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Unlike current approaches where bioconjugation is typically done following the manufacture of the monoclonal antibody and the cytotoxic drug, the new method begins with the antibody supernatants and eliminates the need for extensive chromatographic purification.
ADC Biotechnology (ADC Bio) announced that it is developing a new bioconjugation method for the development and manufacture of antibody drug conjugates (ADCs). The new method will move the conjugation step into the later stages of downstream processing in contrast to existing approaches where bioconjugation is typically done following the manufacture of the monoclonal antibody (mAb) and the cytotoxic drug.
Conjugation and antibody purification will be carried out concurrently under the new “downstream bioconjugation” approach. The starting point for conjugation will no longer be after production of the purified antibodies, but it will instead begin with the antibody supernatants. This approach forgoes the need for extensive chromatographic purification techniques to deliver purified antibodies.
“The major benefit, and the reason this approach will prove so disruptive, is that it will save several months of manufacturing time and up to 25% of the overall costs. But it will require much of the industry, with its current ingrained manufacturing methods, to re-evaluate exactly how it structures the supply chain that often uses three CMOs,” commented Charlie Johnson, CEO of ADC Bio, in a press statement.
Starting from antibody supernatant, ADC Bio’s approach uses its patented Lock-Release* technology to facilitate both the antibody capture step and subsequent conjugation to the ADC payload, essentially replacing the Protein A resin and assembling the ADC in an efficient manner. The subsequent viral inactivation, removal, and polishing will then occur post-conjugation.
The benefits of eliminating the need for proteinaceous A and G resins goes beyond cost savings. Incidental leaching of these proteins from their purification media increases the impurities in a biopharmaceutical drug product. Moreover, Protein A is known to cause immunogenic responses in humans and has proven toxic in a number of clinical studies. It is, therefore, mandatory to remove these impurities in subsequent chromatography polishing steps before an antibody can be used for any therapeutic application.
Johnson added, “In essence, we are telescoping antibody downstream processing and conjugation, providing just one set of analytical development and release processes, whilst bringing in the use of much more cost effective and safer resins. We have already successfully piloted our new development process in a number of applications. As the next step, we have just launched our Specialist Process Innovation Group-which will be responsible for fostering all further technological innovations moving forwards-with its first project being to validate our new downstream conjugation approach over the course of the next 18 months.”
*ADC Bio’s proprietary Lock-Release technology allows immobilization of antibodies onto a solid-phase support, thereby segregating them and preventing aggregation during the critical conjugation steps. Following conjugation to payload, the ADCs are subsequently released into an optimal formulation containing stabilizing excipients that suppress aggregation.
Source: ADC Bio