Antibody Lineage Analysis for Efficient Screening
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Solution Overview
Problem
Current methods for identifying and isolating lineage-related antibodies from an immunized animal's repertoire are inefficient and complex, often requiring individual screening of millions of antibodies and introducing biases in PCR-based methods that limit sequence diversity.
Innovation Solution
A computational method involving obtaining nucleotide sequences of heavy and light chain-encoding nucleic acids from a first antibody, screening the antibody repertoire to identify lineage-related sequences, and expressing these sequences in a host cell to produce antibodies that bind to the same antigen.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If individual screening of millions of antibodies is performed, then antibodies with desirable properties can be identified, but the process becomes inefficient and time-consuming
Solution Approach 1:
The patent segments the antibody repertoire into lineage groups based on sequence similarity (e.g., sharing common CDR3 regions). Instead of screening all antibodies individually, the method identifies representative antibodies from each lineage group, reducing the screening pool from millions to a manageable number while maintaining identification accuracy.
Solution Approach 2:
The patent performs preliminary computational analysis to identify lineage-related antibodies and select representative candidates before bioassay screening. This preliminary sorting based on sequence homology prepares the antibody pool in advance, allowing efficient subsequent testing of only the most promising candidates.
2Quantity of substance
If PCR-based methods are used to amplify antibody sequences, then sequence diversity can be obtained, but biases are introduced that limit the diversity of sequences
Solution Approach 1:
The patent uses computational copying of sequence information from high-throughput sequencing data to identify lineage-related antibodies, rather than relying on PCR amplification. This in silico approach replicates sequence diversity without introducing PCR biases, maintaining accurate representation of the original antibody repertoire.
3Adaptability or versatility
If a large number of antibodies are sampled from the repertoire, then antibodies with similar or improved properties can be identified, but the complexity of the identification process increases
Solution Approach 1:
The patent replaces complex manual screening and sorting processes with computational algorithms that automatically analyze sequence data, identify lineage relationships, and select representative antibodies. This substitution of computational mechanics for manual procedures reduces process complexity while handling large numbers of antibody sequences.
Data Source
AI summary
A method of screening is provided. In certain embodiments, the method involves a) obtaining the nucleotide sequences of: i. a heavy chain-encoding nucleic acid that encodes the variable domain of a heavy chain of a first antibody of an animal; and ii. a light chain-encoding nucleic acid that encodes the variable domain of a light chain of the first antibody; b) obtaining nucleotide sequences of cDNAs encoding at least a portion of the antibody repertoire of the animal; c) computationally screening the sequences obtained in b) to identify heavy and light chain sequences that are related by lineage to the heavy and light chain sequences of a); and d) testing at least one pair of the heavy and light chain sequences identified in c) to identify a second antibody that binds to the same antigen as the first antibody.