A New Generation of Recombinant Monoclonal Antibodies

The production of antibodies has thus far been limited to a small number of species, most often murine, which has led to availability and scalability challenges for scientists.

Technology Networks spoke with Isaku Tanida, Head of Protein and Pathway Technologies, Life Science at Merck to learn about Merck's ZooMAb® recombinant antibodies. These antibodies are developed from a B-cell immortalization technology which enables production in a variety of species. 

Molly Campbell (MC): Why has antibody production been limited to a small number of species thus far?

Isaku Tanida (IT): Antibody production diversity is truly driven by the request from the researchers, which is often a combination of specificity, affinity and reproducibility. Rats and mice have a long history as sources for antibody production, but recent advances in the understanding of animal immune systems have shown that rabbits can create antibodies with greater specificity and affinity than their murine counterparts. Outside of endogenous immune systems, antibody producers have developed methods such as hybridoma technology to increase specificity and reproducibility, but these technologies often have biological bottlenecks that restrict the possible number of species available.

MC: Why did Merck develop ZooMAb® recombinant antibodies?

IT: Merck is committed to providing innovative solutions that mirror the needs of the research community. Market reports from Biocompare, a leading public source for life science product reviews and information, show that in 2017 40% of the global research community wants to use or is already using recombinant antibodies, and this number has increased to 47.9% in 2019. Investing in recombinant technology allows us to more readily scale antibody production with our researchers’ needs more quickly and enables our customers to answer new questions upon the future launch of additional host species.

MC: What challenges exist in the development of the new antibodies?

IT: Ultimately the challenge resides in the manipulation of biology to produce a tool that meets the needs of researchers while maintaining endogenous integrity and performance. Antibodies must be specific to their target but must also bind with a certain degree of affinity and be functionally validated to meet the rigorous standards of the modern research project.

Traditional antibodies require functionally undesirable additives for preservation during shipment, which can limit accessibility in some countries and impacts long-term stability. Our R&D teams are focused and committed to creating and selecting the best clones possible to ensure exceptional and reproducible performance.

MC: How do the new antibodies offer reproducibility and sustainability? Why is this important?

IT: Polyclonal antibodies are great tools for certain applications but are limited by high variation between lots and low specificity. Traditional monoclonal antibodies offer more specificity and higher reproducibility, but hybridoma technology is subject to genetic drift, requires the combination of multiple genomes, and is finite. Once the antibody production from a hybridoma source is compromised, you must start the expensive and arduous process from the very beginning and will not end up with a genetically identical antibody.

ZooMAb® recombinant monoclonal antibodies offer superior reproducibility to traditional monoclonal antibodies due to the nature of the recombinant antibody production process. Once a high performing antibody clone is identified, its genetic code is sequenced – captured in time indefinitely. This gives our team the ability to revisit that genetic code time and time again to produce a genetically identical antibody the first time a customer needs it, and any time in the future. The proprietary ZooMAb® antibody manufacturing process also allows us to scale up manufacturing agilely, providing greater flexibility to potential changes or demands in a researcher’s project timeline. ZooMAb® antibodies are pre-aliquoted, lyophilized and highly stable, allowing multi-year storage of product. Use what you need, when you need it, store the rest at 2-8C and get the same data the next time your experiment calls for it.

MC: How do you envision ZooMAb® recombinant antibodies will impact the field of biopharmaceutical development?

IT: ZooMAb® recombinant monoclonal antibodies will help researchers fuel the initial discovery phase of biopharmaceutical testing to enable their downstream processes. Further, the purity of ZooMAb® antibodies enables access of the highest-quality antibodies to emerging regions and regions with strict biological regulations—further expanding the opportunity for discovery. The future implementation of additional species into the ZooMAb® portfolio will provide researchers with different immune systems to create novel options to visualize and detect molecules and events of interest.

MC: What are Merck's next steps in this space?

IT: As the ZooMAb® portfolio continues to evolve, we are taking steps to introduce additional species to provide more options in aiding researchers’ discovery. We plan to continue frequently adding new targets, guided by research trends and demands, to provide support to more research areas. In line with our commitment to global access of high quality research antibodies, we will continue our expansion of supply networks to enable and improve ease of delivery. Further, we will continue to develop and expand our library of traditional antibodies to provide a complete suite of options for our customers. We want our researchers to be limited only by their imagination, not by commercial availability.

Isaku Tanida, Head of Protein and Pathway Technologies, Life Science, at Merck, was speaking with Molly Campbell, Science Writer, Technology Networks.