Balancing the Affinity and Pharmacokinetics of Antibodies by Modulating the Size of Charge Patches on Complementarity-Determining Regions.
Antibody(s)
Chromatography
Pharmacokinetics
Protein binding
Surface plasmon resonance (SPR) spectroscopy
Journal
Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
27
03
2020
revised:
01
09
2020
accepted:
02
09
2020
pubmed:
11
9
2020
medline:
22
5
2021
entrez:
10
9
2020
Statut:
ppublish
Résumé
A localized positive charge on IgG (referred to as a "charge patch") shows an adverse effect on pharmacokinetics (PK), so it would seem to be best practice to avoid charge patches during the discovery stage and closely monitor charge interactions during the development process. In certain circumstances, however, charge patches are required for target binding, in which case completely removing charge patches is not feasible. Therefore, quantitative measurement of a charge patch and its impact on PK is critical to the success of therapeutic antibody development. In this article, we generated mutations of a recombinant human antibody (referred to as mAb1) with disrupted charge patches to investigate how charge patches on IgG antibodies impact both target-binding affinity and PK-related factors. We conclude that it is important to modulate the size of the charge patch in order to balance target-binding affinity and PK.
Identifiants
pubmed: 32910947
pii: S0022-3549(20)30497-4
doi: 10.1016/j.xphs.2020.09.003
pii:
doi:
Substances chimiques
Complementarity Determining Regions
0
Immunoglobulin G
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3690-3696Informations de copyright
Copyright © 2020. Published by Elsevier Inc.