Biotechnology Flashcards
(25 cards)
Define biologics
Any virus, therapeutic serum, toxin, antitoxin, used in the prevention, treatment or cure of diseases in humans
How are small molecules developed?
Through high throughput SCREENING.
How are biologics developed? Steps?
CONSTRUCT instead of screen
1.choose a target
2. Construct biologic candidates
3. Experimental testing
4. Clinical trials
Development, Validation, Manufacture, Formulation
When is Q5D and Q5E quality control used
Q5D
- used when deriving new substrates for biotechnology purposes
Q5E
- used when making biosimilars
What are the 3 enzymatic regulatory activity?
- Replacement of deficient/abnormal proteins
- Augment existing pathways
- Novel function or activity
enzymatic regulatory activity:
What do we use replacement of deficient/abnormal proteins for? (3)
a. hormone deficiencies:
- insulin, genotropic for (hGH deficiencies)
b. Hemostasis, thrombosis;
- clotting factors (8, 7a)
c. Gi disorders
- lactaid
- pancreatic enzymes
enzymatic regulatory activity:
How do we augment existing pathways?
a. Anemia
- augment the erythropoiesis pathway
b. Immunoregulation:
- produce WBCs, platelets, and modulate immune response
enzymatic regulatory activity
How do we use novel function/activity?
a. Degrade existing molecules
- disrupt neuromuscular junction, lung mucus viscosity reduction
b. hemostasis, thrombosis
- produce anticoagulants
In special targeting activity:
How do we interfere with molecule/organism
a. Prevent infectious diseases
- Stop HIV entry
B. Cancer
- bind surface receptors of cancer cells
c. Immunoregulation
- Bind TNF, prevent inflammatory cascade
In special targeting activity:
How do we deliver molecules
Cancer
- deliver cytotoxic agents to cancer cells
What type of cells produce antibodies?
B cells
What is the structure of antibodies? Fc vs Fab
Large Y shape
4 protein chains connected by disulfide bonds
Fc (crystallisable) = constant region
Fab (antigen binding) = variable region
How do hypervariable regions in FAB work?
Target specific parts of antigens in a “lock and key”
Define polyclonal antibodies
generated from an Immune response to an antigen
- Different B cell receptors produce a range of antibodies
- multiple lineages of B cells = polyclonal antibodies
Define monoclonal antibodies
single line of B cells, selected to produce the SAME antibodies (-mab)
In humanization of antibodies define
Chimeric
Humanized
Human
FC region from mice leads to shorter half life, less immune response, inefficient effect
- Chimeric: Human FC + mouse-derived FAB (variable) region -OMAB
- Bad for half life, immune response
- Humanized: human Ab + mouse CDR -IMAB
- Human: no mouse genetic sequences -ZUMAB
Define antibody drug conjugates
Characterisitics?
Small molecule is attached to mAB to make use of its specificity
- can be cleavable, non-cleavable
- Attachment site can be Fc or FAB
What do the following excipients do to aid stability/delivery
Salts
Surfactants
Buffers
Cyclodesxtrins
Polyalcohols
PEG
Salts
- decrease denaturation, aggregation
Surfactants
- prevent adsorption of proteins
Buffers
- maintenance of pH
Cyclodesxtrins
- decrease aggregation
Polyalcohols
- stabilize, maintain isotonicity
PEG: INCREASE HALF LIFE OF PROTEINS DRUGS
Describe lyophilization. Issue?
“freeze drying”
- remove water from product –> form dry powder. Good for long-term storage
Issue: protein aggregation
- stabilizers (sucrose)
- Surfactants
- DO NOT SHAKE
What is Q5C
Define potency and purity in this
Q5C
- stability testing of biotechnological/biological products
Potency: ability of a product to achieve its intended effect
Purity: relative, dependant on the product
Which protein takes the longest to develop in vaccines? quickest?
Longest: protein VLP
quickest: mRNA
Define antisense gene therapy
Antisense RNA binds to sense sequence to block protein synthesis
Define cell therapy
Vivo cell therapy?
Allogenic cell therapy?
Using THE WHOLE CELL to bring effect
* Blood transfusions, bone marrow transplants, stem cells for regenerative medicine
Ex vivo cell therapy: modifying the patients OWN cells but OUTSIDE the body
Allogenic cell therapy: using cells from a DONOR
Differentiate between somatic cells and germline cells in genome editing
Changes to somatic cells are not passed on to offspring,
Changes to germline cells are passed to offspring
