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Developing biotherapeutics requires a detailed understanding of their biological properties. This, in turn, brings about the importance of characterizing higher\u2010order protein structures at each stage, from production to patient. The flexibility and size of the mAbs often prevent achieving atomic\u2010level structural information in the pharmaceutical formulation by traditional methods. In this study, we introduce an integration of solid\u2010state nuclear magnetic resonance (SSNMR) and hydrogen\u2013deuterium exchange mass spectrometry (HDX\u2010MS) to explore the interaction between Avelumab and the programmed cell death\u2010ligand 1 (PD\u2010L1). With this approach, we were able to obtain epitope (by both NMR and HDX) and paratope mapping (by HDX), together with a detailed characterization of the structural rearrangements arising upon binding. This methodology provides both mechanistic and structural insights important for the design and optimization of biotherapeutics.<\/jats:p>","DOI":"10.1002\/anie.1540355","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T09:20:38Z","timestamp":1787390438000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Full\u2010Length Antibody Complexes Through HDX\u2010Mass Spectrometry Coupled With NMR Spectroscopy: New Insight Into Avelumab\/PD\u2010L1 Interaction"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-7993","authenticated-orcid":false,"given":"Francesca","family":"Sacco","sequence":"first","affiliation":[{"name":"CERM\u2010CIRMMP University of Florence  Sesto Fiorentino Italy"},{"name":"Analytical Development &amp; Innovation, NBE, EMD Serono Inc Guidonia  Rome 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