Format

Send to

Choose Destination
See comment in PubMed Commons below
FEBS Lett. 2014 Mar 18;588(6):936-41. doi: 10.1016/j.febslet.2014.01.051. Epub 2014 Feb 12.

Competing aggregation pathways for monoclonal antibodies.

Author information

1
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19711, USA; Department of Biotherapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
2
Department of Biotherapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
3
Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA 70118, USA; Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19711, USA.
4
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19711, USA. Electronic address: cjr@udel.edu.

Abstract

Aggregation is mediated by local unfolding to allow aggregation "hot spot(s)" to become solvent exposed and available to associate with a hot spot on another partially unfolded protein. Historically, the unfolding of either the crystallizable fragment (Fc) or the antigen binding fragment (Fab) regions of a given monoclonal antibody (MAb) has been implicated in aggregation, with differing results across different proteins. The present work focuses on separately quantifying the aggregation kinetics of isolated Fc, isolated Fab, and intact MAb as a function of pH under accelerated (high temperature) conditions. The results show that both Fab and Fc are aggregation prone and compete within the same MAb.

KEYWORDS:

Aggregation; Hot-spot; MAb

PMID:
24530501
DOI:
10.1016/j.febslet.2014.01.051
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center