Evaluation of Product Equivalence During Process Optimization for Manufacture of a Human IgM Monoclonal Antibody

Maiorella, B.; Ferris, R.D.; Thomson, Jackie; White, Caitlin; Brannon, Mark; Hora, Maninder; Henriksson, Thomas; Triglia, Richard P.; Kunitani, Michael; Kresin, Lilia; Dollinger, Gavin; Jones, Robert E.; Senyk, George; Young, Judy; Moyer, Bryan D.; McEntire, John E.; Dougherty, Jennifer; Monica, Thomas J.; Goochee, Charles F.

doi:10.1006/biol.1993.1076

Cited by 14 publications

(2 citation statements)

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“…Second, the material tested by Barth was isolated from human serum, whereas most of the other IgMs were produced in mouse, rat, or hamster (e.g., CHO) cells. Since changes in production host cells and culture conditions for IgGs are known to result in changes in glycosylation [188], and similar changes have been noted with IgM antibodies [189], such differences in PK are not unanticipated. Lastly, differences in analytical techniques (isotope vs. ELISA) and subject populations (normal vs. diseased) are also contributing factors.…”

Section: Igm Pharmacokineticsmentioning

confidence: 86%

Structure, Function, and Therapeutic Use of IgM Antibodies

et al. 2020

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Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro-immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract. Several naturally occurring IgM antibodies have been explored as therapeutics in clinical trials, and a new class of molecules, engineered IgM antibodies with enhanced binding and/or additional functional properties are being evaluated in humans. Here, we review the considerable progress that has been made regarding the understanding of biology, structure, function, manufacturing, and therapeutic potential of IgM antibodies since their discovery more than 80 years ago.

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Section: Igm Pharmacokineticsmentioning

confidence: 86%

Structure, Function, and Therapeutic Use of IgM Antibodies

et al. 2020

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“…Even though the relationship between an antibody's biochemical characteristics and its pharmacokinetics has not been fully determined, the production of a consistent product remains an important issue from a regulatory viewpoint. Equally important is the necessity to demonstrate product equivalence upon implementing process changes (Maiorella, 1993b).…”

Section: Mohan Et Al Recently Observed the Degradation Of Anmentioning

confidence: 99%

In Pursuit of the Optimal Fed‐Batch Process for Monoclonal Antibody Production

Bibila

Robinson

1995

Biotechnology Progress

238

142

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Fed-batch culture currently represents the most attractive choice for large scale production for monoclonal antibodies (MAbs), due to its operational simplicity, reliability, and flexibility for implementation in multipurpose facilities. Development of highly productive cell lines, maximization of cell culture longevity, and maintenance of high specific antibody secretion rates through genetic engineering techniques, nutrition supplementation, waste product minimization, and control of environmental conditions are important for the design of high-yield fed-batch processes. Initially simple supplementation protocols have evolved into sophisticated serum-free multi-nutrient feeds that result in MAb titers on the order of 1-2 g/L. Limited research has been published to date on the effect of various culture parameters on potentially important quality issues, such as MAb glycosylation and stability. Although most fed-batch protocols to date have relied on relatively simple control schemes, increasingly sophisticated algorithms must be applied in order to take full advantage of the potentially additive effects of manipulating nutrient and environmental parameters to maximize fed-batch process productivity.

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Utilization of Mass Spectrometry for the Structural Characterization of Biopharmaceutical Protein Products

Lim

Barnes

2011

Protein and Peptide Mass Spectrometry in Drug Discovery

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Evaluation of Product Equivalence During Process Optimization for Manufacture of a Human IgM Monoclonal Antibody

Cited by 14 publications

References 0 publications

Structure, Function, and Therapeutic Use of IgM Antibodies

Structure, Function, and Therapeutic Use of IgM Antibodies

In Pursuit of the Optimal Fed‐Batch Process for Monoclonal Antibody Production

Utilization of Mass Spectrometry for the Structural Characterization of Biopharmaceutical Protein Products

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