biostudies-literatureUnknown15(1)Ow SYCSL Ltd. Parkville, AustraliaCSL LimitedHageman factor (FXII) is an essential component in the intrinsic coagulation cascade and a therapeutic target for the prophylactic treatment of hereditary angioedema (HAE). CSL312 (garadacimab) is a novel high-affinity human antibody capable of blocking activated FXII activity that is currently undergoing Phase 3 clinical trials in HAE. Structural studies using hydrogen/deuterium exchange coupled to mass spectrometry revealed evidence of interaction between the antibody and regions surrounding the S1 specificity pocket of FXII, including the 99-loop, 140-loop, 180-loop, and neighboring regions. We propose complementarity-determining regions (CDRs) in heavy-chain CDR2 and CDR3 as potential paratopes on garadacimab, and the 99-loop, 140-loop, 180-loop, and 220-loop as binding sites on the bemAbs2163459https://www.ebi.ac.uk/biostudies/studies/S-EPMC9839371biostudies-literatureHDX-MS study on garadacimab binding to activated FXII reveals potential binding interfaces through differential solvent exposure.PMC9839371Zalewski AOw SYKapp EASimmonds JTomasetig VPelzing MNash ADPanousis CWilson MJfalseHDX-MS study on garadacimab binding to activated FXII reveals potential binding interfaces through differential solvent exposure.Hageman factor (FXII) is an essential component in the intrinsic coagulation cascade and a therapeutic target for the prophylactic treatment of hereditary angioedema (HAE). CSL312 (garadacimab) is a novel high-affinity human antibody capable of blocking activated FXII activity that is currently undergoing Phase 3 clinical trials in HAE. Structural studies using hydrogen/deuterium exchange coupled to mass spectrometry revealed evidence of interaction between the antibody and regions surrounding the S1 specificity pocket of FXII, including the 99-loop, 140-loop, 180-loop, and neighboring regions. We propose complementarity-determining regions (CDRs) in heavy-chain CDR2 and CDR3 as potential paratopes on garadacimab, and the 99-loop, 140-loop, 180-loop, and 220-loop as binding sites on the be2023-01-01T00:00:00Z2023 Jan-Dec2026-07-14T20:16:07.649Z2025-04-25T17:07:52.283ZS-EPMC98393713662846810.1080/19420862.2022.2163459