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Biotechnology
Biotechnology
126
Other
Graduate
01/10/2014

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Term
What are the 3 advantages of using biotechnology?
Definition
1. makes product production possible
2. cost effective
3. safer
Term
What safety concerns exist with protein products from animal sources? human source?
Definition
Animal source - allergic reaction possible

Human source - infection risk (HIV, hepatitis)
Term
Why are protein drugs NOT given by mouth?
Definition
They are labile and degrade in the GI tract. Rapid metabolism by the liver and rapid eliminated by the kidney.
Term
What effect does Large size protein drugs have on administration?
Definition
They are poorly permeable to Passive transport and are given by injection.
Term
What effect does overheating have on protein drugs?
Definition
Overheating cause a Chemical change of protein denaturation that is irreversible.
Term
What effect does Freezing have on protein drugs?
Definition
Freezing results in a Physical change of aggregation which is generally irreversible.
Term
What are the three steps of lyophilization?
Definition
1. Freezing
2. Primary Drying
3. Secondary Drying
Term
What is the site of action for mucosal immunity?
Definition
Tissue in the intestinal walls; only a fraction of antigen is needed to elicit an immune reaction
Term
Why does a vaccine tattoo induce a better immune response?
Definition
Better DNA uptake by non-antigen and antigen presenting cells. The duration of expression is longer and there is induced trauma from the tattoo process.
Term
Which excipient in a protein formulation is responsible for: Decrease aggregation and interfacial tension?
Definition
Solubility enhancer
Term
Which excipient in a protein formulation is responsible for: decrease adsorption of protein to interfaces
Definition
Anti-adsorption agent
Term
Which excipient in a protein formulation is responsible for: stabilize pH to improve physical and chemical stability of the protein?
Definition
Buffer system
Term
Which excipient in a protein formulation is responsible for: reduce oxidation of amino acids?
Definition
Antioxidant
Term
Which excipient in a protein formulation is responsible for: use if metal ion does Not play a integral role in protein function
Definition
Chelating agent
Term
Which excipient in a protein formulation is responsible for: protections of protein during freezing?
Definition
Lyoprotectant
Term
A protein drug has a small Vd, how does it obtain adequate concentration in the target organ?
Definition
Use of receptor-mediated uptake.
Term
How can you determine if a drug is has been distributed to the target organ?
Definition
Biodistribution studies; using radio-labeled compounds measuring intensity and duration.
Term
To increase the half-life of proteins; what are the 2 types of chemical modifications?
Definition
1. PEGylation
2. Glycosylation (prosthetic sugar groups)
Term
What effect do neutralizing antibodies have on the body?
Definition
They reduce the amount of drug that reaches and binds to the site of action.
They can cause protein precipitation and aggregation at the injection site.
Term
What are the 3 steps in recombinant DNA technology?
Definition
1. Cutting
2. Pasting
3. Copying
Term
Why is PCR an improvement over Cohen-Boyer method?
Definition
PCR allows for selective amplify of DNA in a few hours without involving bacteria.
Cohen-Boyer was cumbersome and slow method.
Term
What are the 3 steps in PCR and how do they work?
Definition
1. Denaturation (heat 95C, strands separate)
2. Annealing (ADD primers, -55C)
3. Extension (ADD DNA polymerase, 75C)
Term
DNA polymerase had a problem in the early days of PCR, what was it and how was it resolved?
Definition
DNA polymerase was destroyed at 95C, so after each cycle it had to be added and was expensive.
Taq polymerase from hot springs is now used because it is stable at 95C
Term
What are the advantages of bacterial expression systems in protein production?
Definition
1. Lack ability for post-translational modifications.
2. Cannot accomodate very large proteins
3. higher replication rate
4. cheaper production method.
Term
When would the use of yeast or mammalian cell lines be preferred?
Definition
If you wanted to allow post-translational modifications.
Term
What is bio-pharming?
Definition
Growing proteins inside plants and animals; then extracting the proteins from the milk.
