SAR-443809 is a monoclonal antibody targeting complement factor Bb that inhibits the alternative complement pathway. SAR-443809 blocks the cleavage of C3 and factor B via selective binding to the activated form factor Bb, with a K D of 7.3 nM for human factor Bb. SAR-443809 inhibits the amplification loop of the alternative complement pathway and C3 activation, reduces C3b deposition, and blocks the activation of pathways associated with intravascular and extravascular hemolysis. SAR-443809 can be used for research on hematological and renal disorders mediated by abnormal alternative complement pathway activity [1].
In Vivo, SAR-443809 (15 mg/kg; i.v./s.c.; single dose) delivers sustained (≥ 288 hours) 90% inhibition of complement alternative pathway activity in female cynomolgus monkeys [1].
In Vitro, SAR-443809 (Human FB: 6-500 nM; human FBb: 0.4-30 nM; SAR443809 Fab: 3.7-300 nM; 25°C during assay) binds with high affinity to human factor Bb (KD = 7.3 nM) and cynomolgus factor Bb (KD = 61 nM), and its Fab fragment binds to the active alternative pathway C3 convertase (C3bBb) with high affinity (KD = 0.5 nM)[1]. SAR-443809 (50 minutes at 37°C) inhibits alternative pathway-mediated hemolysis of rabbit erythrocytes with an IC50 of 28.45 μg/mL[1]. SAR-443809 (50 minutes at 37°C) inhibits alternative pathway-mediated C3b deposition on rabbit erythrocytes with an apparent IC50 of 33.8 μg/mL[1]. SAR-443809 potently and selectively inhibits the human complement alternative pathway (IC50 = 8.47 μg/mL) and cynomolgus monkey complement alternative pathway (IC50 = 15.72 μg/mL) by blocking cleavage of C3 and factor B, without inhibiting the classical or lectin pathways[1]. SAR-443809 selectively binds to human factor Bb (EC50 = 30.9 ng/mL) and shows no specific binding to other tested plasma serine proteases, including most complement system enzymes[1]. SAR-443809 (100 μg/mL; 30 minutes at 37°C) inhibits unregulated fluid-phase C3 cleavage in factor H-depleted human serum, preventing consumption of C3 via alternative pathway tickover[1].
References:
[1]. Rajagopal V, et al. SAR443809: a selective inhibitor of the complement alternative pathway, targeting complement factor Bb. Blood Adv. 2023;7(16):4258-4268.
In Vivo, SAR-443809 (15 mg/kg; i.v./s.c.; single dose) delivers sustained (≥ 288 hours) 90% inhibition of complement alternative pathway activity in female cynomolgus monkeys [1].
In Vitro, SAR-443809 (Human FB: 6-500 nM; human FBb: 0.4-30 nM; SAR443809 Fab: 3.7-300 nM; 25°C during assay) binds with high affinity to human factor Bb (KD = 7.3 nM) and cynomolgus factor Bb (KD = 61 nM), and its Fab fragment binds to the active alternative pathway C3 convertase (C3bBb) with high affinity (KD = 0.5 nM)[1]. SAR-443809 (50 minutes at 37°C) inhibits alternative pathway-mediated hemolysis of rabbit erythrocytes with an IC50 of 28.45 μg/mL[1]. SAR-443809 (50 minutes at 37°C) inhibits alternative pathway-mediated C3b deposition on rabbit erythrocytes with an apparent IC50 of 33.8 μg/mL[1]. SAR-443809 potently and selectively inhibits the human complement alternative pathway (IC50 = 8.47 μg/mL) and cynomolgus monkey complement alternative pathway (IC50 = 15.72 μg/mL) by blocking cleavage of C3 and factor B, without inhibiting the classical or lectin pathways[1]. SAR-443809 selectively binds to human factor Bb (EC50 = 30.9 ng/mL) and shows no specific binding to other tested plasma serine proteases, including most complement system enzymes[1]. SAR-443809 (100 μg/mL; 30 minutes at 37°C) inhibits unregulated fluid-phase C3 cleavage in factor H-depleted human serum, preventing consumption of C3 via alternative pathway tickover[1].
References:
[1]. Rajagopal V, et al. SAR443809: a selective inhibitor of the complement alternative pathway, targeting complement factor Bb. Blood Adv. 2023;7(16):4258-4268.