January 13 - 17, 2014
Renaissance Hotel and Palm Springs Convention Center Palm Springs, California

A Community Dedicated to the
Evolving Field and Future of Biotherapeutics
2014 Archived Content

Cambridge Healthtech Institute’s Fifth Annual
Protein Aggregation and Emerging Analytical Tools
Mechanistic, Predictive, Screening and Formulation Challenges
January 16-17, 2014





Day 1 | Day 2 | Download Development Brochure | Speaker Biographies 

FRIDAY, JANUARY 17

7:15 am Conference Registration

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


Predictive Tools and High-Throughput Screening 

8:30 Chairperson’s Remarks

Murali Bilikallahalli 2Murali Bilikallahalli, Ph.D., Associate Director, Formulation Sciences, Proteins, Vaccines & Oligos, MedImmune





Featured Presentation

8:35 Aggregation of Isolated Antibody Domains and Drug Conjugates

Dimiter DimitrovDimiter S. Dimitrov, Ph.D., Senior Investigator, Protein Interaction Group, FNLCR, NCI, NIH

Aggregation of isolated antibody domains will be overviewed and our recent work on CH2 will be discussed in detail (Gong R at al Mol Pharm. 2013, unpublished). Aggregation of antibody drug conjugates (ADCs) will be also discussed. Experimental data and computational models will be presented for some of our ADCs.

9:05 Predictability and Implementation of HTS Technologies during Early Formulation Development

Hardeep Samra, Ph.D., Scientist II, Formulation Sciences Department, MedImmune, Inc.

9:35 High-Throughput Detection of Antibody Self-Interaction by Biolayer Interferometry

Yingda XuYingda Xu, Ph.D., Group Leader, Protein Analytics, Adimab

Self-interaction of an antibody may lead to aggregation, low solubility or high viscosity. Rapid identification of highly developable leads remains challenging. Using bio-layer interferometry (BLI) technology, a high-throughput method to screen for antibodies prone to clone self-interaction (CSI) was developed that correlates well with SIC and CIC. This method allows hundreds of candidates to be screened in a matter of hours with minimal material consumption.

10:05 Selected Oral Poster Presentation: Peptide Aggregation Measurement and Prevention

Jeffrey Lampert, Research Scientist, Technical Service/Manufacturing Science, Eli Lilly and Company

Peptide aggregation can be controlled and even reversed by lowering pH without adjusting other parameters that have the potential to influence aggregation. A simple test using filtration and optical density measurements for quantifying aggregation was developed to allow time-point measurements and determination of aggregation rates.

10:20 Coffee Break in the Exhibit Hall with Poster Awards


Analytical Methods for Assessment of Protein Aggregation 

11:15 Applications of Spin Labeling to Aggregated Proteins: A Sensitive Diagnostic Technique for Protein Structure, Folding and Misfolding

Lawrence Berliner, Professor of Chemistry and Biochemistry, Chemistry and Biochemistry, University of Denver; Emeritus, Ohio State University

The spin labeling technique utilizes aminoxyl radical (nitroxide) labels which are tailored to either covalently or non-covalently bind to the system of choice. The distinct advantage of electron spin resonance electron paramagnetic resonance (EPR or ESR) is the sensitivity to protein motion with is a unique marker of aggregation. It is not complicated by optical opacity and solids or aggregates.

11:45 Detecting the Aggregation Propensity of Proteins by Bis-ANS: Binding Kinetics and Thermodynamics

Murali Bilikallahalli 2

Murali Bilikallahalli, Ph.D., Associate Director, Formulation Sciences, Proteins, Vaccines & Oligos, MedImmune

Aggregation is a major concern in therapeutic protein formulations especially in liquid form for extended shelf life. Aggregate levels often grow with time and detection of aggregation prone precursor is a challenging task in protein science. In this study we have used BiS-ANS, an hydrophobic ligand, to probe the aggregation propensity of different classes of IgGs and human serum albumin in native and physically stressed conditions. Calorimetric and millisecond fast kinetic studies are used to evaluate the thermodynamics and kinetics of ligand binding and evaluate the aggregation propensity of proteins.

Featured Presentation

12:15 pm Fluorogenic Tagging to Rapidly Screen for Oxidized and Covalently Aggregated Proteins

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

To efficiently monitor protein oxidation and/or covalent aggregates, we developed and optimized a methodology for fluorogenic tagging, using either HPLC-fluorescence detection/mass spectrometry, SEC-fluorescence detection or fluorescence detection on a plate reader. This technique enables the detection of phenylalanine and tyrosine oxidation, products which are present in significant yields in covalent protein aggregates such as of insulin and IgG1. Derivatization times are short, and fluorescence detection allows for high sensitivity.


