Protein therapeutics is the fastest growing segment in the biotechnology and pharmaceutical industry. Protein therapeutics includes monoclonal antibodies, recombinant proteins, chimeric proteins and other protein receptor constructs. It is expected to reach over $70 billion in sales by 2010. A major hurdle in the development of proteins as pharmaceutical drugs is their formulation in a safe and stable form. The identification of buffer, ligand and excipient conditions that maximize their stability and eliminate protein aggregation is critical during development and often requires the evaluation of hundreds of conditions. This time-consuming task is compounded by the absence of completely automated instruments with the capability of accurately measuring the stability/aggregation matrix of a protein. The goal of this proposal is to develop a fully automated, protein chemical denaturation, fluorescence/OD instrument aimed at measuring multi-dimensional protein stability and aggregation matrices. In this instrument, the user will only need to provide protein and bulk formulation solutions. The instrument will automatically prepare all solutions, perform the measurements, analyze the data and present the results to the user. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1
Public Health Relevance: This instrument will significantly accelerate the development of protein therapeutics and find a significant market. In addition, it will provide a new way to study protein stability and aggregation, and contribute to the development of a better scientific understanding of these issues. By providing a rapid and cost-effective means to test Formulations at relevant temperatures (storage and biological), researchers will have the practical opportunity to test more Formulations and to select the Formulation that is optimal for any specific biologic. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1
Thesaurus Terms: Address;Analysis, Data;Antibodies;Automation;Biologic Development;Biologic Products;Biological;Biological Agent;Biological Products;Biosynthetic Proteins;Biotechnology;Buffers;Calorimetry, Differential Scanning;Chemicals;Chimera Protein;Chimeric Proteins;Data;Data Analyses;Detection;Development;Development And Research;Device Or Instrument Development;Differential Scanning Calorimetry;Differential Thermal Analysis, Calorimetric;Drug Formulations;Drug Industry;Drugs;Egfr;Erbb Protein;Erbb1;Ensure;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Kinase;Epidermal Growth Factor Receptor Protein-Tyrosine Kinase;Evaluation;Excipients;Fluorescence;Formulation;Formulations, Drug;Funding;Fusion Protein;Goals;Her1;High Temperature Of Physical Object;Industry, Pharmaceutic;Investigators;Laboratories;Ligands;Marketing;Measurement;Measures;Medication;Methods And Techniques;Methods, Other;Moab, Clinical Treatment;Monoclonal Antibodies;Pharmaceutic Preparations;Pharmaceutical Agent;Pharmaceutical Industry;Pharmaceutical Preparations;Pharmaceuticals;Pharmacologic Substance;Pharmacological Substance;Phase;Predictive Value;Preparation;Principal Investigator;Process;Programs (Pt);Programs [publication Type];Protein Analysis;Protein Denaturation;Proteins;R &D;R&D;Receptor Protein;Receptor, Egf;Receptor, Tgf-Alpha;Receptor, Urogastrone;Receptors, Epidermal Growth Factor-Urogastrone;Recombinant Proteins;Research;Research Personnel;Researchers;Sched;Sales;Sampling;Schedule;Solutions;System;System, Loinc Axis 4;Techniques;Temperature;Testing;Thermodynamic;Thermodynamics;Time;Transforming Growth Factor Alpha Receptor;Antibody;Biopharmaceutical;Biotherapeutic Agent;C-Erbb-1;C-Erbb-1 Protein;Cost Effective;Device Development;Drug /Agent;Drug/Agent;Erbb-1;Erbb-1 Proto-Oncogene Protein;Erbbl;Gene Product;High Temperature;Indexing;Instrument;Instrument Development;Monoclonal Antibody;Programs;Protein Aggregation;Proto-Oncogene Protein C-Erbb-1;Prototype;Receptor;Research And Development;Sensor;Therapeutic Protein
