ENGINEERING HUMAN PHYSIOLOGY: DISCOVERY AND PRECLINICAUCLINICAL DEVELOPMENT OF THERAPEUTIC PROTEINS IN AN ACADEMIC SETTING

摘要

After a 20+ year career focuses on E.coli genetics and physiology, protein biogenesis and protein engineering methods, lab became refocused on engineering of human biology namely: (i) the discovery, preclinical and clinical development of protein therapeutics and (ii) the molecular analysis of human adaptive immune responses with emphasis on the discovery on new therapeutic approaches. As part of this talk I will briefly discuss the challenges and rewards of making a mid- to late career and the many fascinating aspects of protein therapeutics discovery and development. So far our work on new biologics has led to one approved protein therapeutic, a second protein drug currently in 3 phase I trials and two more that we expect to enter clinical evaluation in early 2018. The two preclinical drugs are both enzymes for the treatment of cancer through very novel mechanisms that rely on the modulation of human metabolic processes. As an example of our approach, this presentation will discuss: (i) the biological underpinnings and mechanism of action of these two drugs; (ii) protein engineering strategies that had to be invented to generate the respective clinical candidate enzymes; (iii) the essential role of chemistry, manufacturing and control (CMC) and many the many challenges encountered in the development of new biologics and; (iv) pharmacology. We have found that every aspect of this work greatly benefits from engineering analysis.