2. Drug discovery involves systematically identifying which protein is causing a problem in the body - either because it is absent, defective, or excessive -- and then identifying and engineering a protein or related molecule to correct the problem. Because biological molecules are naturally very specific in their interactions, biotech medicines, are more precise and predictable. Engineering recombinant therapeutics Source:Genentech DNA and proteins are the biological molecules most often used in biotechnology. DNA provides instructions for making cells and performing cellular tasks, while proteins provide the building materials for producing new cells and are responsible for carrying out the DNA's instructions. Recombinant DNA technology, the science of cutting a protein-coding sequence of DNA from one organism and pasting it into a vector to be carried into another organism that reproduces to make proteins of potential therapeutic value, is the technology at the foundation of biomedical biotechnology. Recently, newer technologies, including computer visualization of molecules, microarrays and sensitive assaying techniques, have become increasingly important in biomedical biotech research, as have advances in genomics and molecular biology itself.

3. Mammalian cell lines Example: Chinese Hamster Ovary (CHO) Suspension Pilot-scale GLP Production Pilot-scale GLP Production (100-200L CHO cell bioreactors) Scale- up 12,000L Bioreactor Scale- up 12,000L Bioreactor CHO cells secrete therapeutic- CHO cells secrete therapeutic-  Avastin Humanized Monoclonal Antibody  Enbrel Harvesting and separation Harvesting and separation Centrifugation, Filtration Centrifugation, Filtration  Low-shear continuous centrifuge  Tangential flow filtration systems for micro- and ultra-filtration Scale up and Harvesting Source: Genentech

4. Protein Isolation Enrichment and purification  Chromatography Ion-Exchange Affinity Gel Filtration, Hydrophobic interaction (HIC)  Columns Preparative-Scale (30-cm. Dia) High-Performance, High-Dynamic Capacity Resins, Macro-Prep, Fastflow

5. Quality Control Verification of protein identity: Characterization (Is it the right Protein?) SDS Polyacrylamide gel electrophoresis (PAGE) Immunoblot Mass Spectrometer Analytical HPLC Functional Assay (Does it work?) Cell tissue and animal models ELISA Concerns: - Safety - Contamination by adventitious agents extant in animal-derived materials, potential immunogenicity - Efficacy of the Therapeutic

6. Formulation and Marketing Stabilization and Delivery Physical and chemical stability Bioavailability The PRESENT Lyophilization Delivery Subcutaneous Injection Transfusion The FUTURE! Nanoparticle Design and Microfabrication -Recombinant Protein and Peptide Delivery Nasal, Pulmonary, Oral