Our rapidly improving understanding of biological systems is leading to unparalleled discovery of novel targets whose modulation provides the potential for effective treatment of disease. These targets include both protein-protein and protein-nucleic acid interactions, and modulation of either is often refractory to classic small-molecule therapeutic approaches. This long-recognized challenge has motivated in part the development and expansion of protein-based therapeutics, most notably humanized monoclonal antibodies (mAbs), that have proven effective in modulating important extracellular targets with excellent selectivity and potency. However, mAbs and other recombinant protein therapeutics are generally not effective against intracellular targets due to a variety of factors, including poor membrane permeability. Equally limiting is the fact that current biologic therapeutics typically are not orally available. A host of biologic modalities are therefore being developed to address unmet clinical needs. New, often non-natural biologic and hybrid chemi-biologic molecules (e.g. bioconjugates) offer the potential to successfully target a far broader biological space and to modulate targets in different ways. While these new modalities are expected to provide effective therapies against a host of diseases, their chemical diversity will no doubt challenge, sometimes in seemingly insurmountable ways, current paradigms and platforms for downstream process development, scale up and validated implementation. A concern? Yes, but also a unique opportunity to create purification unit operations in concert with new biologic modalities, and to thereby advanced downstream process development platforms amenable to those modalities. In this talk, I will describe progress within the biotech industry, technology development companies, and my laboratory aimed at addressing this opportunity juxtaposed to the current state.

Retooling downstream processing to address or enable an ever-expanding diversity of therapeutic modalities

255th National Meeting (2018)

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