biostudies-literatureUnknown16(1)Condado-Morales INovo Nordisk STAR FellowshipEngineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics. We measured 15 biophysical properties related to activity, manufacturing, and stability, scoring variants with a flag-based risk approach and a recent <i>in silico</i> developability profiler. Our comparative assesmAbs2403156https://www.ebi.ac.uk/biostudies/studies/S-EPMC11457596biostudies-literatureA comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs.PMC11457596Hummer AMPatel BRose Bjelke JBennet ALorenzen NArosio PRaybould MIJTurnbull OMCondado-Morales IEgebjerg TDeane CMDingfelder FCao ZWaibel INedergaard Grell SfalseA comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs.Engineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics. We measured 15 biophysical properties related to activity, manufacturing, and stability, scoring variants with a flag-based risk approach and a recent <i>in silico</i> developability profiler. Our comparative asses2024-01-01T00:00:00Z2024 Jan-Dec2025-04-26T20:13:21.725Z2025-04-06T16:23:34.693ZS-EPMC114575963936479610.1080/19420862.2024.2403156