THE ESSENTIAL PROTEIN ENGINEERING SUMMIT May 1-5

Total Page:16

File Type:pdf, Size:1020Kb

THE ESSENTIAL PROTEIN ENGINEERING SUMMIT May 1-5 FINAL DAYS 13TH ANNUAL TO REGISTER COVER CONFERENCE-AT-A-GLANCE SPONSORS May 1-5, 2017 • Seaport World Trade Center SHORT COURSES TRAINING SEMINARS ENGINEERING THE ESSENTIAL PROTEIN ENGINEERING SUMMIT STREAM ONCOLOGY STREAM PLENARY KEYNOTE: EVENT FEATURES: IMMUNOTHERAPY STREAM Sir Gregory Winter, Ph.D., NEW Young Scientist Keynote Presentation FRS, Master, Trinity College and 2,200+ Global 19 Short Courses EXPRESSION STREAM Co-Founder and Director, Bicycle Attendees 325+ Influential Therapeutics 22 Conference Speakers ANALYTICAL Tracks STREAM 100+ Exhibiting 6 Training Seminars Companies IMMUNOGENICITY & BIOASSAY STREAM BIOCONJUGATES STREAM THERAPEUTICS STREAM SPONSOR & EXHIBITOR INFO HOTEL & TRAVEL REGISTRATION INFORMATION Register Online! PEGSummit.com Premier Sponsors A Division of Cambridge Innovation Institute PEGSummit.com | 1 FINAL DAYS TO REGISTER CONFERENCE AT A GLANCE COVER CONFERENCE-AT-A-GLANCE SPONSORS SHORT COURSES SUNDAY MONDAY TUESDAY WEDNESDAY THURSDAY FRIDAY TRAINING SEMINARS April 29 May 1 May 2 May 3 May 4 May 5 ENGINEERING Engineering Display of Antibodies Engineering Antibodies STREAM Bispecific Antibodies ONCOLOGY Antibodies for Advancing Bispecific Antibodies ADCs II: STREAM Cancer Therapy to the Clinic for Oncology Advancing Toward the Clinic IMMUNOTHERAPY Preventing Toxicity Adoptive Agonist STREAM in Immunotherapy T-Cell Therapy Immunotherapy Targets Optimizing Protein Expression EXPRESSION Difficult to Express Proteins STREAM Protein Expression System Engineering ANALYTICAL Characterization Biophysical Analysis of Protein Aggregation STREAM of Biotherapeutics Biotherapeutics and Stability IMMUNOGENICITY & Immunogenicity: Regulatory Strategies for Immunogenicity Optimizing Bioassays for BIOASSAY STREAM and Clinical Relevance Assay Assessment Biologics ADCs I: New Targets, Payloads ADCs II: BIOCONJUGATES Fusion Protein Therapeutics STREAM and Alternative Formats Advancing Toward the Clinic THERAPEUTICS Drug Discovery for Biologics and Vaccines Agonist Immunotherapy STREAM Autoimmunity and Inflammation for Infectious Disease Targets SPONSOR & EXHIBITOR INFO Dinner Dinner Short Courses* Short Courses* HOTEL & TRAVEL Cambridge Healthtech Immunology for Drug REGISTRATION INFORMATION Discovery Scientists Regulatory Requirements Across Introduction to Structure-Based PRE-CONFERENCE SHORT COURSES* Introduction to Protein Engineering Register Online! the Product Development Lifecycle Drug Design and Development PEGSummit.com Introduction to Immunogenicity Next-Generation Sequencing for Antibody Discovery & Engineering A Division of Cambridge Innovation Institute *Separate Registration Required PEGSummit.com | 2 FINAL DAYS PEGS SPONSORS TO REGISTER Premier Sponsors COVER CONFERENCE-AT-A-GLANCE SPONSORS SHORT COURSES TRAINING SEMINARS Corporate Sponsors ENGINEERING STREAM ONCOLOGY STREAM IMMUNOTHERAPY STREAM Crystal EXPRESSION B ioscience STREAM ANALYTICAL STREAM IMMUNOGENICITY & BIOASSAY STREAM BIOCONJUGATES STREAM THERAPEUTICS STREAM SPONSOR & EXHIBITOR INFO HOTEL & TRAVEL REGISTRATION INFORMATION Register Online! PEGSummit.com