We have constructed several human synthetic antibody libraries by the phage-display system for scFv and VHH format. These libraries were designed by structural bioinformatics analysis, big data integration, and AI-related techniques. Their framework of variable domain comes from the human germline gene and the complexities are all larger than 1011. For more than 25 protein antigens including cancer biomarkers, immune checkpoint molecular antigens, and important viral antigens, nearly 900 antibody hits have been initially screened from our antibody libraries. For some hits, the follow-up functional tests at the cell level have been conducted for subsequent new drug product development.
For natural antibody source, we also constructed the phage-display libraries from immunized llama and rabbits for VHH and scFv format, respectively. More than 50 VHHs from Alpaca and 100 scFvs from rabbits were identified from these immunized libraries.
Protein engineering and characterization
We have set up the process of protein and antibody production by a stable clone of mammalian cells. In addition, we not only perform the general protein engineering based on structure and functional information for antigen but also routinely modify
Fc engineering for antibody function like effector function or extending half-life. Other convention antibody characterization like the epitope mapping and surface plasmon resonance (SPR) analysis based on Biacore systems are also routinely performed.
In addition, we also have established the pipeline for antibody affinity maturation based on our phage-display system. This antibody optimization pipeline can significantly improve the affinity or effect of the antibody without changing the epitope. For example, we demonstrated that it could increase the inhibition capacity of our SARS-CoV2 neutralizing antibody by two orders of magnitude. We can optimize any antibody sequences within 6-8 weeks by this pipeline.
Cell-based bioassay
We also constructed a series of cell-based bioassay including high throughput scFv/VHH cell-binding assay, selection stable single clone of the cell line, ADCC and ADCP report assay for evaluation of our antibody hits to possible leads. For example, to verify whether the screened antibodies can recognize the correct structure of cell surface proteins, we have developed High throughput scFv/VHH cell-binding platform for rapid screening. The stable clone isolation for different cell lines including HEK293 and CHO-GFP is well-established.
For COVID-19 related antibody evaluation, we also constructed the corresponding pseudovirus neutralization assay and surrogate virus neutralization platform.
Pre-clinical study
We also build drug safety experiments for the pre-clinical study, including Hemolysis assay, Blood cell-binding assay, PK/PD, and Cytokine release assay to evaluate our drug leads. Our animal experiment department has also established many cancer animal models like Xenograft huPBMC-ASID mice shown here.
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