Nanobody Discovery via HAPPY Screening for High-Affinity Binding
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Solution Overview
Problem
Current antibody discovery processes are labor-intensive and lack high-throughput capabilities for selecting antibodies against multiple antigens simultaneously, limiting the identification of antibodies with high affinity for therapeutic and diagnostic applications.
Innovation Solution
Development of a novel high-throughput screening technique, referred to as HAPPY, for discovering nanobodies that bind to extracellular and secreted proteins with high affinity, utilizing machine learning algorithms and phage display libraries to identify antibodies or antibody fragments that specifically target secreted or extracellular proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional antibody discovery methods are used, then antibodies can be identified with high specificity, but the process is labor-intensive and lacks high-throughput capabilities
Solution Approach 1:
The patent segments the antibody discovery process by focusing on nanobodies (single-domain antibody fragments) rather than full-length antibodies. This segmentation enables higher throughput selection because nanobodies can be displayed on phage particles and selected against multiple antigens simultaneously, reducing the complexity and time of the discovery process while maintaining high binding affinity
Solution Approach 2:
The patent creates a universal nanobody platform that can be applied to multiple antigen targets. By developing a standardized nanobody library and selection methodology that works across different antigen types (secreted and extracellular proteins), the system achieves multi-functionality, allowing high-throughput selection against many antigens simultaneously without requiring separate optimization for each target
2Productivity
If robotics are used to perform multiple individual antibody selections in parallel, then throughput increases, but device complexity and cost increase
Solution Approach 1:
The patent uses phage display technology where nanobodies are displayed on the surface of phage particles. This creates a physical copy of the nanobody library that can be selected against multiple antigens simultaneously in a single experiment, eliminating the need for robotic automation of individual selections while achieving high throughput through the inherent parallelism of the phage display system
Solution Approach 2:
The patent adds the dimension of antigen diversity by enabling simultaneous selection against multiple different antigens in parallel. Instead of selecting against one antigen at a time, the system displays multiple antigens and selects nanobodies that bind to any of them, effectively moving from a one-dimensional sequential selection process to a multi-dimensional parallel selection process
Data Source
AI summary
The invention provides methods for identifying nanobodies that bind with high affinity to secreted proteins or extracellular proteins, as well and compositions comprising the identified nanobodies and methods of use thereof.