DOCSLIB.ORG

Affimer Technology Nov 2017

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
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. • Loops are randomised to create large libraries of diversity ~1010 and Affimers are selected by phage display. Key Benefits • Smaller (14 kDa), simpler (no disulphide bridges and no post- translational modifications), more robust (thermally and chemically) than antibodies. • High affinity (single digit nM) Affimers generated for new targets in a few weeks • Exquisite specificity obtained by control of phage selection process. • Easily modified (chemically and as fusion proteins) and easily manufactured in bacterial, yeast or mammalian systems with high expression yields. • Intracellular survival and activity. • Core Affimer protein is non-immunogenic. © Avacta Group plc 4 Core Intellectual Property Broad IP coverage across the cystatin protein family First Generation • Acquired from the Medical Research Council and Leeds University UK in 2012. • Based on human stefin A with multiple mutations to reduce dimerisation and prevent binding to cathepsin. • Patents granted in EU, US, Asia; Priority date: 2006. • Current technology for therapeutic programmes. Second Generation • Affimer technology based on plant cystatin consensus sequence; high stability suitable for challenging applications in research and diagnostics. • IP exclusively licensed to Avacta by Leeds University; Priority date: 2014. Third Generation • Developed in-house and based on human stefin A with improved biophysical properties and minimal mutations from human sequence for therapeutics; broad claims based on protein engineering and not on a specific sequence. • Priority date: July 2017. • New technology for future therapeutic programmes. © Avacta Group plc 5 Avacta’s Business Model Low down-side risk with significant up-side potential of therapeutics 1 Reagents 2 Therapeutics Building a profitable reagents Building a pipeline of Affimer business through licensing drug candidates in immuno- oncology for partnering © Avacta Group plc 6 Affimer® Therapeutics • Opportunities for Affimer Therapeutics • Avacta Therapeutics Strategy • Pipeline and Research Collaborations • Affimer Therapeutic Molecule Formats • PD-L1 Programme Update: In-vitro activity, in-vivo efficacy and Affimer/PD-L1 co-crystal structure • Affimer Technology Immunogenicity • Pharmacokinetics and Half-life Extension 7 Opportunities for Affimer Therapeutics A novel class of therapeutics with favourable drug properties Affimer-Drug Respiratory Ocular Conjugates o Small size (relative to antibodies) o Potential for a significantly lower dose, o Adaptable for topical delivery in front- favors extravasation/tissue lower cost of goods, lower systemic of-eye conditions and intravitreal & penetration. target engagement with potentially sub-retinal injection for back-of-eye fewer systemic side effects and therapeutics. May have differentiated PK/ADME properties particularly beneficial for treating: increased patient convenience. o Target tissues include cornea, vitreous humor, neurosensory retina (retinal o fibrotic diseases and fibrotic tumors o Can be engineered for high affinity ganglion and photoreceptors) and (breast and pancreatic tumors, uterine and specificity, and low/null systemic RPE/choroidal layers. fibroids). availability. o poorly or abnormally vascularized tissues o Ability to tune duration of action and and tissues with high interstitial pressures. o Stability allows longer duration of reduce frequency of injection for o Tunable serum half-life - can be used action than small molecules. protein therapeutics generally. to limit toxicity in peripheral tissues o Protease stability in diseased lung o Improved intra-ocular pharmacokinetics and improve therapeutic index. (protease inhibitor scaffold). through intravitreal half-life extension by fusion with HA-binding Affimers o Bi-paratopic and bispecific formats to o Non-toxic metabolic products (amino improve both specificity and acids). o Small molecular weight and internalisation. o Thermal stability for nebulisers. compactness of Affimers allows for higher molar loading and better/ o Site directed labeling and biophysics o Attributes suggest compatibility with consistent release kinetics over time to improve manufacturability. inhalable powders/particles. for implantable drug eluting devices. TM o New Approaches: AfDC program o With ability to optimize particle size, o Opportunity for gene delivery for exploring linker/warhead morphology, hygroscopicity, electrical charge and density per application. constitutively expressing recombinant combinations for TME drug release Affimer drug product in eye. with bystander effects. o Exemplars include anti-VEGF Affimers for o PD-L1 Affimer to target tumor and inhibit wet AMD, and bispecific anti-Factor D/C5 PD-1 axis coupled to highly potent drug and anti-b-amyloid