Recombinant Human Antibody (mAb 2021) is capable of binding to TFPI, expressed in HEK 293 cells. Expressed as the combination of a heavy chain (HC) containing VH from anti-TFPI mAb and CH1-3 region of human IgG1 and a light chain (LC) encoding VL from anti-TFPI proteins mAb and CL of human kappa light chain. Exists as a disulfide linked dimer of the HC and LC hetero-dimer under non-reducing condition. This high-affinity (K(D) = 25pM) mAb against TFPI was investigated. Binding of mAb 2021 to TFPI effectively prevented inhibition of FVIIa/TF/FXa and improved clot formation in hemophilia blood and plasma.
Figure 1 Hemostatic effect of mAb 2021 in hemophilia-like plasma and blood.
Hemophilia-like conditions were induced by incubation of normal human plasma or blood with 100 ug/mL FVIII Ab (sheep anti–human FVIII; Hematologic Technologies Inc) for 30 minutes at room temperature. (A) dPT clot analysis with various concentrations of mAb 2021 spiked into normal human plasma (E) and into FVIII-neutralized plasma (F). Results are presented as mean SD (n 3). (B-C) Clot time (B) and clot development values (C) obtained by TEG analysis when various concentrations of mAb 2021 were spiked into FVIII-neutralized human blood. Data are presented as results from individual donors (donor 1:Œ, donor 2:f, donor 3:F, donor 4: ). In the absence of mAb 2021 and anti-FVIII Ab the mean ( SD) clot time obtained in normal blood from the 4 donors was 12.4 3.8 minutes and the clot development was 6.8 1.2 mm 100 s1.
Hilden, I., Lauritzen, B., Sørensen, B. B., Clausen, J. T., Jespersgaard, C., Krogh, B. O., ... & Petersen, H. H. (2012). Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa and TFPI in a rabbit hemophilia model. Blood, blood-2012.
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CAT | Product Name | Application | Type |
---|---|---|---|
TAB-734 | Anti-TFPI Recombinant Antibody (Concizumab) | ELISA, IP, FC, FuncS, Neut, IF, WB | IgG4 - kappa |
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