title: Validation of preclinical pharmacokinetic and immunogenicity assays for an anti-PCSK9 antibody.
abstract: Pharmacokinetic data derived from assays that accurately and precisely quantitate a therapeutic drug in circulation are critical to appropriately designing suitable dosing schedules. This manuscript describes the validation and implementation of methods to quantitate a therapeutic anti-human PCSK9 monoclonal antibody in rat and monkey sera as well as immunogenicity methods to screen the possible presence of rat and monkey antibodies directed against the antibody. As soluble, endogenous PCSK9 can interfere with a PCSK9-mediated capture step in ELISA, an indirect target-capture assay was used that potentially could capture free and target-engaged therapeutic mAb. Immunogenicity assays were based on a standard bridge ELISA using the therapeutic antibody for capture and detection. Both pharmacokinetic and immunogenicity assays were implemented in preclinical studies of the therapeutic antibody. The methods presented here may enable further pharmacokinetic studies.
authors: Merck & Co., Inc., West Point, Pennsylvania 19486, USA.
authors: Shannon D
authors: SD
authors: Chilewski
authors: Thy
authors: T
authors: Follmer
authors: Frances
authors: F
authors: Ansbro
authors: Dave
authors: D
authors: Chen
authors: Qinjian
authors: Q
authors: Zhao
authors: Jennifer
authors: J
authors: Teyral
authors: Ray
authors: R
authors: Bakhtiar
authors: Thorsten
authors: T
authors: Verch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000276:immunology / Q000493:pharmacokinetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000882:Haplorhini; D006801:Humans; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000032:analysis* / Q000276:immunology / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D000911:Antibodies, Monoclonal; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases