However, such acceleration of clearance can give rise to a decline of only log (1/aV) = 0.75-0.86 log10 copies/mL (Fig. 2), because viral load during accelerated clearance will reach a new steady state at V0/a (Supporting Material, Equation 6). This is considerably less than the viral decline observed here, and thus accelerated clearance is a necessary but not sufficient explanation of the antiviral mechanism. The observed HBV

DNA kinetics during HepeX-B infusion can be explained by assuming a combination of two mechanisms of action: an accelerated CH5424802 HBV clearance from the circulation (aV > 1), mediated by the infused antibodies, together with partial blocking of virion release from infected cells (1 > εV > 0), as shown in Fig. 2. Using this assumption, we performed nonlinear fitting for all patients (Fig. 3 and Table 1A), assuming either a slow or a rapid intrinsic half-life of HBV

virions, thus giving, accordingly, low and high estimates of the effectiveness in blocking virion release of εV = 76.2%-96.1% (97%-99.5%). The analysis of HBsAg kinetics following HepeX-B infusion yields similar conclusions with higher acceleration of clearance and effectiveness in blocking release (Fig. 3). Analysis of HBsAg decline during treatment with lamivudine shows decline with a half-life of 38 days, which we use as a maximal estimate of HBsAg half-life, with a minimal estimate of 1 day (data not shown). Nonlinear fitting of HBsAg decline during HepeX-B gives a half-life of 0.09-0.19 Adriamycin hours, thus corresponding to a minimal (maximal) estimate of the acceleration of HBsAg clearance from circulation of aA = 126-282 (4,800-10,729) times an intrinsic half-life of 1 (38) days. As for the HBV DNA kinetics, accelerated clearance of HBsAg cannot by itself explain the total decline, and thus a maximal (minimal) estimate of effectiveness in

blocking release of HBsAg particles from infected cells is εA = 98.6-99.5% (46.2%-82.4%). Note, that because all patients reached undetectable levels of HBsAg, the decline is probably larger and thus the estimates of effectiveness of blocking HBsAg release are most probably underestimated next here. In addition to the three patients who received a single infusion of 40 mg HepeX-B, six patients received multiple HepeX-B doses of 40 and 80 mg (Fig. 1C-F), but those patients had less frequent sampling and the duration of infusion was only 4 hours. We have therefore tested in the first three patients with frequent samples whether the estimation of decline half-life and total decline from 0.5 to 4 hours is accurate enough. We found that although both values were slightly underestimated with less frequent samples, the estimate of effectiveness in blocking release with the 4-hour sample was still accurate within 90%-110% of the nonlinear fitting (Table 1B). In five of six patients who received multiple doses of HepeX-B, a rapid decline with a half-life 0.31-0.66 hours and magnitude of 1.6-3.