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Ten FAQs With Bio-Rad

This blog post was written in partnership with Bio-Rad, a global leader in developing, manufacturing and marketing a broad range of innovative products for the life science research and clinical diagnostic markets. In this blog post, Bio-Rad answers ten frequently asked questions about their most popular service offering on the platform.

1. What is the most popular service/product that Bio-Rad provides on Scientist.com?

Bio-Rad’s standout offering on Scientist.com is our custom recombinant monoclonal antibody generation service. Our service centers on the well-established and powerful HuCAL® technology and CysDisplay®, a proprietary method of phage display, combined with automated, high-throughput processes, which have been developed and enhanced by our own scientists since we began in 2003. The HuCAL PLATINUM® phage library contains 45 billion unique human antibodies in Fab format. Tailoring our approach to each client’s unique requirements, we employ this expansive library to target specific antigens of interest. Our selection process is meticulously guided by diverse criteria, such as mitigating or keeping cross-reactivity to closely related molecules, performing under specific conditions (including media, pH values and buffer conditions) and optimizing for particular applications such as ELISA, western blotting and flow cytometry.

2. How does Bio-Rad ensure collaborative projects are well taken care of?

Bio-Rad has 20 years of experience in generating custom antibodies. Our team of highly skilled scientists, based in Munich, Germany, dedicated to custom antibody generation has delivered more than 60,000 antibodies, ranging from antibodies to CAR-T cell constructs and fusion proteins to phosphorylated antigens. The Custom Antibody Service Team has worked with many challenging antigens, ensuring customers can follow their project progress and are happy with their final product(s). Bio-Rad’s streamlined approach starts with a conversation with Technical Sales Managers who discuss our clients’ specific requirements and liaise with our lab scientists to facilitate effective communication for optimal project delivery. We provide regular updates on projects and ensure our clients are fully satisfied with the results. This effective approach underscores Bio-Rad’s commitment to delivering high-quality custom antibody generation services.

3. What differentiates HuCAL from other phage display libraries?

The antibody genes have been optimized to avoid undesirable glycosylation sites and to increase expression levels in E. coli and mammalian cells. A diversification strategy was used to replicate the natural amino acid distribution, with particular attention to the key antigen recognition region, HCDR3. These features lead to a high diversity of selected antibodies and provide a wider range of promising antibody candidates to choose from during an initial screening of the library with respect to affinity and specificity.

CysDisplay technology, a proprietary and efficient display method for selecting high affinity binders, was adopted in HuCAL. It combines the advantages of monovalent phage display technology, such as phenotype-genotype linkage, with the additional feature of a cleavable disulfide bond. Therefore, it allows the efficient elution of interacting partners during the panning procedure (Figure 1).

Fig. 1. CysDisplay Screening Technology. Fab fragments are linked to phage particles by a disulfide bond rather than a peptide bond. This allows elution of phage with reducing agents during antibody selection.

4. What are the applications of antibodies generated from HuCAL?

Using HuCAL Technology, recombinant antibodies have been successfully generated for a wide range of purposes, including:

  • In vitro and in vivo research
  • Diagnostic immunoassay development (as detection reagents, sera replacements, and fully human controls)
  • Preclinical and clinical drug monitoring in pharmacokinetic (PK) and anti-drug antibody assays (ADA)
  • Quality control (QC) release assays for drugs and vaccines
  • Purification of drugs
  • Food testing
  • Biodefense assays
  • Medical devices

5. What are the advantages of HuCAL over conventional antibody generation approaches, such as hybridoma method?

HuCAL offers many advantages when compared to conventional monoclonal antibody generation and production as summarized in Table 1, as well as benefits that extend beyond both conventional methods and other recombinant libraries.

Table 1. Advantages of HuCAL over conventional monoclonal antibodies

6. Are anti-idiotypic antibodies available from Bio-Rad?

Yes, our scientists have led the way in anti-idiotypic (anti-ID) antibody generation developing an extensive range of off-the-shelf anti-IDs, with more than 150 products — one of the largest ranges on the market. These catalog anti-IDs provide customers with extensive data sets and protocols for the use of every antibody in PK and ADA assays. The monoclonal nature of Bio-Rad’s anti-IDs means customers can rely on a stable supply of consistently QC’ed reagents. Our team has been a leader in anti-ID generation and introduced proprietary type 3 anti-idiotypic antibodies using phage display which recognize a drug-target complex allowing the study of bound drug exclusively. We also provide bespoke generation of anti-IDs using HuCAL against clients’ antibody drugs, to support their regulatory applications, biosimilar development, or research studies on biologics.

7. Can Bio-Rad generate an antibody to block an enzyme active site?

Yes. A team of researchers, led by Dr Alex Strongin from the Sanford Burnham Prebys Medical Discovery Institute (USA), worked with scientists from Bio-Rad to isolate high affinity antibodies using phage display blocking strategies from HuCAL. These antibodies were specific to the active site of West Nile Virus NS2B-NS3 proteinase, providing antibody research tools that enabled scientists to carry out inhibition experiments and structural studies (Shiryaev et al. 2010). Download the poster of this extraordinary work.

8. Can Bio-Rad generate antibodies which discriminate between only 1 or 2 amino acids?

Yes. Scientist from Bio-Rad performed serial panning of the HuCAL Library, and isolated selective probes which permit differential quantification for two forms of the inflammatory chemokine CXCL10 in biological samples. The antibodies bind specifically to either native CXCL10 or an antagonist form, which is truncated by just two amino acids at the N-terminus. Assays with these antibodies have revealed high levels of antagonist chemokine in chronic HCV patients. Download the poster of this project.

9. How fast can antibodies be delivered to clients?

Thanks to our HuCAL Technology, combined with automated, high-throughput processes developed by the scientists at Bio-Rad, we deliver antibodies in as little as 8 weeks, however we can shorten the project’s timeline to just 4 weeks when customers opt for the Fast Track Service Bio-Rad offers.

10. Can antibodies generated from HuCAL be used as biotherapeutics?

Custom antibodies that we generate for clients using HuCAL Technology are for research and diagnostic use only. If clients want to discover antibodies for therapeutic use, Bio-Rad has recently launched the Pioneer™ Antibody Discovery Platform. The Pioneer Antibody Discovery Platform is a truly unique fully human platform serviced by some of the most experienced scientists in the field. Its phage display library offers unprecedented diversity with more than 200 billion unique functional binders which to our knowledge is one of the most diverse libraries created. With the Pioneer Platform, Bio-Rad offers clients services for affinity maturation, lead characterization (e.g. developability to functional assays), prototyping of candidates in different formats (e.g. monovalent Fab or IgG or bispecifics) 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.

To utilize Bio-Rad’s HuCAL Technology for your next research project or to explore more of their extensive service offerings on Scientist.com, click the button below!

BIO-RAD, TRAILBLAZER, and PIONEER are trademarks of Bio-Rad Laboratories, Inc. HuCAL, HuCAL PLATINUM, and CysDisplay are trademarks of MorphoSys AG in certain jurisdictions. All trademarks used herein are the property of their respective owner.