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Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies
Predictive QSAR tools to aid in early process development of monoclonal antibodies John Micael Andreas Karlberg Published work submitted to Newcastle University for the degree of Doctor of Philosophy in the School of Engineering November 2019 Abstract Monoclonal antibodies (mAbs) have become one of the fastest growing markets for diagnostic and therapeutic treatments over the last 30 years with a global sales revenue around $89 billion reported in 2017. A popular framework widely used in pharmaceutical industries for designing manufacturing processes for mAbs is Quality by Design (QbD) due to providing a structured and systematic approach in investigation and screening process parameters that might influence the product quality. However, due to the large number of product quality attributes (CQAs) and process parameters that exist in an mAb process platform, extensive investigation is needed to characterise their impact on the product quality which makes the process development costly and time consuming. There is thus an urgent need for methods and tools that can be used for early risk-based selection of critical product properties and process factors to reduce the number of potential factors that have to be investigated, thereby aiding in speeding up the process development and reduce costs. In this study, a framework for predictive model development based on Quantitative Structure- Activity Relationship (QSAR) modelling was developed to link structural features and properties of mAbs to Hydrophobic Interaction Chromatography (HIC) retention times and expressed mAb yield from HEK cells. Model development was based on a structured approach for incremental model refinement and evaluation that aided in increasing model performance until becoming acceptable in accordance to the OECD guidelines for QSAR models. -
Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives
International Journal of Molecular Sciences Review Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives In-Ho Kim 1 and Hyo-Jin Lee 2,* 1 Department of Internal Medicine, Division of Medical Oncology, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul 06591, Korea; [email protected] 2 Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 35015, Korea * Correspondence: [email protected]; Tel.: +82-42-280-8369; Fax: +82-42-257-5753 Abstract: Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which re- sults in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoad- juvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative im- munotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive Citation: Kim, I.-H.; Lee, H.-J. bladder cancer. Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Keywords: bladder cancer; immunotherapy; perioperative systemic treatment Current Evidence and Future Perspectives. -
The Names of Wind -Summer 2009
The Names of Wind ccording to the Western Abenaki of New England, the winds of their world Awere generated by a giant eagle that lived on a craggy peak and flapped its wings continuously. Various nomadic tribes of central Asia had a comparable myth. They believed that the wind originated from a vast hole in a mountain somewhere to the west. And the Inuit of Alaska thought that the winds issued forth from an opening in the sky. Here in the West, we believe that the wind is generated by the mother of all earthly things, our own star Sun. According to our legend, the sun beats down on the equatorial tropics, heating the air, which subsequently rises high into the stratosphere, creating a vacuum all along the equator. Because of the physical phenomenon known as the Coriolis effect, air from both the north and the south rushes in to fill the space, thereby creating, because of the rotation of the earth, the ever-reliable trade winds. This basic system is much complicated by landforms such as deserts and mountain ranges, which churn and blend the moving airs, creating a variety of local winds. Some of these such as the foehn are warm dry winds that flow down the lee side of the mountains. Some, such as the sirocco, are bred in deserts and drawn northward by low-pressure areas. Many of these local winds are notorious for their strength as well as their effect on the human psyche, and most of them are named, a fact that has added to the rich tapestry of languages. -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
Atopic Dermatitis (AD)
