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. 2023 Feb 23;15(1):2171248. doi: 10.1080/19420862.2023.2171248

Figure 1.

A flow chart with antibodies originating from different sources being analyzed with various assay during the development of biologics. As the first step in the development of biologics, we present different sources of antibodies, i.e., human, mouse, rabbit, llama, sheep, and DNA. Then, we suggest two antibody discovery pathways, namely display technologies and immunization technologies. To represent the display technology, we provide a schematic showing antibodies displayed on phages binding to antigen, while for the immunization technologies, we show immunization of a mouse as an example. We then depict the critical steps in developing biologics, predicting/determining biophysical properties, by different sized gears. The central gear represents the biochemical in vitro assays, while molecular dynamics and machine learning based strategies are illustrated as two smaller gears. As part of the biochemical in vitro assays, we show instruments used for screening, such as HPLC and PCR. In silico tools are outlined by a computer screen showing both structure and sequence-based antibody characterizations. The next step is the manufacturing section showing the final product, which shows a schematic representation of an antibody (blue) as the final product. The manufacturing process is followed by clinical trials, depicted as a patient in bed.

Schematic overview of antibody sources, discovery strategies, in vitro assays, and in silico methods used to assess developability properties during the development of biologics. Antibodies can be of either natural or synthetic origin and are typically discovered using various display technologies or immunization strategies, or a combination of these. In addition, antibodies can be derived from patient populations. During the development of antibodies, various in vitro assays in combination with in silico methods for machine learning and molecular dynamics can be applied to assess the antibodies’ developability properties and select candidates with the best developability profile.