Affimers for dry AMD. ablating tumor associated macrophages. © Avacta Group plc 8 Opportunities for Affimer Therapeutics A novel class of therapeutics with favourable drug properties Gene Delivery Dermatological Oral/GI o Small size means recombinant coding o Dermal and transdermal delivery o pH stability + enteric coating or sequence amenable to wide range of embodiments. suppository for intraluminal delivery viral or other coding sequence o Transdermal – skin is the most accessible to large or small intestines. delivery platforms. organ of the body with a large surface o pH stability for intraluminal or area. o Ease of cellular expression and submucusal (endoscopic) delivery to secretion. o Needle-free topical application routes esophagus. - small molecular weight, compactness o Flexible formatting. and stability of Affimers may be o Potential for selective GPCR agonist o Anticipate high specific activity of secreted exploited to enhance the dermal and antagonists for inflammatory gut recombinant Affimers. diseases. permeability of Affimers and o Potential for generating Affimers that associated proteins. o Potential for use in drug eluting alter intracellular targets. o Amendable to fusion protein formats devices (esophageal and intestinal o Modify epigenetics, mitotic activity, and/or use of penetrant enhancers. stents and collars). viability, or other characteristics. o May enable penetration of the stratum o Exploring engineered Affimers and o Cell surface retained embodiments for corneum and entry into the viable formulations strategies permitting epidermis. altering cell trafficking, cellular half- systemic exposure from orally dosed life, immunogenicity or other function. o Readily adaptable to Affimers. o Secreted IO Affimers from engineered microneedle/dermal rollers, CAR-T or ACTR cell therapies. noninvasive jet injectors and electroporation for delivery. o Targeting moieties for viral delivery to o Should be able to achieve delivery of specific cells. Affimers at >1mg/cm2. © Avacta Group plc 9 Avacta Therapeutics Strategy Leveraging Affimer key benefits to create differentiated medicines In-house Pipeline Proof-of-Concept Research Collaborations • Immune-checkpoint inhibitors (combinations, • Gene delivery (Moderna Tx Inc) bispecifics, biparatopics) • CAR-T (Memorial Sloan Kettering) • T-cell engagers • Drug conjugates (Glythera) • Agonists Key Benefit of Affimers Key Benefits of Affimers Ease of creating and manufacturing “multimers” Small size, stability and ease of production by cells that combine multiple Affimers © Avacta Group plc 10 In-house Pipeline Leveraging Affimer key benefits to create differentiated medicines T-cell Engagers Agonists T-cell Tumour Targeting Immune Activators GITR, CD27 CD3e CD19 Other Potential Targets:
Load more

Recommended publications
  • 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.
    [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]
  • 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
    [Show full text]
  • Selection and Characterisation of Affimers Specific for CEA Recognition
    www.nature.com/scientificreports OPEN Selection and characterisation of Afmers specifc for CEA recognition Shazana Hilda Shamsuddin1,2*, David G. Jayne5, Darren C. Tomlinson3,4, Michael J. McPherson3,4 & Paul A. Millner1* Carcinoembryonic antigen (CEA) is the only blood based protein biomarker at present, used for preoperative screening of advanced colorectal cancer (CRC) patients to determine the appropriate curative treatments and post-surveillance screening for tumour recurrence. Current diagnostics for CRC detection have several limitations and development of a highly sensitive, specifc and rapid diagnostic device is required. The majority of such devices developed to date are antibody-based and sufer from shortcomings including multimeric binding, cost and difculties in mass production. To circumvent antibody-derived limitations, the present study focused on the development of Afmer proteins as a novel alternative binding reagent for CEA detection. Here, we describe the selection, from a phage display library, of Afmers specifc to CEA protein. Characterization of three anti-CEA Afmers reveal that these bind specifcally and selectively to protein epitopes of CEA from cell culture lysate and on fxed cells. Kinetic binding analysis by SPR show that the Afmers bind to CEA with high afnity and within the nM range. Therefore, they have substantial potential for used as novel afnity reagents in diagnostic imaging, targeted CRC therapy, afnity purifcation and biosensor applications. Colorectal cancer (CRC) is the fourth leading cause of cancer-related death and the third most commonly diag- nosed malignancy worldwide1. Despite improvements in cancer treatment, advanced technologies in cancer diagnostics and augmentation of cancer awareness, the incidence and mortality rates of CRC still remain high.
