Quantitative determination of humanized monoclonal antibody rhuMAb2H7 in cynomolgus monkey serum using a Generic Immunoglobulin Pharmacokinetic (GRIP) assay

Journal of Immunological Methods
Jihong YangValerie Quarmby

Abstract

Preclinical pharmacokinetic (PK) assays are important to help evaluate the safety and efficacy of a potential biotherapeutic before clinical studies. The assay typically requires a biotherapeutic-specific reagent to minimize matrix effects especially when the host species are non-human primates such as cynomolgus monkeys and the biotherapeutic is a humanized monoclonal antibody (MAb). Recombinant humanized mAb 2H7 (rhuMAb2H7) binds to the extracellular domain of CD20 that is expressed on B cells and results in B cell depletion. It is currently being evaluated for its therapeutic potential in rheumatoid arthritis (RA) in clinical studies. During the early development of rhuMAb2H7, a cynomolgus monkey PK assay was needed to help assess the pharmacokinetic parameters of rhuMAb2H7 in a pilot cynomolgus monkey study. However, development of a cynomolgus monkey PK assay was challenging due to lack of rhuMAb2H7-specific reagents. Here we describe an alternative method for detection of rhuMAb2H7 in cynomolgus monkey serum using polyclonal antibodies against human IgGs. This assay quantifies rhuMAb2H7 in 10% cynomolgus monkey serum with high sensitivity, accuracy, and precision. This assay successfully supported the rhuMAb2H7 developmen...Continue Reading

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Citations

Mar 23, 2011·Bioanalysis·Lorin K RoskosMeina Liang
May 23, 2012·Bioanalysis·Tracey H Clark, Lindsay E King
Mar 1, 2011·Therapeutic Delivery·Jean W Lee, Marian Kelley
Nov 5, 2013·Bioanalysis·Denise M O'Hara, Valerie Theobald
Dec 15, 2010·Journal of Pharmacological and Toxicological Methods·Jeanette RomanThorsten Verch
Feb 13, 2010·Journal of Pharmaceutical and Biomedical Analysis·Julie Doucet, Alexandre Avrameas

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