Immunoglobulin molecules with improved characteristics
View Patent ↗The present invention provides for IgG1 molecules with improved characteristics. In particular, substitution mutations are provided that, in combination, facilitate improved placental transfer, improved serum half-life and improved FcRn binding. Substitution mutations are also provided, that in combination, can be used to block FcRn function and thereby increase the clearance rates of other (endogenous or exogenous) IgGs, block placental transport of IgGs and have increased affinity/reduced pH dependence for FcRn binding.
1. An IgG molecule comprising a human Fc domain wherein (EU numbering) His433 is changed to Lys433, Asn434 is changed to Phe434, and Tyr436 is unchanged.
2. The IgG molecule of claim 1 , wherein the IgG molecule is an IgG1 molecule.
3. The IgG molecule of claim 1 , wherein the IgG molecule Fc domain contains wild-type residues at positions 252, 254 and 256.
4. The IgG molecule of claim 1 , wherein the IgG molecule Fc domain contains wild-type residues at all positions other than 433 and 434.