    [Show full text]
  • Affimers: from Discovery to Drug Delivery
    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 Abstract 1 Introduction 1 Affinity-based applications in the detection, analysis & manipulation of protein targets 2 2 4 5 Antibodies and their limitations as affinity binders 6 7 7 7 8 8 9 Alternatives to antibodies 10 10 11 11 12 Affimer binders: what’s different? 14 16 16 16 16 Conclusion 17 References 18 Contents Abstract 1 Abstract Introduction 1 Introduction Affinity-based applications in the detection, analysis & manipulation of protein targets 2 Affinity-based applications in the detection, analysis and manipulation of protein targets 2 In vitro applications 4 Diagnostic applications 5 Therapeutic applications Antibodies and their limitations as affinity binders 6 Antibodies and their limitations as affinity binders 7 Size and structural complexity 7 Stability under assay conditions 7 Immobilisation onto solid support 8 Limitations of antibodies as therapeutics – immunogenicity, toxicity and 3D structure recognition 8 Success rate 9 Antibody engineering: future directions Alternatives to antibodies 10 Alternatives to antibodies 10 Engineered antibody fragments 11 Aptamers 11 Aptamer engineering – future enhancements 12 Non-antibody protein scaffolds Affimer binders: what’s different? 14 Affimer binders: what’s different? 16 Affimer binders can be generated to almost any protein target, and show high discriminatory powers 16 In practice:
    [Show full text]
  • Affimer Therapeutics: a Novel Human Scaffold for the Generation of Bi-Specific Molecules
    Affimer Therapeutics: A Novel Human Scaffold for the Generation of Bi-specific Molecules NGPT 2019, San Francisco Amrik Basran Chief Scientific Officer Disclaimer: Important Notice No representation or warranty, expressed or implied, is made or given by or on behalf of Avacta Group plc (the “Company” and, together with its subsidiaries and subsidiary undertakings, the “Group”) or any of its directors or any other person as to the accuracy, completeness or fairness of the information contained in this presentation and no responsibility or liability is accepted for any such information. This presentation does not constitute an offer of securities by the Company and no investment decision or transaction in the securities of the Company should be made solely on the basis of the information contained in this presentation. This presentation contains certain information which the Company’s management believes is required to understand the performance of the Group. However, not all of the information in this presentation has been audited. Further, this presentation includes or implies statements or information that are, or may deemed to be, "forward-looking statements". These forward-looking statements may use forward-looking terminology, including the terms "believes", "estimates", "anticipates", "expects", "intends", "may", "will" or "should". By their nature, forward-looking statements involve risks and uncertainties and recipients are cautioned that any such forward-looking statements are not guarantees of future performance. The Company's or the Group’s actual results and performance may differ materially from the impression created by the forward-looking statements or any other information in this presentation. The Company undertakes no obligation to update or revise any information contained in this presentation, except as may be required by applicable law or regulation.
