Table 1 Affinity (KD), PK, and PD parameters of antibodies dosed in mouse models
From: Leveraging neonatal Fc receptor (FcRn) to enhance antibody transport across the blood brain barrier
Study | Fc Variant | Affinity (KD) at pH6.0 (nM) | Affinity (KD) at pH7.4 (nM) | Serum Cmaxa | Serum AUCa | Brain Cmaxa | Brain AUCa | Brain:Serum Ratio % |
|---|---|---|---|---|---|---|---|---|
WT mice hIgG1 (KD to mFcRn) | anti-BACE1 WT | 238 | 6940 | 1.0 | 1.0 | 1.0 | 1.0 | 0.23 |
anti-BACE1 YTE | 14.8 | 836 | 1.4 | 0.7 | 3.2 | 4.0 | 1.23 | |
anti-gD WT | ND | ND | 1.8 | 1.3 | 1.4 | 1.5 | 0.26 | |
hFcRn mice hIgG1 (KD to hFcRn) | anti-BACE1 WT | 1012 | >10000 | 1.0 | 1.0 | 1.0 | 1.0 | 0.25 |
anti-BACE1 YTE | 105 | >10000 | 1.8 | 1.6 | 0.8 | 0.9 | 0.14 | |
anti-gD WT | ND | ND | 1.6 | 1.6 | 1.3 | 1.3 | 0.20 | |
WT mice mIgG2a (KD to mFcRn) | WT | 1380 | >10000 | 1.0 | 1.0 | 1.0 | 1.0 | 0.12 |
M252F | 74 | 3320 | 1.0 | 1.0 | 1.8 | 1.9 | 0.23 | |
M252Y | 16 | 826 | 1.0 | 0.6 | 3.2 | 3.0 | 0.58 | |
M252Y.Q309T | 6.2 | 308 | 1.0 | 0.3 | 4.9 | 3.4 | 1.26 | |
hFcRn mice hIgG1 (KD to hFcRn) | anti-BACE1 WT | 1012 | >10000 | 1.0 | 1.0 | 1.0 | 1.0 | 0.04 |
anti-BACE1 YY | 13 | 981 | 1.5 | 0.5 | 2.0 | 1.5 | 0.12 | |
anti-BACE1 YQAY | 6.9 | 234 | 1.1 | 0.7 | 5.2 | 4.3 | 0.27 |
