Product attributes of the Li81 mAb, Fab2, Fab, and PEG-Fab
Li81 samples were characterized for size and percentage of monomer by SEC, binding to LINGO-1 by ELISA, activity using the OPC differentiation bioassay, serum pharmacokinetic parameters in Sprague Dawley rats (Cmax, t1/2, Vz/F, Cl/F), and in vivo efficacy using procedures described under Materials and Methods. Bioassay values indicate the lowest concentration that promoted MBP expression.
| Property | Li81 mAb | Fab2 | Fab | PEG-Fab |
|---|---|---|---|---|
| Valency | Bivalent | Bivalent | Monovalent | Monovalent |
| Effector function | Low | None | None | None |
| Mass, Da | 144,444 | 96,688 | 47,340 | 66,000 |
| Size SEC, Da | 140,000 | 100,000 | 50,000 | 250,000 |
| Percentage monomer SEC | 99 | 98 | 95 | 98 |
| EC50, nM ELISA | 0.017 | 0.017 | 0.041 | 0.15 |
| EC50, nM FACS | 0.02 | N.D. | N.D. | 3.0 |
| OPC assay, nM | 0.7 | 1.0 | 2.0 | 2.0 |
| Cmax, μg/ml | 27 | 13 | 3.7 | 27 |
| t1/2, h | 120 | 12 | 2.7 | 26 |
| AUC, μg · h/ml | 3600 | 300 | 27 | 1300 |
| Vz/F, ml/kg | 140 | 180 | 430 | 90 |
| Cl/F, ml · h/kg | 0.8 | 10 | 110 | 2.3 |
| Efficacy LPC model in Sprague Dawley rats | 1 mg/kg, 1×/week | 2 mg/kg, 3×/week | N.D. | 1.5 mg/kg, 3×/week |
| Efficacy EAE model in Brown Norway rats | 3 mg/kg, 1×/week | 6 mg/kg, 3×/week | N.D. | N.D. |
N.D., not determined.