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An accelerated surface-mediated stress assay of antibody instability for developability studies

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An accelerated surface-mediated stress assay of antibody instability for developability studies. / Kopp, Marie R.G.; Wolf Pérez, Adriana Michelle; Zucca, Marta Virginia; Capasso Palmiero, Umberto; Friedrichsen, Brigitte; Lorenzen, Nikolai; Arosio, Paolo.

In: mAbs, Vol. 12, No. 1, 1815995, 2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Kopp, MRG, Wolf Pérez, AM, Zucca, MV, Capasso Palmiero, U, Friedrichsen, B, Lorenzen, N & Arosio, P 2020, 'An accelerated surface-mediated stress assay of antibody instability for developability studies', mAbs, vol. 12, no. 1, 1815995. https://doi.org/10.1080/19420862.2020.1815995

APA

Kopp, M. R. G., Wolf Pérez, A. M., Zucca, M. V., Capasso Palmiero, U., Friedrichsen, B., Lorenzen, N., & Arosio, P. (2020). An accelerated surface-mediated stress assay of antibody instability for developability studies. mAbs, 12(1), [1815995]. https://doi.org/10.1080/19420862.2020.1815995

CBE

Kopp MRG, Wolf Pérez AM, Zucca MV, Capasso Palmiero U, Friedrichsen B, Lorenzen N, Arosio P. 2020. An accelerated surface-mediated stress assay of antibody instability for developability studies. mAbs. 12(1):Article 1815995. https://doi.org/10.1080/19420862.2020.1815995

MLA

Vancouver

Kopp MRG, Wolf Pérez AM, Zucca MV, Capasso Palmiero U, Friedrichsen B, Lorenzen N et al. An accelerated surface-mediated stress assay of antibody instability for developability studies. mAbs. 2020;12(1). 1815995. https://doi.org/10.1080/19420862.2020.1815995

Author

Kopp, Marie R.G. ; Wolf Pérez, Adriana Michelle ; Zucca, Marta Virginia ; Capasso Palmiero, Umberto ; Friedrichsen, Brigitte ; Lorenzen, Nikolai ; Arosio, Paolo. / An accelerated surface-mediated stress assay of antibody instability for developability studies. In: mAbs. 2020 ; Vol. 12, No. 1.

Bibtex

@article{9911d15bca8e4fa3b72594de12843701,
title = "An accelerated surface-mediated stress assay of antibody instability for developability studies",
abstract = "High physical stability is required for the development of monoclonal antibodies (mAbs) into successful therapeutic products. Developability assays are used to predict physical stability issues such as high viscosity and poor conformational stability, but protein aggregation remains a challenging property to predict. Among different types of stresses, air–water and solid–liquid interfaces are well known to potentially trigger protein instability and induce aggregation. Yet, in contrast to the increasing number of developability assays to evaluate bulk properties, there is still a lack of experimental methods to evaluate antibody stability against interfaces. Here, we investigate the potential of a hydrophobic nanoparticle surface-mediated stress assay to assess the stability of mAbs during the early stages of development. We evaluate this surface-mediated accelerated stability assay on a rationally designed library of 14 variants of a humanized IgG4, featuring a broad span of solubility values and other developability properties. The assay could identify variants characterized by high instability against agitation in the presence of air–water interfaces. Remarkably, for the set of investigated molecules, we observe strong correlations between the extent of aggregation induced by the surface-mediated stress assay and other developability properties of the molecules, such as aggregation upon storage at 45°C, self-association (evaluated by affinity-capture self-interaction nanoparticle spectroscopy) and nonspecific interactions (estimated by cross-interaction chromatography, stand-up monolayer chromatography (SMAC), SMAC*). This highly controlled surface-mediated stress assay has the potential to complement and increase the ability of the current set of screening techniques to assess protein aggregation and developability potential of mAbs during the early stages of drug development. Abbreviations:AC-SINS: Affinity-Capture Self-Interaction Nanoparticle Spectroscopy; AMS: Ammonium sulfate precipitation; ANS: 1-anilinonaphtalene-8-sulfonate; CIC: Cross-interaction chromatography; DLS: Dynamic light scattering; HIC: Hydrophobic interaction chromatography; HNSSA: Hydrophobic nanoparticles surface-stress assay; mAb: Monoclonal antibody; NP: Nanoparticle; SEC: Size exclusion chromatography; SMAC: Stand-up monolayer chromatography; WT: Wild type.",
keywords = "aggregation, antibodies, developability, formulation, interfaces, stability, surfaces",
author = "Kopp, {Marie R.G.} and {Wolf P{\'e}rez}, {Adriana Michelle} and Zucca, {Marta Virginia} and {Capasso Palmiero}, Umberto and Brigitte Friedrichsen and Nikolai Lorenzen and Paolo Arosio",
year = "2020",
doi = "10.1080/19420862.2020.1815995",
language = "English",
volume = "12",
journal = "mAbs",
issn = "1942-0862",
publisher = "Taylor & Francis ",
number = "1",

}

RIS

TY - JOUR

T1 - An accelerated surface-mediated stress assay of antibody instability for developability studies

AU - Kopp, Marie R.G.

