{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:31:26Z","timestamp":1791329486623,"version":"4.3.1"},"reference-count":48,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005713","name":"Technische Universit\u00e4t M\u00fcnchen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004385","name":"Universiteit Gent","doi-asserted-by":"publisher","award":["BOF\/STA\/202109\/034"],"award-info":[{"award-number":["BOF\/STA\/202109\/034"]}],"id":[{"id":"10.13039\/501100004385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jpharmsci.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.xphs.2025.104142","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T16:14:27Z","timestamp":1766506467000},"page":"104142","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["A pharmaceutical developability perspective on antibodies with ultra-long CDRs"],"prefix":"10.1016","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9776-4992","authenticated-orcid":false,"given":"Marcel","family":"Passon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefaan","family":"De Smedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-9569","authenticated-orcid":false,"given":"Hristo L.","family":"Svilenov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0001","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2024.2443538","article-title":"Antibodies to watch in 2025","volume":"17","author":"Crescioli","year":"2025","journal-title":"MAbs"},{"key":"10.1016\/j.xphs.2025.104142_bib0002","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev-bioeng-071114-040733","article-title":"Advances in antibody design","volume":"17","author":"Tiller","year":"2015","journal-title":"Annu Rev Biomed Eng"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0003","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2023.2185924","article-title":"Blueprint for antibody biologics developability","volume":"15","author":"Mieczkowski","year":"2023","journal-title":"MAbs"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0004","first-page":"13","article-title":"Developability assessment at early-stage discovery to enable development of antibody-derived therapeutics","volume":"6","author":"Zhang","year":"2022","journal-title":"Antib Ther"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0005","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2020.1743053","article-title":"Predicting antibody developability profiles through early stage discovery screening","volume":"12","author":"Bailly","year":"2020","journal-title":"MAbs"},{"issue":"6","key":"10.1016\/j.xphs.2025.104142_bib0006","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1002\/jps.24430","article-title":"Developability assessment during the selection of novel therapeutic antibodies","volume":"104","author":"Jarasch","year":"2015","journal-title":"J Pharm Sci"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0007","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2024.2403156","article-title":"A comparative study of the developability of full-length antibodies, fragments, and bispecific formats reveals higher stability risks for engineered constructs","volume":"16","author":"Condado-Morales","year":"2024","journal-title":"MAbs"},{"issue":"10","key":"10.1016\/j.xphs.2025.104142_bib0008","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1073\/pnas.1810576116","article-title":"Five computational developability guidelines for therapeutic antibody profiling","volume":"116","author":"Raybould","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.xphs.2025.104142_bib0009","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coi.2016.02.003","article-title":"Distinct antibody species: structural differences creating therapeutic opportunities","volume":"40","author":"Muyldermans","year":"2016","journal-title":"Curr Opin Immunol"},{"key":"10.1016\/j.xphs.2025.104142_bib0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.biotechadv.2023.108120","article-title":"Principles of antibodies with ultralong complementarity-determining regions and picobodies","volume":"64","author":"Passon","year":"2023","journal-title":"Biotechnol Adv"},{"issue":"6","key":"10.1016\/j.xphs.2025.104142_bib0011","first-page":"1379","volume":"153","author":"Wang","year":"2013","journal-title":"Reshaping Antibody Diversity. Cell"},{"issue":"7665","key":"10.1016\/j.xphs.2025.104142_bib0012","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature23301","article-title":"Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows","volume":"548","author":"Sok","year":"2017","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0013","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s42003-025-08036-5","article-title":"Stability convergence in natural antibodies with ultra-long hypervariable loops","volume":"8","author":"Passon","year":"2025","journal-title":"Commun Biol"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0014","doi-asserted-by":"crossref","first-page":"6737","DOI":"10.1038\/s41467-021-27103-z","article-title":"Mechanistic principles of an ultra-long bovine CDR reveal strategies for antibody design","volume":"12","author":"Svilenov","year":"2021","journal-title":"Nat Commun"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0015","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0021-9258(18)86000-8","article-title":"A buffer solution for colorimetric comparison","volume":"49","author":"McIlvaine","year":"1921","journal-title":"J