Corporate Support Sponsors A Division of Cambridge Innovation Institute PEGSummit.com | 3 FINAL DAYS PLENARY KEYNOTE SESSION TO REGISTER Monday, May 1 | 4:00 - 5:40 pm COVER Bicycles and Bicycle Drug Conjugates: Next Young Scientist Keynote: Programming Proteins by CONFERENCE-AT-A-GLANCE Generation Therapeutics Deep Sequencing and Design SPONSORS Sir Gregory Winter, Ph.D., Tim Whitehead, Ph.D., FRS, Master, Trinity College and Co-Founder and Assistant Professor, Chemical Engineering and Materials SHORT COURSES Director, Bicycle Therapeutics Science, Michigan State University Bicycles® are a novel therapeutic class of constrained bicyclic peptides Next-generation sequencing has presented protein scientists with the TRAINING SEMINARS that combine antibody-like affinity and selectivity with small molecule-like ability to observe entire populations of molecules before, during, and after tissue penetration, tunable exposure and chemical synthesis. They have a high-throughput screen or selection for function. My group leverages this potential in many indications, including oncology, where Bicycles’ unique unprecedented wealth of sequence-function information to design and ENGINEERING properties have been used to develop Bicycle Drug Conjugates™ (BDCs); engineer protein affinity, specificity, and function and to infer structural STREAM a novel toxin delivery platform which greatly improves toxin loading into complexes of proteins. My talk will present an overview of the above and detail tumour tissues. This presentation will describe both the Bicycle® and BDC methodological improvements that enable the engineering work. ONCOLOGY platforms. STREAM About About Tim Whitehead is an Assistant Professor at Michigan State University in the IMMUNOTHERAPY Sir Gregory Winter is the Master of Trinity College Cambridge and was Departments of Chemical Engineering and Materials Science, Biomedical STREAM until recently a member of the Medical Research Council Laboratory of Engineering, and Biosystems Engineering. He has won an NSF CAREER award, Molecular Biology (LMB) in Cambridge, U.K., and has served as both Deputy holds 6 patents (5 licensed), and has published over 30 research articles in and Acting Director. He was one of the early pioneers of the science of journals like Science, Nature Biotechnology, and Nature Methods. EXPRESSION protein engineering, focusing first on enzymes (with Alan Fersht) and STREAM then antibodies. In particular he invented techniques to humanise rodent The PEGS Young Scientist Keynote antibodies for use as therapeutics, in the course of which he helped to The PEGS Boston Young Scientist Keynote recognizes a rising star in the ANALYTICAL develop alemtuzumab/Campath-1H. Later, he developed methods to field of protein science who has completed a postdoc in the last five years. STREAM make fully human antibodies against human self-antigens using antibody Nominations of candidates for this role were solicited from leading industry libraries. His inventions are used in most of the antibody products on the and academic research labs in the fall of 2016, and the final selection was IMMUNOGENICITY & market, including the humanised antibodies alemtuzumab/Campath-1H, made on the basis of input