BTB Flashcards
Biologics
The manufacture of biomacromolecular drugs.
What are biomacromolecular drugs?
Large biological molecules that have therapeutic effects. Eg insulin, erythropoietin, monoclonal antibody IgG1. Other biologics: siRNA, Crispr-Cas9 gene editing technologies, plasmid based gene delivery approaches.
Advantages of biologics large Mw>2kD
Large surface area good for binding exquisite specifically.
Drawbacks: Not accessible by chemical synthesis not memebrane permeable antigenic.
Alternative Delivery routes needed.
Large complex and each biologics can is manufactured in a unique living cell line similar but not identical copies can be made. Difficult to fully characterise, more sensitive than small molecule medicines to handling and storage conditions. Higher potential always need to be tested during development.
250 bio pharmaceuticals on the market. Eg adenovirus based gene therapy, Ebola vaccine, antibody-drug conjugates & monoclonal antibody.
Advantages of small molecules eg Aspirin : accessible by chemical synthesis membrane permeable. Simple well defined, predictable chemical process so identical copies can be made. Easy to characterise, usually unstable and usually unpredictable.
How are biomacromolecular drugs made?
Unlike small molecule drugs, biologics can’t be synthesised. Instead we must exploit living machinery to do the jobs for us:
We need to conceive cells to make the protein we want eg Insulin.
Insulin is a small peptide, consists of 2 peptide chains:
A chain:21 residues
B chain: 30 residues
Chains linked by disluphide bridges
Human insulin: 5808 Da
First line for type I DM
Last resort for type II DM