Term
What is glycosylation and what is its advantage?
Definition
Glycosylation is the most common post-translational modification involving the attachment of a polysaccaride chain to a specific amino acid. Such that N-linked correlates to Asparagine and O-linked correlates to Serine or Threonine. This allows for increase stability and increased potency.
Term
What is PEGlation and its advantages?
Definition
Peglation is a post-translation modification where a polyethylene glycol unit is conjugated to a protein. This changes the immune response, resulting in an increase half-life and less frequent dosing.
Term
Trangenic glow in the dark mice are used for what purpose?
Definition
Use to trace spread of cancer or infection. They could speed up the drug approval process and be used in gene therapies.
Term
What is a knockout animal and its benefits?
Definition
A knockout is when an endogenous gene is inactivated by replacing it with a null allele.
The benefit is its use to study genetic disease and determine the function of a specific gene.
Term
What is site-directed mutagenesis?
Definition
It a point mutation that allows for a specific alternation of an amino acid sequence to create a new chemical entity
Term
What is the subpart E of the Accelerated drug development?
Definition
Allows for expedited development, evaluation, and marking of new drug therapies for drugs to treat life-threatening or severely debilitating illnesses.
Term
What two types of approvals are allowed under Subpart E?
Definition
1. R- restriced - approved with restriction to assure safe use.
2. S - surrogate - approved base on a surrogate endpoint.
Term
What was the Tysabri controversy?
Definition
Tysabri was approved after 1 yr and 2 trials. PML occured in patients taking it with avonex. Manufacturer withdrew, then markets again with risk-minimization plan.
Term
What is the Orphan Drug Act?
Definition
It was developed to give incentives to drug companies to develop products for treating rare diseases.
Term
What are the 3 interferon products approved under Orphan drug Act?
Definition
1.Betaseron (beta-1b) - orphan staus prior to approval
2. Avonex (beta-1a) - significantly better safety profile than betaseron
3. Rebif (beta-1b) superiority requirement over avonex.
Term
What is a patent and what 3 criteria is needed?
Definition
Patent - contract between inventor and the public.
1. useful 2. novel 3. non-obvious
Term
Diamond v. Chakrabarty at an importance from a patent standpoint, what was it?
Definition
Patent on genetic material in a microorganism.
Proved it was useful and novel.
Term
What is the harvard mouse, who can get it, and canada's opinion on it?
Definition
Harvard mouse is a genetically engineered mouse injected with a cancer gene.
One may pay a licensing fee for the mouse or the technology to produce the mouse.
Canada states; animals do not quality as inventions.
Term
What is a trade secret, how does it differ from a patent?
Definition
A trade secret proscribes misappropriation of proprietary information.; it fills in the missing gaps in protection of intellectual property.
Term
What does biosimilar mean?
Definition
Biosimilar - independently developed medicinal product intended to have same action as the innovator and to treat the same disease.
Term
How does a biosimilar product differ from the inovator?
Definition
No 2 cell lines developed Independently can be considered identical. There could be a difference in the side effects.
Term
What is a follow-on protein?
Definition
Simple protein, biopharmaceutical approved or on track for approval.
Term
Why is there an absence of complex generic biotech products on the market?
Definition
Manfacturing process is highly specific for product standards, tests, assays and there is a potential for immunogenic response.
Term
The patient Protection and Affordable Care Act give exclusivity for innovator products for how many years?
Definition
12 years
Term
How many years of exclusivity for innovator products would be given with Obama deficit reduction plan?
Definition
7 years
Term
What are the reasons the House members opposed the new change of exclusivity years?
Definition
1. undermine the health care reform legislature.
2. US biotechology companies would move overseas
3. FDA would have to deal with more applications than planned for.
Term
Why would a company prefer to submit a drug through BLA pathway instead of biosimilar pathway?
Definition
1. Biosimilarity present with uncertainty in timing and cost
2. Sales and market infrastructure to market a new molecule.
3. Company want to jump on biosimilar competitors
4. Market drug as differentiated, improve molecule
Term
How are therapeutic, embryo, and reproductive cloning differ and similar to each other?
