Biologics

Question 1

How are monoclonal antibody preparations made?

Answer 1

1. Inject antigen to stimulate antibody production in rats
2. Grow (immune) tumour cells in tissue culture
3. Each immune cell will to fuse with with one antibody– forms hybridomas

Question 2

Explain the details of the original technology developed by Medicago for quick and mass production of antibodies.

Answer 2

• has a greenhouse + extraction and purification unit that can produce more than 10 mil doses of vaccines per month
  1. Light chain and Heavy chain of DNA is collected and inserted into a cloning vector
  2. Insert cloning vector in plant leaves (vac infiltration) –> most of these cells will not contain the DNA to produce that specific antibody
  3. expression of genes and production of antibodies within plant cells

Question 3

Different steps and intermolecular interactions involved in the formation of an antigen-antibody complex.

Answer 3

• Antigen = epitope –> binds to antibody = Paratope (4-10 amino acids)
• interaction only requires 2 amino acids
  1. Attracted by long range forces (ionic/hydrophobic bonds)
  2. Short range structural fit (van der waals and some ionic interaction)
  3. Affinity depends on goodness of fit between the 2 surfaces and total contact area

Question 4

Monoclonal antibody

Answer 4

• an antibody produced by a single clone of cells or cell line and consisting of identical antibody molecules
• one antibody for one antigen

Question 5

Polyclonal antibody

Answer 5

• They are a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope
• several antibodies on one anitgen

Question 6

Biosimilars in biologics/biomolecules

Answer 6

• Product has to be HIGHLY SIMILAR to an FDA approved reference biomolecule
• There has to be no clinicalyly meaningful differences in terms of safety and effectiveness from ref drug.
• NEED some research to assure equivalence but no need to start from scratch

Question 7

Biomolecules/Biologics

Answer 7

• Large structures (than conventional drugs) that are stereospecific
• ex. DNA or proteins (larger cells or organs)
• AA sequence has to be altered to make it more similar to what naturally happens in humans

Question 8

Biologics… here to stay?

Answer 8

• Conventional drugs are starting to decline as biomolecules increase but biologics are more expensive

Question 9

Biologics (Production, structure, prep, stability, generic)

Answer 9

1. Produced in living cells
2. Large complex structure
3. need to do several tests (multiple isoforms can exist)
4. Stability of product can be impacted very easily (various factors - heat etc) + can change over time as cell lines evolve
5. Difficult to replicate using current technology

Question 10

Small-molecule drugs (Production, structure, prep, stability, generic)

Answer 10

1. Produced using standard chemical reactions
2. Simple, small structure
3. Well defined and prepared + can be purified quite easily
4. Stable under most conditions
5. Easy for companies to replicate

Question 11

Bioequivalence in conventional drugs

Answer 11

• 90% interval to fall between 80-125%
• no need to repeat clinical studies (only PK is needed)
• FDA only allows 20% variation
• Generic brands don’t need to do clinical trials or prove that it works

Question 12

Possible resistance to antibody drugs?

Answer 12

• TNF (tumour necrotic factor) triggers inflammation needs to be inhibited by anti-TNF antibodies