International Nonproprietary Names for Pharmaceutical Substances (INN)
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Strategies to support the COVID-19 response in LMICs A virtual seminar series Therapeutics Landscape for COVID-19 Natasha Mubeen Chida, MD MSPH Associate Program Director, Infectious Disease Fellowship Program Assistant Professor, Division of Infectious Diseases Johns Hopkins University School of Medicine Objectives • Review biological plausibility of Remdesivir for SARS-CoV-2 treatment • Review clinical data on Remdesivir • Review biological plausibility of Hydroxychloroquine for SARS-CoV-2 treatment • Review clinical data on Hydroxychloroquine • Discuss cytokine release syndrome in COVID-19 • Discuss use of anti IL-6 blockade for management of CRS • State ongoing clinical trials for Remdesivir, hydroxychloroquine, IL-6 blockade Sample of COVID-19 Therapeutic Landscape Antivirals Immune Modulators Other Baloxavir Anakinra ACEI/ARB Chloroquine/Hydroxychloroquine Convalescent Plasma Ascorbic Acid DAS-181 Corticosteroids Azithromycin Favipiravir IVIG Epoprostenol Interferon Lenzilumab Indomethacin Lopinavir/Ritonavir Ruxolitinib Ivermectin Neuraminidase inhibitors Sarilumab Niclosamide Remdesivir Sirolimus Nitazoxanide Ribavarin Tocilizumab Statins Umifenovir Acalabrutinib SARS-CoV-2 Liu C, et al. ACS Cent Sci. doi: 10.1021/acscentsci.0c00272 (2020). Jiang S, Hillyer C, Du L. Trends Immunol doi: 10.1016/j.it.2020.03.007 (2020). “Antivirals” Remdesivir • 2013 Ebola outbreak • CDC/USAMRIDD/Gilead Sciences identified nucleoside lead à prodrug, RDV • Metabolized to active form, adenosine nucleoside analog • Interferes with RNA polymerase • Evades -
Precision Medicine for Human Cancers with Notch Signaling Dysregulation (Review)
INTERNATIONAL JOURNAL OF MOleCular meDICine 45: 279-297, 2020 Precision medicine for human cancers with Notch signaling dysregulation (Review) MASUKO KATOH1 and MASARU KATOH2 1M & M PrecMed, Tokyo 113-0033; 2Department of Omics Network, National Cancer Center, Tokyo 104-0045, Japan Received September 16, 2019; Accepted November 20, 2019 DOI: 10.3892/ijmm.2019.4418 Abstract. NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are conjugate (ADC) Rova-T, and DLL3-targeting chimeric antigen transmembrane receptors that transduce juxtacrine signals of receptor‑modified T cells (CAR‑Ts), AMG 119, are promising the delta-like canonical Notch ligand (DLL)1, DLL3, DLL4, anti-cancer therapeutics, as are other ADCs or CAR-Ts targeting jagged canonical Notch ligand (JAG)1 and JAG2. Canonical tumor necrosis factor receptor superfamily member 17, Notch signaling activates the transcription of BMI1 proto-onco- CD19, CD22, CD30, CD79B, CD205, Claudin 18.2, fibro- gene polycomb ring finger, cyclin D1, CD44, cyclin dependent blast growth factor receptor (FGFR)2, FGFR3, receptor-type kinase inhibitor 1A, hes family bHLH transcription factor 1, tyrosine-protein kinase FLT3, HER2, hepatocyte growth factor hes related family bHLH transcription factor with YRPW receptor, NECTIN4, inactive tyrosine-protein kinase 7, inac- motif 1, MYC, NOTCH3, RE1 silencing transcription factor and tive tyrosine-protein kinase transmembrane receptor ROR1 transcription factor 7 in a cellular context-dependent manner, and tumor-associated calcium signal transducer 2. ADCs and while non-canonical Notch signaling activates NF-κB and Rac CAR-Ts could alter the therapeutic framework for refractory family small GTPase 1. Notch signaling is aberrantly activated cancers, especially diffuse-type gastric cancer, ovarian cancer in breast cancer, non-small-cell lung cancer and hematological and pancreatic cancer with peritoneal dissemination. -
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. -
