Pipeline 1 :Protein Aggregation Day 2

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Day 1 | Day 2

Thursday, January 14

7:00 am Registration

7:30 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:15 Chairperson’s Opening Remarks

8:20 Controlling Aggregation Pathways and Kinetics via Protein Interactions and Rational Design

Christopher Roberts, Ph.D., Associate Professor, Department of Chemical Engineering, University of Delaware

Proteins can unfold and aggregate along different pathways that lead to structurally distinct final aggregate states. Control of which state is reached, and the associated aggregation rates, is critical to product stability and shelf life, as well as potentially impacting immunogenicity. The presentation will focus on our recent findings regarding how the kinetics and pathway can be controlled by adjusting formulation conditions and/or protein engineering to affect protein-protein interactions.

8:50 Novel Pathways of Oxidative and Photolytic Peptide and Protein Disulfide Degradation Leading to Covalent Cross-Links

Christian Schöneich, Ph.D., Professor and Chair, Department of Pharmaceutical Chemistry, University of Kansas

The exposure of disulfide-containing peptides and proteins to light leads to a series of reaction products, including D-amino acids and dithiohemiacetals, of which the latter show high photolytic and thermal instability, leading to covalent thioether cross-links. Product formation depends on the wavelength of incident light. Impact on pharmaceutical processing and stabilization and the underlying mechanisms will be discussed, together with the potential impact on aggregation and the formation of new epitopes.
9:20 Predicting Stability of Concentrated Protein Formulations from Dilute
Solution Properties
Kevin Mattison Ph.D., Senior Bioanalytical Scientist, Malvern Instruments
Ulf Nobbmann Ph.D., Sales Specialist, Malvern Instruments
A common manifestation of solution based formulation instability is an increase in particle size, which can impose limits on the shelf life of the pharmaceutical, particularly when aggregation is found to be correlated with a loss of activity. Due to it’s sensitivity to trace amounts of aggregate, light scattering is routinely used in this area; but has historically occupied a “monitoring” role, wherein sample aggregation is tracked as a function of time or shelf life. This talks focuses on the use of non-invasive light scattering techniques to “predict” formulation stability, using zeta potential, melting points, virial coefficients, and polydispersity measurements of the dilute solution.

9:50 Sponsored Presentation (Sponsorship Opportunity Available)

10:05 Networking Coffee Break in the Exhibit Hall

10:45 High-Throughput Measurements of Protein Self-Association as a Guide to Engineering and Formulating Aggregation-Resistant Antibodies

Pete Tessier, Ph.D., Assistant Professor, Chemical & Biological Engineering, Rennsaelaer Polytechnic Institute

A common challenge in the development of therapeutic proteins is the propensity of these macromolecules to self-associate and aggregate. To overcome such undesirable protein self-association behavior in a rational manner, we are developing a nanoparticle-based platform, namely self-interaction nanoparticle spectroscopy (SINS), to rapidly detect protein self-interactions for hundreds of solution conditions and/or protein variants in a near simultaneous manner. In this presentation we will discuss how SINS can be used to characterize the self-association behavior for a series of homologous antibodies (as well as other globular proteins), and how these measurements can be used to develop highly soluble therapeutic proteins.

11:15 Protein Refolding with a Little Help from REFOLD

Stephen Bottomley, Ph.D., Professor, Senior Research Fellow, Biochemistry and Molecular Biology, Monash University

The solubilization and refolding of recombinant proteins from inclusion bodies is a major challenge in biotechnology and biomedical research. Publications in the literature are essentially ad hoc reports consisting of a dazzling array of experimental protocols and buffer cocktails that presents enormous challenges to the scientist. The REFOLD database (http://refold.med.monash.edu.au), is a freely available, open repository for protocols describing the refolding and purification of recombinant proteins. Using this information we describe some of the practical considerations in refolding and we will demonstrate how refolding procedures can be designed and modified using the information in REFOLD.

11:45 A Novel High-Throughput Technology for Formulation Optimization

Larry DeLucas, Ph.D., Professor, Director, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham

A quantitative measure of protein-protein interaction is given by a statistical thermodynamic interpretation noted as the second virial coefficient (B). B is a quantitative predictor for physical stability and solubility of protein solutions. High-throughput self-interaction chromatography and an incomplete factorial screen of excipient conditions are used to measure B-values. The conditions and measured B-values are subsequently input to a neural net program that predicts B-values for the complete factorial, thereby yielding new solution conditions with novel excipient combinations and concentrations. Examples demonstrating its utility for rapidly optimizing protein solubility and physical stability will be presented.

12:15 pm Close of Morning Session

12:30 Luncheon Presentation (Sponsorship Opportunity Available ) or Lunch on Your Own

1:30 Close of Protein Aggregation

Day 1 | Day 2