Table 3. Scale-up of the Maleimide Modification of 4 into 5.
| microscalea,b | production scaleb | |
|---|---|---|
| amine/protein molar ratio in 4 post-buffer exchange | 27.1 ± 1.9 | 29.5 |
| amine/protein molar ratio in 5 | 5.1 ± 2.0 | 3.3 |
| total amount of modified amines in 5 | 22.1 ± 0.6 | 20.9 |
| amount of aggregates in concentrated 4 (%) | 29.9 ± 3.4 | 30.1 |
| amount of aggregates in 5 (%) | 36.8 ± 3.8 | 33.9 |
| aggregate induction (%)c | 7.0 ± 3.0 | 3.8 |
a
Microscale experiments results show average and 1 × standard deviation (SD) (n = 5).
b
GMPTT used for both preclinical and clinical batches was of the same lot.
c
Aggregate induction = amount of aggregates in 5 (%) – amount of aggregates in concentrated 4 (%).