RT+IO Therapy in NSCLC Draft 4 Clinical Cancer Research 1
Author Manuscript Published OnlineFirst on June 26, 2018; DOI: 10.1158/1078-0432.CCR-17-3620 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. RT+IO Therapy in NSCLC Draft 4 Clinical Cancer Research Title: The Integration of Radiotherapy With Immunotherapy for the Treatment of Non-Small Cell Lung Cancer Running title: Radiotherapy and Immunotherapy in Non-Small Cell Lung Cancer Eric C. Ko1, David Raben2, Silvia C. Formenti1 1Department of Radiation Oncology, Weill Cornell Medicine, New York, New York 2Department of Radiation Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado Corresponding Author: Silvia C. Formenti, New York-Presbyterian/Weill Cornell Medicine, 525 East 68th Street, N-046, Box 169, New York, NY 10065-4885; Phone: 212-746-3608; Fax: 212-746-8850; E-mail: [email protected]. Confirmed Target Journal: Clinical Cancer Research Journal Specs (Review Article): Word Count (limit 3750 words): 4090 Abstract Word Count (unstructured, limit ≤250 words): 209 Number of References (≤75): 79 Number of Figures/Tables (5): 1 table, 3 figures 1 Downloaded from clincancerres.aacrjournals.org on September 24, 2021. © 2018 American Association for Cancer Research. Author Manuscript Published OnlineFirst on June 26, 2018; DOI: 10.1158/1078-0432.CCR-17-3620 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. RT+IO Therapy in NSCLC Draft 4 Clinical Cancer Research Abstract Five-year survival rates for non-small cell lung cancer (NSCLC) range from 14% to 49% for stage I to stage IIIA disease, and are <5% for stage IIIB/IV disease. -
Celldex Therapeutics Presents Phase 1 Study of Varlilumab and Opdivo® at 2017 ASCO Annual Meeting
June 5, 2017 Celldex Therapeutics Presents Phase 1 Study of Varlilumab and Opdivo® at 2017 ASCO Annual Meeting Early signs of clinical activity without increased toxicity observed HAMPTON, N.J., June 05, 2017 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (Nasdaq:CLDX) announced today data from the Phase 1 portion of a Phase 1/2 dose escalation and cohort expansion study examining the combination of varlilumab, Celldex's CD27 targeting investigational immune-activating antibody, and Bristol-Myers Squibb's anti-PD-1 immunotherapy Opdivo® (nivolumab). Rachel E. Sanborn, M.D., Co-director of the Providence Thoracic Oncology Program; and Phase I Clinical Trials Program, at the Earle A. Chiles Research Institute, Providence Cancer Center, in Portland, Ore. presented results from the study in an oral presentation entitled, "Clinical Results with Combination of Anti-CD27 Agonist Antibody, Varlilumab, with Anti-PD1 Antibody Nivolumab in Advanced Cancer Patients" at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The primary objective of the Phase 1 portion (n=36) of the study was to evaluate the safety and tolerability of the combination. The Phase 2 portion of the study is expected to complete enrollment in early 2018. "Combining PD-1 inhibition with a potent T cell activating agent provides the opportunity to broaden the number of patients that benefit from checkpoint blockade," said Dr. Sanborn. "While early, we have evidence that this combination does not add toxicity, can turn some ‘immune-cold' tumors hot, and may have clinical benefit, including in some patients who are not likely to respond to monotherapy. Further elucidating the role of intermittent versus chronic T cell activation through the comparison of alternate varlilumab dosing regimens is an essential component of the ongoing Phase 2 study and could be important in optimizing the potential of this combination." Key Highlights • The majority of patients enrolled in the study had PD-L1 negative tumor at baseline and presented with Stage IV, heavily- pretreated disease. -
