Learning outcomes of the course unit
At the end of the course the student has become familiar with basic notions on the production of biotech proteins and on their therapeutic and diagnostic application. The examples of biotech proteins treated during the course 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. Understand the processes, techniques and issues related to the production, characterization and use of biotech drugs. Know in detail the structure, 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 processes like 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 in the wider 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 (Making judgements).
4. Report with proper language, to specialists and non-specialists, knowledge and concepts related to biopharmaceuticals, concerning general aspects related to the production of biotech drugs as well as more detailed information about the properties of the specific drugs treated during the course (Communication skills).
5. Autonomously deepen his/her knowledge and expertise in the development, application and therapeutic application of biotech drugs, using proper bibliographic resources, with integration of information from other disciplines (Learning skills).
Basic concepts of medicinal chemistry, biochemistry, organic chemistry, immunology and pharmacology 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 functional groups of organic chemistry and of the main metabolic transformation of drugs is another prerequisite of the course.
Course contents summary
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. Examples of biosimilars and biobetter drugs are 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 and monoclonal antibodies. For each drug, relevant aspects related to production, mechanism of action, therapeutic application, as well as pharmacokinetic properties 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.
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; erythropoietin.
Blood proteins: tissue-type plasminogen activator, clotting factors (VII, VIII, IX).
Enzymes: human deoxyribonuclease, beta-glucocerebrosidase.
Recombinant vaccines: genetically improved live vaccines, live vectors, genetically improved subunit vaccines.
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
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. (for the specific chapter related to pharmaceutical biotechnology. An English version of this book is available)
Daan J.A. Crommelin, Robert D. Sindelar, Bernd Meibohm, Pharmaceutical Biotechnology, Fifth Edition, Springer, 2019.
Pdf files of the slides commented during the course and other material is available for students before the beginning of the lessons at the Elly web site (https://elly.saf.unipr.it/2019/).
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. 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, is conducted to 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 on general and/or peculiar aspects discussed during the examination. 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 the discussion. During the examination use of a proper terminology and language is also assessed. The grade for the course of Biotechnological Drugs/ Supplement to Pharmaceutical Chemistry will be the average grade obtained for the two modules.