    [Show full text]
  • University of Copenhagen, DK-2200 København N, Denmark * Correspondence: [email protected]; Tel.: +45-2988-1134 † These Authors Contributed Equally to This Work
    Toxin Neutralization Using Alternative Binding Proteins Jenkins, Timothy Patrick; Fryer, Thomas; Dehli, Rasmus Ibsen; Jürgensen, Jonas Arnold; Fuglsang-Madsen, Albert; Føns, Sofie; Laustsen, Andreas Hougaard Published in: Toxins DOI: 10.3390/toxins11010053 Publication date: 2019 Document version Publisher's PDF, also known as Version of record Citation for published version (APA): Jenkins, T. P., Fryer, T., Dehli, R. I., Jürgensen, J. A., Fuglsang-Madsen, A., Føns, S., & Laustsen, A. H. (2019). Toxin Neutralization Using Alternative Binding Proteins. Toxins, 11(1). https://doi.org/10.3390/toxins11010053 Download date: 09. apr.. 2020 toxins Review Toxin Neutralization Using Alternative Binding Proteins Timothy Patrick Jenkins 1,† , Thomas Fryer 2,† , Rasmus Ibsen Dehli 3, Jonas Arnold Jürgensen 3, Albert Fuglsang-Madsen 3,4, Sofie Føns 3 and Andreas Hougaard Laustsen 3,* 1 Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK; [email protected] 2 Department of Biochemistry, University of Cambridge, Cambridge CB3 0ES, UK; [email protected] 3 Department of Biotechnology and Biomedicine, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; [email protected] (R.I.D.); [email protected] (J.A.J.); [email protected] (A.F.-M.); sofi[email protected] (S.F.) 4 Department of Biology, University of Copenhagen, DK-2200 København N, Denmark * Correspondence: [email protected]; Tel.: +45-2988-1134 † These authors contributed equally to this work. Received: 15 December 2018; Accepted: 12 January 2019; Published: 17 January 2019 Abstract: Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year.
    [Show full text]
  • WO 2017/147538 Al 31 August 2017 (31.08.2017) P O P C T
    (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 2017/147538 Al 31 August 2017 (31.08.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12N 15/85 (2006.01) C12N 15/90 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, PCT/US2017/01953 1 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, 24 February 2017 (24.02.2017) KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (25) Filing Language: English NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (26) Publication Language: English RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (30) Priority Data: ZA, ZM, ZW. 62/300,387 26 February 2016 (26.02.2016) U S (84) Designated States (unless otherwise indicated, for every (71) Applicant: POSEIDA THERAPEUTICS, INC. kind of regional protection available): ARIPO (BW, GH, [US/US]; 4242 Campus Point Ct #700, San Diego, Califor GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, nia 92121 (US).
    [Show full text]
  • “Avacta” Or “The Group” Or “The Company”
    For immediate release 2 October 2018 Avacta Group plc (“Avacta” or “the Group” or “the Company”) Preliminary Results for the Year Ending 31 July 2018 Continued strong operational delivery towards key commercial, pre-clinical and clinical goals Avacta Group plc (AIM: AVCT), the developer of Affimer® biotherapeutics and reagents, is pleased to announce its preliminary results for the year ending 31 July 2018. Operating Highlights Affimer Therapeutics • Good progress with in-house programmes: o Significant progress in its second therapeutic programme, a LAG-3 inhibitor, has allowed the Group to leap-frog the planned clinical trials for a PD-L1 inhibitor on its own and, on a similar timescale, aim for first-time-in-human clinical data for a PD-L1/LAG-3 bispecific therapy - a potentially much more valuable asset. o Discovery programme continues to deliver a pipeline of Affimer binders to other important immuno-oncology targets for future partnering or development. o Positive pharmacokinetic data obtained in mouse for Affimer XT™ half-life extension platform. • Solid progress with partners: o Moderna research collaboration extended and delivery of Affimer assets to Moderna for evaluation for potential future development. o Major therapeutic partnership with Tufts University School of Medicine announced which will develop a new class of Affimer drug conjugate therapies with a novel mode of action that combines Avacta's Affimer technology with drug conjugates developed at Tufts. o Research collaboration with FIT Biotech Oy successfully completed a proof-of-concept study with excellent data, showing sustained production of Affimer molecules by muscle tissue in mice. o Positive outcome of initial work with Iksuda Therapeutics Ltd.