AU - Wolf Pérez, Adriana Michelle

AU - Zucca, Marta Virginia

AU - Capasso Palmiero, Umberto

AU - Friedrichsen, Brigitte

AU - Lorenzen, Nikolai

AU - Arosio, Paolo

PY - 2020

Y1 - 2020

N2 - High physical stability is required for the development of monoclonal antibodies (mAbs) into successful therapeutic products. Developability assays are used to predict physical stability issues such as high viscosity and poor conformational stability, but protein aggregation remains a challenging property to predict. Among different types of stresses, air–water and solid–liquid interfaces are well known to potentially trigger protein instability and induce aggregation. Yet, in contrast to the increasing number of developability assays to evaluate bulk properties, there is still a lack of experimental methods to evaluate antibody stability against interfaces. Here, we investigate the potential of a hydrophobic nanoparticle surface-mediated stress assay to assess the stability of mAbs during the early stages of development. We evaluate this surface-mediated accelerated stability assay on a rationally designed library of 14 variants of a humanized IgG4, featuring a broad span of solubility values and other developability properties. The assay could identify variants characterized by high instability against agitation in the presence of air–water interfaces. Remarkably, for the set of investigated molecules, we observe strong correlations between the extent of aggregation induced by the surface-mediated stress assay and other developability properties of the molecules, such as aggregation upon storage at 45°C, self-association (evaluated by affinity-capture self-interaction nanoparticle spectroscopy) and nonspecific interactions (estimated by cross-interaction chromatography, stand-up monolayer chromatography (SMAC), SMAC*). This highly controlled surface-mediated stress assay has the potential to complement and increase the ability of the current set of screening techniques to assess protein aggregation and developability potential of mAbs during the early stages of drug development. Abbreviations:AC-SINS: Affinity-Capture Self-Interaction Nanoparticle Spectroscopy; AMS: Ammonium sulfate precipitation; ANS: 1-anilinonaphtalene-8-sulfonate; CIC: Cross-interaction chromatography; DLS: Dynamic light scattering; HIC: Hydrophobic interaction chromatography; HNSSA: Hydrophobic nanoparticles surface-stress assay; mAb: Monoclonal antibody; NP: Nanoparticle; SEC: Size exclusion chromatography; SMAC: Stand-up monolayer chromatography; WT: Wild type.

AB - High physical stability is required for the development of monoclonal antibodies (mAbs) into successful therapeutic products. Developability assays are used to predict physical stability issues such as high viscosity and poor conformational stability, but protein aggregation remains a challenging property to predict. Among different types of stresses, air–water and solid–liquid interfaces are well known to potentially trigger protein instability and induce aggregation. Yet, in contrast to the increasing number of developability assays to evaluate bulk properties, there is still a lack of experimental methods to evaluate antibody stability against interfaces. Here, we investigate the potential of a hydrophobic nanoparticle surface-mediated stress assay to assess the stability of mAbs during the early stages of development. We evaluate this surface-mediated accelerated stability assay on a rationally designed library of 14 variants of a humanized IgG4, featuring a broad span of solubility values and other developability properties. The assay could identify variants characterized by high instability against agitation in the presence of air–water interfaces. Remarkably, for the set of investigated molecules, we observe strong correlations between the extent of aggregation induced by the surface-mediated stress assay and other developability properties of the molecules, such as aggregation upon storage at 45°C, self-association (evaluated by affinity-capture self-interaction nanoparticle spectroscopy) and nonspecific interactions (estimated by cross-interaction chromatography, stand-up monolayer chromatography (SMAC), SMAC*). This highly controlled surface-mediated stress assay has the potential to complement and increase the ability of the current set of screening techniques to assess protein aggregation and developability potential of mAbs during the early stages of drug development. Abbreviations:AC-SINS: Affinity-Capture Self-Interaction Nanoparticle Spectroscopy; AMS: Ammonium sulfate precipitation; ANS: 1-anilinonaphtalene-8-sulfonate; CIC: Cross-interaction chromatography; DLS: Dynamic light scattering; HIC: Hydrophobic interaction chromatography; HNSSA: Hydrophobic nanoparticles surface-stress assay; mAb: Monoclonal antibody; NP: Nanoparticle; SEC: Size exclusion chromatography; SMAC: Stand-up monolayer chromatography; WT: Wild type.

KW - aggregation

KW - antibodies

KW - developability

KW - formulation

KW - interfaces

KW - stability

KW - surfaces

UR - http://www.scopus.com/inward/record.url?scp=85091266327&partnerID=8YFLogxK

U2 - 10.1080/19420862.2020.1815995

DO - 10.1080/19420862.2020.1815995

M3 - Journal article

C2 - 32954930

AN - SCOPUS:85091266327

VL - 12

JO - mAbs

JF - mAbs

SN - 1942-0862

IS - 1

M1 - 1815995

ER -