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First published March 12, 2026 Application Aachen patent C – Chemistry & metallurgy

AN ANTIBODY MOLECULE BINDING HUMAN UPAR

Espacenet Family 93376457

Abstract

The present invention relates to an antibody molecule or an antigen binding fragment targeting human urokinase plasminogen activator receptor (uPAR) and an antibody-conjugate comprising an antibody molecule or antigen binding fragment according to any aspect of the invention; and a coupling moiety. The invention further relates to the uses of these antibody molecules, antigen binding fragments or antibody-conjugates.

Inventors 4

  1. Alexander L. Vahrmeijer Aachen author as filed: Vahrmeijer, Alexander Lucas
  2. Victor M. Baart Aachen author as filed: Baart, Victor Michiel
  3. Cornelis F.M. Sier Aachen author as filed: Sier, Cornelis Frederikus Maria
  4. Kuppen, Petrus Johannes Karel

Inventors are linked to an Aachen author when surname and first name match exactly one author.

Applicants

  • ACADEMISCH ZIEKENHUIS LEIDEN (H.O.D.N. LUMC) GBS Leiden

Cited papers 10 in the database

Non-patent literature as cited (73)
  • - HELLSTROM ET AL.: "Sequences of proteins of Immunological Interest", 1987, MARCEL DEKKER, INC., article "Antibodies For Drug Delivery", pages: 623 - 53
  • - KESSLER ET AL., J. NEUROCHEM, vol. 142, 2017, pages 7 - 18
  • - LLINAS ET AL., EMBOJ, vol. 24, no. 9, 2005, pages 1655 - 63
  • - HUAI ET AL., SCIENCE, vol. 311, no. 5761, 2006, pages 656 - 9
  • - CHELSEA ET AL., HUMAN GENOMICS, vol. 10, 2016, pages 10
  • - DESMEDT ET AL., CRIT. REV. CLIN. LAB. SEI, vol. 54, no. 2, 2017, pages 117 - 133
  • - WAGNER ET AL., NATURE, vol. 583, no. 7814, 2020, pages 37 - 38
  • - AMOR ET AL., NATURE, vol. 583, no. 7814, July 2020 (2020-07-01), pages 127 - 132
  • - HARVEY ET AL., NAT. REV. MOL. CELL BIOL, vol. 11, 2010, pages 23 - 36
  • - FOCA ET AL., GYNECOL. ONCOL., vol. 79, no. 2, 2000, pages 244 - 50
  • - HATA ET AL., BLOOD, vol. 81, 1993, pages 3357 - 3364
  • - MC BENE ET AL., LEUKEMIA, vol. 18, 2004, pages 394 - 400
  • - BO ET AL., ONCOL. REP., vol. 14, no. 1, 2005, pages 105 - 12
  • - FOEKENS ET AL., CANCER RES., vol. 60, no. 3, 2000, pages 636 - 43
  • - "UniProt", Database accession no. Q03405-1
  • - WARD ET AL., NATURE, vol. 341, 1989, pages 544 - 546
  • - DONGEN ET AL., THE ONCOLOGIST, vol. 12, 2007, pages 1379 - 1389
  • - PORTOLANO ET AL., J. IMMUNOL., vol. 150, 1993, pages 880 - 887
  • - CLARKSON ET AL., NATURE, vol. 352, 1991, pages 624 - 628
  • - E. MEYERSW. MILLER, COMPUT APPL BIOSCI, vol. 14, 1988, pages 11 - 17
  • - NEEDLEMANWUNSCH, J MOL BIOL, vol. 48, 1970, pages 444 - 453
  • - ALTSCHUL ET AL., J MOL BIOL, vol. 215, 1990, pages 403 - 10
  • - ALTSCHUL, NUCLEIC ACIDS RES, vol. 25, no. 17, 1997, pages 3389 - 3402
  • - CHARI ET AL., CANCER RESEARCH, vol. 52, 1992, pages 127 - 131
  • - AGNEW, CHEM INTL. ED. ENGL., vol. 33, 1994, pages 183 - 186
  • - AMON ET AL.: "Monoclonal Antibodies And Cancer Therapy", 1985, ALAN R. LISS, INC, article "Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy", pages: 243 - 56
