Expanding the Boundaries of Biotherapeutics with Bispecific
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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 -
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. -
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 ................................................................... -
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]. -
WO 2017/013231 Al 26 January 2017 (26.01.2017) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2017/013231 Al 26 January 2017 (26.01.2017) P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, C07K 14/705 (2006.01) C07K 16/00 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/EP20 16/067468 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 2 1 July 20 16 (21 .07.2016) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/194,882 2 1 July 2015 (21.07.2015) TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, 62/364,414 20 July 2016 (20.07.2016) TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (72) Inventors; and LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (71) Applicants : XIANG, Sue D. -
Protein Scaffolds Proteingerüste Structures Protéiques
(19) TZZ _ _T (11) EP 2 215 246 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C12N 15/10 (2006.01) C12N 15/62 (2006.01) 07.01.2015 Bulletin 2015/02 C07K 14/78 (2006.01) C40B 40/10 (2006.01) (21) Application number: 08845766.8 (86) International application number: PCT/US2008/012398 (22) Date of filing: 31.10.2008 (87) International publication number: WO 2009/058379 (07.05.2009 Gazette 2009/19) (54) PROTEIN SCAFFOLDS PROTEINGERÜSTE STRUCTURES PROTÉIQUES (84) Designated Contracting States: US-B1- 6 482 410 US-B1- 6 818 418 AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT • KOIDE A ET AL: "The fibronectin type III domain RO SE SI SK TR as a scaffold for novel binding proteins", JOURNAL OF MOLECULAR BIOLOGY, LONDON, (30) Priority: 31.10.2007 US 984209 P GB, vol. 284, no. 4, 11 December 1998 (1998-12-11), pages 1141-1151, XP004455886, (43) Date of publication of application: ISSN: 0022-2836, DOI: DOI:10.1006/JMBI. 11.08.2010 Bulletin 2010/32 1998.2238 • BATORI V ET AL: "Exploring the potential of the (73) Proprietor: MedImmune, LLC monobody scaffold:effects of loop elongation on Gaithersburg, MD 20878 (US) the stability of a fibronectin type III domain", PROTEIN ENGINEERING, OXFORD UNIVERSITY (72) Inventors: PRESS, SURREY, GB, vol. 15, no. 12, 1 January • WU, Herren 2002 (2002-01-01), pages 1015-1020, Boyds,MD 20841 (US) XP002996047, ISSN: 0269-2139, DOI: DOI: • BACA, Manuel 10.1093/PROTEIN/15.12.1015 Gaithersburg,MD 20878 (US) • KOIDE AKIKO ET AL: "Monobodies: antibody •SWERS,Jeffrey mimics based on the scaffold of the fibronectin Rockville,MD 20852 (US) type III domain", METHODS IN MOLECULAR • CHACKO, Benoy BIOLOGY, HUMANA PRESS INC, NJ, US, vol. -
Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy
Published OnlineFirst June 9, 2021; DOI: 10.1158/1078-0432.CCR-20-3770 CLINICAL CANCER RESEARCH | REVIEW Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy A C Belen Blanco1,2, Carmen Domínguez-Alonso1,2, and Luis Alvarez-Vallina1,2 ABSTRACT ◥ The recent advances in the field of immuno-oncology have here referred to as bispecific immunomodulatory antibodies, dramatically changed the therapeutic strategy against advanced have the potential to improve clinical efficacy and safety profile malignancies. Bispecific antibody-based immunotherapies have and are envisioned as a second wave of cancer immunotherapies. gained momentum in preclinical and clinical investigations Currently, there are more than 50 bispecific antibodies under following the regulatory approval of the T cell–redirecting clinical development for a range of indications, with promising antibody blinatumomab. In this review, we focus on emerging signs of therapeutic activity. We also discuss two approaches for and novel mechanisms of action of bispecific antibodies inter- in vivo secretion, direct gene delivery, and infusion of ex vivo acting with immune cells with at least one of their arms to gene-modified cells, which may become instrumental for the regulate the activity of the immune system by redirecting and/or clinical application of next-generation bispecific immunomod- reactivating effector cells toward tumor cells. These molecules, ulatory antibodies. Introduction of antibodies, such as linear gene fusions, domain-swapping strat- egies, and self-associating peptides and protein domains (Fig. 1B). The past decade has witnessed a number of cancer immunotherapy Multiple technology platforms are available for the design of bsAbs, breakthroughs, all of which involve the modulation of T cell–mediated allowing fine-tuning of binding valence, stoichiometry, size, flexi- immunity. -
