Developing A Downstream Bio-Conjugation Process.

ADC BIO announces the development of a revolutionary, ‘downstream bio-conjugation’ method that will present a new paradigm in Antibody Drug Conjugate (ADC) development and manufacturing. In contrast to the existing approaches – which undertake bio-conjugation after both the mAb and cytotoxic have been manufactured – this new approach moves the conjugation step into the later stages of the downstream processing (DSP), with conjugation and antibody purification carried out concurrently.

“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.

Using this ‘downstream bio-conjugation’ approach, potentially means less time at the antibody manufacturer (i.e. less time in traditional downstream processing), with the remaining downstream processing and conjugation service both transferring to the bio-conjugation CMO. The result is a refined, simpler and much more efficient system – saving up to three months of development time and resources plus creating large cost savings.

Under the Company’s new process, the starting point for the conjugation will no longer be post-creation of purified antibodies and will instead begin with antibody supernatants. This persuasive approach forgoes the need for extensive chromatographic purification techniques to deliver purified antibody.

The Company’s groundbreaking production technique – yet to be formally named – would also remove the need for expensive Protein A resins, instead replacing them with capture resins that are at the heart of the Company’s core ‘Lock-Release’ technology. In ADC manufacturing, the Protein A capture step is the most costly in downstream processing, delivering semi-purified antibody. Now, starting from antibody supernatant, ADC Bio’s unique approach will see their patented ‘Lock-Release’ technology 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 & G resins extends beyond substantial cost savings. Incidental leaching of these proteins from their purification media increases the impurities in a biopharmaceutical drug product – all of which have to be removed in subsequent chromatography polishing steps before an antibody can be used for any therapeutic application. Moreover, Protein A is known to cause immunogenic responses in humans and has proven toxic in a number of clinical studies – thus its removal is mandatory.