Content

BEC 495/595-301
Chemical Modifications of Protein Therapeutics

Course Description

Biopharmaceuticals are life-changing medicines used for the prevention and treatment of a variety diseases. Therapeutic proteins represent the largest class of biopharmaceuticals and are commonly produced using genetically engineered cells. These therapeutics have many uses, including in enzyme replacement therapy, to treat a variety of cancers, and for the treatment of metabolic disorders. Protein therapeutics can also be chemically modified or enhanced to expand their functionality. For example, therapeutic proteins can be PEGylated (polyethylene glycol attached) to improve the systemic circulation half-life or conjugated to a cytotoxic moiety for targeted treatment of cancer as in the case of antibody drug conjugates (ADC).

This course provides an overview of chemically modified proteins that are currently on the market and the methods that are employed to modify them. It also covers biomanufacturing methods, chemical reactions, analytical characterization techniques, and process optimization necessary to produce modified therapeutic proteins. The course highlights PEGylated proteins and antibody drug conjugates as examples of clinically relevant chemically modified protein therapeutics.

By the end of the course, participants will be able to do the following:

• Identify different types of chemical modifications and benefits of each.
• Explain how conjugation steps are carried out and list the reaction parameters that must be controlled to ensure consistency and quality of the product.
• Discuss the purification steps following modification that are required to remove process- and product-related impurities resulting from the conjugation reaction.
• Identify basic analytical methods used to assess the quantity and quality of the modified protein.
• Evaluate analytical results from a chemical modification reaction.
• Select parameters that optimize conjugation reaction performance.
• Evaluate results from a study to chromatographically separate desired products from impurities.
• Distinguish stochastic and site-selective approaches for chemical modification reactions.
• Assess protein reactive sites and their impact on site-selective approaches.
• Analyze novel chemical modification approaches from relevant literature.

In addition to those outcomes, BEC 595 students will also be able to:

• Evaluate and present a contemporary study developing a chemical modification reaction for protein therapeutics.