Learning outcomes of the course unit
The main goal of this course is to provide basic information to know and understand the properties, application and problems related to the production and use of drugs of biotechnological origin.
The comprehensive introduction about methodologies for production, characterization and purification of protein therapeutics and the treatment of their pharmacodynamic and pharmacokinetic properties, their toxicity and immunogenicity will allow the student to apply its knowledge to the identification and evaluation of the relevant properties and the potential problems related to each biotech drug.
Basic knowledge of medicinal chemistry, biochemistry, organic chemistry, immunology and pharmacology are needed to understand the structure, composition, application and limitations of recombinant therapeutic proteins.
Course contents summary
The first part of the course will provide basic knowledge about fundamental biotech methodologies and biotechnology-related techniques and their application to the design, production, downstream processing and characterization of biotech drugs.
The second part of the course will cover the most important classes of biotech drugs for different therapeutic areas, such as hormones, enzymes, cytokines, monoclonal antibodies. For each drug, relevant aspects of its production, mechanism of action, therapeutic application, as well as its pharmacokinetic properties and toxicity will be treated.
Structure-activity and structure-property relationships will be described for those biotech drugs having an amino acid composition different from the physiological protein. Their modified/improved pharmacodynamic or pharmacokinetic properties will be commented.
Introduction to biotechnology.
Basic elements of molecular biotechnology.
Production of biotech compounds: cultivation and downstream processing.
Biophysical and biochemical analyses of recombinant proteins.
Chemical and physicochemical properties and reactivity of recombinant proteins; stability of proteins and mechanisms of degradation.
Pegylation of therapeutic proteins
Fusion proteins and soluble receptors.
Hormones: insulin, glucagon, growth hormone, follicle-stimulating hormone, luteinizing hormone, parathyroid hormone.
Cytokines: interleukines (IL-1, IL-2); interferons; hematopoietic growth factors (G-SCF, erythropoietin).
Blood proteins: tissue-type plasminogen activator, clotting factors (VII, VIII, IX).
Enzymes: human deoxyribonuclease, beta-glucocerebrosidase, alpha-galactisodase.
Recombinant vaccines: genetically improved live vaccines, live vectors, genetically improved subunit vaccines
Monoclonal antibodies, immunoconjugates and radioimmunoconjugates: rituximab, ofatumumab, ibritumomab tiuxetan, gemtuzumab ozogamicin, muromonab, catumaxomab, daclizumab, basiliximab, infliximab, adalimumab, certolizumab pegol, cetuximab, bevacizumab, ranibizumab.
Soluble receptors: etanercept, abatacept.
Maria Luisa Calabrò, Compendio di Biotecnologie Farmaceutiche, EdiSES, Napoli, 2008.
Daan J.A. Crommelin, Robert D. Sindelar, Biotecnologie Farmaceutiche, Zanichelli, Bologna.
Thomas L. Lemke, David A. Williams, Victoria F. Roche, S. William Zito, Foye’s Principi di Chimica Farmaceutica, sesta edizione italiana, Piccin, Padova, 2013.
Daan J.A. Crommelin, Robert D. Sindelar, Bernd Meibohm, Pharmaceutical Biotechnology, Fourth Edition, Springer, 2013.
Teacher-led lessons with slides.
Assessment methods and criteria
An oral examination, with questions related to all the topics treated during the course, will be used to assess the knowledge and the comprehension of the contents of the course achieved by the student. The ability of the student to apply the acquired knowledge will be also evaluated through connections among topics.
Preparation will be sufficient when the student will show knowledge and understanding of the basic aspects of each topic and will be able to apply this knowledge to the discussion. During the examination, acquisition by the student of an appropriate terminology for the topics treated will also be assessed.
The grade for the course of Biotechnological Drugs/ Supplement to Pharmaceutical Chemistry will be the average grade obtained for the two modules.