Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates.

Autor: Kenneth W Walker, Hossein Salimi-Moosavi, Gregory E Arnold, Qing Chen, Marcus Soto, Frederick W Jacobsen, John Hui
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS ONE, Vol 14, Iss 5, p e0217061 (2019)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0217061
Popis: In this study we compared the pharmacokinetic profile of four unrelated antibodies, which do not bind to mammalian antigens, in IgG1 and IgG2 frameworks in both rats and non-human primates (NHP). This allowed for extensive cross comparison of the impact of antibody isotype, complementarity determining regions (CDR) and model species on pharmacokinetics without the confounding influence of antigen binding in the hosts. While antibody isotype had no significant impact on the pharmacokinetics, the CDRs do alter the profile, and there is an inverse correlation between the neonatal Fc receptor (FcRn) affinity and pharmacokinetic performance. Faster clearance rates were also associated with higher isoelectric points; however, although this panel of antibodies all possess basic isoelectric points, ranging from 8.44 to 9.18, they also have exceptional in vivo half-lives, averaging 369 hours, and low clearance rates, averaging 0.18 ml/h/kg in NHPs. This pattern of pharmacokinetic characteristics was conserved between rats and NHPs.
Databáze: Directory of Open Access Journals
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