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
|
|
Term
| Which excipient in a protein formulation is responsible for: decrease adsorption of protein to interfaces |
|
Definition
|
|
Term
| Which excipient in a protein formulation is responsible for: stabilize pH to improve physical and chemical stability of the protein? |
|
Definition
|
|
Term
| Which excipient in a protein formulation is responsible for: reduce oxidation of amino acids? |
|
Definition
|
|
Term
| Which excipient in a protein formulation is responsible for: use if metal ion does Not play a integral role in protein function |
|
Definition
|
|
Term
| Which excipient in a protein formulation is responsible for: protections of protein during freezing? |
|
Definition
|
|
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
|
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
|
|
Term
| How many years of exclusivity for innovator products would be given with Obama deficit reduction plan? |
|
Definition
|
|
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
|
|
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
|
|
Term
| This potency allows for the ability to make any organ or tissue. |
|
Definition
|
|
Term
| This potency allows for nearly all cell types. |
|
Definition
|
|
Term
| This potency allows for closely related family cells. |
|
Definition
|
|
Term
| This potency allows for few cells types. |
|
Definition
|
|
Term
| This potency allows for only production of their own cell type. |
|
Definition
|
|
Term
| This allows a stem cell to be capable of becoming specialized not originally associated with its germ type. |
|
Definition
|
|
Term
| This is the ability of a cell of one tissue to switch into a cell type characteristic of another tissue |
|
Definition
|
|
Term
| Who and when were the first human embryonic stem cells created? |
|
Definition
|
|
Term
| Which stem cell type is immortal? |
|
Definition
|
|
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
|
|
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
|
|
Term
| This component of Fab is most responsible for antigen recognition site. |
|
Definition
|
|
Term
| This fragment mediates complement-induce cell lysis and antibody-dependent cellular functions. |
|
Definition
|
|
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. |
|
|