Biol Chem"},{"issue":"12","key":"10.1016\/j.xphs.2025.104142_bib0016","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1002\/pro.2809","article-title":"Robust and convenient analysis of protein thermal and chemical stability","volume":"24","author":"Niklasson","year":"2015","journal-title":"Protein Sci"},{"key":"10.1016\/j.xphs.2025.104142_bib0017","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1021\/ac60214a047","article-title":"Smoothing and differentiation of data by simplified least squares procedures","volume":"36","author":"Savitzky","year":"1964","journal-title":"Anal Chem"},{"issue":"6","key":"10.1016\/j.xphs.2025.104142_bib0018","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat Methods"},{"issue":"11","key":"10.1016\/j.xphs.2025.104142_bib0019","doi-asserted-by":"crossref","first-page":"e4792","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX: tools for structure building and analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci"},{"key":"10.1016\/j.xphs.2025.104142_bib0020","series-title":"The Proteomics Protocols Handbook","first-page":"571","article-title":"Protein identification and analysis tools on the ExPASy server","author":"Wilkins","year":"2005"},{"issue":"2","key":"10.1016\/j.xphs.2025.104142_bib0021","doi-asserted-by":"crossref","first-page":"bbad004","DOI":"10.1093\/bib\/bbad004","article-title":"Sequence-based prediction of pH-dependent protein solubility using CamSol","volume":"24","author":"Oeller","year":"2023","journal-title":"Brief Bioinform"},{"issue":"8","key":"10.1016\/j.xphs.2025.104142_bib0022","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1248\/bpb.33.1413","article-title":"Influence of pH on heat-induced aggregation and degradation of therapeutic monoclonal antibodies","volume":"33","author":"Ishikawa","year":"2010","journal-title":"Biol Pharm Bull"},{"issue":"7","key":"10.1016\/j.xphs.2025.104142_bib0023","doi-asserted-by":"crossref","DOI":"10.1016\/j.xphs.2021.03.017","article-title":"A review of formulations of commercially available antibodies","volume":"110","author":"Strickley","year":"2021","journal-title":"J Pharm Sci"},{"issue":"1\u20132","key":"10.1016\/j.xphs.2025.104142_bib0024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2004.11.014","article-title":"Protein aggregation and its inhibition in biopharmaceutics","volume":"289","author":"Wang","year":"2005","journal-title":"Int J Pharm"},{"issue":"5","key":"10.1016\/j.xphs.2025.104142_bib0025","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1073\/pnas.1616408114","article-title":"Biophysical properties of the clinical-stage antibody landscape","volume":"114","author":"Jain","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"10.1016\/j.xphs.2025.104142_bib0026","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1021\/acs.molpharmaceut.3c00013","article-title":"Chemometrics in protein formulation: stability governed by repulsion and protein unfolding","volume":"20","author":"Kulakova","year":"2023","journal-title":"Mol Pharm"},{"issue":"21","key":"10.1016\/j.xphs.2025.104142_bib0027","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1021\/acs.biochem.9b00089","article-title":"Thermally versus chemically denatured protein states","volume":"58","author":"Narayan","year":"2019","journal-title":"Biochemistry"},{"issue":"7","key":"10.1016\/j.xphs.2025.104142_bib0028","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1021\/acs.molpharmaceut.0c00330","article-title":"Modulated scanning fluorimetry can quickly assess thermal protein unfolding reversibility in microvolume samples","volume":"17","author":"Svilenov","year":"2020","journal-title":"Mol Pharm"},{"key":"10.1016\/j.xphs.2025.104142_bib0029","doi-asserted-by":"crossref","DOI":"10.1016\/j.ab.2024.115729","article-title":"Survey of chemical unfolding complexity as a unique stability assessment assay for monoclonal antibodies","volume":"698","author":"Floyd","year":"2025","journal-title":"Anal Biochem"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0030","doi-asserted-by":"crossref","first-page":"9321","DOI":"10.1038\/s41598-022-13370-3","article-title":"Non-covalent Fc-Fab interactions significantly alter internal dynamics of an IgG1 antibody","volume":"12","author":"Natesan","year":"2022","journal-title":"Sci Rep"},{"issue":"8","key":"10.1016\/j.xphs.2025.104142_bib0031","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1073\/pnas.0812588106","article-title":"Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group","volume":"106","author":"Lim","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"11","key":"10.1016\/j.xphs.2025.104142_bib0032","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/pro.5560031110","article-title":"Protein denaturation with guanidine hydrochloride or urea provides a different estimate of stability depending on the contributions of electrostatic interactions","volume":"3","author":"Monera","year":"1994","journal-title":"Protein Sci"},{"key":"10.1016\/j.xphs.2025.104142_bib0033","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2025.125321","article-title":"Effects of salts, buffers and sucrose on protein-protein attractive and repulsive interactions","volume":"672","author":"Francis","year":"2025","journal-title":"Int J Pharm"},{"issue":"32","key":"10.1016\/j.xphs.2025.104142_bib0034","doi-asserted-by":"crossref","first-page":"eabb0372","DOI":"10.1126\/sciadv.abb0372","article-title":"A single molecular descriptor to