Fresh Approaches to Antibody and Protein Discovery, Development, and Manufacturing

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New tools for manufacturing antibodies and other therapeutic proteins were discussed at the San Diego Antibody Engineering and Therapeutics Conference in December. These advances include vector and cell lines as well as consolidation of services offered by businesses.

One particularly groundbreaking company is LakePharma, headquartered in the San Francisco Bay area, which offers assistance with antibody discovery, development of lead proteins, and scaling up, all the way through good manufacturing practice (GMP).

“One key strength of LakePharma is our ability to assist our customers with several processes all under one roof (Figure 1). We, as a company, offer clients drug discovery, optimization of antibody candidates, scale up, and manufacturing,” explained Hua Tu, PhD, founder and CEO of LakePharma. “Historically, these processes are divided between two different types of businesses: CROs (contract research organizations) and CMOs (contract manufacturing organizations). Drug discovery, compound validation, and lead optimizations have traditionally been done by CROs; scaling up, GMP manufacturing, and commercial manufacturing are completed by CMOs.”

“Many of the problems arising when transitioning from a CRO to a CMO can be avoided all together by having all of these steps done by one entity,” continued Tu. “To explain our advantages to clients, we refer to LakePharma as a Contract Research, Development, and Manufacturing Organization (CRDMO),” he said. “Integrating all the steps of drug discovery and development permits us to avoid common pitfalls during this transition of a program from a CRO to a CMO. Another facet of LakePharma, which makes us attractive to customers, is that we commit to not develop a pipeline of our own. This intentionally allows us to focus on our client’s needs and not worry about our own development timelines. We do this so as to not compete with our customers.”

In additional to experience with all aspects of developing a drug and bringing it to market, LakePharma also has experience with a variety of techniques used in antibody discovery, development, and manufacturing. “We are proficient in classical yeast and phage display systems for antibody discovery, as well as in vivo (whole animal) approaches,” explained Tu. “One example of our capability is performing antibody humanization and affinity maturation at the same time, rather than sequentially, saving time and effort. This is especially important because humanization and affinity maturation can work at cross-purposes to one another. For example, humanizing antibodies can detrimentally affect affinity maturation (while making the antibody more human, the affinity maturation can suffer) and vice versa. By doing both processes at the same time, we ensure that optimal antibody humanization and affinity maturation are reached with minimal labor.”

A 97% success rate for over 100 targets offers a glimpse of LakePharma’s excellent track record, noted Tu, including the development of antibodies against small molecules. Many programs have reached the clinical stage of investigation.

Another strength Tu said the company brings is in the arena of cell lines used to produce the antibodies. Once lead candidates are established, the TunaCHOTM platform produces the protein of interest. This cell line shares the same parental cell line (CHO-K1) as the other cell lines used in LakePharma platforms. Thus, proteins produced on a different platform (such as CHO-GSNTM) will have similar activity and post-translational modification profile.

“We have found the use of HEK293 cells to produce antibodies is trending down. Transfection optimization of CHO cells by LakePharma produces large amounts and higher quality proteins than 293 cells,” added Tu. “Furthermore, glycosylation variation is often the thorn inside of manufacturing. By utilizing a technology developed by Roche, glycosylation is done in vitro. Not only is TunaCHO quicker than transfecting all the genes necessary for in vivo glycosylation, but the process is better controlled with great consistency from batch to batch.”

In summary, LakePharma combines technical expertise, encompassing all aspects of drug discovery and development through manufacturing as a convenient “one-stop shop” for therapeutic proteins. Tapping into this capability will assist companies, improving their efficiency, saving time and resources in the discovery, development, and manufacturing of antibodies.

For more information on IVGE (in vitro glycoengineering) visit custombiotech.roche.com