Core B: Industrialization Core

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ABSTRACT: CORE B Monoclonal antibodies (mAbs) are one of the most successful classes of drugs with the proven ability to address a variety of human health needs ranging from oncology, inflammatory diseases, and infectious diseases. Recent studies have demonstrated efficacy of mAbs against the most virulent infections including Nipah, Hendra, Ebola, Marburg and Lassa. Antibodies isolated from human survivors, the focus of the Prometheus CETR, have the advantage of having been a component of a successful host response to a pathogen. Further, these mAbs were positively selected for by the human immune response to the target pathogen. Therefore, these survivor mAbs will have an increased chance of being safe and efficacious compared to mAbs generated from other platforms. MAbs also offer a stunning degree of customization based on the importance of mechanisms of action. Different classes, sub-types, point mutations and N-glycosylation states can dramatically impact the potency of a prophylactic or therapeutic mAb candidate. The manufacturing platforms, formulation methods, and safety profiles of mAbs are well-established. Thus, mAbs offer a low-risk technology platform for prophylactics and therapeutics for the Category A threats (i.e. agents that pose the highest risk to national security and public health) to be addressed by the Prometheus CETR. Core B, in conjunction with Research Project III, will also evaluate the use of DNA-encoded mAbs (DMAbs), a potentially transformative technology that turns the patient’s own muscle cells into mAb producers. The Industrialization Core (Core B) is focused on ensuring the down-selection process of the CETR results in: 1. Manufacturable mAbs; 2. A product that satisfies the Target Product Profile (TPP); 3. Data sets and materials (e.g. cell banks) that are appropriate and supportive of regulatory filings with the Food and Drug Administration (FDA) to transition the products into advanced development. The Industrialization Core has two Aims: 1) Provide product development experience to Research Projects and the Cores to assure studies are compatible with industry and regulatory expectations, and 2) Transition products to advanced development.