  • - THORPE ET AL.: "Monoclonal Antibodies '84: Biological And Clinical Applications", 1985, article "Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review", pages: 475 - 506
  • - "Monoclonal Antibodies For Cancer Detection And Therapy", 1985, ACADEMIC PRESS, article "Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy", pages: 303 - 16
  • - THORPE ET AL.: "The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates", IMMUNOL. REV., vol. 62, 1982, pages 119 - 58, XP001179872, DOI: 10.1111/j.1600-065X.1982.tb00392.x
  • - VEREL ET AL., J. NUCL. MED., vol. 44, 2003, pages 1271 - 1281
  • - SINGLETONSAINSBURY: "Dictionary of Microbiology and Molecular Biology", 1994, JOHN WILEY AND SONS
  • - HALEMARHAM: "The Harper Collins Dictionary of Biology", 1991, HARPER PERENNIAL
  • - MULLARD A.: "FDA approves 100th monoclonal antibody product.", NATURE REVIEWS DRUG DISCOVERY., vol. 20, 2021, pages 491 - 5, XP037497171, DOI: 10.1038/d41573-021-00079-7
  • - BARTELINK IHJONES EFSHAHIDI-LATHAM SKLEE PREZHENG YVICINI P ET AL.: "Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle.", CLIN PHARMACOL THER., vol. 106, 2019, pages 148 - 63
  • - LU GNISHIO NVAN DEN BERG NSMARTIN BAFAKURNEJAD SVAN KEULEN S ET AL.: "Co-administered antibody improves penetration of antibody-dye conjugate into human cancers with implications for antibody-drug conjugates", NATURE COMMUNICATIONS., vol. 11, 2020
  • - MINCHINTON ALTANNOCK IF: "Drug penetration in solid tumours", NAT REV CANCER., vol. 6, 2006, pages 583 - 92
  • - FLAJNIK MFDESCHACHT NMUYLDERMANS S.: "A case of convergence: why did a simple alternative to canonical antibodies arise in sharks and camels", PLOS BIOL., vol. 9, 2011, pages e1001120
  • - STIJLEMANS BCONRATH KCORTEZ-RETAMOZO VVAN XONG HWYNS LSENTER P ET AL.: "Efficient targeting of conserved cryptic epitopes of infectious agents by single domain antibodies. African trypanosomes as paradigm.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, 2004, pages 1256 - 61, XP002367544, DOI: 10.1074/jbc.M307341200
  • - DALEY LPKUTZLER MABENNETT BWSMITH MCGLASER ALAPPLETON JA.: "Effector functions of camelid heavy-chain antibodies in immunity to West Nile virus.", CLIN VACCINE IMMUNOL., vol. 17, 2010, pages 239 - 46
  • - MUYLDERMANS S.: "Nanobodies: natural single-domain antibodies.", ANNU REV BIOCHEM., vol. 82, 2013, pages 775 - 97, XP055083831, DOI: 10.1146/annurev-biochem-063011-092449
  • - DE VOS J, DEVOOGDT N, LAHOUTTE T, MUYLDERMANS S.: "Camelid single-domain antibody-fragment engineering for (pre)clinical in vivo molecular imaging applications adjusting the bullet to its target:", EXPERT OPIN BIOL THER., vol. 13, 2013, pages 1149 - 60
  • - CHAKRAVARTY RGOEL SCAI W.: "Nanobody: the ''magic bullet'' for molecular imaging", THERANOSTICS, vol. 4, 2014, pages 386 - 98
  • - JOVČEVSKA IMUYLDERMANS S.: "The Therapeutic Potential of Nanobodies.", BIODRUGS., vol. 34, 2020, pages 11 - 26, XP055872374, DOI: 10.1007/s40259-019-00392-z
  • - MORRISON C.: "Nanobody approval gives domain antibodies a boost.", NATURE REVIEWS DRUG DISCOVERY., vol. 18, 2019, pages 485 - 7, XP037991332, DOI: 10.1038/d41573-019-00104-w
