Monoclonal antibodies (mAbs) can be used as "magic bullets" for the treatments of cancer and other diseases due to their specificities. They are the fastest growing class of drugs over the past decade. The process of antibody-based drug discovery is lengthy and costly, requiring many years of development and millions or even billions of dollars of investment (Figure 1).
With recent scientific discovery on new mechanism of immune-oncology, more and more potential drug development candidates are on the horizon. How to quickly finish pre-clinical development and push to clinical stage becomes Biopharm’s top priority, since the valuation of the company is highly dependent on whoever makes the first positive clinical report. In the meantime, more innovative antibody drug formats, such as bi-specific antibody, ADC, etc, were explored and tested in clinical trials. To screen for new lead antibody molecules to adapt into new therapeutic antibody format is in urgent need . All these will push Biopharms to drive fiercely on its pre-clinical development capacity. To Scale up internal R&D team or contract-out to CROs become the new normal for Biopharms. Both options have their Pros and Cons, as summarized in the table 1. Due to the complexity and unpredictability of therapeutic lead mAb discovery process, there will be no guarantees of success at this stage, which impose a bottleneck for the current antibody drug development (Table 1).
To help Biopharm accelerate its pace on pre-clinical antibody drug lead selection, DIMA, equipped with its proprietary single B cell discovery platform, launched an “All Druggable Targets (ADT)” lead discovery program. With this program, DIMA will pre-develop lead mAb molecules and their corresponding DimAb B cell libraries for all druggable targets. The ultimate goal for this program is to make these pre-developed and pre-validated lead mAb molecules as on-shelf products, so that Biopharms do not have to wait or spend unnecessary resources on early stage of the discovery phases. In a simple word, DIMA will ease the burden of Biopharms on antigen preparation and FACS binder screening for drug lead screening. By this way, Biopharms can exert more energy or resources on downstream assay development and clinical stage. Right now, DIMA already finished more than 140 drug target projects (The list of all available targets can be found here).
After in-vitro and in-vivo screenings of the pre-selected mAbs, one or several druggable mAbs can be picked up for the downstream clinical studies. Both antibody sequences and DNA construct encoding the mAb can be obtained from DIMA biotech. No extra work is needed for mAb sequencing and cloning. You can easily get a large amount of the final mAb molecules for downstream studies, and greatly reduce the time and cost required for the mAb drug development . We also offer pre-made B cell seed libraries for additional screening If none of the pre-selected antibodies works for you.
- Antigens with native structures and post-translational modifications: To develop mAbs for therapeutic applications, one of the key requirements is to utilize the protein immunogens that best mimic the native state of the target protein. DIMA’s functional protein development team has created the best solutions for this requirement. All our immunogens were generated using HEK293 secretion expression system. Most of the druggable targets for antibody-based therapy are membrane proteins, which are notoriously hard to express. To find the best immunogen production strategy, we individually study and design expression construct for each membrane protein target. To tackle on the crown jewels of full length multi-transmembrane proteins, such as GPCR and Claudin series proteins, we also invested heavily on new expression and extraction technologies. Details can be found on our protein technology webpage.
- Innovative DimAb single B cell cloning platform for monoclonal antibody development: By enriching and cultivating B cells from immunized animals, we can directly isolate and clone positive IgG genes. Comparing to traditional hybridoma and phage display platforms, our technology strength is clearly elucidated on this DimAb development webpage .