Structural highlights
Function
IGHG4_HUMAN
Publication Abstract from PubMed
In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.
In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance.,Shan L, Dyk NV, Haskins N, Cook KM, Rosenthal KL, Mazor R, Dragulin-Otto S, Jiang Y, Wu H, Dall'Acqua WF, Borrok MJ, Damschroder MM, Oganesyan V Commun Biol. 2021 Sep 8;4(1):1048. doi: 10.1038/s42003-021-02565-5. PMID:34497355[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shan L, Dyk NV, Haskins N, Cook KM, Rosenthal KL, Mazor R, Dragulin-Otto S, Jiang Y, Wu H, Dall'Acqua WF, Borrok MJ, Damschroder MM, Oganesyan V. In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance. Commun Biol. 2021 Sep 8;4(1):1048. doi: 10.1038/s42003-021-02565-5. PMID:34497355 doi:https://dx.doi.org/10.1038/s42003-021-02565-5