Definition
Therapeutic = sick people; cells/organ replacement
Embryo = produce twin animals
Reproductive = duplicate animal.
All make a genetically identical animal.
Term
What type of clone was Dolly?
Definition
Reproductive clone
Term
What is a telomere and how was dolly affected?
Definition
Telomere is the DNA sequence on the end of the chromosomes. Dolly's telomeres were 40% shorter than expected for her age.
Term
What extinct species has been clone?
What the clone to die?
Plan to reincarnate the species is?
Definition
1. Bucardo mountain goat
2. Physical defect in the lungs
3. Plan to make several clones and reestablish species
Term
What are the advantages of cloning endangered and extinct species?
Definition
1. preserve and propagate the species that reproduce poorly in zoos.
2. introduce genes back into the gene pool
3. give time for habitat to be restored.
Term
What are the advantages of cloning endangered and extinct species?
Definition
1. preserve and propagate the species that reproduce poorly in zoos.
2. introduce genes back into the gene pool
3. give time for habitat to be restored.
Term
What challenges need to be overcome when cloning endangered and extinct species?
Definition
Only X chromosome; so need a Y chromosome from a closely related species.
DNA doesn't last forever
Term
What does hair from wooly mammoth yield more intact hair than from the animals' bones?
Definition
The DNA inside the hair shaft is protected by a plastic-like hair.
Term
Why is it difficult to obtain DNA from wooly mammoth and tasmanian tiger specimens?
Definition
DNA is degraded at the temperature of melting ice and snow.
Term
What procedure might work to reincarnate the wooly mammoth?
Definition
Converting tissue cells into stem cells.
Using coax cells to develop sperm and egg for in vitro fertilization.
Term
Why does xenotransplantation often result in transplant rejection?
Definition
Animals have different protein coats on the cell surface.
Term
Why are double-knockout pigs of medical use?
Definition
The size of the heart, pig anatomy, and blood pressure are similar to humans; they also lack the alpha gal gene so there is no acute reaction.
Term
What are the problems and solutions for transgenic pigs?
Definition
Problem is a long term attack by immune system that leads to rejection.
Solution is to add three more genes
Term
What are 2 reasons why sheep with genetic lung defects are used for cystic fibrosis?
Definition
1. similar to human lungs
2. sheep live much longer than mice, so can study over time.
Term
Why did the first cloned cat, not physically resemble the cat it was cloned from?
Definition
It was due to X-inactivation.
Term
What is the advantage of cloning a gelding? Is this allowed by the Jockey Club?
Definition
Gelding cloning advantage is sterile.
Jockey club forbids cloning of thoroughbred race horses; monetary implications.
Term
What is the advantage of cloning in breeding stock livestock?
Definition
Multiply genetically superior or highly productive animals.
No labeling or tracking is required.
Term
Why does cloning lead to increased genetic diversity in endangered animals while this is not true of livestock animals?
Definition
Microscopic shifts activate some traits; but the offspring of livestock are eaten and cannot pass on the activated traits.
Term
This is the ability to go through numerous cycles of cell division maintaining undifferentiated state.
Definition
Self-renewal
Term
This potency allows for the ability to make any organ or tissue.
Definition
Totipotent
Term
This potency allows for nearly all cell types.
Definition
Pluripotent
Term
This potency allows for closely related family cells.
Definition
Multipotent
Term
This potency allows for few cells types.
Definition
Oligopotent
Term
This potency allows for only production of their own cell type.
Definition
Unipotent
Term
This allows a stem cell to be capable of becoming specialized not originally associated with its germ type.
Definition
Plasticity
Term
This is the ability of a cell of one tissue to switch into a cell type characteristic of another tissue
Definition
Transdifferentiation
Term
Who and when were the first human embryonic stem cells created?
Definition
1998 by James Thomson
Term
Which stem cell type is immortal?
Definition
Embryonic
Term
Which stem cell types are pluripotent?
