title: Quantitative determination of humanized monoclonal antibody rhuMAb2H7 in cynomolgus monkey serum using a Generic Immunoglobulin Pharmacokinetic (GRIP) assay.
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 development, and has the potential to be used to quantify other humanized MAb biotherapeutics in serum from a variety of non-human species.
authors.affiliation: Department of Bioanalytical Research & Development, Genentech Inc, South San Francisco, CA 94080, USA. jihong@gene.com
authors.forename: Jihong
authors.initials: J
authors.lastname: Yang
authors.forename: Carl
authors.initials: C
authors.lastname: Ng
authors.forename: Henry
authors.initials: H
authors.lastname: Lowman
authors.forename: Regina
authors.initials: R
authors.lastname: Chestnut
authors.forename: Cheryl
authors.initials: C
authors.lastname: Schofield
authors.forename: Bryan
authors.initials: B
authors.lastname: Sandlund
authors.forename: James
authors.initials: J
authors.lastname: Ernst
authors.forename: Gregory
authors.initials: G
authors.lastname: Bennett
authors.forename: Valerie
authors.initials: V
authors.lastname: Quarmby
mesh_terms: D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000915:Antibody Affinity; D000918:Antibody Specificity; D018951:Antigens, CD20 / Q000276:immunology*; D018501:Antirheumatic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008252:Macaca fascicularis; D011933:Reagent Kits, Diagnostic; D011994:Recombinant Proteins / Q000097:blood; D015203:Reproducibility of Results; D012756:Sheep
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D011933:Reagent Kits, Diagnostic; D011994:Recombinant Proteins; C529853:rhuMAb2H7