Human Anti-PCSK9 Recombinant Antibody (clone 1D05) (CAT#: PABZ-101)

Figure 1 1D05-IgG2 inhibits PCSK9 function.

A: Effect of 1D05-IgG2 on PCSK9-LDLR interaction. TR-FRET experiments were performed using 4 nM Eu3+-LDLr ectodomain and 10 nM AF 647-labeled PCSK9. Increasing concentrations of 1D05-IgG2 was titrated into reaction mixtures containing a preformed complex of AF 647-PCSK9 (10 nM) and Eu3+-LDLr (4 nM) at pH 7.4. Data are means ± SD of triplicates. B: Effect of 1D05-IgG2 on PCSK9-mediated inhibition of LDLc uptake in HEK293 cells. AF 546-LDL uptake was measured in cells incubated with human or mouse PCSK9 (5 µg/ml). C: Effect of 1D05-IgG2 on gain-of-function human PCSK9 S127R mutation-mediated inhibition of LDL uptake. AF 546-LDL uptake was measured in HepG2 cells incubated with 1 µg/ml S127R.

Ni, Y. G., Di Marco, S., Condra, J. H., Peterson, L. B., Wang, W., Wang, F., ... & Wood, D. D. (2011). A PCSK9-binding antibody that structurally mimics the EGF (A) domain of LDL-receptor reduces LDL cholesterol in vivo. Journal of lipid research, 52(1), 78-86.

Figure 2 1D05-IgG2 reduces LDLc in CETP/LDLr-hemi mice.

A: Dose-response study of the effect of 1D05-IgG2. Mice were injected with a single iv dose of 1D05-IgG2 at the indicated doses. Plasma LDLc levels were measured at 48 h postdose. B: The time course of the LDL-lowering effect of 1D05-IgG2 is shown. Mice were injected with a single iv dose of 30 mg/kg 1D05-IgG2. Plasma LDLc was measured at indicated times postinjection. C, D: Time courses of changes in LDLR protein abundance in mice treated with 30 mg/kg 1D05-IgG2 are shown. Liver tissues were collected from mice treated with 1D05-IgG2 and used to prepare tissue lysate. Tubulin was used as loading control. The percentages of changes were calculated relative to those of the PBS vehicle control group. Results are means ± SEM from n = 8–10 replicates.

Ni, Y. G., Di Marco, S., Condra, J. H., Peterson, L. B., Wang, W., Wang, F., ... & Wood, D. D. (2011). A PCSK9-binding antibody that structurally mimics the EGF (A) domain of LDL-receptor reduces LDL cholesterol in vivo. Journal of lipid research, 52(1), 78-86.

Figure 3 1D05-IgG2 reduces LDLc in rhesus monkeys.

A: Effects of1D05-IgG2 treatment on levels of plasma LDLc, total cholesterol, and total and free PCSK9. Plasma samples were collected at the indicated times following 1D05-IgG2 iv injection (3 mg/kg). Total and 1D05-IgG2-free PCSK9 levels were measured using two rhesus PCSK9 DELFIAs. The percentage of antibody-captured PCSK9 was calculated as described in Experimental Procedures. B: Change in total and free circulating PCSK9 following 1D05-IgG2 treatment. C: Effect of 1D05-IgG2 on total cholesterol. All results are means ± SEM from n = 3 replicates.

Ni, Y. G., Di Marco, S., Condra, J. H., Peterson, L. B., Wang, W., Wang, F., ... & Wood, D. D. (2011). A PCSK9-binding antibody that structurally mimics the EGF (A) domain of LDL-receptor reduces LDL cholesterol in vivo. Journal of lipid research, 52(1), 78-86.