Influence of pH on Heat-Induced Aggregation and Degradation of Therapeutic Monoclonal Antibodies
スポンサーリンク
概要
- 論文の詳細を見る
Monoclonal antibodies are widely used for the treatment of various diseases, and because therapeutic monoclonal antibodies are stored in an aqueous solution or in a lyophilized state, the preparation of a stabilizing formulation that prevents their deterioration (degradation and aggregation) is crucial. Given the structural similarities of the immunoglobulin G (IgG) framework regions and a diversity of only four subclasses, we aimed to find common conditions that stabilize many different antibodies. In this study, we analyzed the effect of pH (the most critical factor in establishing a stable formulation) on human monoclonal antibodies from subclasses IgG1, IgG2, and IgG4, all of which have been utilized in antibody therapeutics. We found that human IgGs are stable with minimal heat-induced degradation and aggregation at pH 5.0—5.5 irrespective of their subclass. We also found that IgG1 is more susceptible to fragmentation, whereas IgG4 is more susceptible to aggregation. This basic information emphasizing the influence of pH on IgG stability should facilitate the optimization of formulation conditions tailored to individual antibodies for specific uses.
- 公益社団法人 日本薬学会の論文
著者
-
Sawa Eiji
Bio Process Res. And Dev. Laboratories Production Div. Kyowa Hakko Kirin Co. Ltd.
-
Wakamatsu Kaori
Department Of Biochemical And Chemical Engineering Gunma University
-
Ishikawa Tomoyoshi
Bio Process Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd.
-
Ito Takahiko
Bio Process Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd.
-
Endo Ryosuke
Bio Process Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd.
-
Nakagawa Keiko
Bio Process Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd.
-
Sawa Eiji
Bio Process Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd.
関連論文
- 2P050 Structural Analysis of G-Protein-Bound Mastoparan-X by Solid-State NMR(29. Protein structure and dynamics (II),Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)
- Structure Determination of an Immunopotentiator Peptide, Cinnamycin, Complexed with Lysophosphatidylethanolamine by H-NMR^1
- Robust and Efficient Expression System for Stable Isotope-Labeled Peptides
- Investigation of Signaling Mechanisms Induced by Mitocryptides in Neutrophilic/granulocytic Cells
- Functional Cryptic Peptides and Their Accumulative Signaling Mechanisms
- Prediction and Identification of Endogenous Functional Cryptic Peptides that Directly Activate G Proteins
- Functional Cryptic Peptides : Identification of Bioactive Peptides Hidden in Protein Structures
- Synthesis and Properties of High-Molecular-Weight Polypeptides Containing Tryptophan III. Synthesis and Properties of Copolypeptides Containing 1-N_-Formyltryptophan with Alanine^
- Effect of Proline Residue in Polypeptides on the Interactions between Polypeptides and DNA^
- The Influence of Serine Residue on the Poly (Ser-co-Lys) in HFIP/Water Solutions
- Synthesis and Properties of High-Molecular-Weight Polypeptides Containing Tryptophan II. Copolypeptides of Tryptophan with Various Amino Acids^
- Evaluation of the Aggregation States of Monoclonal Antibodies by Diverse and Complementary Methods
- GDP-GTP Exchange Processes of Gα_ Protein are Accelerated/Decelerated Depending on the Type and the Concentration of Added Detergents
- Influence of pH on Heat-Induced Aggregation and Degradation of Therapeutic Monoclonal Antibodies
- Inhibition of Amyloid Formation by Choline-O-Sulfate
- Prevention of Stirring-Induced Microparticle Formation in Monoclonal Antibody Solutions