  • - YANG EYSHAH K.: "Nanobodies: Next Generation of Cancer Diagnostics and Therapeutics.", FRONTIERS IN ONCOLOGY., vol. 10, 2020, pages 1182
  • - HANAHAN DWEINBERG RA.: "Hallmarks of cancer: the next generation.", CELL., vol. 144, 2011, pages 646 - 74, XP028185429, DOI: 10.1016/j.cell.2011.02.013
  • - SMITH HWMARSHALL CJ: "Regulation of cell signalling by uPAR. Nature reviews", MOLECULAR CELL BIOLOGY., vol. 11, 2010, pages 23 - 36
  • - BAART VMHOUVAST RDDE GEUS-OEI LFQUAX PHAKUPPEN PJKVAHRMEIJER AL ET AL.: "Molecular imaging of the urokinase plasminogen activator receptor: opportunities beyond cancer.", EJNMMI RES., vol. 10, 2020, pages 87
  • - AHN SBMOHAMEDALI APASCOVICI DADHIKARI SSHARMA SNICE EC ET AL.: "Proteomics Reveals Cell-Surface Urokinase Plasminogen Activator Receptor Expression Impacts Most Hallmarks of Cancer.", PROTEOMICS., vol. 19, 2019, pages e1900026
  • - BOONSTRA MCVERSPAGET HWGANESH SKUBBEN FJVAHRMEIJER ALVAN DE VELDE CJ ET AL.: "Clinical applications of the urokinase receptor (uPAR) for cancer patients", CURRENT PHARMACEUTICAL DESIGN., vol. 17, 2011, pages 1890 - 910
  • - MAHMOOD NMIHALCIOIU CRABBANI SA.: "Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications.", FRONTIERS IN ONCOLOGY., vol. 8, 2018, pages 24
  • - BAART VMVAN DER HORST GDEKEN MMBHAIROSINGH SSSCHOMANN TSIER VQ ET AL.: "A multimodal molecular imaging approach targeting urokinase plasminogen activator receptor for the diagnosis, resection and surveillance of urothelial cell carcinoma", EUROPEAN JOURNAL OF CANCER (OXFORD, ENGLAND : 1990, vol. 146, 2021, pages 11 - 20
  • - SKJGTH-RASMUSSEN JAZAM ALARSEN CCSCHEIE DJUHL KKJAER A.: "A new uPAR-targeting fluorescent probe for optical guided intracranial surgery in resection of a meningioma-a case report.", ACTA NEUROCHIR (WIEN)., 2021
  • - BAART VMVAN MANEN LBHAIROSINGH SSVUIJK FALAMELE LDE JONGE H ET AL.: "Side-by-Side Comparison of uPAR-Targeting Optical Imaging Antibodies and Antibody Fragments for Fluorescence-Guided Surgery of Solid Tumors.", MOL IMAGING BIOL., 2021
  • - JUHL KCHRISTENSEN APERSSON MPLOUG MKJAER A: "Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105.", PLOS ONE., vol. 11, 2016, pages e0147428
  • - VERBEEK FPVAN DER VORST JRTUMMERS QRBOONSTRA MCDE ROOIJ KELOWIK CW ET AL.: "Near-infrared fluorescence imaging of both colorectal cancer and ureters using a low-dose integrin targeted probe", ANNALS OF SURGICAL ONCOLOGY, vol. 4, 2014, pages 528 - 37, XP055883516, DOI: 10.1245/s10434-014-3524-x
  • - WILTON EEOPYR MPKAILASAM SKOTHE RFWIEDEN HJ.: "sdAb-DB: The Single Domain Antibody Database.", ACS SYNTH BIOL., vol. 7, 2018, pages 2480 - 4, XP055919233, DOI: 10.1021/acssynbio.8b00407
  • - XU XCAI YWEI YDONATE FJUAREZ JPARRY G ET AL.: "Identification of a new epitope in uPAR as a target for the cancer therapeutic monoclonal antibody ATN-658, a structural homolog of the uPAR binding integrin CD11b (alphaM", PLOS ONE, vol. 9, 2014, pages e85349
  • - LLINAS PLE DU MHGARDSVOLL HDANØ KPLOUG MGILQUIN B ET AL.: "Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide.", THE EMBO JOURNAL., vol. 24, 2005, pages 1655 - 63, XP002519848, DOI: 10.1038/SJ.EMBOJ.7600635
