Overordnede kursusmål
This course aims to cover an introduction to the chemical
modification of therapeutic proteins. This is an advanced technique
of great importance to the future production of therapeutic
proteins, therefore the modification of these proteins will be
placed in the context of the current biopharmaceutical industry.
Læringsmål
En studerende, der fuldt ud har opfyldt kursets mål, vil kunne:
- Describe chemical modification techniques relevant to protein
therapeutics and their benefits, including acylation, PEGylation,
and antibody-drug conjugation.
- Understand appropriate procedures to perform basic protein
modifications, including reactor types and operation.
- List reaction parameters that must be controlled for successful
modification.
- Describe the purification steps following modification required
to remove residual reaction components and isolate the target,
including process chromatography.
- Understand the approaches to analysis, such that modifications
can be carefully controlled.
- Understand the potential of new methods of chemical
modification, such as enzymatic methods.
- Understand opportunities for new medicines based on these
technologies
- Understand remaining limitations in new chemical-modification
procedures
Kursusindhold
1. Introduction to chemical modification of therapeutic proteins in
the context of drug development, including the benefits of such
modifications. Techniques will include acylation, PEGylation and
antibody-drug conjugation.
2. Processes for the production of chemically modified proteins,
including reactor selection. Background chemistry to include
sufhydryl and amino group chemistry.
3. Downstream processing, including impurity removal and product
isolation, also via process chromatography (hydrophobic
interaction, size exclusion and ion exchange) .
4. Analytical methods to assess reactor and downstream performance,
and ensure adequate control, also via on-line monitoring (SDS-PAGE,
MALDI-TOF and HPLC).
5. Workshop to explore enzymatic methods for chemical modification
of therapeutic proteins, especially antibody-drug conjugation.
6. Report to evaluate new enzymatic methods for chemical
modification of therapeutic proteins.
Litteraturhenvisninger
A variety of research articles. Some examples are given beneath:
• Walsh, G. 2018. Biopharmaceutical benchmarks 2018. Nature
Biotechnol 36(12), 1136-1145.
• Gong, H.H., Ihle, N., Jones, M.T., Kelly, L., Raglione. T.,
Whitlock, S., Zhang, Q., Zheng, J. 2018. Control strategy for small
molecule impurities in antibody-drug conjugates. AAPS PharmSciTech
19(3), 971-977.
• Hutchinson, M.H., Hendricks, R.S., Lin, X.X, Olson, D.A. 2018.
Chapter 40 – process development and manufacturing of antibody-drug
conjugates. Elsevier, pp. 813
Bemærkninger
N/A
Sidst opdateret
02. maj, 2024