B2847 - Biological Drugs and Methodologies for Clinical Trials

Learning outcomes

At the end of the module 1 the student: - knows the structure and post-translational processes of recombinant proteins and therapeutic targets of biological drugs on the market; - knows the different classes of therapeutic proteins and monoclonal antibodies and their pharmacodynamic and pharmacokinetic profile; - knows the profile of activity, immunogenicity and safety of biological drugs and biosimilars; - knows how to apply the knowledge learned for the conduct of the profession, for the proper conservation and dispensation of biological drugs and to inform and educate patients in their use and monitor the management of appropriateness in their use and the continuity of adherence to drug therapy in chronic therapies.

By the end of the module 2, the student will have acquired knowledge on the methodology of clinical drug trials, design of the study protocol, methods of enrolling subjects, evaluation of treatment efficacy and tolerability, and regulatory procedures governing pharmacological clinical trials.

Course contents

MODULE 1

BIOLOGICAL DRUGS

GENETIC ENGINEERING AND RECOMBINANT DNA
Gene cloning. Cellular genetic engineering for drug-protein production. Methods of DNA transfer in cultured cells. Cell systems for the study and production of recombinant proteins. Cloning of a human gene. Post-translational modifications of proteins. Pharmacological applications of recombinant cell lines. Transgenic animals in drug research, development and production
MONOCLONAL ANTIBODIES
Structure of antibodies. Activity and recycling of antibodies. Biotechnological synthesis of antibodies. Growth and selection of hybridomas. Chimeric, humanized and fully human monoclonal antibodies. Modifications that improve the pharmacological properties of monoclonal antibodies. Small molecule conjugated antibodies

OLIGONUCLEOTIDES AS DRUGS
Classification of oligonucleotides. Mechanism of action of oligonucleotides.
PHARMACODYNAMICS and PHARMACOKINETICS, ADVERSE EFFECTS

CLINICAL USE OF BIOLOGICAL DRUGS

DRUGS FOR THE CARDIOVASCULAR SYSTEM
Dyslipidemias: cardiovascular risk factors. Monoclonal antibodies for the treatment of dyslipidemias. Fibrinolytic drugs. New potential therapeutic targets
Diseases of the bone and calcium metabolism.
The recombinant parathyroid hormone. Denosumab (RANKL inhibitor). Recombinant Calcitonin
DRUGS FOR THE CENTRAL NERVOUS SYSTEM
Multiple sclerosis therapy. Migraine therapy. Anti-CGRP monoclonal antibodies. Alzheimer's disease, biotech drugs in development
DRUGS FOR THE RESPIRATORY SYSTEM
Biotechnological and innovative drugs in asthma therapy. Anti-IgE, Anti-IL5, Anti-IL5 receptor, Anti-IL4 receptor
New molecules or new targets in development for asthma therapy Anti-IL13 / IL17, Anticalins, Aptamers.
ADVANCED THERAPIES:
Cells as drugs
GENE THERAPY
Definition and concept of gene therapy. Types of gene therapy approaches. Ex vivo gene therapy. In vivo gene therapy.
The tools of gene therapy. Viruses as safe vectors for gene therapy. The clinical applications of gene therapy. CAR-T. In vivo gene therapy drugs
TARGET THERAPY
Signal transducers. Gene mutations in human tumors. Tyrosine kinase inhibitors. Targeted therapy on the Bcr-Abl protein.
Targeted therapy on EGFR1, HER2 / neu. Inhibitors of VEGF and angiogenesis. RAF and MEK kinase inhibitors. PI3K kinase inhibitors
TARGETED DRUGS IN ONCOLOGY
Development of targeted anticancer chemotherapy. Drugs acting on tyrosine kinase receptors.
EPIGENETIC DRUGS
DRUGS FOR ONCOLOGY
Therapeutic strategies. Monoclonal antibody therapies. Active immunotherapy. Checkpoint inhibitors. Clinical information. Cell-mediated therapies. Cytokine therapies. Inhibitors of IL6. Inhibitors of IL1. Inhibitors of IL12 and IL23. Anti-IL17. Inhibitors of surface antigens of B and T lymphocytes
DRUGS FOR THE IMMUNE SYSTEM
Biotechnological drugs for chronic autoimmune inflammatory diseases. Inhibitors of TNFalpha

Module 2 CLINICAL STUDIES METODOLOGY

Course contents

• Introduction to clinical trials: general aspects
• Phase 0 and I clinical trials
• The healthy volunteer in the clinical trial
• Placebo in clinical trials
• Adverse reactions in clinical trials
• Phase II clinical trials
• Phase III clinical trials
• Phase IV clinical trials
• Biomarkers, endpoints and surrogate markers
• Regulatory aspects and experimental studies on generic drugs

Readings/Bibliography

Selected chapters from:Pharmaceutical Biotechnology, Fundamentals and Applications
Crommelin D.J.A., Sindelar R.D., Meibohm B. Eds, Fifth Edition, Springer

Specific scientific articles and PPT slides

Teaching methods

Frontal lessons

Students can interact with the Teacher to ask questions.

Assessment methods

Verification of learning consists in an oral exam, for each module, which aims to verify and evaluate the achievement of the learning objectives.
The student evaluations takes into account the correctness of the answers, the understanding of the principles learned showed by the student. In addition, the level of exposure, also in relation to the previous knowledge necessary for the understanding of the specific exam subject will be considered. The two modules can be given separately.The duration of the oral exam is on average 20-30 minutes. Application on Almaesami

The marks obtained for each module, in proportion to the number of credits, contribute to the final grade of thirty.

Teaching tools

PC, Projector. PowerPoint; the slides used during lessons will be available on the VIRTUALE platform

Office hours

See the website of Patrizia Romualdi

See the website of Gloria Ravegnini