provided by a 14-person group of scientific BIOASSAY STREAM trastuzumab/Herceptin, bevacizumab/Avastin, palivizumab/Synagis and advisors. the first human antibody (adalimumab/Humira) to be approved by the U.S. CHI’s Young Scientist Keynotes join the company’s Student Fellowships and Food and Drug Administration. Featured Poster Presentations as ways of supporting the increased visibility BIOCONJUGATES of those new to our field. Please visit the PEGS website following the 2017 STREAM Sir Gregory has also acted as an entrepreneur to translate his scientific meeting for details on how you can nominate a candidate for the 2018 inventions to medicines. He was a founder of Cambridge Antibody meeting. THERAPEUTICS Technology (1989) and Domantis (2000) and Bicycle Therapeutics STREAM (2009); these companies pioneered the use of antibody libraries to make fully human antibody therapeutics including adalimumab/Humira and SPONSOR & EXHIBITOR INFO belimumab/Benlysta. HOTEL & TRAVEL REGISTRATION INFORMATION Register Online! PEGSummit.com A Division of Cambridge Innovation Institute PEGSummit.com | 4 FINAL DAYS TO REGISTER SHORT COURSES* COVER SUNDAY, APRIL 30 CONFERENCE-AT-A-GLANCE MORNING 10:00 AM - 1:00 PM AFTERNOON 2:00 - 5:00 PM SPONSORS SC1: Preclinical and Clinical Immunogenicity Bioanalysis: ADCs, SC7: Translational Considerations for Development of Monoclonal SHORT COURSES Multi-Domain Biotherapeutics and New Modalities Antibodies Part II: Focus on Nonclinical Development to the Clinic Darshana Jani, M.S., Senior Manager, Pfizer, Inc. Gadi Bornstein, Ph.D., Global Correlative Science Leader, Director, Novartis TRAINING SEMINARS Seema Kumar, Ph.D., Associate Director, EMD Serono Pharmaceuticals Corinna Krinos Fiorotti, Ph.D., Business Development Manager, Bioagilytix Enrique Escandon Ph.D., Senior Principal Scientist, DMPK and Disposition, Merck Research Laboratories Priya Sriraman, Ph.D., Principal Investigator, Biotherapeutics Development, ENGINEERING Vaishnavi Ganti, Ph.D., Associate Principal Scientist, Biologics Discovery- Celgene Corp STREAM DMPK, Merck Research Laboratories SC2: Translational Considerations for Development of Monoclonal Veronica Juan, Ph.D., Principal Scientist, Protein Sciences, Merck Research ONCOLOGY Antibodies Part I: Focus on Early Discovery Labs STREAM Gadi Bornstein, Ph.D., Global Correlative Science Leader, Director, Novartis Scott L. Klakamp, Ph.D., Vice President of Chemistry and Biochemistry, Pharmaceuticals Bioptix IMMUNOTHERAPY Enrique Escandon Ph.D., Senior Principal Scientist, DMPK and Disposition, Mohammad Tabrizi, Ph.D., Director Biologics Discovery, Merck Research STREAM Merck Research Laboratories Laboratories Vaishnavi Ganti, Ph.D., Associate Principal Scientist, Biologics Discovery- DMPK, Merck Research Laboratories SC8: In silico Immunogenicity Predictions – A Hands-On Workshop EXPRESSION Vinodh B. Kurella, Ph.D., Senior Scientist, Molecular Engineering Unit, Intrexon STREAM Veronica Juan, Ph.D., Principal Scientist, Protein Sciences, Merck Research Labs Corp. Scott L. Klakamp, Ph.D., Principal, SKD Consulting LLC ANALYTICAL SC9: Target Selection for Biologics STREAM Mohammad Tabrizi, Ph.D., Director Biologics Discovery, Merck Research William R.
