Biologics Flashcards
biologics treat mainly?
long term diseases
cancer
arthritis
diabetes
why are biologics harder to manufacture than small molecules?
their complexity and size
___% of the drug market is biologicals
37
TF: biologicals are faster to get onto the market?
why?
true
due to the way they’re produced and tested
what is the main reasons for small drug failure?
‘one drug suits all’ methodology
what can biologics do to diseased tissue functionality?
replace
protein hormones and blood factors
biologics vs small molecule versatility?
replace diseased tissue as well as modify it
biologics are highly ______
therefore?
specific
therefore, no unspecific binding to molecular structures
half life of biologics are usually?
2-3 weeks
what region of mAbs are modified?
CDR region
biologics vs small molecules. immunogenic effects are worse for? why?
biologics
as the immune system can detect it easier than small molecules
what are ADCs?
antibody drug conjugates
a mAbs where there’s cytotoxic drug attached
what are ADCs usually used for?
cancer
what can lipid nanoparticles be used for?
. Instead of producing the antibody and injecting to patient. You carry the mRNA to produce the protein inside the cell and it gets expressed. These are quite complex. Thought they will be used for very specific diseases.
explain the process of producing monoclonal antibodies (mAbs). UPPER BIOPROCESSES
UPPER BIOPROCESSES
immunisation- injected with antigen
Abs are isolated for in vitro hybridoma production
myeloma cells are immobilised cells which are fused with spleen cells= hybridoma capable of unlimited growth
fusion: myeloma cells and isolated splenocytes are fused in the presence of PEG- attracts water causing cell membranes to break and fuse
scale up and wean: scale up clone and wean off the selection agents
expand the clones to produce the desired antibody- using bio reactors
what are used to expand the clones to produce the desired antibody?
bioreactors
what is used to fuse myeloma cells and spleen cells? how?
PEG
Attracts water molecules causing cell membranes to break
forms hybridoma
what happens after the upper bioprocesses?
downstream processes where you mass produce the antibody
why are the mAbs produced in batches?
they have a life span
have cycles which breaks continuous production- people want to change this
what was an issue with using mouse to create human hybridomas?
immunogenic reactions and rapid clearance
why was there rapid clearance when using mice to create human hybridomas?
lack of Fc effector
not recycled as Fc doesn’t bind
how long was mice used to create human hybridomas?
11 years
after using mice what has started to be used more. what does this result in?
recombinant engineering
- chimeric
- humanised
- fully humanised
what are chimeric?
mouse variable region
what are humanised?
mouse antigen binding loops (CDRs)
mAbs therapeutic functions?
complement dependent cytotoxicity
Antibody dependent cell medicated cytotoxicity
conjugates
apoptosis induction
explain CDC (complement dependent cytotoxicity) have a therapeutic effect
antibody will bind to the surface and complement molecules attached- cytotoxicity
explain how conjugates have a therapeutic effect
antibody attaches to antigen
can have toxins attached
explain how apoptosis induction works?
Receptor blockages- ligand therefore cannot bind to receptor, this lack of binding means nothing can penetrate or be produced
explain how Antibody dependent cell medicated cytotoxicity works?
the antibody binds to the antigen on surface, using the fc receptor you get a neutrophil that attaches to the antibody and induces cytotoxicity
what does the glycol receptor on mAbs contribute too?
glycol mediated clearance and tissue distribution
what is the Fc region made from?
how does this give a long half life
ch2 and ch3 fragments
IgG recycling for long half life
the fab region has lots of _____
charges
what is the fab region effected by? what’s it made up of
charge or isoelectric point
Vh and Vr
how are biologics usually administered?
sc or im injections
at high concentrations
absorption of biologics from sc administration?
20-95%- facilitated by the
what is sc absorption facilitated by?
the lymphatic system
sc/ IM rate of absorption?
slow
sc/ IM maximal plasma concentration after how long
1-8 days
how are biologics eliminated?
proteolytic catabolism by lysosomal degradation
target mediated clearance
Fc gamma receptor
how does target mediated elimination pathways work?
involves interaction between a mAb and its pharmacological target, and represents the primary route of antibody clearance- binds when it reaches target and then is cleared by the reticulo-endothelial system. The resulting immune complexes are then cleared from the body through reticulo-endothelial system (RES).
how does proteolytic catabolism by lysosomal degradation work?
your antibody enters the cells, cannot evade the endosome. Amino acids are absorbed into the cells for recycling
what is pharmacodynamics
effects of drug on the body
why are PK/ PD relationships of mAbs unique?
as the pharmacokinetics are markedly influenced by the biology of the target antigen
