Characterization, Stabilization and Formulation Design of IgG and Secretory IgA Monoclonal Antibody Candidates during Storage and Administration
type: CreativeWork
description: ABSTRACT Monoclonal antibodies (mAbs) have become a class of therapeutic protein-based drugs of high importance for treating numerous human diseases. As a complex, delicate three dimensional molecule, a mAb can be sensitive to ambient environments and thus often display colloidal/conformational instability during manufacturing, storage, and administration. The use of formulation strategies, such as employing specific excipients and/or particular solution conditions (e.g., pH and buffers), can significantly improve a mAb’s pharmaceutical stability properties. In this Ph.D. thesis research work, both formulation/storage stability as well as stability during in vitro models of mAb administration in vivo are evaluated with two different of classes of immunoglobulin molecules (IgG and IgA). In addition, the effect of specific classes of excipients and solution conditions are examined by using a wide variety of physicochemical and immunological binding analytical techniques. Specifically, the second and third chapters of the Ph.D. thesis work focus on the formulation development of high-concentration mAb dosage forms for subcutaneous (SC) injections. Reversible self-association (RSA) of mAbs, which is primarily due to intermolecular protein-protein interactions (PPIs) between mAb molecules, has emerged as an important formulation challenge in terms of significantly increasing solution viscosity and turbidity as well as initiating phase separation. In these two chapters, two different human IgG1 molecules (mAb-J and mAb-C), which showed strong RSA propensity at relatively high protein concentrations, were comprehensively studied to better understand their solution properties and molecular behaviors by both biophysical techniques as well as hydrogen-deuterium exchange mass spectrometry (HX-MS). The aim is to not only characterize mAb molecular properties and solution behavior at relatively high protein concentrations, but also to develop a better mechanistic understanding b…
abstract: ABSTRACT Monoclonal antibodies (mAbs) have become a class of therapeutic protein-based drugs of high importance for treating numerous human diseases. As a complex, delicate three dimensional molecule, a mAb can be sensitive to ambient environments and thus often display colloidal/conformational instability during manufacturing, storage, and administration. The use of formulation strategies, such as employing specific excipients and/or particular solution conditions (e.g., pH and buffers), can significantly improve a mAb’s pharmaceutical stability properties. In this Ph.D. thesis research work, both formulation/storage stability as well as stability during in vitro models of mAb administration in vivo are evaluated with two different of classes of immunoglobulin molecules (IgG and IgA). In addition, the effect of specific classes of excipients and solution conditions are examined by using a wide variety of physicochemical and immunological binding analytical techniques. Specifically, the second and third chapters of the Ph.D. thesis work focus on the formulation development of high-concentration mAb dosage forms for subcutaneous (SC) injections. Reversible self-association (RSA) of mAbs, which is primarily due to intermolecular protein-protein interactions (PPIs) between mAb molecules, has emerged as an important formulation challenge in terms of significantly increasing solution viscosity and turbidity as well as initiating phase separation. In these two chapters, two different human IgG1 molecules (mAb-J and mAb-C), which showed strong RSA propensity at relatively high protein concentrations, were comprehensively studied to better understand their solution properties and molecular behaviors by both biophysical techniques as well as hydrogen-deuterium exchange mass spectrometry (HX-MS). The aim is to not only characterize mAb molecular properties and solution behavior at relatively high protein concentrations, but also to develop a better mechanistic understanding b…
author: Hu, Yue
language: en
keywords: Pharmaceutical sciences
date published: 2019-05-31
date modified: 2026-07-24T02:47:03Z
provider: University of Kansas
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Kansas

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1808/29546