biologics Flashcards

1
Q

advantages compared to small molecules

A
versatile 
specific binding 
half life
less frequent dosing 
different structured for indications
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2
Q

5 functions of mabs

A
apoptosis induction 
CDC 
antibody dependent cell mediated cytotoxicity (neutrophils) 
conjugates 
ligand blockade
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3
Q

which region of the antibody does the antigen bind

A

Fab region

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4
Q

what ligand binds to the Fc region of the antibody

A

FcRn neonatal fc receptor

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5
Q

what factors can affect antigen binding

A

charge, isoelectric point

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6
Q

which region of the antibody does the glycol receptor bind

A

to the gylcan side chain

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7
Q

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

A

clearance and tissue distribution.

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8
Q

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

A

subcutaneous

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9
Q

what is the function of the neonatal fc recoptor

A

recycling of IgG and albumin

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10
Q

at what ph does igG bind

A

acidic ph

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11
Q

what happens to unbound igG

A

degraded in lysosomes

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12
Q

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

A

the Fv region

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13
Q

which igGs have a longer half life and what is it

A

1 2 4 and 21 days

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14
Q

what is the PI of most mAbs

A

8

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15
Q

an increasing PI =

A

increased clearance but decreased half life

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16
Q

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

A

formation of ADAs can form complexes with mAbs

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17
Q

what are the advantages of fusion proteins

A

increased half life

18
Q

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

A

ranibizumab

19
Q

what is an example of an antibody drug conjugate

A

trastuzumab

20
Q

what are the disadvantages of novel formats

A

decrease in conformational stability and solubility

21
Q

what side groups are there in a hydrophobic protein core

A

non polar aliphatic

aromatic

22
Q

what side groups are there in a hydrophilic shell

A

polar uncharged

positive and neg charge

23
Q

what is the function of salt bridges in a mAb conformation

A

rigidifies structure

24
Q

what happens to mAbs with an increase in temp

A

aggregation

25
Q

what happens to mAbs with pressure

A

promote protein unfolding

26
Q

what happens to mAbs with pH towards the isoelectric point

A

increase in ionic strength which favours aggregation

27
Q

what are 2 causes of instability

A

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

28
Q

compare preferential exclusion and interaction

A

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

29
Q

give an example of a stabiliser that works through preferential exclusion

A

amino acids, polymers

30
Q

moa of surface engineering

A

modifies amino acid sequence to remove parts likely to cause aggregation

31
Q

moa of surfactants

A

competitive absorption at interfaces

32
Q

what is the aim of long term stability testing

A

to determine shelf life

33
Q

what is the aim of accelerated stability testing

A

to support the established shelf life

34
Q

aim of stress studies

A

to revel patterns of degredation

35
Q

advantage of freezing

A

extend shelf life

36
Q

disadvantages of freezing

A

change in pH, ionisation, h bonds = damage

repeated freezing and thawing= aggregation

37
Q

what is cryoprotection

A

stabilising sample via preferential exclusion

38
Q

advantages of freeze-drying

A

long term stability

39
Q

disadvantages of freeze-drying

A

aggregation

denaturation and reactions continue

40
Q

how can the issues with freeze drying be improved

A

refrigeration to decrease denaturation rate

sealing vial to avoid hygroscope