Question

Problem 1

Monoclonal antibodies (mAbs) are large protein molecules (molecular mass approx. 144000) that are widely used as biopharmaceuticals for treating many challenging diseases. In order to inactivate viruses during mAb manufacture, the process stream containing the mAb is typically held in a storage vessel at low pH for a period of about an hour. An extended low-pH hold may lead to formation of mAb aggregates, which can be deleterious to patients and must therefore be removed during further purification. Because of a processing difficulty, a mAb solution has been held for several hours at low pH, so the extent of mAb formation is higher than usual; the table below shows the fraction of mAb remaining as monomer (M) after different times. The reaction is written as M ! aggregates but the order of the reaction is not known. The initial monomer concentration was 24 mg/mL.

t (minutes) 0 30 60 90 120 150 180

Fraction M remaining 100 99.0 98.3 97.5 96.3 95.6 94.7

(a) Explain why the measurements in the table effectively represent batch aggregation data.

(b) Derive suitable equations and use the corresponding data plots to analyze the data in terms of a (i) first-order, (ii) second-order aggregation reaction; in each case you should estimate the corresponding rate constant. What can you conclude about the reaction order? How would you go about obtaining more informative data?

(c) Find the ratio between your estimates of the first- and second-order rate constants, including units. why do you think this result is obtained?

Answer 1

a) it is a batch aggregation data because in this, the reaction data is recorded regular intervals of time.

b) picture attached.

c) picture attached.