker region between the heavy-chain and light-chain variable regions of scFv, regardless of CDR sequences, allowing it to recognize a wide variety of scFvs and avoiding immunogenic regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If an antibody is designed to bind to the linker region of scFv, then specificity to scFv is improved, but binding affinity to other immunoglobulins may increase
Solution Approach 1:
The antibody is designed to bind specifically to the linker region between the variable heavy chain and variable light chain of scFv, rather than binding to common immunoglobulin structures. This localized binding approach targets a unique structural feature of scFv, achieving high specificity while avoiding cross-reactivity with other immunoglobulins
Solution Approach 2:
The scFv structure is segmented into distinct regions (variable heavy chain, linker, variable light chain), and the antibody targets the linker segment specifically. This segmentation allows the antibody to distinguish scFv from intact immunoglobulins, which have different structural arrangements and do not expose the same linker epitope
2Adaptability or versatility
If a flexible linker is used in scFv to avoid structural restriction, then functional versatility is improved, but immunogenicity decreases
Solution Approach 1:
The antibody serves as an intermediary that recognizes the linker region of scFv, enabling detection and purification of scFv without requiring the linker itself to be highly immunogenic. The antibody mediates the interaction between the detection system and the scFv-linker fusion protein, overcoming the low immunogenicity of flexible linkers
Solution Approach 2:
The invention changes the binding target from the linker sequence itself (which has low immunogenicity) to the junction region between the variable domains and linker. This parameter change in epitope selection allows antibody binding while maintaining the flexibility and low immunogenicity benefits of the GS linker
Data Source
AI summary
The present invention provides an antibody that binds to a linker in a new style of binding. More specifically, the present invention provides an antibody that binds to the linking part between a first region and a linker and the linking part between a linker and a second region in an scFv structure.