biologics Flashcards
what is the importance of biologics?
- revoluntionsed treatment for life threatening and rare disease
- hard to manufacture
- high specific binding to modify or block function to target
what are the different types of biologics?
- Peptides – 50 amino acids insulin is just on this limit.
- Protein fragments
- mAbs – major part of monoclonal antibodies.
- ADCs – antibody drug conjugates a mAb with cytotoxic drug attached to it, conveyed through the cells and then released, mainly used in cancer
- Viruses
- Vaccines
- New modalities such as LNP – lipid nanoparticles. Instead of producing antibody you carry the micro RNA to carry into the target cell
what is the bioprocess?
immunisation preparation of myeloma cells fusion clone screening and picking functional characterisation scale up and wean expansion
what is the advantage of biologics over small molecules?
- Versatility: replaced diseased tissue as well as modify
- Unspecific binding to molecular structures other than molecular target can cause toxicity: not applicable with therapeutic proteins only for the small molecules
- Blood levels of drug and duration of action in man not appropriate (e.g. elimination half life too long/too short; critical metabolite spectrum) – not applicable to mAbs
- Less frequent dosing – long circulation times compared to small molecules drugs (week vs hours), this can be a benefit. This is a reason why you have s/c and i/m for proteins so you can slowly have a steady release of the proteins.
- Different structures for each indication – not applicable to the similarly structured monoclonal antibodies
- Inappropriate molecular target applies to both
- Immunogenic effects – higher risk for therapeutic proteins, addressed by Humanisation of proteins.
what is the human antibody development?
started with mouse as creating human hybridomas was difficult (immunological reactions and rapid clearance)
then we moved to recombinant engineering over the last few decades
- chimeric mouse variable region
- humanised mouse antigigen binding loops
- fully human antibodies
what is the function of mAbs?
- complement dependent cytotoxicity
- conjugates
- apoptosis induction
- antibody dependent cell mediated cytotoxicity
how are mAbs absorbed?
- admin i/v or s/c or i/m
- for s/c absorption is variable 20-95% facilated by the lymph system
- rate of absorption is slow 1-8 days of sc or im injection
how are mAbs eliminated?
this process is not clearly understood
- eliminated by proteolytic catabolism by lysosomal digestion
- other mechanisms include target mediated clearance
- this involves a interaction between mAb and its pharmacological taregt
what are they pharmacodynamics of the mAbs?
- PD refers to pharmacological effects elicited by a drug in the body.
- Differs from small drugs.
- PK/PD relationship of mAbs are unique due to mAB pK are markedly influenced by the biology of the target antigen (TMDD)
how big is aspirin?
around 2000 daltons - very small
how big are proteins?
19000 - much bigger then aspirin
what makes up most of mAbs?
IgG - which is a type of antibody
what is a myeloma cell?
Myeloma is a type of cancer that develops from cells in the bone marrow called plasma cells
what happens during the process of fusion?
fusion is the process by which uninuclear cells combine to form a multinuclear cell.
whatc is complement dependetn cytotoxicity?
antibody will bind to the surface and complement molecules that are attached to it, so this will induce cytotoxicity
