Aggregation risk prediction for antibodies and its application to biotherapeutic development

MAbs
Olga ObrezanovaYvette Stallwood

Abstract

Aggregation is a common problem affecting biopharmaceutical development that can have a significant effect on the quality of the product, as well as the safety to patients, particularly because of the increased risk of immune reactions. Here, we describe a new high-throughput screening algorithm developed to classify antibody molecules based on their propensity to aggregate. The tool, constructed and validated on experimental aggregation data for over 500 antibodies, is able to discern molecules with a high aggregation propensity as defined by experimental criteria relevant to bioprocessing and manufacturing of these molecules. Furthermore, we show how this tool can be combined with other computational approaches during early drug development to select molecules with reduced risk of aggregation and optimal developability properties.

References

Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·E A PadlanD R Davies
Jul 1, 1987·Journal of Medicinal Chemistry·S HellbergS Wold
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jun 1, 2000·Applied and Environmental Microbiology·W A DuetzB Witholt
Sep 14, 2004·Nature Biotechnology·Ana-Maria Fernandez-EscamillaLuis Serrano
Oct 1, 2005·Protein Science : a Publication of the Protein Society·Gian Gaetano TartagliaAmedeo Caflisch
Oct 10, 2006·The AAPS Journal·Amy S Rosenberg
Feb 21, 2007·Expert Opinion on Biological Therapy·Ivo Van WalleIgnace Lasters
Jul 3, 2007·Journal of Chemical Information and Modeling·Olga ObrezanovaMatthew D Segall
Jun 17, 2009·Journal of Molecular Biology·Naresh ChennamsettyBernhardt L Trout
Nov 26, 2010·BMC Bioinformatics·Peng WangBjoern Peters
Apr 12, 2011·Biotechnology and Bioengineering·María Vázquez-Rey, Dietmar A Lang
Jun 18, 2011·EMBO Reports·Mattia BelliFabrizio Chiti
Jul 27, 2011·Journal of Pharmaceutical Sciences·Neeraj J AgrawalBernhardt L Trout
Sep 22, 2011·Journal of Pharmaceutical Sciences·Timothy M LauerBernhardt L Trout
Sep 22, 2011·Proteins·Juan C AlmagroGary L Gilliland

❮ Previous
Next ❯

Citations

Jun 16, 2015·BioMed Research International·Jesús ZurdoIngmarie Höidén-Guthenberg
Apr 26, 2016·Biotechnology Progress·Jennifer PurdieDonald Olson
Jan 18, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tushar JainK Dane Wittrup
Mar 9, 2018·Critical Reviews in Biotechnology·Micael KarlbergJarka Glassey
Sep 5, 2018·Chemical Communications : Chem Comm·Mouhamad ReslanVeysel Kayser
Dec 2, 2017·Nature Reviews. Drug Discovery·Paul J Carter, Greg A Lazar
May 16, 2020·The Journal of Biological Chemistry·Claire Marks, Charlotte M Deane
Oct 19, 2019·Briefings in Bioinformatics·Richard A NormanKonrad Krawczyk
Feb 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Matthew I J RaybouldCharlotte M Deane
Jan 28, 2021·Trends in Pharmacological Sciences·Harini NarayananPaolo Arosio
Nov 13, 2020·Scientific Reports·Yoichi KurumidaTomoshi Kameda
Dec 5, 2020·Scientific Reports·Hongyu Zhang, Paul A Dalby
Dec 22, 2020·Journal of Pharmaceutical Sciences·Pin-Kuang LaiBernhardt L Trout
Oct 16, 2020·International Journal of Molecular Sciences·Manali S SawantPeter M Tessier
Apr 7, 2021·The Journal of Physical Chemistry. B·Hassan ShahfarChristopher J Roberts
Apr 27, 2021·Molecular Therapy. Methods & Clinical Development·Jared A DelmarXiaoyu Chen
Apr 15, 2021·Annual Review of Chemical and Biomolecular Engineering·Margarita PertsevaSai T Reddy
Oct 17, 2020·Omics : a Journal of Integrative Biology·Nguyen Hoang AnhNguyen Phuoc Long
Sep 14, 2018·Analytical Chemistry·Li ZhouWilliam Blaine Stine
Feb 16, 2018·Analytical Chemistry·Sarah H M HedbergDaryl R Williams
Nov 15, 2017·The Journal of Physical Chemistry. B·Alexander B KuhnLars V Schäfer

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
enzyme-linked immunosorbent assay
transfection
Assay
size-exclusion chromatography
deamidation
transfections

Software Mentioned

Developability Index ( DI ) tool
SAP
Matlab
DI
Discovery
Discovery Studio
Chemstation
MODELLER

Related Concepts

Related Feeds

Related Papers

Journal of the American Pharmaceutical Association
A K Herd
Biotechnology and Bioengineering
María Vázquez-Rey, Dietmar A Lang
Giornale Italiano Di Dermatologia E Venereologia : Organo Ufficiale, Società Italiana Di Dermatologia E Sifilografia
G BorroniE Berti
© 2021 Meta ULC. All rights reserved