This activity is provided by PRIME Education. There is no fee to participate. This activity is supported by education grants from AbbVie, Inc., Sanofi Genzyme and Regeneron Pharmaceuticals. © 2019 PRIME® Education, LLC. All Rights Reserved.. Overview This downloadable fact‐sheet provides an easy‐to‐follow collection of the latest evidence shaping the treatment and management of psoriasis (PsO) and atopic dermatitis (AD). Learn about validated tools, evidence‐based strategies, and new and emerging targeted therapies that can be incorporated in daily practice to improve outcomes for patients with these conditions. © 2019 PRIME® Education, LLC. All Rights Reserved.. 2 1 Learning Objectives • Identify major barriers to evidence‐based treatment and management in federal and public sectors • Implement appropriate methods for diagnosis and assessment of disease activity • Assess current evidence on targeted biologic and small‐molecule therapies to guide treatment decisions for patients with moderate to severe disease • Monitor treatment responses according to treat‐to‐target principles and methods • Apply current evidence and guidelines to inform treatment decisions for patients with inadequate responses to initial therapies • Incorporate patient‐reported outcomes and shared decision‐making into clinical practice • Apply effective strategies for multidisciplinary care coordination and shared patient management © 2019 PRIME® Education, LLC. All Rights Reserved.. 3 Accreditation In support of improving patient care, PRIME® is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. This activity was planned by and for the healthcare team, and learners will receive 2.25 Interprofessional Continuing Education (IPCE) credits for learning and change. -
Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories
bioRxiv preprint doi: https://doi.org/10.1101/572958; this version posted March 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Title: Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories. Authors: Konrad Krawczyk1*, Matthew Raybould2, Aleksandr Kovaltsuk2, Charlotte M. Deane2 1 NaturalAntibody, Hamburg, Germany 2 Oxford University Department of Statistics, Oxford, UK *Correspondence to [email protected] Abstract: Recently it has become possible to query the great diversity of natural antibody repertoires using Next Generation Sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare Clinical Stage Therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space Database. Of the 242 post Phase I antibodies, we find 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the discovery of antibody therapeutics and the legal protection of commercial antibodies. Introduction Antibodies are proteins in jawed vertebrates that recognize noxious molecules (antigens) for elimination. An organism expresses millions of diverse antibodies to increase the chances that some of them will be able to bind the foreign antigen, initiating the adaptive immune response. -
The Two Tontti Tudiul Lui Hi Ha Unit
THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int . -
Antibodies to Watch in 2021 Hélène Kaplona and Janice M
MABS 2021, VOL. 13, NO. 1, e1860476 (34 pages) https://doi.org/10.1080/19420862.2020.1860476 PERSPECTIVE Antibodies to watch in 2021 Hélène Kaplona and Janice M. Reichert b aInstitut De Recherches Internationales Servier, Translational Medicine Department, Suresnes, France; bThe Antibody Society, Inc., Framingham, MA, USA ABSTRACT ARTICLE HISTORY In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody Received 1 December 2020 therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The Accepted 1 December 2020 coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the KEYWORDS healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two Antibody therapeutics; anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were cancer; COVID-19; Food and authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed Drug Administration; antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 European Medicines Agency; in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the immune-mediated disorders; first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may Sars-CoV-2 be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. -
“Talk” on Albanian Territories (1392–1402)
Doctoral Dissertation A Model to Decode Venetian Senate Deliberations: Pregadi “Talk” on Albanian Territories (1392–1402) By: Grabiela Rojas Molina Supervisors: Gerhard Jaritz and Katalin Szende Submitted to the Medieval Studies Department Central European University, Budapest In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medieval Studies, Budapest, Hungary 2020 CEU eTD Collection To my parents CEU eTD Collection Table of Contents Acknowledgments .................................................................................................................................. 1 List of Maps, Charts and Tables .......................................................................................................... 2 Introduction ............................................................................................................................................ 3 A Survey of the Scholarship ........................................................................................................................... 8 a) The Myth of Venice ........................................................................................................................... 8 b) The Humanistic Outlook .................................................................................................................. 11 c) Chronicles, Histories and Diaries ..................................................................................................... 14 d) Albania as a Field of Study ............................................................................................................. -
