Pharmaceutics SEM 1 - biologics

Question 1

what is a biologic?

Answer 1

A biologic drug (biologics) is a product that is produced from living organisms or contain components of living organisms.

Question 2

name 2 advantages of biologics

Answer 2

Replace diseased tissue functionality (e.g. protein hormones and blood factors, gene therapy and tissue engineering
Highly specific binding to modify or block function to target

Question 3

What are the advantages of biologics over small molecules?

Answer 3

Versatile (replace or modify tissue)

• Faster to market
• More specific binding (reduced toxicity)
• Less frequent dosing needed ( half life usually weeks, rather than hours for small molecules)
• Blockbuster drugs (£1 Billion+ sales)
• Lower failure rates in discovery pipeline
• Function can be changed easily

Question 4

what types of biologics are on the market?

Answer 4

Peptides,
Protein fragments
mAbs,
ADCs (antibody drug conjugate)
Viruses
Vaccines
New modalities such as LNP

Question 5

describe the structure of an ADC

Answer 5

a mAB with a cytotoxic drug -

Question 6

what is the major molecule in most mABs

Answer 6

IgG

Question 7

what are disadvantages of biologics

Answer 7

size can make them difficult to formulate

immunogenicity

Question 8

How can immunogenic effects be reduced

Answer 8

by humanising proteins

Question 9

what is one problem with the production of biologics

Answer 9

as it involves cell cycles, it is a batch process

Question 10

describe the human antibody development

Answer 10

started using mice (chimeric ) immunogenic reaction and rapid clearance due to lack of Fc effector functions
then humanised
then fully human antibodies

Question 11

what is another name for variable region

Answer 11

the Fv or antigen binding region

Question 12

how do mAB

Answer 12

CDC - bind to surface , complent cytotoxicity - induce cytotoxicity
conjugate -antibodie binds to antigen, which can be toxin or cytotokine

apoptosis induction by binding
receptor biinds to molecule stopping ligand binding

ADCC - antibody binds to specific antigen or receptor, using fc receptors neutrophils bind to cause cytotoxicity

Question 13

how are biologics administered? describe the rate of absorption

Answer 13

Administration either i.v., SC or IM injections
Absorption for SC is variable (20-95%) facilitated by lymph system
Rate of absorption is slow (maximal plasma concentration between 1-8 days following SC or IM injection

Question 14

describe how mAbs are eliminated?

Answer 14

Not clearly understood
Eliminated by proteolytic catabolism or by lysosomal degradation

Other mechanisms include target mediated clearance,
non-specific pynocytosis 9kind of endocytotcisis) ,
Fc gamma receptor (FcR) mediated clearance.

target-mediated elimination pathway involves interaction between a mAb and its pharmacological target, and represents the primary route of antibody clearance. (essentially reaches target, binds and then destroyed by RES) reticulo-endothelial system (RES).

Question 15

why do biologics have unique pk profiles?

Answer 15

TMDD is the phenomenon in which a drug binds with high affinity to its pharmacological target site (such as a receptor) to such an extent that this affects its pharmacokinetic (PK) characteristics

Question 16

describe mAbs recycling

Answer 16

echoing og albumin or IgG occurs
FC region binds to fcRN
IgG travels in blood, endocytosis into cell
pH becomes more acidic causing gig to bind to the fcRn
anything that isn’t bound moves towards the lysosomes and is destroyed to amino acids level
pH in bound protein vesicles increases back to pH7.4 as vesicle moves to cell surface, binding stops and IgG released back into the blood

Question 17

what is the neonatal Fc receptor?

Answer 17

mediates recalling of albumin and IgG

Question 18

what is the isoelectric point

Answer 18

zwitterion formed, overall protein charge neutral