Definition
Embryonic
MUSE cells
Adult epithelial cells reprogrammed.
Term
Which stem cell types are multipotent?
Definition
Fetal
Adult
Amniotic
Cord blood
Term
Why are pluripotent stem cells desired?
Definition
They can develop into any cell type.
Offer insight into human development.
Drug testing
Artificial immune system
Term
What are multipotent stem cells have good potential for cell transplantation; when are they inadequate?
Definition
1. no risk of rejection
2. genetic defect is still present
Term
Adult stem cells are multipotent when?
Definition
Stem cells from bone marrow can differentiate into blood cells and muscle tissue.
Term
What does MUSE stand for?
Source derived from?
Importance is?
Definition
1. Multi-lineage differentiating stress enduring cells.
2. reside in mesenchymal tissue
3. non-tumorigenic; low telomerase activity
Term
In the Rio/Houston heart stem cell trial, What improvements occurred?
Definition
After 2 months; fewer heart failure/angina symptoms and increased ability to pump blood.
After 4 months; stable cardiac pumping function and no irregular heart rhythms
Term
Why is parkinson's disease an effective candidate for stem cell therapy?
Definition
The nerves do not need rewired; just need to get the stem cells into the brain.
Term
What are the 3 main risks of stem cell therapy?
Definition
1. immune rejection
2. development of benign tumors
3. gene shuffling
Term
What treatment does Vet Stem perform?
Definition
Repair shredded ligaments in horses
Term
Why is the conversion of adult epithelial cells into embryonic stem cells controversial?
Definition
The cloning techinque requires the use of human eggs which may lead to coercion of women into donation and fears it may lead to human cloning.
Term
What FDA approved trial is currently ongoing in stem cell research?
Definition
ACT: Advanced cell technology.
Use hES cells for age-related macular degeneration.
Term
What are the results from the diabetes; Chinese cord blood cell trial?
Definition
Improved c-peptide lvel, A1c levels, lower amounts of insulin needed.
Term
What are the results from the ALS; neuralstem trial?
Definition
Substantial slowing of muscle degeneration
Term
What are the results from the spinal cord injury; StemCells trial?
Definition
Gains in sensory function persisting 112 months after transplant.
Term
What is the Dickey Amendment?
Definition
Prohibited Federally appropriated funds for research where human embryos are either created or destroyed.
NIH may give funding to lines already in existence.
Term
What problems existed in the available stem cell lines following 2001 legislature?
Definition
1. most were grown in culture containing mouse cells.
2. stem cell lines wear out over time
Term
What effect did the 2001 legislature have on the state legislature over stem cell research?
Definition
It did not prevent the states from adopting their own laws.
IL - $10 million in tax money for stem cell research.
Term
Obama executive order to remove some restrictions and Omnibus Appropriations act of 2009 have allowed what to researchers?
Definition
Cannot create new cell line with federal money.
Can get federal funding using private or state-level funding created lines
Term
What modification leads to the hypoallergenic nature of Allerca cats and dogs?
Definition
Silence of the gene that produces the Fel d 1 glycoprotein.
Term
What precautions have been taken by Allerca to prevent breeders from selling non-hypoallergenic animals?
Definition
Allerca sells them neutered or pre-spayed
Term
Discuss Golden Rice; biopharm.
Definition
Beta-carotene from daffodil gene.
For Vitamin A deficiency
Large amounts of rice consumption needed for effect.
Term
Discuss Quest Cigarettes; Biopharm.
Definition
GMO tobacco; discontinued due to lack of demand.
Cross-pollination lawsuit with Philip Morris.
Term
Discuss Rice containing human genes; biopharm.
Definition
Lactoferrin, human albumin. Cheap production of proteins to help children recover faster from severe diarrhea.
Anheuser-Busch threatened to boycott all rice grown.
Difficult to control the dose.
Term
Discuss the safflower seed containing insulin or ApoAl.
Definition
Improved cost and scale up over current production methods.