Version Introducing VHIO Foreword
2017SCIENTIFIC REPORT Vall d'Hebron Institute of Oncology (VHIO) CELLEX CENTER C/Natzaret, 115 – 117 08035 Barcelona, Spain Tel. +34 93 254 34 50 www.vhio.net Direction: Amanda Wren Design: Parra estudio Photography: Katherin Wermke Vall d'Hebron Institute of Oncology (VHIO) | 2018 VHIO Scientific Report 2017 Index Scientific Report INTRODUCING VHIO CORE TECHNOLOGIES 02 Foreword 92 Cancer Genomics Group 08 2017: marking the next chapter of 94 Molecular Oncology Group VHIO's translational story 96 Proteomics Group 18 Scientific Productivity: research articles VHIO'S TRANSVERSAL CLINICAL 19 Selection of some of the most relevant TRIALS CORE SERVICES & UNITS articles by VHIO researchers published in 2017 100 Clinical Trials Office 25 A Golden Decade: reflecting on the 102 Research Unit for Molecular Therapy past 10 years of VHIO's translational of Cancer (UITM) – ”la Caixa” success story 104 Clinical Research Oncology Nurses 106 Clinical Research Oncology Pharmacy PRECLINICAL RESEARCH Unit 49 From the Director 50 Experimental Therapeutics Group RECENTLY INCORPORATED GROUPS 52 Growth Factors Group 110 Cellular Plasticity & Cancer Group 54 Mouse Models of Cancer Therapies 112 Experimental Hematology Group Group 114 Tumor Immunology 56 Tumor Biomarkers Group & Immunotherapy Group 116 Applied Genetics of Metastatic Cancer TRANSLATIONAL RESEARCH Group 61 From the Director 118 Chromatin Dynamics in Cancer Group 62 Gene Expression & Cancer Group 120 Prostate Cancer Translational Research Group 64 Stem Cells & Cancer Group 122 Radiomics Group CLINICAL -
Roche/Genentech Managed RG7986 ADC R/R NHL CHU Chugai Managed IONIS IONIS Managed 74 Status As of January 28, 2016 PRO Proximagen Managed
Roche 2015 results London, 28 January 2016 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche’s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website www.roche.com All mentioned trademarks are legally protected. -
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. -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor -
2017 Immuno-Oncology Medicines in Development
2017 Immuno-Oncology Medicines in Development Adoptive Cell Therapies Drug Name Organization Indication Development Phase ACTR087 + rituximab Unum Therapeutics B-cell lymphoma Phase I (antibody-coupled T-cell receptor Cambridge, MA www.unumrx.com immunotherapy + rituximab) AFP TCR Adaptimmune liver Phase I (T-cell receptor cell therapy) Philadelphia, PA www.adaptimmune.com anti-BCMA CAR-T cell therapy Juno Therapeutics multiple myeloma Phase I Seattle, WA www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 "armored" CAR-T Juno Therapeutics recurrent/relapsed chronic Phase I cell therapy Seattle, WA lymphocytic leukemia (CLL) www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 CAR-T cell therapy Intrexon B-cell malignancies Phase I Germantown, MD www.dna.com ZIOPHARM Oncology www.ziopharm.com Boston, MA anti-CD19 CAR-T cell therapy Kite Pharma hematological malignancies Phase I (second generation) Santa Monica, CA www.kitepharma.com National Cancer Institute Bethesda, MD Medicines in Development: Immuno-Oncology 1 Adoptive Cell Therapies Drug Name Organization Indication Development Phase anti-CEA CAR-T therapy Sorrento Therapeutics liver metastases Phase I San Diego, CA www.sorrentotherapeutics.com TNK Therapeutics San Diego, CA anti-PSMA CAR-T cell therapy TNK Therapeutics cancer Phase I San Diego, CA www.sorrentotherapeutics.com Sorrento Therapeutics San Diego, CA ATA520 Atara Biotherapeutics multiple myeloma, Phase I (WT1-specific T lymphocyte South San Francisco, CA plasma cell leukemia www.atarabio.com -
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 .