Accelerated manufacturing of large-scale, full-length, human-like glycosylated antibodies for bio-defense.

Abstract

From the point of DNA sequence confirmation until production of meaningful clinical quantities of novel therapeutics, current manufacturing systems for many glycosylated proteins require several months of development. Consequently, in the event of mass-casualty epidemics, current systems will fail to provide sufficient and timely quantities of emergency medical counter measures. As the identity of many new biological threats are unlikely to be known in advance, pre-emptive manufacturing and stockpiling of countermeasures cannot always be performed. Preparedness for all biological catastrophes requires a radical solution to replace the current slow scale-up and manufacture of certain lifesaving medical countermeasures. Current clinical and commercial manufacturing methods for glycosylated proteins use stable cell lines for protein expression, wherein the gene coding for the protein of interest is stably integrated into the host cell genome. The generation, identification, banking, testing, and scale-up of suitable stable clones generally takes many months. Because this development time is not compatible with emergency manufacturing, an alternative method for rapid production of medical counter measure antibodies is needed. One such potential technique is transient gene expression. Transient gene expression is a common approach for production of research-grade antibodies. It is frequently used to generate milligram to gram quantities of material within two to three weeks of DNA sequence confirmation. In the past, transient systems have been considered for emergency production of large quantities of antibodies, but dismissed due to low titers, high cost of DNA, uncertain regulatory environment, and the lack of sufficient, available manufacturing capacity. Recent developments, however, have substantially enhanced the viability of such an approach. This article will explore these developments and investigate the use of transient gene expression for rapid production of antibody-based medical countermeasures.