12:45 Mid-Infrared Method for Protein Quantitation, Antibodies Aggregation Monitoring and Lipid Content Analysis of Biological Samples 

EMD Millipore Strug_IvonaIvona Strug, Ph.D., Senior Biochemical Scientist, EMD Millipore 

Biological samples represent a range of complexities from homogeneous purified protein to multi-component mixtures containing proteins, aggregates, lipids and other macromolecules. The ability to accurately qualify these samples is paramount to downstream applications. Here we present a novel analytical method based on mid-infrared (MIR) spectroscopy that offers protein quantitation, possibility to monitor HCP and antibodies aggregation, analysis of lipid or detergent species, as well as the identification of other bio-molecules, present in biological samples.

Partical Sizing Systems1:15 Luncheon Presentation: Counting and Sizing Protein Aggregates Down to 0.15 um in sub-mL Samples Using New Focused Beam SPOS Technology

Nicoli_DavidDavid F. Nicoli, Ph.D., Vice President, R&D, Particle Sizing Systems, LLC

A new approach to single-particle optical sizing (SPOS), based on both light-extinction and scattering, using a focused laser beam, quickly counts and sizes protein aggregates from 0.15 to 20 microns, and at much higher concentrations than possible using conventional SPOS sensors. Analysis requires only a relatively small volume (< 1-mL) of protein suspension and does not consume the sample. High sample viscosities resulting from high protein concentrations (>100 mg/mL) can be accommodated.


Ensuring Safety And Efficacy of Biologics 

2:00 Chairperson’s Remarks

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

 

2:05 Structure-based Predictive Modeling of Methionine Oxidation Stability in Proteins

Vishal NashineVishal C. Nashine, Ph.D., Senior Research Investigator, Drug Product Science & Technology, Bristol-Myers Squibb Co.

Oxidation of Methionine (Met) residues in therapeutic proteins may significantly impact their safety and efficacy. Met oxidation may also result in protein aggregation. We describe application of MD simulations towards prediction of the oxidation propensities of Met within several proteins.  Our results show that the 2-shell water coordination number (2-SWCN) and simulation averaged solvent accessible area (SAA) are highly predictive of the relative oxidation rates of Met residues.

2:35 Correlating Monoclonal Antibody stability with Local Dynamics using H/D Exchange Mass Spectrometry

Prakash ManikwarPrakash Manikwar, Ph.D., Scientist I, Formulation Sciences, MedImmune, Inc.

In this study, we investigated how sucrose and arginine impact both thelocal flexibility and physical stability of an IgG1 mAb. These excipients showed differential effects on conformational stability, storage stability, aggregation rates, and local flexibility of the mAb. New insights and preliminary correlations between local flexibility within specific segments of the CH2 domain and the mAb’s overall physical stability will be provided. 

3:05 Overview of Current Glass Delamination Issues and Implications

Edward J. Smith, Ph.D., Principal, Packaging Science Resources, LLC

Recently there have been many reports of significant recalls due to particulate matter in vials of drug products due to glass delamination which is a combination of chemical alteration and mechanical failure of the glass surface. This presentation will discuss the types of drugs and vials that present the most risk and review the efforts of glass manufacturers, drug packagers, and standards organizations to assess risk and preclude recalls.

3:35 Adapting to Biology: Maintaining Container Closure System Compatibility with the Biopharmaceutical Revolution

Dominick DeGrazioDominick DeGrazio, Associate Scientist, Analytical Laboratory, West Pharmaceutical Services

Alternative measures must be established that aim to preserve the efficacy and functionality of a biologic—from production to patient administration. Sustaining a stable equilibrium for proteins depends upon the ability of container closure systems to maintain compatibility with biological dynamics. Failure of packaging components to adapt can compromise patient safety, drug productivity, and biological stability.

4:05 Close of Conference

 

Alumni Discount

Cambridge Healthtech Institute (CHI) appreciates your past participation at PepTalk. Through loyalty like yours, CHI has been able to build this event into a must-attend for senior-level decision makers.

As a result of the great loyalty you have shown us, we are pleased to extend to you the exclusive opportunity to save an additional 20% off the registration rate. Just check off the box marked Alumni Discount on the registration form to receive the discount! Please note: Our records must indicate you were an attendee of PepTalk in the past to qualify.



Day 1 | Day 2 | Download Development Brochure | Speaker Biographies 

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      Premier Sponsors: 

EMD Millipore 

 Novozymes (white) 

PerkinElmer NEW 2009 

 Protein Simple  

  

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Training Seminars 

Mon-Tues, January 13-14 

Biologics Formulation and Delivery  

 


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