Acid hydrolysis of monoclonal antibodies

Davagnino, Juan; Wong, C; Shelton, Lorraine; Mankarious, Samia

doi:10.1016/0022-1759(95)00110-v

Cited by 12 publications

(7 citation statements)

References 2 publications

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“…41 Starting slightly at pH 5 and increasing dramatically at lower pH, two specific sites within the CH2 domain (Fig. 3), G 236 -G 237 , 4,13 and D 270 -P 271 , 34,40,53 undergo cleavage rapidly. The D 270 -P 271 bond is subject to acid hydrolysis involving the Asp side chain, and therefore, is specifically accelerated under low pH conditions.…”

Section: Constant Immunoglobulin Domainsmentioning

confidence: 99%

“…CE-SDS is now commonly used in the pharmaceutical industry due to the straightforward quantification, often better resolution compared with the traditional slab gel SDS PAGE and improved sensitivity with fluorescence detection. 45,46 Identification of the cleavage sites, however, is hindered by the difficulty of fraction collection, and consequently, very little 31,34 has been published regarding the identity of the observed fragments. Further development is…”

mentioning

confidence: 99%

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Fragmentation of monoclonal antibodies

Vlasak

Ionescu

2011

mAbs

288

230

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Section: Constant Immunoglobulin Domainsmentioning

confidence: 99%

mentioning

confidence: 99%

Fragmentation of monoclonal antibodies

Vlasak

Ionescu

2011

mAbs

288

230

View full text Add to dashboard Cite

“…Based on the mechanisms of separation, these methods can be divided into two groups: size-based and chemistry of amino acid side chains. Size-based separation methods include size-exclusion chromatography (SEC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and capillary electrophoresis with SDS (CE-SDS) (Dada, Rao, Jones, Jaya, & Salas-Solano, 2017;Davagnino, Wong, Shelton, & Mankarious, 1995;H. Liu, Gaza-Bulseco, & Chumsae, 2009;Rao & Kroon).…”

Section: Analytical Methods For Disulfide Bond Reduction Monitoring and Analysismentioning

confidence: 99%

Antibody Disulfide Bond Reduction and Recovery during Biopharmaceutical Process Development - A Review

Ren

Tan

Ehamparanathan

et al. 2020

Preprint

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Disulfide bond reduction has been a challenging issue in antibody manufacturing, as it leads to reduced product purity, failed product specifications and more importantly, impacting drug safety and efficacy. Scientists across industry have been examining the root causes and developing mitigation strategies to address the challenge. In recent years, with the development of high-titer mammalian cell culture processes to meet the rapidly growing demand for antibody biopharmaceuticals, disulfide bond reduction has been observed more frequently. Thus, it is necessary to continue evolving the disulfide reduction mitigation strategy and development of novel approaches to achieve high product quality. Additionally, in recent years as more complex molecules emerge such as bispecific and trispecific antibodies, the molecular heterogeneity due to incomplete formation of the interchain disulfide bonds becomes a more imperative issue. Given the disulfide reduction challenges that our industry are facing, in this review, we provide a comprehensive contemporary scientific insight into the root cause analysis of disulfide reduction during process development of antibody therapeutics, mitigation strategies and recovery based on our expertise in commercial and clinical manufacturing of biologics. First, this paper intended to highlight different aspects of the root cause for disulfide reduction. Secondly, to provide a broader understanding of the disulfide bond reduction in downstream process, this paper discussed disulfide bond reduction impact to product stability and process performance, analytical methods for detection and characterization, process control strategies and their manufacturing implementation. In addition, brief perspectives on development of future mitigation strategies will also be reviewed, including platform alignment, mitigation strategy application for bi- and tri-specific antibodies and using machine learning to identify molecule susceptibility of disulfide bond reduction. The data in this review are originated from both the published papers and our internal development work.

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“…Especially CE-SDS is used in pharmaceutical industry due to the straightforward quantification and better resolution compared to the traditional slab gel SDS PAGE [180], and the opportunity to improve the sensitivity with fluorescence detection to detect fragmentation patterns [203,204]. But the identification of cleavage sites is complicated due to its difficulty to collect the fractions [205,206]. The exact identification of fragmentation sites is carried out by HPLC methods coupled with MS (LC-MS) or N-terminal sequencing [207,208].…”

Section: Structural Perturbations Due To Photo-oxidationmentioning

confidence: 99%

Photo-Oxidation of Therapeutic Protein Formulations: From Radical Formation to Analytical Techniques

et al. 2021

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UV and ambient light-induced modifications and related degradation of therapeutic proteins are observed during manufacturing and storage. Therefore, to ensure product quality, protein formulations need to be analyzed with respect to photo-degradation processes and eventually protected from light exposure. This task usually demands the application and combination of various analytical methods. This review addresses analytical aspects of investigating photo-oxidation products and related mediators such as reactive oxygen species generated via UV and ambient light with well-established and novel techniques.

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Acid hydrolysis of monoclonal antibodies

Cited by 12 publications

References 2 publications

Fragmentation of monoclonal antibodies

Fragmentation of monoclonal antibodies

Antibody Disulfide Bond Reduction and Recovery during Biopharmaceutical Process Development - A Review

Photo-Oxidation of Therapeutic Protein Formulations: From Radical Formation to Analytical Techniques

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