NeuroMab™ Anti-NGF BBB Shuttle Antibody, Clone E3

Fig.1 is a graph comparing the effect of blocking NGF of various Fab in the presence of human NGF 0.04 ng / ml.

Elimination was measured with an antibody-dependent cell cytotoxicity assay ("ADCC").

Fig.2 It is a graph that representss resting pain evaluated 24 hours after surgery and shows that treatment with anti-NGF E3 antibody 0.02 mg / kg, 0.1 mg / kg, 0.6 mg / kg or 1 mg / kg reduced pain. "*" Indicates a statistically significant difference (p <0.5) of the negative control.

Elimination was measured with an antibody-dependent cell cytotoxicity assay ("ADCC").

Fig.3 is a graph showing the results of BIAcore analysis of the human NGF binding affinity of the E3 (Fab) antibody (called "Fab 3E"). E3 was linked to human NGF with a KD of approximately 0.07 nM (and with a kon of approximately 6.0 x 105 M-1 s-1 and a koff of approximately 4.2 x 10-5 s-1).

Elimination was measured with an antibody-dependent cell cytotoxicity assay ("ADCC").

Fig.4 is a graph representsing that the E3 antibody blocks the interaction of NGF with its receptors, trkA and p75.

The X axis corresponds to the concentration of 3E antibody (Fab) and the Y axis corresponds to NGF binding (percentage of maximum UR). Increased concentrations of Fab E3 blocked the interaction of NGF with both p75 and trkA, as shown by signal reduction (measured in UR). When the concentration of E3 antibody (Fab) was equalized with the concentration of NGF, no NGF binding was observed (as shown by a zero signal).

Fig.5 is a graph that representss the capacity of various concentrations (20, 4, 0.8, 0.16, 0.032, 0.0064, 0.00128 and 0.0 nM) of antibody E3 (solid triangles; called “ 3E ”), antibody 911 (solid circles) and a trkA receptor immunoadhesin (shaded squares; called“ trkA-Fc) to inhibit NGF-dependent survival of trigeminal neurons E13.5.

The X axis corresponds to the concentration of 3E antibody (Fab) and the Y axis corresponds to NGF binding (percentage of maximum UR). Increased concentrations of Fab E3 blocked the interaction of NGF with both p75 and trkA, as shown by signal reduction (measured in UR). When the concentration of E3 antibody (Fab) was equalized with the concentration of NGF, no NGF binding was observed (as shown by a zero signal).

Fig.6 It is a graph that demonstrates the nociceptive response in arthritic rats (rheumatoid arthritis model) after administration of anti-NGF antibodies (E3 and 911) in D14 and D19.

The X axis corresponds to the concentration of 3E antibody (Fab) and the Y axis corresponds to NGF binding (percentage of maximum UR). Increased concentrations of Fab E3 blocked the interaction of NGF with both p75 and trkA, as shown by signal reduction (measured in UR). When the concentration of E3 antibody (Fab) was equalized with the concentration of NGF, no NGF binding was observed (as shown by a zero signal).

Fig.7 It is a graph that demonstrates the effects of anti-NGF antibodies on body weight in arthritis in rats (rheumatoid arthritis model) after administration of anti-NGF antibodies in D14 and D19.

The X axis corresponds to the concentration of 3E antibody (Fab) and the Y axis corresponds to NGF binding (percentage of maximum UR). Increased concentrations of Fab E3 blocked the interaction of NGF with both p75 and trkA, as shown by signal reduction (measured in UR). When the concentration of E3 antibody (Fab) was equalized with the concentration of NGF, no NGF binding was observed (as shown by a zero signal).