Learning objectives
At the end of the course the student will be familiar with basic notions on the production of biotech proteins and on their therapeutic and diagnostic application. Examples of biotech drugs will provide not only specific information on these drugs, but also an overview on the variety of products, production, purification and characterization techniques and application of biotech products currently available. In particular, at the end of the course, the student is expected to:
1. Know and understand the processes, techniques and specific issues related to the production, characterization and use of biotech drugs. Know in detail the structure, properties, functions, production techniques and application of biotech drugs treated during the course. Know the meaning and examples of biosimilar and biobetter drugs and understand the rationale for pegylation and hyper-glycosylation of drugs, production of fusion proteins and conjugation of small molecules with macromolecules (Knowledge and understanding).
2. Interpret and critically comment information on biotech drugs, also in the context of production and use of biotech pharmaceuticals. Apply acquired notions to the understanding of strategies of protein modification aimed at improving product properties (Applying knowledge and understanding).
3. Identify relevant properties of specific biotech drugs and draw conclusions on their production, potential for structural modification and application. Analyze pros and cons of techniques for the production of biotech drugs. Properly answer to questions, suggestions and criticisms, and formulate opinions on the topics treated in the course (Making judgements).
4. Report with proper language, to specialists and non-specialists, knowledge and concepts related to biopharmaceuticals, concerning both general aspects on the production of biotech drugs and detailed information on the properties of drugs treated during the course (Communication skills).
5. Autonomously deepen his/her knowledge and expertise in the development and therapeutic application of biotech drugs, using bibliographic resources, integrating information from other disciplines (Learning skills).
Prerequisites
Basic concepts of organic and medicinal chemistry, biochemistry, pharmacology and immunology are needed to understand the structure, action, application and critical aspects of recombinant therapeutic proteins. In particular, the student should be familiar with structure and function of amino acids and proteins, nucleotides, DNA and RNA and he/she should know the processes of DNA replication and transcription and of protein synthesis. Basic principles of immunology, structure and function of antibodies are also required. Knowledge of acid-base equilibria, redox reactions, functional groups of organic chemistry and of the main metabolic transformation of drugs is another prerequisite of the course.
Course unit content
The first part of the course provides basic knowledge about biotech methodologies and biotechnology-related techniques, and their application to the design, production, downstream processing and characterization of biopharmaceuticals. The process and aims of drug pegylation are described, with examples of pegylated drugs. Examples of biosimilars and biobetter drugs are also presented and discussed, in comparison with generic drugs. Basic notions related to diagnostic and analytical application of protein biologics are also provided. The second part of the course covers the most important biotech drugs used in several therapeutic areas, including hormones, enzymes, cytokines, vaccines, monoclonal antibodies and immunoconjugates. For each drug, relevant aspects related to structural properties, production, mechanism of action, therapeutic application, as well as pharmacokinetics and toxicity are described. Immunoconjugates and radioimmunoconjugates are presented, with examples of drugs used in the clinics. Structure-activity and structure-property relationships will be discussed to rationalize the production of analogs of physiological proteins with modified/improved pharmacodynamic and/or pharmacokinetic properties.
Full programme
Introduction to biotechnology. Basic concepts of molecular biotechnology. Production of biotech products: 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. Pharmacokinetics and metabolic processes. Immunogenicity of biopharmaceuticals. Pegylation of therapeutic proteins. Fusion proteins and soluble receptors. Biosimilars and biobetters.
Hormones: insulin, growth hormone, follicle-stimulating hormone, luteinizing hormone.
Cytokines: interleukins (IL-1, IL-2) and derivatives; interferons; hematopoietic growth factors (G-SCF, erythropoietin).
Blood proteins: tissue-type plasminogen activator, clotting factors (VII, VIII, IX).
Enzymes: human deoxyribonuclease, beta-glucocerebrosidase, alpha-galactosidase.
Recombinant vaccines: genetically improved live vaccines against salmonella and cholera, live vectors for veterinary use and experimental vaccines against covid-19, genetically improved subunit vaccines against hepatitis B, papillomavirus, diphtheria and whooping cough, glycoconjugated vaccines against pneumococcus and Neisseria meningitidis.
Monoclonal antibodies, immunoconjugates and radioimmunoconjugates; murine, chimeric, humanized, human, bispecific antibodies and antibody fragments; rituximab, ofatumumab, ibritumomab tiuxetan, brentuximab vedotin, muromonab, catumaxomab, basiliximab, infliximab, adalimumab, certolizumab pegol, abciximab, ibalizumab.
Soluble receptors: etanercept.
Fusion proteins: denileukin diftitox.
Bibliography
M.L. Calabrò: "Compendio di Biotecnologie Farmaceutiche"; EdiSES, Napoli, 2008.
A.J. Crommelin, R.D. Sindelar, B. Meibohm: "Pharmaceutical Biotechnology: Fundamentals and Applications", Fifth Edition, Springer, 2019.
Per consultation and further information:
E. Vegeto, A. Maggi, P. Minghetti: "Farmaci biotecnologici e terapia personalizzata. Aspetti farmacologici e clinici." Casa Editrice Ambrosiana, 2019.
Pdf files of the slides commented during the lessons will be available for students before the beginning of the course at the Elly web site (https://elly2020.saf.unipr.it/course/view.php?id=143).
Teaching methods
Teacher-led lessons (40 hours corresponding to 5 CFU) with slide projection which provides the information required to describe and discuss the topics and examples of each lesson. Lessons will be delivered in presence, with students attending the lesson upon seat booking previously performed using the app provided by UniPr. Lessons can be attended also online, via Teams software. The student is expected to study using the textbook and the material provided through the ELLY platform (slides and supplementary material). The teacher is available for explanations and discussion of the course contents at the end of the lesson, or by appointment (e-mail request).
Assessment methods and criteria
An oral examination, with questions related to all the topics treated during the course, will assess the knowledge and comprehension of the contents of the course achieved by the student. The ability of the student to apply the acquired knowledge is also evaluated through connections among topics and personal comments/evaluations related to the program content. Preparation is considered sufficient if the student proves knowledge and understanding of the basic aspects of each topic and is able to apply this knowledge to a simple discussion. During the examination, use of a proper terminology and language will be also assessed. The grade for the course of Biotechnological Drugs/ Supplement to Pharmaceutical Chemistry will be the average grade obtained for the two modules. Online examination of students will be performed though MS Teams software ((http://selma.unipr.it for user guide). Online exams will be structured in the same way as those in presence.
Other information
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