Bio-Rad Laboratories – Pioneer Antibody Discovery Platform

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Enhancing therapeutic antibody development with phage display technology
Phage display technology has played a crucial role in the discovery and optimization of antibodies for a wide range of clinical and research applications, with the greatest impact seen in the development of antibody-based drugs. This novel approach enables the identification of fully human therapeutic monoclonal antibodies (mAbs) from antibody fragments presented on the surface of bacteriophages, resulting in the formation of functional phage particles displaying PIII-antibody fusions, facilitating the creation of a diverse collection of antibody fragments, known as a phage display library. 

Leveraging bioengineering innovations – including generation of bispecific antibodies
While phage display technology offers distinct advantages over other display systems, there have previously been limitations including challenges associated with library diversity, expression and folding, and different antibody formats.
Bio-Rad developed its Pioneer Antibody Discovery Platform to overcome this, combining a fully synthetic, state-of-the-art phage display human antibody library with over 20 years of expertise to deliver a bespoke antibody discovery service, providing prototypes of therapeutic antibodies in a multitude of formats for streamlined lead identification. 

In 2024, Bio-Rad expanded the Pioneer Antibody Discovery Platform with the addition of fast generation and screening of bispecific antibodies using its SpyLock technology. Able to produce a bispecific antibody in 90 minutes, SpyLock facilitates rapid delivery of high-quality candidates, providing an ideal solution for swiftly generating bispecifics tailored for high-throughput screening, and enabling researchers to identify effective antibody combinations to take forward into clinical development.

A peer-reviewed study published in Nature Communications, “Engineered reversible inhibition of SpyCatcher reactivity enables rapid generation of bispecific antibodies”(1), demonstrates the utility of Bio-Rad’s SpyLock technology to generate and screen bispecific antibodies, allowing for greatly accelerated functional validation of bispecifics.

The study describes the method used to engineer functional control into SpyCatcher protein, resulting in a reversibly inhibitable mutant termed SpyLock, which is in turn fused to a regular SpyCatcher to create BiLockCatcher protein, which provides a rapid route to antibody generation.

Pioneer: Bespoke antibody discovery
The Pioneer platform is a fully synthetic, fully human Fab antibody library specifically designed to minimize nonproductive cloning artefacts, comprising:
Pioneer Antibody Library with exceptional size and broad functional diversity: The Pioneer Antibody Library is one of the largest functional phage display libraries ever created, with over 200 billion unique antibody sequences. The library has been validated for both diversity and developability, delivering a high number of unique hits from standard selection, and providing antibodies with excellent scalable, tailored formats.
Proprietary SpyDisplay for accelerated candidate selection: SpyDisplay is an innovative method of phage display that uses SpyTag technology - phage display libraries are engineered with protein ligation technology to enable high, well-balanced expression of all antibody clones, and facilitating display of correctly folded antibodies. SpyTag also eliminates the need for subcloning between the selection and expression steps, increasing efficiency and streamlining the discovery process.

Prototyping of therapeutic candidates in a multitude of formats with TrailBlazer technology: Design and optimization of immunoassays is complex and time-consuming, and is limited by antibody format. TrailBlazer antibodies incorporate SpyTag-SpyCatcher technology into Bio-Rad’s custom HuCAL recombinant antibody generation service, providing an extensive antibody toolbox that enables rapid development of robust assays.
Rapid generation of bispecific antibodies for high-throughput screening with SpyLock technology: Introduction of the SpyLock technology into Pioneer enables customers to identify effective antibody combinations to take forward into drug development.  
World-class specialists and scientists: Bio-Rad’s team of specialists accelerates and simplifies the antibody discovery journey, enabling the identification of functional biologics for a target of interest, and delivering a customized service designed to meet each client’s needs and success criteria.

Enhancing antibody therapeutics
The emergence of next generation antibody-based therapeutics has dramatically increased the need for optimized antibody discovery platforms that can address challenges associated with screening and bioanalysis of complex drug modalities, including bispecific antibodies.
Bio-Rad’s Pioneer Antibody Discovery Platform and the SpyLock service provides a cutting-edge solution to support the screening of antibody candidates and bispecifics, increasing their chances of passing clinical trials and ultimately bringing effective antibody treatments to market faster.

1.    Hentrich, C., Putyrski, M., Hanuschka, H. et al. Engineered reversible inhibition of SpyCatcher reactivity enables rapid generation of bispecific antibodies. Nat Commun 15, 5939 (2024). https://doi.org/10.1038/s41467-024-50296-y