To Marine Meteorological Services
WORLD METEOROLOGICAL ORGANIZATION Guide to Marine Meteorological Services Third edition PLEASE NOTE THAT THIS PUBLICATION IS GOING TO BE UPDATED BY END OF 2010. WMO-No. 471 Secretariat of the World Meteorological Organization - Geneva - Switzerland 2001 © 2001, World Meteorological Organization ISBN 92-63-13471-5 NOTE The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Meteorological Organization concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. TABLE FOR NOTING SUPPLEMENTS RECEIVED Supplement Dated Inserted in the publication No. by date 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 CONTENTS Page FOREWORD................................................................................................................................................. ix INTRODUCTION......................................................................................................................................... xi CHAPTER 1 — MARINE METEOROLOGICAL SERVICES ........................................................... 1-1 1.1 Introduction .................................................................................................................................... 1-1 1.2 Requirements for marine meteorological information....................................................................... 1-1 1.2.1 -
The Image Imagining Ourselves
Eighth International Conference on The Image Imagining Ourselves 31 OCTOBER–1 NOVEMBER 2017 | VENICE INTERNATIONAL UNIVERSITY | VENICE, ITALY ONTHEIMAGE.COM Eighth International Conference on The Image “Imagining Ourselves” 31 October–1 November 2017 | Venice International University | Venice, Italy www.ontheimage.com www.facebook.com/OnTheImage @ontheimage | #ICOTI17 Eighth International Conference on the Image www.ontheimage.com First published in 2017 in Champaign, Illinois, USA by Common Ground Research Networks www.cgnetworks.org © 2017 Common Ground Research Networks All rights reserved. Apart from fair dealing for the purpose of study, research, criticism, or review as permitted under the applicable copyright legislation, no part of this work may be reproduced by any process without written permission from the publisher. For permissions and other inquiries, please contact [email protected]. Common Ground Research Networks may at times take pictures of plenary sessions, presentation rooms, and conference activities which may be used on Common Ground’s various social media sites or websites. By attending this conference, you consent and hereby grant permission to Common Ground to use pictures which may contain your appearance at this event. Designed by Ebony Jackson Cover image by Phillip Kalantzis-Cope The Image ontheimage.com Dear Image Conference Delegates, Welcome to Venice and to the Eighth International Conference on The Image. The Image Research Network—its conference, journal, and book imprint—is brought together around -
Barry Lawrence Ruderman Antique Maps Inc
Barry Lawrence Ruderman Antique Maps Inc. 7407 La Jolla Boulevard www.raremaps.com (858) 551-8500 La Jolla, CA 92037 [email protected] Carte de L'Amerique Nouvellement dressee suivant les Nouvelles descouvertes . 1661 [and] Carte Nouvelle de L'Europe Asie & Afrique Nouvellement . Stock#: 74198 Map Maker: Tavernier Date: 1661 Place: Paris Color: Hand Colored Condition: VG+ Size: 24 x 12 inches Price: $ 3,400.00 Description: Rare pair of eastern and western hemispheric maps, published by Melchior Tavernier. Tavernier's map provides a fine blend of contemporary cartographic information with unique details in the concentric circles outside of the geographical hemisphere. In the outermost circle, Tavernier names the 32 compass point directions in French. In the center circle, are the names of the 12 Classical Winds described by Timothenes of Rhodes (circa 282 BC) in both Latin and the original Greek spellings (see below). In the innermost circle, the 8 Winds of the Mediterranean (the modern compass points) are named (Tramontane, Greco (Grecale), Levante, Sirocco, Austral (Ostro or Mezzogiorno), Sebaca (Libeccio or Garbino), Ponent (Ponente) and Maestral (Mistral or Maestro). Cartographically, the map is a marvelous blend of information and conjecture. Tavernier treats the massive northwestern landmass to the north of California as conjecture, employing a lighter coastal outline to signify that the lands depicted are not known with certainty. California is shown as a curiously shaped island, not consistent with either the Briggs or Sanson models. A single Great Lake is depicted. In the Arctic regions, a notation describes Thomas Button's search for a Northwest Passage. In South America, there is a small Lake Parime in Guiana, and both the Amazon and Rio de la Plata flow from the large interior Lago de los Xarayes.