HMM304: Therapeutic Development — Week 3, Class 8

Flashcards cover key concepts from Week 3 Class 8: small molecules vs biopharmaceuticals, production methods, major biopharmaceutical classes, delivery challenges, gene therapy, RNA-based approaches, and related historical context.

What is the main difference between conventional small molecule drugs and biopharmaceuticals?

Small molecules are typically <500 Da and chemically synthesized; biopharmaceuticals are manufactured from living organisms and include larger, more complex biologics such as peptides, proteins, and antibodies.

What is the typical molecular weight limit for a small molecule?

Less than 500 Daltons (Da).—

Why might biopharmaceutical methods be chosen over synthetic methods for drug production?

Because they enable production of larger, more complex proteins/peptides with post‑translational modifications and endogenous ligands, and allow manipulation via recombinant DNA technologies.

List common advantages of biopharmaceuticals compared with synthetic small molecules.

Broader therapeutic scope; more complex structures and post-translational modifications; potential for quicker discovery starting from endogenous ligands; often greater selectivity and potentially lower toxicity; increasing share of new drugs.

List common disadvantages of biopharmaceuticals compared with synthetic small molecules.

Expensive and complex to mass-produce; variability between lots; not orally active; shorter half-lives; poor blood–brain barrier permeability; longer development times; potential immunogenicity.

What is serotherapy in biopharmaceutical history?

Use of serum from immune animals or humans to treat and protect against infectious diseases.

What are biopharmaceuticals?

Drugs manufactured from living organisms, including peptides/proteins, gene-related products, and other biologics produced via biological systems.

Why is recombinant insulin often preferred over animal-derived insulin?

Recombinant human insulin reduces immunological reactions because it incorporates parts of the human insulin sequence.

How are larger peptides and proteins produced in modern biopharmaceuticals?

Using expression systems and recombinant DNA technology, including cell culture or transgenic animals to produce the proteins.

Name two growth factors used to support chemotherapy and their roles.

G-CSF (granulocyte colony-stimulating factor) and GM-CSF (granulocyte-macrophage CSF) to maintain neutrophil counts; EPO to stimulate red blood cell production.

What coagulation factors are common biopharmaceuticals?

Recombinant factor VIII and factor IX.

What are antithrombotic biopharmaceuticals?

Recombinant thrombin inhibitors, gpIIb/IIIa antagonists, and plasminogen activators like streptokinase/urokinase or tissue plasminogen activator (tPA).

How were monoclonal antibodies originally produced?

Using the mouse-based hybridoma technique to generate antibodies from a single B-cell clone.

How are monoclonal antibodies used in cancer therapy and immunosuppression?

In cancer therapy, they can deliver cytotoxic agents to tumor cells; in transplantation, they enable selective immunosuppression by targeting T-cell antigens.

What is a monoclonal antibody?

An antibody produced from a single clonal cell line with a single antigen specificity.

What is a biopharmaceutical vaccine?

A vaccine produced as a peptide/protein subunit via biopharmaceutical methods; some vaccines involve attenuated pathogens but are still biopharmaceuticals.

What are common routes of administration challenges for protein biopharmaceuticals?

Oral delivery is often ineffective due to size/charge/proteolysis; nasal or pulmonary routes can be better with protective formulations; parenteral administration is common; BBB permeability is poor.

What is gene therapy in simple terms?

Introducing a working copy of a missing or dysfunctional gene into a patient to fix the problem, often using viral vectors.

Which vectors are commonly used in gene therapy?

Viral vectors, most notably adenoviruses, among others.

When and what was the first successful gene therapy trial?

1990, to replace the dysfunctional ADA gene causing SCID (severe combined immunodeficiency).

What major safety concerns emerged in gene therapy in the late 1990s/early 2000s?

Immune reactions and insertional mutagenesis leading to leukemia; the death of Jesse Gelsinger highlighted trial safety issues.

What is CRISPR?

A genome editing technology using engineered nucleases (molecular scissors) to insert, delete, or replace DNA at precise locations.

What are RNA-based biopharmaceuticals?

Therapies that manipulate gene expression via RNA species such as antisense RNA, siRNA, RNA interference (RNAi), and microRNA (miRNA).

What is adoptive cell transfer (e.g., CAR-T)?

A therapy where patient T-cells are engineered to express chimeric antigen receptors to target and attack cancer cells.

How can transgenic animals be used to produce biopharmaceuticals?

Animals (e.g., cows, goats, sheep, rabbits, pigs) are engineered to secrete the desired protein in their milk for easier harvesting.

What is a truncated protein in biopharmaceuticals?

Expressing a domain or shorter version of a protein to improve stability, production, or delivery.

What is a fusion protein?

A protein engineered by fusing two or more functional domains to enhance stability or alter function.

What defines not-biopharmaceutical peptides in this context?

Small peptides that can be chemically synthesized and do not require biological production.

What is the general takeaway about peptide/protein biopharmaceuticals from Week 3?

They include growth factors, hormones, coagulation/antithrombotic factors, monoclonal antibodies, and some vaccines; production methods include extraction historically and recombinant expression today; gene therapy and RNA-based approaches represent additional biopharmaceutical strategies.