Transfer Phenomena in Chromatography

Guiochon, Georges; Shirazi, Dean G.; Felinger, Attila; Katti, Anita M.

doi:10.1016/b978-012370537-2/50029-1

Cited by 2 publications

(2 citation statements)

References 133 publications

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“…Therefore, k eff, salt was approximated with r P /3 = 0.0083 mm/s (Rodrigues, 1997). For the protein species, the penetration correlation (Guiochon et al, 2006) enabled the calculation of effective mass transfer parameters k eff, i depending on the hydrodynamic radii of the mAbs and the linear flow rate. Identical hydrodynamic radii of 73 Å were computed based on full‐length homology models resulting in a k eff,i of 0.0013 mm/s for WT, M1, and M2.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, k eff, salt was approximated with r P /3 = 0.0083 mm/s (Rodrigues, 1997). For the protein species, the penetration correlation (Guiochon et al, 2006) 2 visualizes the Yamamoto correlation (Equation 7), which enabled the analytical solution of the characteristic charge ν i and equilibrium constant k eq, i based on the five LGE experiments per mAb.…”

Section: Chromatography Modelingmentioning

confidence: 99%

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Modeling the impact of amino acid substitution in a monoclonal antibody on cation exchange chromatography

Saleh

Hess

Ahlers-Hesse

et al. 2021

Biotech & Bioengineering

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A vital part of biopharmaceutical research is decision making around which lead candidate should be progressed in early-phase development. When multiple antibody candidates show similar biological activity, developability aspects are taken into account to ease the challenges of manufacturing the potential drug candidate.While current strategies for developability assessment mainly focus on drug product stability, only limited information is available on how antibody candidates with minimal differences in their primary structure behave during downstream processing. With increasing time-to-market pressure and an abundance of monoclonal antibodies (mAbs) in development pipelines, developability assessments should also consider the ability of mAbs to integrate into the downstream platform. This study investigates the influence of amino acid substitutions in the complementaritydetermining region (CDR) of a full-length IgG1 mAb on the elution behavior in preparative cation exchange chromatography. Single amino acid substitutions within the investigated mAb resulted in an additional positive charge in the light chain (L) and heavy chain (H) CDR, respectively. The mAb variants showed an increased retention volume in linear gradient elution compared with the wild-type antibody.Furthermore, the substitution of tryptophan with lysine in the H-CDR3 increased charge heterogeneity of the product. A multiscale in silico analysis, consisting of homology modeling, protein surface analysis, and mechanistic chromatography modeling increased understanding of the adsorption mechanism. The results reveal the potential effects of lead optimization during antibody drug discovery on downstream processing.

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Section: Resultsmentioning

confidence: 99%

Section: Chromatography Modelingmentioning

confidence: 99%