Term
Discuss the carrot cells containing taliglucerase alfa
Definition
Use to treat gaucher's disease; more robust and less expensive.
Term
What are the potential advantages of edible vaccines?
Definition
Use in developing countries lacking infrastructure. Also potential for mucosal immunity.
Term
What are the challenges with edible vaccines?
Definition
Dosage, plants vary in size, must consume raw.
Term
What are the advantages of a tomato or banana model over a potato?
Definition
Tomato can produce larger amounts of vaccine.
Banana do not produce seeds, tastes better, infants can eat.
Potato had to eat lots of raw.
Term
What is the difference in protein production in bioreactors and transgenic animals?
Definition
Bioreactors produce proteins at Low concentration while transgenic animals produce proteins at High concentrations.
Term
What is ATryn, which animal model, and approval status?
Definition
Antithrombin III, transgenic goat, 2009 FDA approved.
Term
What is the Transchromo cow and what are the current hurdles?
Definition
Cow that produces polyclonal antibodies
Hurdles include large chromosome sequence to transfer, difficult to grow cells from livestock for extended periods.
Term
What is the Enviro-Pig and its advantages?
Definition
Pig that produces phytase enzymes in salivary glands.
Advantages: excretes 60% less phosphate in manure, use all phosphorus in diet, utilize trace minerals, proteins, and starch more efficiently.
Term
Why was the Beltsville pig an example of failed biopharming?
Definition
It grew fast but have many problems such as arthritis, lameness, mammary development in males, bug-eyed, and bad publicity
Term
What protein does the spider goat produce and what is its potential use?
Definition
Spider silk protein for use in body armour, ropes, and nano-scale fibers.
Term
What are the overall advantages of biopharming process?
Definition
1.Cheaper than drugs produced in mammalian cells.
2. do not need to extract drug from the plant
3. do not need to purify.
Term
What are the disadvantages of biopharming?
Definition
1. Drugs end up in food supply
2. insects eat drug-containing products
3. drugs leak into the soil
4. eating proper dose impractical
Term
What is an immunoglobulin molecule with recognition site for a particular antigen?
Definition
Monoclonal antibody
Term
What does HAMA, HACA, HAHA stand for?
Definition
HAMA (human antimouse antibody response)
HACA (human antichimeric antibody)
HAHA (human antihuman antibody)
Term
This is a component of Fab responsible for antigen binding.
Definition
Fv
Term
This component of Fab is most responsible for antigen recognition site.
Definition
CDR
Term
This fragment mediates complement-induce cell lysis and antibody-dependent cellular functions.
Definition
Fc
Term
What are the 4 components of monoclonal antibody nomenclature?
Definition
1. Prefix - differentiate from others
2. Substem A - target organ/disease state
3. Substem B - species of origin
4. Suffix - mab for immunoglobulin, cept- fusion protein.
Term
What are the substem B designations for mouse, chimeric, humanized, human antibodies
Definition
Mouse - o
Chimeric - xi
Humanized - zu
Human antibody - u
Term
Why are antibody fragments better than intact antibodies at penetration of tissues?
Definition
Small size so easier to absorb/pentrate.
Term
What is the half life of monoclonal antibodies compared to small molecule drugs? compared to antibody fragments?
Definition
MaB- longer half-life; unless antibody fragments are pegylated.
Term
How do the the half-lives of murine, chimeric, and humanized MaB compare?
Definition
Murine < Chimeric < humanized
1-2 days < 4-9.5 days < 3 weeks.
Term
How to the adverse effects of MaB compare to small molecule drugs?
Definition
MaB have less off-target effects and a favorable side effect profile.
Term
In a non-allergic infusion reaction what are the antibodies reacting with?
Definition
T-cell or CD-20 receptors.
First few doses; mild flu-like symptoms.
Cytokine release syndrome.
Term
In allergic infusion reaction is reacting with the foreign proteins?
Definition
IgE
Effects most body systems, quick;delay 10-12hrs.
Type 1 hypersensitivity.
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