Anticalins: a Novel Class of Therapeutic Binding Proteins
IPT 23 2007 30/8/07 08:54 Page 32 Biotechnology Anticalins: a Novel Class of Therapeutic Binding Proteins Anticalins – engineered human lipocalin proteins – provide a novel class of biopharmaceutical drug candidates with similar binding and recognition properties as antibodies, while offering several fundamental advantages. By Andreas M. Hohlbaum and Arne Skerra of Pieris AG Andreas M. Hohlbaum (Dr. rer. nat.) is Director of Science and Preclinical Development and member of the management of Pieris. He received his training in immunology and a PhD from the University of Konstanz, Germany, and pursued postdoctoral research at Boston University School of Medicine, US, in the areas of apoptosis, inflammation, innate immunity and tumour immunology. He obtained first-hand experience in commercially oriented Discovery Research during his time at the biopharmaceutical company, Dyax (Cambridge, Mass). Dr Hohlbaum joined Pieris as a Strategic Research Scientist, in February 2003 and was promoted to Assistant Director of Preclinical Research in February 2004. Since May 2006, he has directed Pieris’s research and development of proprietary and also partnered Anticalin-based biotherapeutics. Arne Skerra (Dipl.-Ing., Dr. rer. nat.) is Founder of Pieris, Member of its Supervisory Board, and Professor at the Technische Universität München, where he heads the Institute of Biological Chemistry. He holds a Diploma degree in Chemistry from the Technische Universität Darmstadt, and a PhD in Biochemistry from the Ludwig-Maximilians-Universität München. After post- doctoral studies at the MRC Laboratory of Molecular Biology in Cambridge, UK, and a group leader position at the Max-Planck- Institute for Biophysics in Frankfurt am Main, he became Associate Professor for Protein Chemistry at the TU Darmstadt. -
Chemical Engineering of Small Affinity Proteins
Chemical Engineering of Small Affinity Proteins Joel Lindgren KTH Royal Institute of Technology School of Biotechnology Stockholm 2014 © Joel Lindgren Stockholm, 2014 KTH Royal Institute of Technology School of Biotechnology AlbaNova University Center SE-106 91 Stockholm Sweden Printed by Universitetsservice US-AB Drottning Kristinas väg 53B SE-106 91 Stockholm Sweden ISBN 978-91-7595-004-4 TRITA-BIO Report 2014:3 ISSN 1654-2312 iii Joel Lindgren (2014): Chemical Engineering of Small Affinity Proteins. School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden. Abstract Small robust affinity proteins have shown great potential for use in therapy, in vivo diagnostics, and various biotechnological applications. However, the affinity proteins often need to be modified or functionalized to be successful in many of these applications. The use of chemical synthesis for the production of the proteins can allow for site-directed functionalization not achievable by recombinant routes, including incorporation of unnatural building blocks. This thesis focuses on chemical engineering of Affibody molecules and an albumin binding domain (ABD), which both are three-helix bundle proteins of 58 and 46 amino acids, respectively, possible to synthesize using solid phase peptide synthesis (SPPS). In the first project, an alternative synthetic route for Affibody molecules using a fragment condensation approach was investigated. This was achieved by using native chemical ligation (NCL) for the condensation reaction, yielding a native peptide bond at the site of ligation. The constant third helix of Affibody molecules enables a combinatorial approach for the preparation of a panel of different Affibody molecules, demonstrated by the synthesis of three different Affibody molecules using the same helix 3 (paper I).