Antibody Library Design for Stability and Expression
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Solution Overview
Problem
Current antibody library technologies face challenges in producing libraries with high diversity and stability, leading to difficulties in obtaining high-affinity antibodies, and existing methods are hindered by toxicity issues and complex experimental processes.
Innovation Solution
A novel antibody library is developed using VH and VL scaffolds derived from human sequences, specifically designed to enhance thermodynamic stability and soluble expression, with rationally controlled CDRs for high specificity and affinity, allowing for the selection of candidate antibodies with improved diversity and reduced repetitive sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional antibody library technologies are used, then antibody diversity can be achieved, but thermodynamic stability and soluble expression are compromised
Solution Approach 1:
The patent applies parameter changes by selecting and optimizing specific framework region sequences (VH and VL scaffolds) from human antibodies to achieve the optimal balance between thermodynamic stability and soluble expression. The framework regions are carefully chosen to provide structural stability while maintaining high expression levels in cellular systems.
Solution Approach 2:
The patent applies local quality by differentiating between framework regions and complementarity-determining regions (CDRs). The framework regions are selected for stability and expression optimization, while the CDRs are designed for antigen binding diversity. This localized optimization allows each region to fulfill its specific function effectively.
2Adaptability or versatility
If high diversity antibody libraries are produced, then affinity for antigens improves, but repetitive sequences increase
Solution Approach 1:
The patent applies local quality by applying different design strategies to different regions: the framework regions use standardized scaffolds for stability, while the CDR regions are designed to maximize diversity. This localized differentiation ensures high antibody diversity without excessive repetition, as each CDR is optimized for unique antigen binding characteristics.
Solution Approach 2:
The patent applies preliminary action by pre-selecting and pre-optimizing the framework region sequences before introducing CDR diversity. This preliminary optimization of the stable scaffold ensures that subsequent CDR variations build upon a foundation of high stability and expression, preventing repetitive sequences while maintaining diversity.
3Measurement precision
If complex experimental processes are used for antibody screening, then selection precision improves, but toxicity issues arise
Solution Approach 1:
The patent applies copying by using computational models and in silico design to predict and select optimal antibody sequences before experimental production. This virtual screening approach allows for precise selection of candidate antibodies with desired properties while avoiding the toxicity issues associated with producing and testing large numbers of antibodies experimentally.
Solution Approach 2:
The patent applies preliminary action by performing computational analysis and sequence optimization before experimental antibody production and screening. This preliminary computational selection identifies the most promising candidates, reducing the need for extensive experimental testing and thereby minimizing toxicity risks while maintaining high selection precision.
Data Source
AI summary
The present invention relates to a novel antibody library and an antibody-screening method using same. Having a human sequence-derived specific VH or VL scaffold, the antibody library according to the present invention exhibits high thermodynamic stability and enjoys the advantages of allowing high soluble expression as well as reversible folding. In addition, the antibody according to the present invention includes a variety of rationally controlled CDRs so as to exhibit high specificity and high affinity to all antigens and thus can be advantageously used for selecting an adequate candidate antibody against a target antigen.