Recommended publications
  • (12) United States Patent (10) Patent No.: US 8,877,688 B2 Vasquez Et Al
    US008877688B2 (12) United States Patent (10) Patent No.: US 8,877,688 B2 Vasquez et al. (45) Date of Patent: *Nov. 4, 2014 (54) RATIONALLY DESIGNED, SYNTHETIC (56) References Cited ANTIBODY LIBRARIES AND USES THEREFOR U.S. PATENT DOCUMENTS 4.946,778 A 8, 1990 Ladner et al. (75) Inventors: Maximiliano Vasquez, Palo Alto, CA 5,118,605 A 6/1992 Urdea (US); Michael Feldhaus, Grantham, NH 5,223,409 A 6/1993 Ladner et al. 5,283,173 A 2f1994 Fields et al. (US); Tillman U. Gerngross, Hanover, 5,380,833. A 1, 1995 Urdea NH (US); K. Dane Wittrup, Chestnut 5,525.490 A 6/1996 Erickson et al. Hill, MA (US) 5,530,101 A 6/1996 Queen et al. 5,565,332 A 10/1996 Hoogenboom et al. (73) Assignee: Adimab, LLC, Lebanon, NH (US) 5,571,698 A 11/1996 Ladner et al. 5,618,920 A 4/1997 Robinson et al. (*) Notice: Subject to any disclaimer, the term of this 5,658,727 A 8, 1997 Barbas et al. patent is extended or adjusted under 35 (Continued) U.S.C. 154(b) by 747 days. FOREIGN PATENT DOCUMENTS This patent is Subject to a terminal dis claimer. DE 19624562 A1 1, 1998 WO WO-88.01649 A1 3, 1988 (21) Appl. No.: 12/404,059 (Continued) OTHER PUBLICATIONS (22) Filed: Mar 13, 2009 Rader et al. (Jul. 21, 1998) Proceedings of the National Academy of (65) Prior Publication Data Sciences USA vol. 95 pp. 8910 to 8915.* US 201O/OO5638.6 A1 Mar. 4, 2010 (Continued) Primary Examiner — Heather Calamita Related U.S.
    [Show full text]
  • Phage Display Libraries for Antibody Therapeutic Discovery and Development
    antibodies Review Phage Display Libraries for Antibody Therapeutic Discovery and Development Juan C. Almagro 1,2,* , Martha Pedraza-Escalona 3, Hugo Iván Arrieta 3 and Sonia Mayra Pérez-Tapia 3 1 GlobalBio, Inc., 320, Cambridge, MA 02138, USA 2 UDIBI, ENCB, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Casco de Santo Tomas, Delegación Miguel Hidalgo, Ciudad de Mexico 11340, Mexico 3 CONACyT-UDIBI, ENCB, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Casco de Santo Tomas, Delegación Miguel Hidalgo, Ciudad de Mexico 11340, Mexico * Correspondence: [email protected] Received: 24 June 2019; Accepted: 15 August 2019; Published: 23 August 2019 Abstract: Phage display technology has played a key role in the remarkable progress of discovering and optimizing antibodies for diverse applications, particularly antibody-based drugs. This technology was initially developed by George Smith in the mid-1980s and applied by John McCafferty and Gregory Winter to antibody engineering at the beginning of 1990s. Here, we compare nine phage display antibody libraries published in the last decade, which represent the state of the art in the discovery and development of therapeutic antibodies using phage display. We first discuss the quality of the libraries and the diverse types of antibody repertoires used as substrates to build the libraries, i.e., naïve, synthetic, and semisynthetic. Second, we review the performance of the libraries in terms of the number of positive clones per panning, hit rate, affinity, and developability of the selected antibodies. Finally, we highlight current opportunities and challenges pertaining to phage display platforms and related display technologies.
    [Show full text]
  • The Generation of Synthetic Antibody Reagents for Clostridium Difficile Toxins
    The Generation of Synthetic Antibody Reagents for Clostridium difficile Toxins by Sylvia Cien Man Wong A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Molecular Genetics University of Toronto © Copyright by Sylvia Wong 2013 The Generation of Synthetic Antibody Reagents for Clostridium difficile Toxins Sylvia Cien Man Wong Master of Science Graduate Department of Molecular Genetics University of Toronto 2013 Abstract The symptoms of C. difficile infection are primarily caused by two toxins, toxin A and toxin B. Some strains produce a third known toxin, C. difficile transferase (CDT) toxin; however, its role in virulence remains unclear. I aimed to develop synthetic antibodies using phage display technology to block toxin entry by binding to the receptor-binding domain (RBD) of the toxins. I first described the generation of anti-toxin A and anti-toxin B Fabs. I presented Fab A3, which bound to the full-length toxin, but did not functionally inhibit toxin entry. In chapter 2, I described the generation of novel anti-CDTb antibodies. I further demonstrated that five of the anti-CDTb antibodies could functionally inhibit CDTb binding in an ELISA-based assay and on cultured cells. These antibodies can be used as tools to understand the toxins’ role in human disease and potentially be used as therapeutics. ii Acknowledgments I am very thankful for having the chance to work with many great scientists in Dr. Jason Moffat’s and Dr. Sachdev Sidhu’s labs. These people made the lab a very motivating, supportive, and intellectually stimulating environment, where I was able to learn and expand my critical thinking skills.
