FunSci2: Pharmaceutical Products of Biotechnology

Biopharmaceuticals are pharmaceutical drug products that are manufactured in or extracted from or semi-synthesized from ______________ sources using cutting-edge _______________________ methods

biological, biotechnological

What is biopharmaceuticals also called?

biologics

Biopharmaceuticals are ___________ _____________ molecules made with the help of ____________ cells

complex larger, living

Biopharmaceuticals are complex larger molecules made with the help of living cells, such as what?

bacteria, yeast, animal or plant cells

Unlike smaller molecules that are given to a patient through tablets, the large molecules (biopharmaceuticals) are typically _______________ into the patient's body

injected

What "project" led to the development of protein drugs?

the human genome project

In order for protein drugs to function properly and be effective, the structure of the _____________ has to be maintained

protein

What kind of technology allows us to produce protein drugs?

recombinant DNA technology

Before recombinant DNA technology, protein drugs were derived from what sources?

humans and animals

What are examples of protein drugs?

rHuman insulin (Humulin), rhuman growth hormone (protropin), recombinant interferons, interleukins

Recombinant DNA technologies involve ______________ modification of organisms

genetic

Recombinant DNA technology: Genetic modification of organisms is done by fusion of any _______ _______________ to _______ _______________ that are able to maintain themselves by autonomous ___________________

DNA fragment, DNA molecule (plasmid), replication

Since DNA molecules (plasmids) are able to maintain themselves by autonomous replication, they are also called what?

replicons

Recombinant DNA/DNA Cloning Technology: This involves fusing ____________ DNA fragments to the isolated ______________ in order to create a ________________ ________ molecule

foreign, plasmid, recombinant DNA

Recombinant DNA/DNA Cloning Technology: Once the foreign DNA is fused into the plasmid, what is the plasmid then called?

a replicon or vector (isnt technically a replicon or recombinant DNA until the foreign DNA is fused into it)

Recombinant DNA/DNA Cloning Technology: What is foreign DNA (DNA that is inserted into plasmids) isolated from?

microbial, plant or animal cells

Recombinant DNA/DNA Cloning Technology: What enzyme is used to cut DNA at specific sites on both the foreign DNA and plasmid?

restriction enzyme

Recombinant DNA/DNA Cloning Technology: What enzyme is used to close the circular recombinant DNA (the plasmid with the foreign DNA inserted into it)

ligase enzyme

Recombinant DNA/DNA Cloning Technology: Once the recombinant DNA (foreign DNA inserted into plasmid) is introduced into the host cell, what is the host cell called?

transformant (transformant = host cell that contains recombinant DNA)

Recombinant DNA/DNA Cloning Technology: Vectors (replicons) __________________ inside of the host cell

replicate

Recombinant DNA/DNA Cloning Technology: Vectors replicate inside of the host cell, thus all ________________ cells in the host cell will inherit a precise copy (a clone) of the ______________________ _______ molecule

daughter, recombinant DNA

Monoclonal Antibodies are _____-shaped

Y

Monoclonal antibodies contain an _____________ binding site

antigen

The antigen binding site on the monoclonal antibody is also called what?

paratope

The antigen binding site on monoclonal antibodies binds to the _______________ on the _____________

epitope, antigen

Monoclonal antibodies bind to antigens via a _________ and _______ mechanism

lock, key

What is considered the "lock" involving monoclonal antibodies binding to antigens?

the antigen binding site on the monoclonal antibody (paratope)

What is considered the "key" involving monoclonal antibodies binding to antigens?

the epitope on the antigen (what the antigen binding site of the monoclonal antibody binds to)

Monoclonal antibodies are highly ______________ to antigens

specific

What two things conjugate together in order to form an antigen?

haptens and proteins

What two "regions" does a monoclonal antibody consist of?

constant (Fc) region and variable region

What is the overall structure of an antibody?

antigen binding fragment, antibody crystallizable region, heavy chains, light chains, variable regions, hinge regions

What is the abbreviation for antigen-binding fragment?

Fab

What is the antibody crystallizable region also known as?

Fc region or constant region

Monoclonal antibodies are typically made by fusing ____________ cells with ______ cells in the _____________ from a mouse that has been _______________ with the desired _______________

myeloma, B, spleen, immunized, antigen

Monoclonal Antibody Production: Once the mouse is immunized with the desired antigen, the mouse's immune system produces _______ cells that accumulate in the spleen

B

Monoclonal Antibody Production: Once the B cells fuse with myeloma cells, what forms?

a hybridoma

Monoclonal Antibody Production: The B cells part of the hybridoma is responsible for what?

producing monoclonal antibodies (antibodies specific to target antigen)

Monoclonal Antibody Production: The myeloma cell part of the hybridoma is reponsible for what?

replication

What are the different type of applications of monoclonal antibodies?

cancer treatment, imaging diagnosis, targeted-specific delivery, transplant rejection suppression

Cancer Treatment: Monoclonal antibodies (mAbs) against _______________ and ______________ have been used as treatment with variable results

leukemia, lymphoma

Imaging Diagnosis: mAbs may be used together with _______________ markers to locate and visualize the location and extent of ______________

radioactive, tumors

Targeted-specific delivery: mAbs may be conjugated to __________ or other delivery systems such as _______________ to allow the specific delivery to target sites

drugs, liposomes

Transplant rejection suppression: In ___________ transplants, there is a mAb that destroys ________, a membrane protein of ____________ ____ cells that causes transplant rejection

kidney, CD3, cytotoxic T

Monoclonal antibodies are named by combining what things?

prefix, antibody target, antibody source, suffix

What is the usual suffix of mAbs?

mab

What are the different types of antibody targets?

bone, cardiovascular, immune-modulating, interleukin, tumor, virus

For mAbs that target bone, what letters are in their name?

