Table III.
Summary of Biological Activity Attributes for ABP 710, Infliximab (US), and Infliximab (EU)
| Analytical Testing/Attribute | ABP 710 Range (n) | Infliximab US Range (n) | Infliximab EU Range (n) |
|---|---|---|---|
| Inhibition of sTNFα-induced apoptosis in U937 (potency) (%) | 87–112 (14) | 78–117 (28) | 89–118 (19) |
| Binding to sTNFα by ELISA (%) | 88–109 (14) | 88–112 (25) | 98–104 (16) |
| Binding to sTNFα by SPR (%) | 92–109 (10) | 90–105 (10) | 89–103 (10) |
| Binding kinetics to sTNFα by SPR (Kd, pM) | 113–135 (6) | 110–144 (6) | 117–142 (6) |
| Inhibition of sTNFα-induced IL-8 release in HUVEC (%) | 97–102 (3) | 98–116 (3) | 92–101 (3) |
| Inhibition of sTNFα-induced cell death in L929 (%) | 94–104 (3) | 100–119 (3) | 92–98 (3) |
| Binding to mbTNFα on CHO MT-3 cells by imaging cytometry (%) | 92–108 (14) | 91–114 (25) | 97–113 (16) |
| Reverse signaling in Jurkat mbTNFα cell line (%) | 95–109 (14) | 90–114 (24) | 96–107 (16) |
| Binding to FcγRIIIa (158V) by SPR (%) | 98–117 (10) | 82–105 (10) | 89–110 (10) |
| Binding kinetics to FcγRIIIa (158V) by SPR (Kd, nM) | 68–80 (10) | 63–93 (10) | 59–89 (10) |
| Binding to FcγRIIIa (158F) by SPR (%) | 88–119 (10) | 86–108 (10) | 87–106 (10) |
| NK92 ADCC activity (%) | 94–-133 (14) | 80–169 (27) | 100–166 (20) |
| PBMC ADCC activity (%) | 90–118 (10) | 82–119 (10) | 86–41 (10) |
| Binding to C1q by ELISA (%) | 83–104 (14) | 60–93 (25) | 61–95 (17) |
| CDC activity (%) | 93–110 (14) | 93–136 (27) | 93–135 (19) |
| Binding to FcγRIIa (131R) by SPR | 101–104 (3) | 98–99 (3) | 100–105 (3) |
| ADCP activity | 97–104 (3) | 94–116 (3) | 95–106 (3) |
| Binding to FcγRIa by AlphaLISA | 92–99 (3) | 92–95 (3) | 92–101 (3) |
| Binding to FcγRIIb by SPR | 91–105 (3) | 91–99 (3) | 96–110 (3) |
| Binding to FcγRIIIb by SPR | 96–117 (10) | 91–111 (10) | 87–106 (10) |
| Binding to FcRn by AlphaScreen (%) | 90–123 (14) | 92–108 (27) | 87–112 (20) |
| Binding to FcRn by SPR (%) | 91–109 (10) | 93–134 (10) | 84–137 (10) |
n = number of lots tested; all relative activity (%) was calculated against ABP 710 reference standard lot
ADCC antibody-dependent cell-mediated cytotoxicity; ADCP antibody-dependent cellular phagocytosis; CDC complement-dependent cytotoxicity; CHO Chinese Hamster Ovary cell; FcRn Fc neonatal receptor; ELISA enzyme-linked immunosorbent assay; HUVEC human umbilical vein cells; infliximab (EU) European Union-authorized infliximab; infliximab (US) United States Food and Drug Administration-licensed infliximab; mbTNF membrane bound tumor necrosis factor; n number of batches; PBMC peripheral blood mononuclear cell; SPR surface plasmon resonance; sTNF soluble tumor necrosis factor; TNF tumor necrosis factor; TNFα tumor necrosis factor-α