    [Show full text]
  • Assessment of Affimer® Protein Technology As Critical Reagents in Bioanalytical Pharmacokinetic (PK) Methods Amy Reeves, Covance Laboratories Ltd, Harrogate, UK
    Assessment of Affimer® Protein Technology as Critical Reagents in Bioanalytical Pharmacokinetic (PK) Methods Amy Reeves, Covance Laboratories Ltd, Harrogate, UK Introduction System Suitability and Range of Quantitation Table 2. Difference from Baseline in Accuracy and Precision of Low and High QC Samples The calibration curve spans a 33-fold quantifiable range from 60 to 2000 ng/mL Antibodies currently represent the “gold standard” of affinity reagents used in – greater than double the working range of the current antibody based method. QC %CV %Bias regulated bioanalysis of therapeutic proteins. Over time, traditional antibodies Standard curve profiles from 6 independent runs are comparable (Fig 4), with have been refined to the point where they are specific, sensitive, and reasonably LQC 1.8 1.8 cumulative recoveries across concentrations within ± 7.5% of nominal, and reliable. Yet, monoclonal and polyclonal antibodies remain limited by their precision (%CV) across standard curve points of ≤ 10.8%. HQC 0.3 2.8 significant size, poor stability and batch-to-batch variation in assay performance. ® Dilutional Linearity What is an Affimer ? The Affimer® (Avacta Life Sciences, UK) is a novel artificial binding protein Dilutional linearity samples above the ULOQ generated a response < ULOQ, (ABP) based on a consensus sequence of plant Cystatin A (Tiede et al., 2014). while samples prepared to a concentration below the LLOQ generated a The Affimer® protein scaffold is biologically inert, biophysically and biochemically response < LLOQ. Samples within the working range were quantified against stable and can be engineered (via peptides inserted at loop 1, loop 2 and the their respective calibration curve and back-calculated concentrations were within amino terminus) for highly specific, high-affinity interactions (Stadler et al., 100% (+/- 20%) (+/- 25% at the assay limits) of the nominal concentration.
    [Show full text]
  • Type of the Paper (Article, Review, Communication
    Review Volume 11, Issue 3, 2021, 10679 - 10689 https://doi.org/10.33263/BRIAC113.1067910689 Selective Preference of Antibody Mimetics over Antibody, as Binding Molecules, for Diagnostic and Therapeutic Applications in Cancer Therapy Pankaj Garg 1,* 1 Department of Chemistry, GLA University, Mathura, 281406, India * Correspondence: [email protected]; Scopus Author ID 571962558738 Received: 5.10.2020; Revised: 3.11.2020; Accepted: 4.11.2020; Published: 7.11.2020 Abstract: Despite wider use of monoclonal and polyclonal antibodies as therapeutic and diagnostic detection agents for different types of cancers, their limitations for biomedical applications have forced scientists to design alternate next-generation molecular binding reagents, the so-called antibody mimetics. The ultimate aim to produce antibody mimetics is to out-perform the intrinsic limitations of antibodies related to their binding affinities, tumor penetration, temperature, and pH stability. The current review highlights the advanced characteristics and constructional modification of alternate antibody mimetics, compared to animal source generated antibodies and their improved applications in bioanalytical chemistry; especially in cancer treatment as a diagnostic and therapeutic tool. Keywords:Antibody mimetic; Monoclonal antibodies (MoAbs); Protein scaffold engineering; Molecular Imaging; cancer therapy. © 2020 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 1. Introduction Antibodies, especially monoclonal antibodies, on account of their high stability and specific affinity, have been identified as effective tools both for therapeutic and diagnostic applications, especially in cancer therapy. Antibodies are Y-shaped glycoproteins produced by the immune system to counteract the effect of any foreign substance or antigen in the body.
    [Show full text]
  • Wednesday March 4Th, 2020 Loews Coronado Bay Resort, San Diego, California
    Monday March 2nd – Wednesday March 4th, 2020 Loews Coronado Bay Resort, San Diego, California Presents 1 Contents Americas Antibody Congress 2020 ............................................................................................................................................................................... 3 Speakers ..................................................................................................................................................................................................................... 3 Day 1 – Monday March 2nd 2020 ............................................................................................................................................................................... 7 Day 2 – Tuesday March 3rd 2020 .............................................................................................................................................................................. 16 Day 3 – Wednesday March 4th 2020 ........................................................................................................................................................................ 28 World Immunotherapy Congress USA 2019 ............................................................................................................................................................... 35 Speakers ..................................................................................................................................................................................................................
    [Show full text]