Pharmaceutical Biotechnology and Biologics (4/20/26) - Pharmaceutics II

What are Small Molecules?

Give an example and include the Molecular Weight of this example molecule.

Molecules synthesized in a classic way, such as by chemical reactions between different organic and / or inorganic compounds

EXAMPLE - Acetylsalicylic Acid (ASA), C9H8O4, the API of Aspirin

- MW = 180 g / mol OR 180 Da

What are Large Molecules?

Give another name for these molecules.

Give examples of Large Molecules.

Class of drugs based on Proteins, Peptides, Monoclonal Antibodies (Mab), and other things

Another name is BIOLOGICS, or Macromolecules

EXAMPLES - Vaccines, Hormones, Antibodies

How heavy can Large Molecules be?

As heavy as 150,000 g / mol, or 150 kDa

Give an example of a common Large Molecule we regularly use in the pharmacy.

Include the Molecular Mass of this Large Molecule.

INSULIN - human Insulin protein is composed of 51 AAs with a molecular mass of 5808 Da

For Small Molecules, describe:

- Relative MW

- Stability at Room Temperature

- How it is Usually Administered

- Synthesis Type

- Immunogenicity Risk

MW - low

STABILITY AT ROOM TEMP - stable

ADMINISTRATION - usually by mouth (po)

SYNTHESIS - organic, inorganic, or chemical synthesis

IMMUNOGENICITY - rare immunogenicity

For Large Molecules, describe:

- Relative MW

- Stability at Room Temperature

- How it is Usually Administered

- Synthesis Type

- Immunogenicity Risk

MW - high

STABILITY AT ROOM TEMP - unstable

ADMINISTRATION - usually parenteral

SYNTHESIS - cells or organisms through biotechnology

IMMUNOGENICITY - higher risk of immunogenicity

What is the main distinguishment between Small Molecules and Large Molecules (Biologics)?

SMALL MOLECULES - chemically synthesized with well-defined structures

LARGE MOLECULES - complex molecules produced by living systems that often require cold chain storage

What are the five various definitions of Biotechnology?

1. Techniques of Genetic Engineering

2. Use of Living Organism to produce beneficial products

3. To make or modify products OR to improve plants or animals for beneficial use, which involve cloning

4. Production of pharmacologically active Recombinant Proteins or Modified Proteins

5. Production of Transgenic bacteria or animals to be used as so-called "Factories" for human and animal pharmaceuticals

What are the potential routes of delivery for biotechnological products?

Nasal

Inhalation

Buccal / Sublingual

Parenteral

Transdermal

Which route of delivery CANNOT be used for Biotechnology Drug Products?

Why?

Oral Route

Often unstable in the strong acidic environment of the stomach

How can Peptide Biologics be synthesized?

Either:

- Isolated from Natural Sources (bacteria, animal, fungi), OR

- Chemically Synthesized

Give three examples of Peptide Biologics derived from Natural Sources.

Include the source they are derived from.

1. INSULIN - originally derived from animal pancreases

2. SOMATOTROPIN (Growth Hormone) - derived from Human Brains

3. COAGULATION FACTOR XIII and HEP B SURFACE ANTIGEN - obtained from human blood

Give three examples of Peptide-Based / Hormone Drugs.

Include their main use.

1. LEUPROLIDE - anti-tumor agent

2. EXENATIDE (BYETTA) - diabetes drug

3. CYCLOSPORINE - immunosuppressant

What is Leuprolide?

What effect does it have on the body?

What is it used to treat?

Man-made Protein / Synthetic Hormone product that acts like a natural hormone in the body

DECREASES Testosterone (men) and DECREASES Estrogen (women)

Used to treat Prostate Cancer in men and Endometriosis, Uterine Fibroids, or other female hormone-related problems in women

What is Byetta?

What it is used for?

also called Exenatide; 39 AA Peptide that is a synthetic version of Exendin-4 and mimics human glucagon-like peptide-1 (GLP-1)

Used for Type 2 Diabetes and glycemic control

What is Erythropoietin (EPO)?

What uses does it have?

Glycoprotein that stimulates the production of red blood cells (Erythrocytes)

Used in treatment of kidney dialysis patients to prevent Anemia

Where is Erythropoietin (EPO) naturally produced?

What does it do?

Naturally produced by Peritubular Cells of the Kidneys in response to cellular hypoxia

Stimulates RBC production in the Bone Marrow

What is the relative number of cells in the Kidney that produce Erythropoietin during Normoxia and Hypoxia?

Normoxia has SOME cells producing Erythropoietin

Hypoxia has MANY cells producing Erythropoietin

What is Tissue Plasminogen Activator (t-PA)?

How does it work?

Natural human protease involved in the breakdown of blood clots

Dissolves thrombi at sites of coronary vessel occlusion by binding to FIBRIN

What is Tissue Plasminogen Activator (t-PA) indicated for?

Indicated for Myocardial Infarction and Stroke

How is t-PA used as a Clot Buster?

t-PA is administered to stroke patients to break up a blood clot and restore blood flow to the brain following a stroke

What is a Vaccine?

Biological preparation that provides ACTIVE ACQUIRED IMMUNITY to a particular disease

How do Vaccines function?

Vaccines expose the immune system to ATTENUATED PATHOGENS (less virulent) or PIECES OF PATHOGENS or INACTIVE AGENTS like virus, all called ANTIGENS

What type of agent do Vaccines typically contain?

