Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Stability of monoclonal antibodies at high-concentration : head-to-head comparison of the IgG1 and IgG4 subclass. / Neergaard, Martin S; Nielsen, Anders D; Parshad, Henrik; van de Weert, Marco.

In: Journal of Pharmaceutical Sciences, Vol. 103, No. 1, 01.2014, p. 115-27.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Neergaard, MS, Nielsen, AD, Parshad, H & van de Weert, M 2014, 'Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass', Journal of Pharmaceutical Sciences, vol. 103, no. 1, pp. 115-27. https://doi.org/10.1002/jps.23788

APA

Neergaard, M. S., Nielsen, A. D., Parshad, H., & van de Weert, M. (2014). Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass. Journal of Pharmaceutical Sciences, 103(1), 115-27. https://doi.org/10.1002/jps.23788

Vancouver

Neergaard MS, Nielsen AD, Parshad H, van de Weert M. Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass. Journal of Pharmaceutical Sciences. 2014 Jan;103(1):115-27. https://doi.org/10.1002/jps.23788

Author

Neergaard, Martin S ; Nielsen, Anders D ; Parshad, Henrik ; van de Weert, Marco. / Stability of monoclonal antibodies at high-concentration : head-to-head comparison of the IgG1 and IgG4 subclass. In: Journal of Pharmaceutical Sciences. 2014 ; Vol. 103, No. 1. pp. 115-27.

Bibtex

@article{5ffd5d5eb49e44a5b8ee55c28cfdc7e5,
title = "Stability of monoclonal antibodies at high-concentration: head-to-head comparison of the IgG1 and IgG4 subclass",
abstract = "Few studies have so far directly compared the impact of antibody subclass on protein stability. This case study investigates two mAbs (one IgG1 and one IgG4 ) with identical variable region. Investigations of mAbs that recognize similar epitopes are necessary to identify possible differences between the IgG subclasses. Both physical and chemical stability were evaluated by applying a range of methods to measure formation of protein aggregates [size-exclusion chromatography (SEC)-HPLC and UV340 nm], structural integrity (circular dichroism and FTIR), thermodynamic stability (differential scanning calorimetry), colloidal interactions (dynamic light scattering), and fragmentation and deamidation (SEC-HPLC and capillary isoelectric focusing). The impact of pH (4-9) and ionic strength (10 and 150 mM) was investigated using highly-concentrated (150 mg/mL) mAb formulations. Lower conformational stability was identified for the IgG4 resulting in increased levels of soluble aggregates. The IgG1 was chemically less stable as compared with the IgG4 , presumably because of the higher flexibility in the IgG1 hinge region. The thermodynamic stability of individual mAb domains was also addressed in detail. The stability of our mAb molecules is clearly affected by the IgG framework, and this study suggests that subclass switching may alter aggregation propensity and aggregation pathway and thus potentially improve the overall formulation stability while retaining antigen specificity.",
author = "Neergaard, {Martin S} and Nielsen, {Anders D} and Henrik Parshad and {van de Weert}, Marco",
note = "{\circledC} 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.",
year = "2014",
month = "1",
doi = "10.1002/jps.23788",
language = "English",
volume = "103",
pages = "115--27",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - Stability of monoclonal antibodies at high-concentration

T2 - head-to-head comparison of the IgG1 and IgG4 subclass

AU - Neergaard, Martin S

AU - Nielsen, Anders D

AU - Parshad, Henrik

AU - van de Weert, Marco

N1 - © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

PY - 2014/1

Y1 - 2014/1

N2 - Few studies have so far directly compared the impact of antibody subclass on protein stability. This case study investigates two mAbs (one IgG1 and one IgG4 ) with identical variable region. Investigations of mAbs that recognize similar epitopes are necessary to identify possible differences between the IgG subclasses. Both physical and chemical stability were evaluated by applying a range of methods to measure formation of protein aggregates [size-exclusion chromatography (SEC)-HPLC and UV340 nm], structural integrity (circular dichroism and FTIR), thermodynamic stability (differential scanning calorimetry), colloidal interactions (dynamic light scattering), and fragmentation and deamidation (SEC-HPLC and capillary isoelectric focusing). The impact of pH (4-9) and ionic strength (10 and 150 mM) was investigated using highly-concentrated (150 mg/mL) mAb formulations. Lower conformational stability was identified for the IgG4 resulting in increased levels of soluble aggregates. The IgG1 was chemically less stable as compared with the IgG4 , presumably because of the higher flexibility in the IgG1 hinge region. The thermodynamic stability of individual mAb domains was also addressed in detail. The stability of our mAb molecules is clearly affected by the IgG framework, and this study suggests that subclass switching may alter aggregation propensity and aggregation pathway and thus potentially improve the overall formulation stability while retaining antigen specificity.

AB - Few studies have so far directly compared the impact of antibody subclass on protein stability. This case study investigates two mAbs (one IgG1 and one IgG4 ) with identical variable region. Investigations of mAbs that recognize similar epitopes are necessary to identify possible differences between the IgG subclasses. Both physical and chemical stability were evaluated by applying a range of methods to measure formation of protein aggregates [size-exclusion chromatography (SEC)-HPLC and UV340 nm], structural integrity (circular dichroism and FTIR), thermodynamic stability (differential scanning calorimetry), colloidal interactions (dynamic light scattering), and fragmentation and deamidation (SEC-HPLC and capillary isoelectric focusing). The impact of pH (4-9) and ionic strength (10 and 150 mM) was investigated using highly-concentrated (150 mg/mL) mAb formulations. Lower conformational stability was identified for the IgG4 resulting in increased levels of soluble aggregates. The IgG1 was chemically less stable as compared with the IgG4 , presumably because of the higher flexibility in the IgG1 hinge region. The thermodynamic stability of individual mAb domains was also addressed in detail. The stability of our mAb molecules is clearly affected by the IgG framework, and this study suggests that subclass switching may alter aggregation propensity and aggregation pathway and thus potentially improve the overall formulation stability while retaining antigen specificity.

U2 - 10.1002/jps.23788

DO - 10.1002/jps.23788

M3 - Journal article

C2 - 24282022

VL - 103

SP - 115

EP - 127

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 1

ER -

ID: 101916939