  • - KANG THJUNG ST.: "Boosting therapeutic potency of antibodies by taming Fc domain functions.", EXP MOL MED., vol. 51, 2019, pages 1 - 9, XP055864199, DOI: 10.1038/s12276-019-0345-9
  • - ZALEVSKY JCHAMBERLAIN AKHORTON HMKARKI SLEUNG IWSPROULE TJ ET AL.: "Enhanced antibody half-life improves in vivo activity.", NAT BIOTECHNOL., vol. 28, 2010, pages 157 - 9, XP055308991, DOI: 10.1038/nbt.1601
  • - LI DLIU SLIU RZHOU YPARK RNAGA K ET AL.: "EphB4-targeted imaging with antibody h131, h131-F(ab')2 and h131-Fab.", MOL PHARM., vol. 10, 2013, pages 4527 - 33
  • - HONG HZHANG YORBAY HVALDOVINOS HFNAYAK TRBEAN J ET AL.: "Positron emission tomography imaging of tumor angiogenesis with a (61/64)Cu-labeled F(ab')(2) antibody fragment.", MOL PHARM., vol. 10, 2013, pages 709 - 16
  • - ZHANG YHONG HORBAY HVALDOVINOS HFNAYAK TRTHEUER CP ET AL.: "PET imaging of CD105/endoglin expression with a /64Cu-labeled Fab antibody fragment.", EUR J NUCL MED MOL IMAGING., vol. 40, 2013, pages 759 - 67, XP035341790, DOI: 10.1007/s00259-012-2334-2
  • - LETH JMPLOUG M.: "Targeting the Urokinase-Type Plasminogen Activator Receptor (uPAR) in Human Diseases With a View to Non-invasive Imaging and Therapeutic Intervention.", FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY., vol. 9, 2021, pages 732015
  • - XENAKI KTOLIVEIRA SVAN BERGEN EN HENEGOUWEN PMP.: "Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors", FRONT IMMUNOL., vol. 8, 2017, pages 1287, XP093175785, DOI: 10.3389/fimmu.2017.01287
  • - SCHMIDT MMWITTRUP KD.: "A modeling analysis of the effects of molecular size and binding affinity on tumor targeting.", MOL CANCER THER., vol. 8, 2009, pages 2861 - 71
  • - EDEN GARCHINTI MFURLAN FMURPHY RDEGRYSE B.: "The urokinase receptor interactome.", CURRENT PHARMACEUTICAL DESIGN., vol. 17, 2011, pages 1874 - 89
  • - AHN SBCHAN CDENT OFMOHAMEDALI AKWUN SYCLARKE C ET AL.: "Epithelial and stromal cell urokinase plasminogen activator receptor expression differentially correlates with survival in rectal cancer stages Band C patients.", PLOS ONE., vol. 10, 2015, pages e0117786
  • - FLOREA AMOTTAGHY FMBAUWENS M.: "Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status.", INT J MOL SCI., vol. 22, 2021
  • - HARRYVAN TJHAWINKELS LMINI-TUMOR WOSTMAN ATEN DIJKE PSTRELL C ET AL.: "A Novel Pancreatic Cancer Mini-tumor Model to Study Desmoplasia and Myofibroblastic Cancer-Associated Fibroblast Differentiation.", GASTRO HEP ADV., vol. 1, no. 4, 2022, pages 678 - 81
  • - VERBEEK FPVAN DER VORST JRTUMMERS QRBOONSTRA MCDE ROOIJ KELOWIK CW ET AL.: "Near-infrared fluorescence imaging of both colorectal cancer and ureters using a low-dose integrin targeted probe.", ANNALS OF SURGICAL ONCOLOGY., vol. 4, no. 0 4, 2014, pages S528 - 37
  • - LI ET AL: "An Anti-urokinase Plasminogen Activator Receptor (uPAR) Antibody: Crystal Structure and Binding Epitope", JOURNAL OF MOLECULAR BIOLOGY, ACADEMIC PRESS, UNITED KINGDOM, vol. 365, no. 4, 30 December 2006 (2006-12-30), pages 1117 - 1129, XP005733680, ISSN: 0022-2836, DOI: 10.1016/J.JMB.2006.10.059

Cited patents 12

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