Streamlining Lead Identification

Bio-Rad recently announced the launch of their new antibody discovery service. Designed specifically for the development of best-in-class biologic candidates, the Pioneer Antibody Discovery Platform is optimized to find candidates that are suitable for drug development.

Utilizing proprietary technology, the Pioneer Platform can provide therapeutic antibodies in a multitude of formats for streamlined lead identification.

To learn more about the Pioneer Antibody Discovery Platform and its potential impact on drug discovery and development, we spoke to Dr. John Cardone, marketing manager, Custom Antibodies at Bio-Rad.

Anna MacDonald (AM): Can you introduce Bio-Rad’s Pioneer Antibody Discovery Platform, why is this an important new launch?

John Cardone (JC): Progress made on improving Alzheimer’s treatment through the biologic drug lecanemab is just the latest milestone of a class of medicines that have proven potential to drastically improve healthcare for a wide range of conditions. However, the discovery of new biologics is arduous and resource intensive. Discovery projects aimed at identifying high quality biologic candidates are inherently high risk due to many technical challenges that need to be overcome in the development process.

With the Pioneer Antibody Discovery Platform, Bio-Rad delivers a bespoke service designed to quickly deliver biotherapeutic candidates that are functional, have high affinities for their targets and most importantly high developability.

The Pioneer Antibody Discovery Platform builds on Bio-Rad’s extensive experience in the generation of custom antibodies for research as we now offer a custom biotherapeutic antibody generation service.

AM: How will the Pioneer Platform impact antibody drug discovery and development?

JC: We understand that each biological target chosen to address a specific disease comes with an array of challenges of its own. Our data from the Pioneer Platform shows we can positively impact customers with challenging projects. For instance, when Pioneer was tested against the biomarker TIGIT (a well-known target in cancer immunotherapy), it was able to identify specific antibodies with sub-nanomolar affinities without running affinity maturation and with higher affinity than a benchmark drug (currently in clinical trials for cancer immunotherapy). The data looks great also from a functional cellular perspective, with Pioneer-derived candidates inhibiting TIGIT’s function as well as the benchmark drug. Importantly the candidates had a desirable developability profile in terms of expression yields, self-aggregation, and stability. 

Most importantly this cutting-edge service developed by Bio-Rad can generate leads within months of starting a project, accelerating discovery projects, and offering clients a swift process run by highly qualified scientists.

AM: The new Pioneer Antibody Library is, to your knowledge, the largest functional phage display Fab antibody library ever generated. Why is library size important?

A key characteristic that the latest generation of antibody libraries seeks to achieve is diversity. High diversity is created by engineering vast libraries containing billions of unique sequences. The correlation between library size and diversity is not implicit. Within the finite space of a sizeable library not all sequences will encode a functional antibody or antibody fragment; therefore, ensuring that the functional size of the library is significant (i.e., >80% of the whole library) is a pivotal step in its development. One of the ways our scientists achieved this is by reducing sequence motifs that cause developability liabilities of lead candidates and hence avoiding loss of interesting candidates later in the development process.

The Pioneer Antibody Library was bioengineered to include more than 200 billion unique sequences with high functionality (functional sequences at ~90% of whole library size) and minimize sequence liabilities.

AM: The Pioneer Platform utilizes Bio-Rad’s newly developed proprietary SpyDisplay selection technology. How does this work and improve the discovery process?

JC: The Pioneer Antibody Library is engineered using a proprietary selection technology, SpyDisplay, harnessing SpyTag methodology. Put simply, in this technology the antibody is synthesised with a tag (SpyTag) and the phage is synthesised with a catcher (SpyCatcher). Tag and catcher quickly react together forming a covalent bond once they are expressed. This allows swift and strong linking of the antibody onto the phage. SpyDisplay removes the need for subcloning during the phage display screening process, reducing error potential and accelerating assay development. SpyDisplay also facilitates proper Fab folding, so more functional Fabs are displayed allowing for an efficient monovalent display for selection of high-affinity antibodies.

AM: How does the Pioneer Platform differ from other commercially available antibody libraries?

JC: The Pioneer Antibody Discovery Platform is a truly unique, synthetic, fully human platform serviced by some of the most experienced scientists in the field.

It offers high diversity with more than 200 billion unique functional binders which to our knowledge is one of the most diverse libraries created.

Our data shows how our germline specific CDR design delivers candidates with desirable developability profiles.

The Pioneer Platform is much more than a library; it includes services for affinity maturation, prototyping of candidates in different formats (e.g. monovalent Fab or IgG) as well as lead characterisation studies, all bespoke to clients' requirements.

To find out how Bio-Rad can advance your drug discovery programs please get in touch with us using the contact form on https://www.bio-rad-antibodies.com/pioneer

Dr. John Cardone was speaking to Anna MacDonald, Science Writer for Technology Networks.