Antibody Screening via Differential Biopanning and Deep Sequencing
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Solution Overview
Problem
Current biopanning methods for identifying anti-ligands specific for differentially expressed ligands are limited in diversity and efficiency, particularly in isolating antibodies specific for low- and intermediary-expressed surface receptors, due to the limitations of conventional sequencing techniques and the need for multiple rounds of panning to reduce non-specific binding.
Innovation Solution
Combining differential biopanning with next-generation deep sequencing and confirmatory screening to generate a pool of high-affinity antibodies specific for differentially expressed surface receptors at various expression levels, allowing for the identification of a greater number of unique antibody clones and increasing the sequencing depth to detect antibodies specific for low-expressed receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional sequencing techniques are used in biopanning methods, then the process is simpler and cheaper, but the diversity and efficiency of identifying anti-ligands specific for low- and intermediary-expressed surface receptors is limited
Solution Approach 1:
The patent applies parameter changes by transitioning from conventional sequencing to next-generation deep sequencing, fundamentally changing the detection parameters (sequencing depth, throughput, and sensitivity) to enable identification of antibodies against low- and intermediary-expressed surface receptors that were previously undetectable
2Reliability
If multiple rounds of panning are performed to reduce non-specific binding, then the specificity of anti-ligands is improved, but the time and complexity of the process increases
Solution Approach 1:
The patent replaces the mechanical iterative process of multiple panning rounds with a molecular biology approach using next-generation sequencing to directly identify and characterize anti-ligands, substituting physical separation iterations with molecular detection and analysis
3Productivity
If the sequencing depth is increased to detect antibodies specific for low-expressed receptors, then the diversity of identified antibody clones is improved, but the cost and complexity of sequencing increases
Solution Approach 1:
The patent applies universality by using next-generation sequencing technology that serves multiple functions simultaneously: it sequences high-throughput to identify diverse clones, achieves deep coverage to detect low-expressed receptors, and provides comprehensive data for characterizing anti-ligand specificity across various expression levels
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enables the generation of a qualitatively and quantitatively unique antibody pool with increased diversity, specifically identifying antibodies for low- and intermediary-expressed surface receptors, enhancing the therapeutic potential of the retrieved antibodies.
Implementation Method 1
identifying anti-ligands specific for differentially and/or infrequently expressed ligands
Implementation Method 2
the protein molecule is, in some manner, physically linked to the genetic information encoding the particular protein molecule
Data Source
AI summary
The present invention relates to improved screening methods and, in particular, to methods of screening anti-ligand libraries for identifying anti-ligands specific for differentially and/or infrequently expressed ligands.