What are they typically made from?

An agent that resembles a disease-causing microorganism

Typically made from a weakened / killed form of the microbe, its toxins, or its surface proteins

What can exposure of our immune system to attenuated Antigens in Vaccines produce?

Produces a "Memory" response, which results in a robust immune response in the individual

In what form can Nucleic Acids be used in pharmaceuticals?

In their DNA and RNA forms

What does Antisense RNA do in Nucleic Acid pharmaceuticals?

Used to either ALTER GENE EXPRESSION or interfere with the translation of RNA into protein

How do Nucleic Acid Biologics work?

1. ssRNA (Single-Stranded RNA) that has a complementary sequence to the RNA of interest is introduced into the cell

2. Antisense drug has highly specific binding to the specific mRNA or gene

3. Specific mRNA or gene is destroyed through an enzymatic process or by blockage of Transcription

What are Aptamers?

Single-stranded Oligonucleotides (~15-60 nucleotides in length) that fold into defined architectures and bind to targets, such as proteins

Why are Aptamers specifically selected for Biologic use?

Specificity and Affinity for proteins or other biological targets

Do Aptamers elicit antibodies?

Why or why not?

No

They contain sugars modified at the 2'-positions and Toll-Like Receptor (TLR)-Mediated innate immune responses are abrogated

What was the first Aptamer approved for therapeutic application by the FDA?

When was it approved?

What is it indicated for?

Pegaptanib Sodium (Macugen)

Approved in 2004 for Pfizer / Eyetech

Indicated for Macular Degeneration

What type of Aptamer is Macugen?

What specifically does it bind to?

Pegylated anti-VEGF (Vascular Endothelial Growth Factor) Aptamer

Specifically binds to VEGF 165

What processes does VEGF 165 play a role in?

How does this relate to the indication of Macugen?

Plays a role in ANGIOGENESIS and increased permeability

These two processes are responsible for Vision Loss associated with Macular Degeneration

What is Recombinant DNA (rDNA)?

How is it created?

Genetically engineered DNA

Created by recombining fragments of DNA from different organisms

What are some examples of Recombinant DNA (rDNA) products?

rDNA Vaccines

rDNA Drugs

rDNA Enzymes

What is Insulin?

What does it enable?

Hormone made by pancreatic beta cells

Enables cells to uptake Glucose from the bloodstream and use it in the production of ATP

What does insufficient Insulin cause?

Diabetes

Before recombinant Insulin became available, where was Insulin obtained from?

Cow or Pig pancreases

How many amino acid differences does Cow (Bovine) Insulin have to Human Insulin?

Pig (Porcine) Insulin?

COW (BOVINE) - 3 AA differences

PIG (PORCINE) - 1 AA difference

What can amino acid differences stimulate?

How does this relate to selection of Insulin sources?

AA differences can stimulate allergic responses

Therefore, Human Insulin is preferred (51 AAs)

What company is responsible for producing Humulin?

Eli Lilly

What is a major advantage of recombinant human insulin over animal-derived insulin?

It has better purity and reduces immunogenicity

What does Human Growth Hormone (HGH) promote?

What condition is associated with insufficient production of HGH?

Promotes overall body growth

DWARFISM is associated with insufficient HGH production by the Pituitary Gland

What was the Old Method for obtaining HGH?

Purification of HGH from cadaver Pituitary Glands

(8 cadavers a year for 8-10 years per patient)

What is the New Method for obtaining HGH?

What specific types of HGH exist and what companies manufacture them?

Gene production for HGH synthesis

PROTROPIN - manufactured by Genentech

HUMATROPE - manufactured by Eli Lilly

What are the five steps in production of HGH?

1. Human gene that produces HGH is isolated

2. HGH production gene is inserted into E.coli DNA

3. E.coli recognizes the inserted DNA as its own and begins producing HGH

4. Bacteria multiplies and produces the HGH in a culturing media

5. HGH is extracted and purified to be ready for injection into children with Dwarfism

Which of the following is a recombinant DNA-derived

product?

A. Leuprolide

B. Aspirin

C. Protropin

D. Metformin

Protropin

What are Antibodies?

Give an example of a type of Antibody.

Proteins produced by the immune system to identify bacteria, viruses, and other foreign substances to fight them off

EXAMPLE - Monoclonal (mAb) Antibodies

How are Monoclonal Antibodies (mAb) made?

What type of Affinity do they have?

How does this affect their binding patterns?

Made by IDENTICAL IMMUNE CELLS that are all clones of a unique parent cell

Have MONOVALENT Affinity

This means they binding to the SAME Epitope (part of antigen recognized by antibody)

What is Hybridoma Technology (HT)?

What is it the most common method for?

Method in which Ab-producing B Lymphocytes are isolated from mice after immunizing them with a specific antigen and fusing them with immortal Myeloma cell lines to form Hybrid Cells called HYBRIDOMA CELL LINES

Most common method to PRODUCE MONOCLONAL ANTIBODIES

Why is Hybridoma Technology (HT) a preferred method of producing mAbs?

The mAbs produced are high purity, highly sensitive, and specific

Describe the flow of using Hybridoma Technology (HT) to produce and use Monoclonal Antibodies (mAb).

honeslt,y idk bro

What is the end product of Hybridoma Technology (HT)?

Monoclonal Antibodies (mAb)

What is the main characteristic of Myeloma Cells used in Hybridoma Technology?

Immortal, but do NOT produce Antibodies