    [Show full text]
  • Wo 2008/048970 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 24 April 2008 (24.04.2008) PCT WO 2008/048970 A2 (51) International Patent Classification: (72) Inventors; and A61K 39/395 (2006 01) (75) Inventors/Applicants (for US only): JOHNSTON, Stephen, Albert [US/US], 8606 S Dorsey Lane, Tempe, (21) International Application Number: AZ 85284 (US) WOODBURY, Neal [US/US], 1001 S PCT/US2007/081536 McAllister Avenue, Tempe, AZ 85287 (US) CHAPUT, John, C. [US/US], 3069 E Dry Creed Road, Phoenix, AZ (22) International Filing Date: 16 October 2007 (16 10 2007) 85048 (US) DIEHNELT, Chris, W. [US/US], 20941 N Leona Boulevard, Maπ copa, AZ 85239 (US) YAN, Hao (25) Filing Language: English [CN/US], 1300 N Brentwood Place, Chandler, AZ 85224 (26) Publication Language: English (US) (74) Agent: LIEBESCHUETZ, Joe, Townsend and Townsend (30) Priority Data: and Crew LLP , 8th floor, Two Embarcadero Center, San 60/852,040 16 October 2006 (16 10 2006) US Francisco, CA 941 11-3834 (US) 60/975,442 26 September 2007 (26 09 2007) US (81) Designated States (unless otherwise indicated, for every (71) Applicant (for all designated States except US): THE kind of national protection available): AE, AG, AL, AM, ARIZONA BOARD OF REGENTS, A BODY COR¬ AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, PORATE OF THE STATE OF ARIZONA acting for CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, and on behalf
    [Show full text]
  • Protein Conjugation with Triazolinediones: Switching from a General Tyrosine-Selective Labeling Method to a Highly Specific Tryptophan Bioconjugation Strategy Klaas W
    Protein Conjugation with Triazolinediones: Switching from a General Tyrosine-Selective Labeling Method to a Highly Specific Tryptophan Bioconjugation Strategy Klaas W. Decoene,† Kamil Unal,‡ An Staes⟠Ψ, Kris Gevaert⟠, Johan M. Winne,‡ Annemieke Madder†* † Organic and Biomimetic Chemistry Research group OBCR, Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281 S4, 9000 Ghent, Belgium ‡ Organic Synthesis group, Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281 S4, 9000 Ghent, Belgium ⟠ VIB Centre for Medical Biotechnology, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium & Department of Bio- molecular Medicine, Ghent University, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium Ψ VIB core facility , VIB Centre for Medical Biotechnology, Technologiepark-Zwijnaarde 75, 9052 Ghent, Belgium ABSTRACT: Selective labeling of tyrosine residues in peptides and proteins can be achieved via a 'tyrosine-click' reaction with triazolinedione reagents (TAD). We have found that tryptophan residues are in fact often also labeled with this reagent. This off-target labeling is only observed at very low levels in protein bioconjugation but remains under the radar due to the low relative abundance of tryptophan compared to tyrosines in natural proteins, and because of the low availability and ac- cessibility of their nucleophilic positions at the solvent-exposed protein surface. Moreover, because TAD-Trp adducts are known to be readily thermoreversible, it can be challenging to detect these physiologically stable but thermally labile modi- fications using several MS/MS techniques. We have found that fully solvent-exposed tryptophan side chains are kinetically favored over tyrosines under almost all conditions, and this selectivity can even be further enhanced by modifying the pH of the aqueous buffer to effect selective Trp-labeling.
    [Show full text]
  • 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.
