Table 3. Constant regions used in the cynomolgus monkey PK study.
Constant region | Backbone | FcRn binding | FcγR & C1q binding | pI |
---|---|---|---|---|
SG406 | human IgG4 | silenced | silenced | low |
SG407 | human IgG4 | enhanced | silenced | low |
SG419 | human IgG4 | enhanced | silenced | high |
SG115 | human IgG1 | enhanced | silenced | high |
The constant region of human IgG4 or IgG1 was engineered in this study. In SG406, FcRn binding was abrogated to prevent the antibody being salvaged back to plasma from the endosomes by FcRn-mediated recycling. In SG419, human IgG4 was engineered to increase the pI. The surface-charge engineering was not incorporated in SG115, because the human IgG1 backbone naturally had high pI.