ELISA Screening for Bispecific Antibody Clone Selection
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Solution Overview
Problem
The development of complex antibody formats is hindered by the lack of high-throughput assays to assess product quality and function at low volumes during cell line development, particularly at the single clone level, leading to difficulties in identifying stable producer cell lines with high expression and low antibody-related side products.
Innovation Solution
A method using ELISA-based screening of recombinant cell clone cultivation supernatants for binding signals to specific antigens, combined with data analysis to select cell clones expressing bispecific antibodies with high titers and low side product content, allowing for the identification of exceptional cell clones capable of producing high-quality complex antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional screening methods are used to identify cell clones expressing complex antibodies, then the screening process can detect antibody expression, but the method requires large sample volumes and cannot provide high-throughput assessment at single clone level
Solution Approach 1:
The patent segments the screening process into multiple independent ELISA assays, each targeting specific antibody formats or side products. By dividing the complex screening into modular steps (capture ELISA, competition ELISA, side product detection), the method enables high-throughput processing of many clones simultaneously while requiring minimal sample volume from each clone
Solution Approach 2:
The patent introduces a new dimensional approach by using ELISA-based detection that measures binding signals in a high-dimensional parameter space (multiple antigens, multiple antibodies, multiple side products). This allows comprehensive quality assessment at single clone level with low sample volume, transforming the screening from a low-throughput bulk method to a high-throughput single-clone method
2Adaptability or versatility
If complex antibody formats are developed to target multiple antigens, then the therapeutic potential increases, but the number of antibody-related side products such as chain mispairings increases
Solution Approach 1:
The patent implements feedback control by using ELISA assays to detect side products early in cell line development. The binding signals from multiple antigens and antibodies provide feedback on correct assembly, allowing selection of cell clones with low side product content before large-scale production, thus preventing harmful factors from propagating
Solution Approach 2:
The patent performs preliminary screening of cell clones at the single-cell level using ELISA assays that detect correct antibody assembly and side products. By identifying and selecting high-quality clones early in the development process (before bulk production), the method prevents the amplification of side products that would occur with complex antibody formats
3Reliability
If screening is performed at later phases of cell line development, then fewer resources are required per clone, but the probability of identifying exceptional high-producing clones decreases
Solution Approach 1:
The patent performs preliminary screening at the earliest possible stage (single clone level) using ELISA assays that require minimal sample volume. By detecting binding signals and side products before bulk expansion, the method identifies exceptional high-producing clones with high reliability, preventing the loss of time that would occur if screening were delayed to later phases
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 method enables the early identification of high-producing cell clones with low side products, increasing the probability of technical success and reducing production costs by shifting the screening process to earlier phases and improving product quality.
Implementation Method 1
determining i) the total protein (in certain embodiments, antibody) concentration in the supernatant (using an immunoassay); ii) the binding signal for each supernatant for binding to the first antigen of the (therapeutic) antibody in an immunoassay
Data Source
AI summary
Herein is reported a novel, high throughput suitable method for the characterization and identification as well as selection of recombinant cell clones expressing a bispecific antibody with high titers and low levels of antibody-related side products. The method according to the current invention uses the binding signals of an immunoassay-based screening of recombinant cell clone cultivation supernatants for isolated as well as simultaneous binding to the respective targets of the antibody. This data allows for the selection of high producer cell clones with desired product profile.