    [Show full text]
  • Computational Design of Peptide Ligands Based on Antibody-Antigen Interface Properties
    Computational design of peptide ligands based on antibody-antigen interface properties By Benjamin Thomas VIART Thesis Advisor Prof. Dra. Liza Figueiredo Felicori Vilela Thesis Co-advisor Dr. Franck Molina Universidade Federal de Minas Gerais Instituto de Ciências Biológicas Programa de Pós-Graduação em Bioinformática Avenida Presidente Antônio Carlos, 6627 Pampulha 31270-901 Belo Horizonte - MG To my parents, ii Acknowledgments • Firstly, I would like to express my sincere gratitude to my advisor Dr. Prof. Liza Figueiredo Felicori Vilela for the continuous support of my Ph.D study, for her patience, motivation and knowledge. Her advices and guidance helped me better understand the scientific gait, the rules of research, the importance of the details. I would like to thank her as well for making feel welcome in Brazil, helping me with the transition to this new culture that is now part of me as the French culture is part of her. • Secondly, I would like to deeply thank my co-advisor Dr Franck Molina, without whom I would never have done this PhD. I am forever grateful to him for believing in me and helping me achieve this goal. • From the department, I would like to thanks Prof. Jader, Prof. Vasco, Prof. Miguel, Prof. Lucas, Prof. Gloria as well as Sheila. • This thesis is dedicated to my parents, Frédéric and Françoise Viart, who helped me throughout my life to become a good person. I thank them for their unconditional love and support. • I would like to thank all my family, especially my sisters, Sophie and Lisa, for their smiles and grimaces; my grand-parents, Bob, Nanou and Mémé for their support and love and also my uncle, Bruno, for all his help when I was in first year of medical school.
    [Show full text]
  • International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU
    ( 2 (51) International Patent Classification: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, A61K 39/42 (2006.01) C07K 16/10 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, C07K 16/08 (2006.01) KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US20 19/033 995 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 24 May 2019 (24.05.2019) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available) . ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 62/676,045 24 May 2018 (24.05.2018) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (71) Applicant: LANKENAU INSTITUTE FOR MEDICAL TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, RESEARCH [US/US]; 100 Lancaster Avenue, Wyn- KM, ML, MR, NE, SN, TD, TG).
    [Show full text]
  • Nanobodies and Recombinant Binders in Cell Biology
    JCB: Review Nanobodies and recombinant binders in cell biology Jonas Helma,1 M. Cristina Cardoso,2 Serge Muyldermans,3 and Heinrich Leonhardt1 1Department of Biology II, Ludwig Maximilians University Munich and Center for Integrated Protein Science Munich, 82152 Planegg-Martinsried, Germany 2Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany 3Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium Antibodies are key reagents to investigate cellular pro- exclusive to small and stable binding molecules and cannot cesses. The development of recombinant antibodies and be performed easily with full-length antibodies, as a result of crucial inter- and intramolecular disulphide bridges that do not binders derived from natural protein scaffolds has ex- form in the cytoplasm. Thus, researchers have found a plethora panded traditional applications, such as immunofluores- of new applications in which binders have been combined with cence, binding arrays, and immunoprecipitation. In enzymatic or structural functionalities in living systems. addition, their small size and high stability in ectopic en- The development of in vitro screening techniques has been a decisive step for the rise and generation of recombinant vironments have enabled their use in all areas of cell re- binding reagents. These methods include classic phage display Downloaded from search, including structural biology, advanced microscopy, but also bacterial and yeast display as well as ribosomal and and intracellular expression. Understanding these novel mRNA display. With such in vitro display techniques at hand, directed evolution strategies and genetic manipulation of binder reagents as genetic modules that can be integrated into sequences allow targeted engineering of key features, such as cellular pathways opens up a broad experimental spec- specificity, valence, affinity, and stability, enable derivatization trum to monitor and manipulate cellular processes.
    [Show full text]
  • 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.
    [Show full text]
  • 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 ...................................................................
    [Show full text]
  • 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].
    [Show full text]