o(s)

For mAbs that target cardiovascular, what letters are in their name?

c(i)

For mAbs that are immune-modulating, what letters are in their name?

l(i)

For mAbs that target interleukins, what letters are in their name?

k(i)

For mAbs that target tumors, what letters are in their name?

t(u)

For mAbs that target viruses, what letters are in their name?

v(i)

For mAbs that are derived from humans, what letters are in their name?

u

For mAbs that are humanized, what letters are in their name?

zu

For mAbs that are chimeric, what letters are in their name?

xi

For mAbs that are derived from rats, what letters are in their name?

a

Gene therapy involves the delivery of a ________________ __________ to _________________ cells in the body to produce a ___________________ that corrects defective _______________ function

recombinant gene (DNA), somatic, protein, biologic

Gene therapy focuses on what kind of gene defects?

single-gene defects

What are examples of single gene defects?

CF, hemophilia, muscular dystrophy, thalassemia, sickle cell anemia

Cystic fibrosis gene therapy involves restoring _________________ _____________, which overall improves ________ expectancy of CF patients

chloride channels, life

Gene therapy involves ___________ and ___________ delivery of recombinant DNA (rDNA)

in-vivo, ex-vivo

Gene Therapy: What are examples of recombinant DNA delivery?

virus-based approach, plasmid vector approach

Gene Therapy: The Virus-based approach involves viruses being used as ______________ in order to transport the therapeutic gene into host cells

vector

Virus-based Approach - Gene Therapy: The gene that codes for the ___________ _____________ is inserted into a __________ or __________ virus

therapeutic protein, RNA, DNA

Virus-based Approach - Gene Therapy: The gene that codes for the therapeutic protein (that is inserted into the virus) is also called what?

transgene

Virus-based Approach - Gene Therapy: What are RNA viruses also called?

retroviruses

Virus-based Approach - Gene Therapy: DNA viruses are outside of ___________________

chromosomes

Virus-based Approach - Gene Therapy: What is an example of a type of DNA virus?

adeno-associated virus (AAV)

Virus-based Approach - Gene Therapy: Do viruses replicate?

no (so if the virus is used as a vector it cannot replicate. normal vectors that arent viruses CAN replicate)

Gene Therapy: The plasmid vector approach is non-__________

viral (not a virus)

Gene Therapy: Ex-vivo delivery of rDNA has less _____________ ________________

systemic toxicity

Gene Therapy: What does CAR T cell stand for?

chimeric antigen receptor T cell

Gene Therapy: Chimeric antigen receptors (CARs) are receptor proteins that have been engineered to give T cells the new ability to do what?

target a specific antigen

Gene Therapy: Chimeric antigen receptors (CARs) are chimeric in that they combine both ______________-_____________ and ____ ________ activating functions into a single receptor

antigen-binding, T cell (the CAR is chimeric because it has two functions in one - allows the T cell to bind to antigens and also activates the T cell)

Gene Therapy: What are examples of approved gene therapies?

abcema, zynteglo, luxturna, skysona, zolgensma, imlygic

What is an example of a CAR T-cell therapy?

kymriah (for leukemia and lymphoma)

What does ASO drug stand for?

antisense oligonucleotide drug

Antisense oligonucleotide (ASOs) drugs are drugs that seek to do what?

block DNA transcription or RNA translation

ASO drugs block DNA transcription or RNA translation in order to moderate many ______________ processes

disease

ASO drugs target ______________ and __________ _______________

cancer, viral infections

ASO drugs are delivered into the body using ______________ as carriers

liposomes

Pharmacokinetics of Biopharmaceuticals: There is rapid _______________ of biopharmaceuticals

degredation

Pharmacokinetics of Biopharmaceuticals: There is rapid degradation of biopharmaceuticals by endogenous _____________ and _______________

proteases, nucleases

Pharmacokinetics of Biopharmaceuticals: Degradation of biopharmaceuticals by proteases/nucleases causes the biopharmaceutical to have low ________________

stability (limits activity)

Pharmacokinetics of Biopharmaceuticals: _______________ DNA and RNA (in biopharmaceuticals) have a short half life (only few minutes)

unmodified (chemical structure hasn't been altered)

Pharmacokinetics of Biopharmaceuticals: What remedies are used to overcome the rapid degradation and short half life of biopharmaceuticals?

Chemical modifications or bioengineering to increase size and decrease excretion (of the biopharmaceutical)

Pharmacokinetics of Biopharmaceuticals: Due to the large size and limited diffusional transport of biopharmaceuticals, they have a low what?

volume of distribution (Vd)

Pharmacokinetics of Biopharmaceuticals: What are examples of delivery systems that biopharmaceuticals utilize?

conjugates, nanoparticles, liposomes, viral vectors

Pharmacokinetics of Biopharmaceuticals: The PK for transgenes (foreign DNA fragment that is inserted into plasmid) is difficult to measure to due low ________________ given

concentration

Pharmacokinetics of Biopharmaceuticals: Liposomal delivery of biopharmaceuticals tends to reduce _______ and may be cleared by the __________ and ______________

Vd, spleen, liver

Pharmacokinetics of Biopharmaceuticals: Liposome delivery systems are coated with what?

PEG

Pharmacokinetics of Biopharmaceuticals: PEG coating of liposomes is used to evade _____________ detection

phagocyte (coating the liposome with PEG prevents phagocytes from detecting it so it'll last in the body longer)

A Biosimilar Is a biologic (biopharmaceutical) that is highly _____________ to and has no clinically meaningful _____________________ from an existing ________________ medicine

similar, differences, biological

The existing biological medicine that the biosimilar is highly similar to is called what?

reference point

The reference point of a biosimilar is already licensed by the

FDA