Table 1.
OS and CS activity of recombinant FVIII-SQ variants
| Production cell type | Recombinant FVIII-SQ variant tested | Clone/production lot/ medium conditions | OS FVIII activity (IU/dL) | CS FVIII activity (IU/dL) | OS/CS ratio |
|---|---|---|---|---|---|
| Sequence polymorphism | |||||
| CHO | Leu1880 (Xyntha-like) | Clone 4-E2 | 96.2 | 92.8 | 1.037 |
| Clone 1-A12 | 132.0 | 129.5 | 1.020 | ||
| Clone 1-A12, 1:10 retest | 11.5 | 14.6 | 0.788 | ||
| CHO | Phe1880 (BMN270-like) | Clone 5-A5 | 44.9 | 54.5 | 0.823 |
| Clone 2-B4 | 29.8 | 39.3 | 0.758 | ||
| Clone 1-F5 | 23.9 | 27.3 | 0.877 | ||
| Production cell type | |||||
| CHO* | Xyntha (Wyeth/Pfizer) | Lot W05255 | 76.0 | 92.7 | 0.820 |
| HepG2 | FVIII-SQ (BioMarin) | Lot 1 | 128.0 | 61.0 | 2.098 |
| Lot 2 | 322.6 | 176.7 | 1.826 | ||
| Lot 3 | 71.5 | 35.2 | 2.031 | ||
| Codon optimization | |||||
| HepG2 | Codon optimized† | Serum-free | 179.1 | 136.0 | 1.317 |
| Serum-containing | 882.1‡ | 456.8 | 1.931 | ||
| HepG2 | Not codon optimized | Serum-free | 5.0 | 3.8 | 1.316 |
| Serum-containing | 28.7 | 14.2 | 2.021 | ||
| HEK 293 | Codon optimized† | Serum-containing | 56.9 | 32.6 | 1.744 |
*
Based on a literature reference.19
†
Same codon optimization as in BMN 270.
‡
The back-calculated result is above the upper reportable limit, but raw data for the diluted test sample were obtained within the validated range of quantification.