predict solution behavior of therapeutic antibodies","volume":"6","author":"Kingsbury","year":"2020","journal-title":"Sci Adv"},{"issue":"10","key":"10.1016\/j.xphs.2025.104142_bib0035","doi-asserted-by":"crossref","first-page":"4219","DOI":"10.1002\/jps.21322","article-title":"Reversible self-association of a concentrated monoclonal antibody solution mediated by Fab-Fab interaction that impacts solution viscosity","volume":"97","author":"Kanai","year":"2008","journal-title":"J Pharm Sci"},{"issue":"4","key":"10.1016\/j.xphs.2025.104142_bib0036","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1002\/jps.21530","article-title":"Overlooking subvisible particles in therapeutic protein products: gaps that may compromise product quality","volume":"98","author":"Carpenter","year":"2009","journal-title":"J Pharm Sci"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0037","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.xphs.2019.08.009","article-title":"Physicochemical stability of monoclonal antibodies: a review","volume":"109","author":"Le Basle","year":"2020","journal-title":"J Pharm Sci"},{"issue":"3","key":"10.1016\/j.xphs.2025.104142_bib0038","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3390\/antib5030019","article-title":"Antibody aggregation: insights from sequence and structure","volume":"5","author":"Li","year":"2016","journal-title":"Antibodies (Basel)"},{"key":"10.1016\/j.xphs.2025.104142_bib0039","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1399438","article-title":"Prospects for the computational humanization of antibodies and nanobodies","volume":"15","author":"Gordon","year":"2024","journal-title":"Front Immunol"},{"issue":"4","key":"10.1016\/j.xphs.2025.104142_bib0040","doi-asserted-by":"crossref","first-page":"bbac267","DOI":"10.1093\/bib\/bbac267","article-title":"Machine-designed biotherapeutics: opportunities, feasibility and advantages of deep learning in computational antibody discovery","volume":"23","author":"Wilman","year":"2022","journal-title":"Brief Bioinform"},{"issue":"10","key":"10.1016\/j.xphs.2025.104142_bib0041","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1007\/s00216-017-0772-1","article-title":"Recent mass spectrometry-based techniques and considerations for disulfide bond characterization in proteins","volume":"410","author":"Lakbub","year":"2018","journal-title":"Anal Bioanal Chem"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0042","first-page":"37","article-title":"Next generation of multispecific antibody engineering","volume":"7","author":"Keri","year":"2023","journal-title":"Antib Ther"},{"key":"10.1016\/j.xphs.2025.104142_bib0043","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2024.1352014","article-title":"Design and engineering of bispecific antibodies: insights and practical considerations","volume":"12","author":"Madsen","year":"2024","journal-title":"Front Bioeng Biotechnol"},{"key":"10.1016\/j.xphs.2025.104142_bib0044","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.801368","article-title":"Grabbing the bull by both horns: bovine ultralong CDR-H3 paratopes enable engineering of 'Almost natural' Common light chain bispecific antibodies suitable for effector cell redirection","volume":"12","author":"Klewinghaus","year":"2022","journal-title":"Front Immunol"},{"issue":"2","key":"10.1016\/j.xphs.2025.104142_bib0045","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/2211-5463.13850","article-title":"Nanobody engineering: computational modelling and design for biomedical and therapeutic applications","volume":"15","author":"El Salamouni","year":"2025","journal-title":"FEBS Open Bio"},{"issue":"7\u20138","key":"10.1016\/j.xphs.2025.104142_bib0046","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1515\/hsz-2023-0370","article-title":"Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-\u03b1 neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features","volume":"405","author":"Arras","year":"2024","journal-title":"Biol Chem"},{"issue":"1","key":"10.1016\/j.xphs.2025.104142_bib0047","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2022.2076295","article-title":"The proximity of the N- and C- termini of bovine knob domains enable engineering of target specificity into polypeptide chains","volume":"14","author":"Hawkins","year":"2022","journal-title":"MAbs"},{"key":"10.1016\/j.xphs.2025.104142_bib0048","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1384467","article-title":"Modular design of bi- and multi-specific knob domain fusions","volume":"15","author":"Kuravsky","year":"2024","journal-title":"Front Immunol"}],"container-title":["Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354925005969?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022354925005969?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:11:39Z","timestamp":1773951099000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022354925005969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["S0022354925005969"],"URL":"https:\/\/doi.org\/10.1016\/j.xphs.2025.104142","relation":{},"ISSN":["0022-3549"],"issn-type":[{"value":"0022-3549","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A pharmaceutical developability perspective on antibodies with ultra-long CDRs","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xphs.2025.104142","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association.","name":"copyright","label":"Copyright"}],"article-number":"104142"}}