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Balancing the Affinity and Pharmacokinetics of Antibodies by Modulating the Size of Charge Patches on Complementarity-Determining Regions
- Source :
- Journal of Pharmaceutical Sciences. 109:3690-3696
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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.
- Subjects :
- biology
Chemistry
Pharmaceutical Science
Charge (physics)
02 engineering and technology
Complementarity determining region
Plasma protein binding
021001 nanoscience & nanotechnology
Complementarity Determining Regions
030226 pharmacology & pharmacy
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Immunoglobulin G
Therapeutic antibody
biology.protein
Biophysics
Humans
Antibody
0210 nano-technology
Target binding
Subjects
Details
- ISSN :
- 00223549
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....2fbfdc970a1bc50b00cc3863d40b3e62
- Full Text :
- https://doi.org/10.1016/j.xphs.2020.09.003