Therapeutic Proteins

Aim

The course shall provide the students with knowledge about the development towards using proteins for therapeutic purposes, and how these differ from small-molecule drugs in central aspects of e.g. targets, interaction mechanisms, pharmacodynamics/-kinetics and regulatory demands (New Drug Applications, NDA vs Biologics License Applications, BLA). The course shall also provide insight about the particular structure and stability properties of protein therapeutics, which influences e.g. formulation, administration and immunogenicity. In addition, the course shall give knowledge about structure/function relationships and applications of various therapeutic proteins and how the specificity, activity, pharmacodynamics etc. of such proteins can be improved.

After the course the student should be able to:

· Account for the fundamental differences between small-molecule drugs and therapeutic proteins and how these differences influences the applicability of therapeutic proteins.

· Classify various therapeutic proteins based on their mode of action.

· Describe gene technology based and chemical methods of improving the applicability of therapeutic proteins.

· Reflect over the structure/function relationships of therapeutic proteins.

· Describe some central diseases molecular pathology and account for how proteins are used to cure or counteract such disease states.

Content

A historical perspective of early purified protein drugs, to contemporary recombinantly produced therapeutic proteins. Classification of therapeutic proteins based on their mode of action. Why and how therapeutic proteins can be genetically modified for improved properties (binding strength, activity, stability, de-immunization, etc.). Physiological considerations in terms of administration, pharmacodynamics/-kinetics (ADME), safety aspects and immunogenicity, partly in comparison to small-molecule drugs. Methods to chemically modify proteins for altered physiological properties.

· An emphasis will be on human antibody structure and function, and humanized antibodies from other species.

· How antibody fragments can be used in combinations (in e.g. bispecific antibodies, antibody-drug conjugates, BiTE, etc.).

· Other binding proteins as complement to antibodies.

· The use of enzymes as therapeutic proteins.

· Other types of protein therapeutics.

· Clinical development of therapeutic proteins and examples of the molecular pathology of diseases, and how antibody-based, enzymatic or other therapeutic proteins acts and are used in such cases.