AMG 133 is a bispecific antibody peptide conjugate for obesity that was engineered by conjugation of human monoclonal GIPR antagonist antibody with 2 GLP-1 agonist peptide analogs. Both targets were shown to have a synergistic effect on weight loss in preclinical species.
Since catabolism of the conjugated GLP-1 peptide may occur in vivo, a hybrid LC-MS/MS assay was developed to monitor AMG 133 antibody and potential clipping of the conjugated GLP-1 peptide. AMG 133 was immunocaptured from human plasma using an anti-idiotypic monoclonal antibody and then enzymatically digested to generate surrogate peptides. Intact AMG 133 was quantified via a surrogate peptide from the conjugated GLP-1 peptide and a surrogate peptide from the stable FC-region of AMG 133 was used to quantify Total AMG 133. The bioanalytical method was fully validated according to FDA guidelines and was successfully used to support a FIH study.
Learning Objectives:
Upon completion, participant will be able to understand unique bioanalytical challenges associated with antibody peptide conjugates (APCs).
Upon completion, participant will be able to understand the method development and validation approaches used for APCs.
Upon completion, participant will be able to understand how hybrid LC-MS/MS methadology can be used to monitor APC clipping in FIH studies.