Intro Biotechnology Flashcards
How are small molecules made?
-Organic synthesis
-small molecule innovation (alteration of the structure -> such that it acts as an antagonist)
-usually <500 MW, beyond 500 the molecule doesn’t get absorbed well
How are biologics (like antibodies) different from small molecules?
-larger (100x)
-more complex, f.e. alkylation on a small molecule, can occur in the para, ortho, or meta position -> with large biologic molecules it is impossible to predict where the alkylation will occur
-structurally less defined
-Synthesis of biologics is made through living organisms or tissue culture
Differences between small molecules and biologics in terms of their properties?
Small molecules:
-produced by chemical synthesis
-low MW
-well-defined physiochemical properties (pKa, ionization, lipophilicity -> because they have less ionizable groups)
-stable
Biologics
-biotechnologically produced by host cell lines
-high MW
-complex physiochemical properties
-sensitive to heat and shear (aggregation)
Differences between small molecules and biologics in terms of administration?
Small molecules:
-different routes possible
-rapid systemic circulation through blood capillaries
-distribution into any organs/tissues
-often specific toxicity
-nonantigenic
Biologics:
-administered parently
-reach circulation via the lymphatic system (proteolysis can occur)
-distribution only to plasma or extracellular fluid
-receptor-mediated toxicity
-antigenic
Differences between small molecules and biologics in terms of analysis and production
Small molecules:
-completely characterized by analytic methods
-easy to purify
-contamination easy to identify and avoid
-not affected by slight changes in production processes
Biologics:
-difficult to characterize
-hard to purify
-a high possibility of contamination
-susceptible to slide changes in the production processes
What is the volume/cost ratio for Biological drugs?
-low number (2-3%)
-but high costs (40% of money spent)
Why are biological drugs so expensive?
-production cost is similar to small molecules
-target patient population is small -> therefore the price is increased for return on investment
-f.e. Taxol (small molecule) is given to most breast cancer patients, whereas Herceptin is given to only 20% of the patients, bc only 20% have HER2 receptors
-Cetuximab (Erbitux) is only for patients with special conditions, EGFr is overexpressed on the tumor and doesn’t have KRAS and BRA
-high effective -> only given for a few weeks -> span of time needed to cure the disease is short -> less time to get the money back
-rare diseases have small patient numbers
Why are biosimilars not called generics?
-for generics, we have identical structures (formulation might be different -> starch instead of cellulose; in the HPLC you would see a peak at the same place for all generics
-for biologics, we have similar but not identical structures
-> if E.coli is used to harvest the biological product instead of yeast, the biosimilar will be somewhat different -> need to check if it is as effective as the original
What are the orphan diseases and the Orphan Drug Act (1983)?
-orphan diseases: <200,000 patients/disease (e.g. Tourette’s,
Amyotrophic Lateral Sclerosis (ALS), Cystic Fibrosis
(CF), Duchenne Muscular Dystrophy
-Ensures that a company can have the exclusive right on the market for a orphan disease drug for 7 years -> time to get their money back
Example of active immunity:
-Edward Jenner injected closely related cowpox virus into a patient with smallpox -> protection against smallpox
What are the discoveries of Louis Pasteur?
-discovered D and L isomeres
-vaccines for rabies, anthrax, and chicken cholera
-preserving milk, beer, and other products -> Pasteurization
Discoveries of Emile von Behring and Kitasato:
-took toxins of diphtheria-causing bacteria (whooping cough) and injected it into horses -> Antibodies created -> Serum from the horse with the antibodies are isolated and injected into diphtheria patient -> PASSIVE IMMUNIZATION
Discoveries of Banting and Bests
-removed the pancreas of a dog -> the dog became diabetic (bc no insulin production in the pancreas) -> isolated insulin from Langerhans -> injected insulin into the dog -> INSULIN THERAPY
Why is insulin harvested from animals not rejected by the human immune system?
-Because there are similar enough to not stimulate an immune response (one amino acid difference)
-porcine and bovine insulin would produce anti-insulin antibodies over time
How is insulin harvested nowadays?
Discovery of Boyer, Cohen, Berg
-recombinant DNA technique used to insert a gene of interest in an organism’s genome (f.e. coding insulin in bacteria) -> so that it will produce the protein in large quantities -> harvested and used in humans
