The neonatal Fc receptor for IgG (FcRn) has been well characterized in the transfer of passive humoral immunity from a mother to her fetus. In addition, throughout life, FcRn protects IgG from degradation, thereby explaining the long half-life of this class of antibody in the serum. In recent years, it has become clear that FcRn is expressed in various sites in adults, where its potential function is now beginning to emerge. In addition, recent studies have examined the interaction between FcRn and the Fc portion of IgG with the aim of either improving the serum half-life of therapeutic monoclonal antibodies or reducing the half-life of pathogenic antibodies. This Review summarizes these two areas of FcRn biology.

FcRn: the neonatal Fc receptor comes of age

Tumor necrosis factor antagonist mechanisms of action: A comprehensive review

Antibodies constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The generation of potent antibody therapeutics, which I review here, is an iterative design process that involves the generation and optimization of antibodies to improve their clinical potential.

Potent antibody therapeutics by design

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/jps.20727

Antibody structure, instability, and formulation

The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the foundation for the discovery and development of future therapeutic antibodies. Here we review how key insights obtained from the development of therapeutic antibodies complemented by newer antibody engineering technologies are delivering a second generation of therapeutic antibodies with promise for greater clinical efficacy and safety.

Therapeutic antibodies for autoimmunity and inflammation

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jps.20178

Antibody pharmacokinetics and pharmacodynamics.

We have recently shown that intravenous immunoglobulin (IVIG) therapy leads to an increased rate of anti-platelet antibody clearance in an animal model of immune thrombocytopenia. The present study was performed to confirm the importance of the FcRn receptor in mediating this effect of IVIG. The pharmacokinetics of an anti-platelet antibody, 7E3, were studied in mice lacking expression of FcRn and in control mice, both in the presence and absence of IVIG. IVIG increased the clearance of 7E3 in mice with functioning FcRn receptors, with an average clearance value of 14.4 ± 1.4 ml/d/kg in IVIG treated mice vs. 5.2 ± 0.3 ml/d/kg in controls (P

Intravenous Immunoglobulin Mediates an Increase in Anti-Platelet Antibody Clearance via the FcRn Receptor

Effects of intravenous immunoglobulin on platelet count and antiplatelet antibody disposition in a rat model of immune thrombocytopenia.

The present invention relates to the field of diabetes. More particularly, the invention relates to PEGylated insulin lispro compounds that are PEGylated with high molecular weight poly(ethylene glycol), are highly soluble at physiological pH, have an extended duration of action, and characterized by pharmacokinetic, pharmacodynamic, and/or activity peak-trough ratios of less than 2. The invention also relates to methods of providing such molecules, to pharmaceutical compositions containing them, and to their therapeutic uses.

Pegylated insulin lispro compounds

Antibodies that target endogenous soluble ligands are an important class of biotherapeutic agents. While much focus has been placed on characterization of antibody pharmacokinetics, less emphasis has been given to characterization of antibody effects on their soluble targets. We describe here the properties of a generalized mechanism-based PK/PD model used to characterize the in vivo interaction of an antibody and an endogenous soluble ligand. The assumptions and properties of the model are explored, and situations are described when deviations from the basic assumptions may be necessary. This model is most useful for in vivo situations where both antibody and ligand levels are available following drug administration. For a given antibody exposure, the extent and duration of suppression of free ligand is impacted by the apparent affinity of the interaction, as well as by the rate of ligand turnover. The applicability of the general equilibrium model of in vivo antibody-ligand interaction is demonstrated with an anti-As antibody.

Ryan John Hansen

Papers

Antibody pharmacokinetics and pharmacodynamics.

Intravenous Immunoglobulin Mediates an Increase in Anti-Platelet Antibody Clearance via the FcRn Receptor

Effects of intravenous immunoglobulin on platelet count and antiplatelet antibody disposition in a rat model of immune thrombocytopenia.

Pegylated insulin lispro compounds

Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets