Alternative Reagents to Antibodies in Imaging Applications
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Affibody Molecules for Epidermal Growth Factor Receptor Targeting
Journal of Nuclear Medicine, published on January 21, 2009 as doi:10.2967/jnumed.108.055525 Affibody Molecules for Epidermal Growth Factor Receptor Targeting In Vivo: Aspects of Dimerization and Labeling Chemistry Vladimir Tolmachev1-3, Mikaela Friedman4, Mattias Sandstrom¨ 5, Tove L.J. Eriksson2, Daniel Rosik2, Monika Hodik1, Stefan Sta˚hl4, Fredrik Y. Frejd1,2, and Anna Orlova1,2 1Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; 2Affibody AB, Bromma, Sweden; 3Department of Medical Sciences, Nuclear Medicine, Uppsala University, Uppsala, Sweden; 4Division of Molecular Biotechnology, School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden; and 5Section of Hospital Physics, Department of Oncology, Uppsala University Hospital, Uppsala, Sweden Noninvasive detection of epidermal growth factor receptor (EGFR) expression in malignant tumors by radionuclide molecu- he epidermal growth factor receptor (EGFR; other lar imaging may provide diagnostic information influencing pa- T designations are HER1 and ErbB-1) is a transmembrane tient management. The aim of this study was to evaluate a tyrosine kinase receptor that regulates cell proliferation, novel EGFR-targeting protein, the ZEGFR:1907 Affibody molecule, for radionuclide imaging of EGFR expression, to determine a motility, and suppression of apoptosis (1). Overexpression suitable tracer format (dimer or monomer) and optimal label. of EGFR is documented in several malignant tumors, such Methods: An EGFR-specific Affibody molecule, ZEGFR:1907, as carcinomas of the breast, urinary bladder, and lung, and 111 and its dimeric form, (ZEGFR:1907)2, were labeled with In using is associated with poor prognosis (2). A high level of EGFR 125 benzyl-diethylenetriaminepentaacetic acid and with I using expression could provide malignant cells with an advantage p-iodobenzoate. -
Wo2015188839a2
Downloaded from orbit.dtu.dk on: Oct 08, 2021 General detection and isolation of specific cells by binding of labeled molecules Pedersen, Henrik; Jakobsen, Søren; Hadrup, Sine Reker; Bentzen, Amalie Kai; Johansen, Kristoffer Haurum Publication date: 2015 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Pedersen, H., Jakobsen, S., Hadrup, S. R., Bentzen, A. K., & Johansen, K. H. (2015). General detection and isolation of specific cells by binding of labeled molecules. (Patent No. WO2015188839). General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/188839 -
Affimer Proteins Inhibit Immune Complex Binding to Fcγriiia with High Specificity Through Competitive and Allosteric Modes of Action
Affimer proteins inhibit immune complex binding to FcγRIIIa with high specificity through competitive and allosteric modes of action James I. Robinsona,b, Euan W. Baxtera,b,1, Robin L. Owenc,1, Maren Thomsend,1, Darren C. Tomlinsond,e,1, Mark P. Waterhousea,b,1, Stephanie J. Wina,b, Joanne E. Nettleshipf,g, Christian Tiedee, Richard J. Fosterd,h, Raymond J. Owensf,g, Colin W. G. Fishwickd,h, Sarah A. Harrisd,i, Adrian Goldmane,j, Michael J. McPhersond,e,2, and Ann W. Morgana,b,2 aLeeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS9 7TF, United Kingdom; bNational Institute of Health Research-Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds LS7 4SA, United Kingdom; cDiamond Light Source, Didcot OX11 0DE, United Kingdom; dAstbury Centre for Structural and Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; eBioScreening Technology Group, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; fOxford Protein Production Facility-United Kingdom Research Complex at Harwell, Rutherford Appleton Laboratory, Oxford OX11 0FA, United Kingdom; gDivision of Structural Biology, Wellcome Trust Centre for Genomic Medicine, Nuffield Department of Medicine, Oxford University, Oxford OX3 7BN, United Kingdom; hSchool of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom; iSchool of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, United Kingdom; and jFaculty of Biological and Environmental Sciences, University of Helsinki, FIN-0014 Helsinki, Finland Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved November 17, 2017 (received for review May 15, 2017) Protein–protein interactions are essential for the control of cellular domains and chains, poor stability, high production costs, and functions and are critical for regulation of the immune system. -
Affimer Technology Nov 2017
Non-confidential Technical Introduction to the Affimer® Technology for Therapeutics and Reagents Dr. Alastair Smith Chief Executive, Avacta Group plc Introduction Avacta Group plc AIM: AVCT • 80 staff over two sites: • 1300 m2 of bespoke laboratory, production and logistics space in Wetherby. • 790 m2 of bespoke laboratory space in Cambridge. • Balance sheet to support existing plans. Wetherby • Experienced management team with interests aligned to shareholders. • Strongly supportive shareholder base. Cambridge London Shareholders >5% . IP Group plc 24.8% Lombard Odier 11.4% Aviva 9.6% Baillie Gifford 7.2% Ruffer LLP 7.1% Fidelity 5.9% J O Hambro 5.7% © Avacta Group plc 2 Leadership Team Dr Alastair Smith, CEO Dr Matt Johnson, CTO Mr Tony Gardiner, CFO • Over 10 years experience as a public • Genetics & Microbiology Molecular • Joined Avacta from AHR, an company CEO Biology international architecture practice • Was a leading UK biophysicist - founded • 8 years at Abcam becoming global • Chief Financial Officer of AIM listed Avacta in 2006 Head of R&D Fusion IP plc 2007 – 2011 which was acquired by IP Group plc in 2014 • World class scientific and technical • Joined Avacta in 2014 knowledge with a highly commercial • Joined Avacta in 2016 mindset Dr Philippe Cotrel, CCO Dr Amrik Basran, CSO • Over 20 years’ commercial experience in senior • Over 10 years’ experience of both the biotech and positions in Amersham Pharmacia Biotech, Oxford pharma industries Glycosciences, Affymetrix and Abcam • Director of Protein Biosciences at Domantis, Head of • Commercial Director of Abcam since 2008 – grew Topical Delivery (Biopharm) at GSK revenue from £36.7m to £144m over a 7-year period • Joined Avacta in 2013 • Joined Avacta in 2016 © Avacta Group plc 3 Affimer Technology Affimer®: A proprietary protein scaffold with key technical benefits What is an Affimer? Binding Surface • Based on a naturally occurring proteins (cystatins) and engineered to stably display two loops which create a binding surface. -
Strategies and Challenges for the Next Generation of Therapeutic Antibodies
FOCUS ON THERAPEUTIC ANTIBODIES PERSPECTIVES ‘validated targets’, either because prior anti- TIMELINE bodies have clearly shown proof of activity in humans (first-generation approved anti- Strategies and challenges for the bodies on the market for clinically validated targets) or because a vast literature exists next generation of therapeutic on the importance of these targets for the disease mechanism in both in vitro and in vivo pharmacological models (experi- antibodies mental validation; although this does not necessarily equate to clinical validation). Alain Beck, Thierry Wurch, Christian Bailly and Nathalie Corvaia Basically, the strategy consists of develop- ing new generations of antibodies specific Abstract | Antibodies and related products are the fastest growing class of for the same antigens but targeting other therapeutic agents. By analysing the regulatory approvals of IgG-based epitopes and/or triggering different mecha- biotherapeutic agents in the past 10 years, we can gain insights into the successful nisms of action (second- or third-generation strategies used by pharmaceutical companies so far to bring innovative drugs to antibodies, as discussed below) or even the market. Many challenges will have to be faced in the next decade to bring specific for the same epitopes but with only one improved property (‘me better’ antibod- more efficient and affordable antibody-based drugs to the clinic. Here, we ies). This validated approach has a high discuss strategies to select the best therapeutic antigen targets, to optimize the probability of success, but there are many structure of IgG antibodies and to design related or new structures with groups working on this class of target pro- additional functions. -
Article in Press
G Model MIMM-4561; No. of Pages 12 ARTICLE IN PRESS Molecular Immunology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Molecular Immunology j ournal homepage: www.elsevier.com/locate/molimm Review Alternative molecular formats and therapeutic applications for ଝ bispecific antibodies ∗ Christoph Spiess, Qianting Zhai, Paul J. Carter Department of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA a r t i c l e i n f o a b s t r a c t Article history: Bispecific antibodies are on the cusp of coming of age as therapeutics more than half a century after they Received 28 November 2014 ® were first described. Two bispecific antibodies, catumaxomab (Removab , anti-EpCAM × anti-CD3) and Received in revised form ® blinatumomab (Blincyto , anti-CD19 × anti-CD3) are approved for therapy, and >30 additional bispecific 30 December 2014 antibodies are currently in clinical development. Many of these investigational bispecific antibody drugs Accepted 2 January 2015 are designed to retarget T cells to kill tumor cells, whereas most others are intended to interact with two Available online xxx different disease mediators such as cell surface receptors, soluble ligands and other proteins. The modular architecture of antibodies has been exploited to create more than 60 different bispecific antibody formats. Keywords: These formats vary in many ways including their molecular weight, number of antigen-binding sites, Bispecific antibodies spatial relationship between different binding sites, valency for each antigen, ability to support secondary Antibody engineering Antibody therapeutics immune functions and pharmacokinetic half-life. These diverse formats provide great opportunity to tailor the design of bispecific antibodies to match the proposed mechanisms of action and the intended clinical application. -
Human Antibodies That Bind CXCR4 and Uses Thereof CXCR4-Bindende Humane Antikörper Und Deren Verwendungen Anticorps Humains Liant Le CXCR4 Et Utilisations Associées
(19) TZZ __T (11) EP 2 486 941 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 39/395 (2006.01) C07K 16/28 (2006.01) 15.03.2017 Bulletin 2017/11 (21) Application number: 12155398.6 (22) Date of filing: 01.10.2007 (54) Human antibodies that bind CXCR4 and uses thereof CXCR4-bindende humane Antikörper und deren Verwendungen Anticorps humains liant le CXCR4 et utilisations associées (84) Designated Contracting States: EP-A- 1 316 801 WO-A-2004/059285 AT BE BG CH CY CZ DE DK EE ES FI FR GB GR WO-A-2006/089141 US-A1- 2003 206 909 HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR • GHOBRIAL IRENE M ET AL: "The role of CXCR4 Designated Extension States: inhibitors as novel antiangiogenesis agents in RS cancer therapy", BLOOD, W.B.SAUNDERS COMPANY, ORLANDO, FL, vol. 104, no. 11 (30) Priority: 02.10.2006 US 827851 P PART1, 1 November 2004 (2004-11-01), pages 365A-366A, XP002458710, ISSN: 0006-4971 (43) Date of publication of application: • ENDRES M J ET AL: "CD4-INDEPENDENT 15.08.2012 Bulletin 2012/33 INFECTION BY HIV-2 IS MEDIATED BY FUSIN/CXCR4", CELL, CELL PRESS, (62) Document number(s) of the earlier application(s) in CAMBRIDGE, NA, US, vol. 87, 15 November 1996 accordance with Art. 76 EPC: (1996-11-15), pages745-756, XP002920421, ISSN: 07867192.2 / 2 066 351 0092-8674 • BARIBAUD FREDERIC ET AL: "Antigenically (73) Proprietor: E. -
EURL ECVAM Recommendation on Non-Animal-Derived Antibodies
EURL ECVAM Recommendation on Non-Animal-Derived Antibodies EUR 30185 EN Joint Research Centre This publication is a Science for Policy report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policymaking process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of this publication. For information on the methodology and quality underlying the data used in this publication for which the source is neither Eurostat nor other Commission services, users should contact the referenced source. EURL ECVAM Recommendations The aim of a EURL ECVAM Recommendation is to provide the views of the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) on the scientific validity of alternative test methods, to advise on possible applications and implications, and to suggest follow-up activities to promote alternative methods and address knowledge gaps. During the development of its Recommendation, EURL ECVAM typically mandates the EURL ECVAM Scientific Advisory Committee (ESAC) to carry out an independent scientific peer review which is communicated as an ESAC Opinion and Working Group report. In addition, EURL ECVAM consults with other Commission services, EURL ECVAM’s advisory body for Preliminary Assessment of Regulatory Relevance (PARERE), the EURL ECVAM Stakeholder Forum (ESTAF) and with partner organisations of the International Collaboration on Alternative Test Methods (ICATM). Contact information European Commission, Joint Research Centre (JRC), Chemical Safety and Alternative Methods Unit (F3) Address: via E. -
Generation of Novel Intracellular Binding Reagents Based on the Human Γb-Crystallin Scaffold
Generation of novel intracellular binding reagents based on the human γB-crystallin scaffold Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Naturwissenschaftlichen Fakultät I-Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg Institut für Biochemie und Biotechnologie von Ewa Mirecka geboren am 17. Dezember 1976 in Gdynia, Polen Table of contents Table of contents 1. INTRODUCTION.........................................................................................................1 1.1 Monoclonal antibodies as a biomolecular scaffold..........................................................1 1.2 Binding molecules derived from non-immunoglobulin scaffolds.....................................3 1.2.1 Alternative protein scaffolds – general considerations............................................................ 3 1.2.2 Application of alternative binding molecules ........................................................................... 6 1.3 Affilin – novel binding molecules based on the human γB-crystallin scaffold................... 6 1.3.1 Human γB-crystallin as a molecular scaffold........................................................................... 6 1.3.2 Generation of a human γB-crystallin library and selection of first-generation Affilin molecules ................................................................................................................................ 8 1.4 Selection of binding proteins by phage display ................................................................... -
Introduction and Key Feature Comparison
