week 9 Flashcards
biologics (biological products, biopharmaceuticals)
- created by living cells/organism, derived from a variety of natural sources
- medical products used to treat/cure diseases/medical conditions, prevent diseases, diagnose diseases
- may be composed of protein, nucleic acids/sugars, or combination, living entities such as cells and tissues
source material for biologics
- mammalian cell-culture
- mice
- humans
- bacteria
- avian cell-culture
- transgenics
- yeast
- plant cell-culture
- insect cell-culture
types of biologics
- blood derivatives
- whole blood
- blood components
- proteins
- human tissues
- vaccines
- allergenic extracts
- cellular and gene therapies
- xenotransplantation products
small molecule drugs vs. biologics
SMD
- chemical synthesis
- generally low molecular weight
- known structures that are well-characterized
- fewer critical process steps
- generally oral solids
- usually retain pharmacies
- innovator (new target)
- generic
biologics
- made with/from living cells organisms
- generally high molecular weight, large complex molecules or mixture of molecules
- complex mixtures that are less easily characterized
- many critical process steps
- often injected or infused
- oftern by doctors/hospitals
- innovator
- biosimilars
biologics- peptides
- chains of amino acods
- insulin
- GLP-1 agonist peptides
stem cell therapy perkinson’s phase 1 clinical trials
- designed to replace dopamine producing neurons lost in parkinson’s disease
- Dopaminergic neuron precursors are derived from human embryonic stem cells
- in surgical procedures, neuron precursors are implanted into brain
- when implanted they have potential to reform neural networks that have been severely affected by parkinsons and restore motor and non-motor functions
what is an antibody
- proteins that play a pivotal role in our immunity against pathogens
- out bodies generate antibodies that specifically bind to particular structures called antigens present on these pathogens
- once bound antibodies neutralize the pathogen directly or attract other parts of the immune system to eliminate pathogen
- certain antigens are found on diseased human cells and therefore antibodies may also be used to treat diseases such as cancer or inflammation
antibody structure
- Y shaped proteins
- consists of variable region and constant region
variable region
- recognizes and binds to antigen
- each antibody-producing cell in the body makes antibodies with a specific variable region
constant region
- determines the mechanism used to destroy the antigen
- antibodies are divided into 5 major classes based on their constant region structure and immune function
polyclonal antibodies
- complex mixture of antibodies produced by many different antibody-producing cells
- each individual antibody in the mixture recognizes and binds to different areas in the antigen
monoclonal antibodies (mAbs)
- identicle antibodies derived from a single antibody-producing cell (or clones of cell)
- each mAb will only recognize and bind to specific on the antigen
- preperations of mAbs are produced in a laboratory
Antibody engineering
- mouse mAbs have a protein sequence that differ from naturally occurring human antibodies
- when administered to humans, mouse mAbs may be recognized as foreign by the immune system (causing dangerous immune reactions, resulting in destruction/removal of mouse mAbs)
- recombinant DNA technology can be used to modify mouse mAbs, enhancing their resemblance to human antibodies and reducing the risk of adverse immune reactions (recombinant DNA is made by combining two or more sources)
alpha-neurotoxins of 3-finger-toxins
- target of the snake toxin: human muscle-type nicotinic acetylcholine receptor (nAChR) at neuromuscular junctions
- paralysis and death by asphyxiation
synthetic antibodies to treat snakebite
- broadly-neutralizing human antibodies directed against snake peptide (3-finger long chain family of snake peptides)
summary of results:
- data showed that single monoclonal antibody can provide broad pre-clinical protection against 3FT-L venoms, exhibits superior efficacy compared to comercialy available anti venom
- structurally characterized by synthetic antibodies indicates that they mimic interactions between venom toxin and human nicotinic acetylcholine
issues with biologics
- complexity
- high specificity
- selectivity often > small molecules due to large surface
- toxicity generally < small molecules due to selectivity
- potential for immunotoxicity
- monoclonal antibodies - long half-life
- high cost
Specialty drug
- high cost
- requires specialized handling, administration and/or monitering
- used to treat complex/rare diseases
- often a biologic, rather than a traditional small molecule drug
