biologics

Question 1

advantages compared to small molecules

Answer 1

versatile 
specific binding 
half life
less frequent dosing 
different structured for indications

Question 2

5 functions of mabs

Answer 2

apoptosis induction 
CDC 
antibody dependent cell mediated cytotoxicity (neutrophils) 
conjugates 
ligand blockade

Question 3

which region of the antibody does the antigen bind

Answer 3

Fab region

Question 4

what ligand binds to the Fc region of the antibody

Answer 4

FcRn neonatal fc receptor

Question 5

what factors can affect antigen binding

Answer 5

charge, isoelectric point

Question 6

which region of the antibody does the glycol receptor bind

Answer 6

to the gylcan side chain

Question 7

what pharmacokinetics does the binding of the glycol receptor have on the antibody

Answer 7

clearance and tissue distribution.

Question 8

what kind of absorption method is variable and facilitated by the lymph system

Answer 8

subcutaneous

Question 9

what is the function of the neonatal fc recoptor

Answer 9

recycling of IgG and albumin

Question 10

at what ph does igG bind

Answer 10

acidic ph

Question 11

what happens to unbound igG

Answer 11

degraded in lysosomes

Question 12

what other region in the antibody can bind to the FcRn receptor

Answer 12

the Fv region

Question 13

which igGs have a longer half life and what is it

Answer 13

1 2 4 and 21 days

Question 14

what is the PI of most mAbs

Answer 14

8

Question 15

an increasing PI =

Answer 15

increased clearance but decreased half life

Question 16

why may some people suffer from hypersensitivity responses e.g. anaphylaxis when administered therapeutic mAbs

Answer 16

formation of ADAs can form complexes with mAbs

Question 17

what are the advantages of fusion proteins

Answer 17

increased half life

Question 18

what is an example of a novel format with the Fab region

Answer 18

ranibizumab

Question 19

what is an example of an antibody drug conjugate

Answer 19

trastuzumab

Question 20

what are the disadvantages of novel formats

Answer 20

decrease in conformational stability and solubility

Question 21

what side groups are there in a hydrophobic protein core

Answer 21

non polar aliphatic

aromatic

Question 22

what side groups are there in a hydrophilic shell

Answer 22

polar uncharged

positive and neg charge

Question 23

what is the function of salt bridges in a mAb conformation

Answer 23

rigidifies structure

Question 24

what happens to mAbs with an increase in temp

Answer 24

aggregation

Question 25

what happens to mAbs with pressure

Answer 25

promote protein unfolding

Question 26

what happens to mAbs with pH towards the isoelectric point

Answer 26

increase in ionic strength which favours aggregation

Question 27

what are 2 causes of instability

Answer 27

chemical e.g. oxidation, physical e.g. pH

Question 28

compare preferential exclusion and interaction

Answer 28

e- low interaction with protein I - interaction with backbone of protein e- higher conc of co solute out of shell I- bonding with aa side chains e- e.g. sucrose I-e.g. urea

Question 29

give an example of a stabiliser that works through preferential exclusion

Answer 29

amino acids, polymers

Question 30

moa of surface engineering

Answer 30

modifies amino acid sequence to remove parts likely to cause aggregation

Question 31

moa of surfactants

Answer 31

competitive absorption at interfaces

Question 32

what is the aim of long term stability testing

Answer 32

to determine shelf life

Question 33

what is the aim of accelerated stability testing

Answer 33

to support the established shelf life

Question 34

aim of stress studies

Answer 34

to revel patterns of degredation

Question 35

advantage of freezing

Answer 35

extend shelf life

Question 36

disadvantages of freezing

Answer 36

change in pH, ionisation, h bonds = damage | repeated freezing and thawing= aggregation

Question 37

what is cryoprotection

Answer 37

stabilising sample via preferential exclusion

Question 38

advantages of freeze-drying

Answer 38

long term stability

Question 39

disadvantages of freeze-drying

Answer 39

aggregation | denaturation and reactions continue

Question 40

how can the issues with freeze drying be improved

Answer 40

refrigeration to decrease denaturation rate | sealing vial to avoid hygroscope