Due to their potential influence on stability, pharmacokinetics, and product consistency, antibody charge variants have attracted considerable attention in the biotechnology industry. Subtle to significant differences in the level of charge variants and new charge variants under various cell culture conditions are often observed during routine manufacturing or process changes and pose a challenge when demonstrating product comparability. To explore potential solutions to control charge heterogeneity, monoclonal antibodies (mAbs) with native, wild-type C-termini, and mutants with C-terminal deletions of either lysine or lysine and glycine were constructed, expressed, purified, and characterized in vitro and in vivo. Analytical and physiological characterization demonstrated that the mAb mutants had greatly reduced levels of basic variants without decreasing antibody biologic activity, structural stability, pharmacokinetics, or subcutaneous bioavailability in rats. This study provides a possible solution to mitigate mAb heterogeneity in C-terminal processing, improve batch-to-batch consistency, and facilitate the comparability study during process changes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.xphs.2016.04.027 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unprecedented Site Preference of Sn in the Structure of CoSn-Type NiInSn ( < 0.7).
Inorg Chem
January 2025
Department of Chemistry, IIT Kharagpur, Kharagpur 721302, India.
A series of compositions NiInSn ( = 0-1) were synthesized by conventional high-temperature synthesis, and as-synthesized samples were checked by powder X-ray diffraction experiments. NiInSn ( < 0.7) mainly forms the ternary variant of the CoSn-type structure (6/), whereas, = 0.
View Article and Find Full Text PDFIdentification of novel RIPK4 variants in a Chinese patient with Arthrogryposis Multiplex Congenita (AMC).
Ital J Pediatr
January 2025
Department of Orthopaedics, Xiangya Hospital of Central South University, Changsha, China.
Background: Arthrogryposis multiplex congenita (AMC) is a congenital disorder characterized by multiple joint involvement, primarily affecting limb mobility and leading to various tissue contractures. Variations in the RIPK4 gene may impact connective tissues, thereby resulting in a spectrum of malformations. This study aimed to identify the genetic etiologies of AMC patients and provide genetic testing information for further diagnosis and treatment of AMC.
View Article and Find Full Text PDFRedox-Active Bisphosphonate-Based Viologens as Negolytes for Aqueous Organic Flow Batteries.
Chemistry
January 2025
University of Turku: Turun Yliopisto, Department of Mechanical and Materials Engineering, FINLAND.
Viologen derivatives feature two reversible one-electron redox processes and have been extensively utilized in aqueous organic flow batteries (AOFBs). However, the early variant, methyl viologen (MVi), exhibits low stability in aqueous electrolytes, restricting its practical implementation in AOFB technology. In this context, leveraging the tunability of organic molecules, various substituents have been incorporated into the viologen core to achieve better stability, lower redox potential, and improved solubility.
View Article and Find Full Text PDFCharacterization for the Similarity Assessment Between the Proposed Biosimilar SB17 and Ustekinumab Reference Product Using State-of-the-Art Analytical Methods.
Drugs R D
January 2025
Quality Evaluation Team, Samsung Bioepis Co., Ltd, Incheon, South Korea.
Background: SB17 is being developed as a biosimilar to ustekinumab reference product (RP), a human monoclonal antibody (IgG1 kappa immunoglobulin) that binds to the common p40 subunit of cytokines interleukin (IL)-23 and IL-12. Binding to this subunit prevents interaction with their receptor, resulting in modulation in the immune system responses that play a key role in inflammatory disease.
Objective: The objective of this study was to demonstrate structural, physicochemical, and biological similarity between ustekinumab RP and SB17 using various state-of-the-art analytical methods.
Ion exchange chromatography of biotherapeutics: Fundamental principles and advanced approaches.
J Chromatogr A
January 2025
School of Pharmaceutical Sciences, University of Geneva, CMU - Rue Michel Servet 1, 1211 Geneva 4, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU - Rue Michel Servet 1, 1211 Geneva 4, Switzerland. Electronic address:
Ion exchange chromatography (IEX) is an important analytical technique for the characterization of biotechnology-derived products, such as monoclonal antibodies (mAbs) and more recently, cell and gene therapy products such as messenger ribonucleic acid (mRNA) and adeno-associated viruses (AAVs). This review paper first outlines the basic principles and separation mechanisms of IEX for charge variant separation of biotherapeutics, and examines the different elution modes based on salt or pH gradients. It then highlights several recent trends when applying IEX for the characterization of biotechnology-derived products, including: i) the effective use of pH gradients, ii) the improvement of selectivity by using organic solvents in the mobile phase, multi-step gradients, or by combining ion pairing and ion exchange, and iii) the increase in analytical throughput using ultra-short columns or automated screening of conditions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!