Affimer® non-Antibody Binders for Affinity Applications: Introduction and Key Feature Comparison Affimer® non-Antibody Binders for Affinity Applications: Introduction and Key Feature Comparison 1 Contents Abstract Introduction Affinity-based applications in the detection, analysis and manipulation of protein targets In vitro applications Diagnostic applications Therapeutic applications Antibodies and their limitations as affinity binders Production considerations: ease, speed, cost and process control Size and structural complexity Stability under assay conditions Immobilisation onto solid support Success rate Limitations of antibodies as biosensors – stability, size and orientation Limitations of antibodies as therapeutics – immunogenicity, toxicity and 3D structure recognition Antibody engineering: future directions Alternatives to antibodies Engineered antibody fragments Aptamers Aptamer engineering – future enhancements Non-antibody protein scaffolds Affimer binders: what’s different? Affimer binders can be generated to almost any protein target, and show high discriminatory powers In practice: Development of novel Affimer diagnostic reagents for Zika virus outbreak management In practice: Affimer binders can be targeted to extracellular effector domains and allosteric regions of receptor proteins In practice: The ability of Affimer proteins to form multimers and fusion proteins allows fine tuning of therapeutic activity and stability in vivo Conclusion References Affimer® non-Antibody Binders for Affinity Applications: Introduction -
WO 2018/098356 Al 31 May 2018 (31.05.2018) W !P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/098356 Al 31 May 2018 (31.05.2018) W !P O PCT (51) International Patent Classification: co, California 94124 (US). DUBRIDGE, Robert B.; 825 A61K 39/395 (2006.01) C07K 16/28 (2006.01) Holly Road, Belmont, California 94002 (US). LEMON, A61P 35/00 (2006.01) C07K 16/46 (2006.01) Bryan D.; 2493 Dell Avenue, Mountain View, California 94043 (US). AUSTIN, Richard J.; 1169 Guerrero Street, (21) International Application Number: San Francisco, California 941 10 (US). PCT/US20 17/063 126 (74) Agent: LIN, Clark Y.; WILSON SONSINI GOODRICH (22) International Filing Date: & ROSATI, 650 Page Mill Road, Palo Alto, California 22 November 201 7 (22. 11.201 7) 94304 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Langi English kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (30) Priority Data: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/426,069 23 November 2016 (23. 11.2016) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/426,077 23 November 2016 (23. 11.2016) US HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (71) Applicant: HARPOON THERAPEUTICS, INC. KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, [US/US]; 4000 Shoreline Court, Suite 250, South San Fran MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, cisco, California 94080 (US). -
Anticalins Versus Antibodies: Made-To-Order Binding Proteins for Small Molecules Gregory a Weiss * and Henry B Lowman
Minireview R177 Anticalins versus antibodies: made-to-order binding proteins for small molecules Gregory A Weiss * and Henry B Lowman Engineering proteins to bind small molecules presents a challenge as daunting as Department of Protein Engineering, Genentech, Inc., drug discovery, for both hinge upon our understanding of receptor^ligand 1 DNA Way, South San Francisco, CA 94080, USA molecular recognition. However, powerful techniques from combinatorial *Present address: Department of Chemistry, molecular biology can be used to rapidly select arti¢cial receptors. While University of California, Irvine, CA 92697, USA traditionally researchers have relied upon antibody technologies as a source of new binding proteins, the lipocalin scaffold has recently emerged as an adaptable Correspondence: HB Lowman receptor for small molecule binding. `Anticalins', engineered lipocalin variants, E-mail: [email protected] offer some advantages over traditional antibody technology and illuminate Keywords: Antibody; Anticalin; Small molecule features of molecular recognition between receptors and small molecule ligands. ligand Received: 19 June 2000 Accepted: 10 July 2000 Published: 1 August 2000 Chemistry & Biology 2000, 7:R177^R184 1074-5521 / 00 / $ ^ see front matter ß 2000 Published by Elsevier Science Ltd. PII: S 1 0 7 4 - 5 5 2 1 ( 0 0 ) 0 0 0 1 6 - 8 Introduction of randomly mutated proteins displayed on the surface of The challenge of discovering small molecule ligands for ¢lamentous bacteriophage, viruses capable of infecting protein receptors is well appreciated by, among others, only bacteria (reviewed in [4]). Diversity can be targeted the pharmaceutical industry, which spent the majority of to particular regions of a displayed protein through stan- its $24 billion pharmaceutical research and development dard molecular biology techniques [5], or can be distrib- budget in 1999 on small molecule drug discovery [1].