Characterization of target binding and AP inhibition of anti-factor Bb monoclonal antibodies
| Antibody . | Target . | Target binding . | Functional assay IC50 (μg/mL) . | |||
|---|---|---|---|---|---|---|
| ka (M–1s–1) . | kd (s–1) . | KD (M) . | Wieslab EIA . | Hemolysis . | ||
| SARXX01 | hFBb | 1.2 × 106∗ | 1.6 × 10–3∗ | 1.4 × 10–9∗ | ND | ND |
| hFB | ND | ND | ND | |||
| SARXX02 | hFBb | 7.0 × 105 ± 1.6 × 105 | 1.0 × 10–3 ± 0.0 × 10-3 | 1.5 × 10–9 ± 0.3 × 10-9 | 3.43 (3.23-3.64) | ND |
| hFB | ND | ND | ND | |||
| SAR443809 | hFBb | 1.9 × 105 ± 0.4 × 105 | 1.4 × 10-3 | 7.3 × 10–9 ± 1.4 × 10-9 | 8.47 (6.60-10.86) | 28.45 (17.93-45.14)† |
| hFB | ND | ND | ND | |||
| cFBb | 1.4 × 105 ± 0.2 × 105 | 8.6 × 10–3 ± 0.5 × 10-3 | 6.1 × 10–8 ± 0.8 × 10-8 | 15.72 (14.41-17.14) | 84.85 (69.43-103.71)† | |
| cFB | ND | ND | ND | |||
| SAR443809 Fab | C3bBb | 2.7 × 105 | 1.8 × 10–4 | 0.5 × 10–9 | NA | NA |
| Antibody . | Target . | Target binding . | Functional assay IC50 (μg/mL) . | |||
|---|---|---|---|---|---|---|
| ka (M–1s–1) . | kd (s–1) . | KD (M) . | Wieslab EIA . | Hemolysis . | ||
| SARXX01 | hFBb | 1.2 × 106∗ | 1.6 × 10–3∗ | 1.4 × 10–9∗ | ND | ND |
| hFB | ND | ND | ND | |||
| SARXX02 | hFBb | 7.0 × 105 ± 1.6 × 105 | 1.0 × 10–3 ± 0.0 × 10-3 | 1.5 × 10–9 ± 0.3 × 10-9 | 3.43 (3.23-3.64) | ND |
| hFB | ND | ND | ND | |||
| SAR443809 | hFBb | 1.9 × 105 ± 0.4 × 105 | 1.4 × 10-3 | 7.3 × 10–9 ± 1.4 × 10-9 | 8.47 (6.60-10.86) | 28.45 (17.93-45.14)† |
| hFB | ND | ND | ND | |||
| cFBb | 1.4 × 105 ± 0.2 × 105 | 8.6 × 10–3 ± 0.5 × 10-3 | 6.1 × 10–8 ± 0.8 × 10-8 | 15.72 (14.41-17.14) | 84.85 (69.43-103.71)† | |
| cFB | ND | ND | ND | |||
| SAR443809 Fab | C3bBb | 2.7 × 105 | 1.8 × 10–4 | 0.5 × 10–9 | NA | NA |
All binding parameters represent mean ± standard deviation from 3 independent experiments. IC50 represented as geometric mean of individual runs (n = 3) and 95% confidence interval.
cFB, cynomolgus factor B; cFBb, cynomolgus factor Bb; ka, association rate constant; Fab, antibody fragment; hFB, human factor B; hFBb, human factor Bb; kd, dissociation rate constant; KD, equilibrium binding constant; NA, not applicable; ND, not determined.
N = 1; values confirmed through parallel BLI measurements.
Same data as in supplemental Table 3.