ePoster Presentation

Whitney Shatz
University of Geneva, Switzerland
Title: Ferritin-antibody fragment conjugates: Protein scaffolds to modify physicochemical and pharmacokinetic properties of biotherapeutics
Submitted Date: 2019-04-05
Biography
Whitney Shatz received her M.S. in Biochemistry and Molecular Biology from the University of California in Santa Barbara, characterizing bacterial enzymes involved in the epigenetic process of DNA methylation. Since 2007, she has worked within the research organization at Genentech, supporting production and characterization of large molecule biologics. During her 11-year tenure, she has made significant contributions to the investigation of structure activity/relationship in antibody-dependent cell cytotoxicity (ADCC), as well as to the advancement of novel bispecific antibodies in a variety of disease areas. More recently, her focus has shifted to the development and characterization of protein-polymer bioconjugates for long-acting drug delivery. In addition, since 2016 she has been concurrently pursuing a doctorate in Pharmaceutical Sciences at the University of Geneva.
Abstract
There is a growing trend in the biotherapeutics field to develop molecules with a high degree of multivalency. This can be useful for receptor clustering, T-cell recruiting, agonist activation, and half-life extension. However, many of the currently available “molecular scaffolds†are polymer-based and raise obvious concerns with respect to biocompatibility and the accumulation of by-products. In contrast, protein-based scaffolds offer an attractive, “natural†alternative for modifying therapeutic agent properties and functionality. Ferritin is a ubiquitous protein found in most cell types of humans in addition to invertebrates, higher plants, fungi and bacteria; its primary function is to store iron (1). In mammals, ferritins are composed of 24 subunits that form an icosahedron with an external diameter of ~12 nm and an overall MW of ~474 kDa (2). Ferritin and its derivatives have already demonstrated their utility as “molecular cages†for applications in drug delivery (3,4). In addition, ferritin can be easily coupled covalently to biomolecules through the presence of multiple surface-exposed lysine residues (5). Site directed mutagenesis and the introduction of new amino acid residues create even more opportunities to introduce new functionality (6). Here, we present preliminary results describing the development of antibody fragment (Fab)-ferritin conjugates. In this first step, a strategy was developed for the covalent attachment of multiple Fab units to the ferritin cage, yielding a conjugate with 24 Fabs per ferritin cage (i.e. one Fab per subunit). Following optimization of the conjugation strategy, an in-depth characterization of the conjugates was performed using multiple techniques – including DLS, SEC-MALS, LC/MS, viscosity measurements, and target activity. The results confirmed that Fab-ferritin conjugation was successfully achieved. In addition to the possible modification of Fab elimination kinetics in vivo and the potential for more prolonged therapeutic effect, the conjugates may offer other attributes well-suited for drug delivery applications that require multivalency.

Gerald C. Hsu
EclaireMD Foundation, USA
Title: Methodology of math-physical medicine (GH-Method)
Submitted Date: 2019-01-30
Biography
Gerald C Hsu has received his PhD in Mathematics and majored in Engineering at MIT. He has attended different universities over 17 years and studied seven academic disciplines. He has spent a huge time research in T2D research. His approach is “Math-Physics and Quantitative Medicine†based on mathematics, physics, engineering modeling, signal processing, computer science, big data analytics, statistics, machine learning and AI. His research focus is on preventive medicine using prediction tools. He believes that the better the prediction, the more control you have.
Abstract
Introduction: This paper describes the math-physical medicine approach (MPM) of medical research utilizing mathematics, physics, engineering models, and computer science, instead of the current biochemical medicine approach (BCM) that mainly utilizes biology and chemistry. \r\nMethodology of MPM on Diabetes Research: Initially, the author spent four years of self-studying six chronic diseases and food nutrition to gain in-depth medical domain knowledge. During 2014, he defined metabolism as a nonlinear, dynamic, and organic mathematical system having 10 categories with ~500 elements. He then applied topology concept with partial differential equation and nonlinear algebra to construct a metabolism equation. He further defined and calculated two variables, metabolism index and general health status unit. During the past 8.5 years, he has collected and processed 1.5 million data. Since 2015, he developed prediction models, i.e. equations, for both postprandial plasma glucose (PPG) and fasting plasma glucose (FPG). He identified 19 influential factors for PPG and five both wave and energy theories, he extended his research into the risk probability of heart attack or stroke. In this risk assessment, he applied structural mechanics concepts, including elasticity, dynamic plastic, and fracture mechanics, to simulate artery rupture and applied fluid dynamics concepts to simulate artery blockage. He further decomposed 1,200 glucose waveforms with 21,000 data and then re-integrated them into 3 distinctive PPG waveform types which revealed different personality traits and psychological behaviors of type 2 diabetes patients between two variables, he used spatial analysis. Furthermore, he also applied Fourier Transform to conduct frequency domain analyses to discover some hidden characteristics of glucose waves. He then developed an AI Glucometer tool for patients to predict their weight, FPG, PPG, and A1C. It uses various computer science tools, including big data analytics, machine learning (self-learning, correction, and simplification), and artificial intelligence to achieve very high accuracy (95% to 99%) mg/dL and A1C is 6.5%. Since his health condition is stable, he no longer suffers from repetitive cardiovascular episodes.