DOCSLIB.ORG

European Patent Office of Opposition to That Patent, in Accordance with the Implementing Regulations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
European Patent Office of Opposition to That Patent, in Accordance with the Implementing Regulations (19) TZZ_ ___T (11) EP 1 945 211 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 471/04 (2006.01) A61K 31/4439 (2006.01) 21.10.2015 Bulletin 2015/43 A61P 31/04 (2006.01) (21) Application number: 06808472.2 (86) International application number: PCT/GB2006/004178 (22) Date of filing: 08.11.2006 (87) International publication number: WO 2007/054693 (18.05.2007 Gazette 2007/20) (54) USE OF PYRROLOQUINOLINE COMPOUNDS TO KILL CLINICALLY LATENT MICROORGANISMS VERWENDUNG VON PYRROCHINOLIN-VERBINDUNGEN ZUR ABTÖTUNG VON KLINISCH LATENTEN MIKROORGANISMEN UTILISATION DE DÉRIVÉS DE PYRROLOQUINOLINE POUR L’ÉLIMINATION DE MICRO- ORGANISMES PERSISTANTS AU NIVEAU CLINIQUE (84) Designated Contracting States: • LONDESBROUGH, Derek, John AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Sunderland SR5 2TQ (GB) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • MILLS, Keith SK TR Hertfordshire SG12 0PT (GB) Designated Extension States: • PALLIN, Thomas, David AL BA HR MK RS Essex CM19 5TR (GB) • REID, Gary, Patrick (30) Priority: 08.11.2005 GB 0522715 Sunderland SR5 2TQ (GB) • STODDART, Gerlinda (43) Date of publication of application: Oxfordshire OX7 3RR (GB) 23.07.2008 Bulletin 2008/30 (74) Representative: D Young & Co LLP (73) Proprietor: Helperby Therapeutics Limited 120 Holborn Selby London EC1N 2DY (GB) North Yorkshire YO8 4PW (GB) (56) References cited: (72) Inventors: EP-A1- 0 307 078 EP-A1- 1 238 979 • BECK, Petra, Helga WO-A-99/09029 WO-A-2005/105802 Oxfordshire OX7 3RR (GB) US-A- 725 745 US-A- 2 691 023 • BROWN, Marc, Barry US-A- 2 714 593 Oxfordshire OX7 3RR (GB) • CLARK, David, Edward • DATABASE CAPLUS CHEMICAL ABSTRACTS Essex CM19 5TR (GB) SERVICE, COLUMBUS, OHIO, US; 1957, • COATES, Anthony XP002419062 accession no. 1957:47059 cited in Cranmer Terrace the application & OZAWA, T ET AL.: YAKUGAKU London SW17 0RE (GB) ZASSHI, vol. 77, 1957, pages 90-93, cited in the • DYKE, Hazel, Joan application Essex CM19 5TR (GB) • DATABASE CAPLUS CHEMICAL ABSTRACTS • HU, Yanmin SERVICE, COLUMBUS, OHIO, US; 1957, Cranmer Terrace XP002419063 accession no. 1957:47058 & London SW17 0RE (GB) OZAWA ET AL.: YAKUGAKU ZASSHI, vol. 77, 1957, pages 85-89, Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 945 211 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 1 945 211 B1 • PARSONS P J ET AL: "The Facile Construction • BROWN T H ET AL: "REVERSIBLE INHIBITORS of Indole Alkaloid Models: A Tandem Cascade OF THE GASTRIC (H+/K+)-ATPASE. 1. 1- ARYL-4- Approach for the Synthesis of a Model for METHYLPYRROLE3,2-CQUINOLINES AS Pseudocopsinine" TETRAHEDRON, ELSEVIER CONFORMATIONALLY RESTRAINED SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. ANALOGUES OF 4-(ARYLAMINO)QUINOLINES" 52, no. 2, 8 January 1996 (1996-01-08), pages JOURNAL OF MEDICINAL CHEMISTRY, 647-660, XP004104539 ISSN: 0040-4020 cited in AMERICAN CHEMICAL SOCIETY. the application WASHINGTON, US, vol. 33, 1990, pages 527-533, • IFE R J ET AL: "Reversible Inhibitors of the XP000919165 ISSN: 0022-2623 cited in the Gastric(H+/K+)-ATPase" JOURNAL OF application MEDICINALCHEMISTRY, AMERICAN CHEMICAL • JI H Y ET AL: "Characterization of human liver SOCIETY. WASHINGTON, US, vol. 38, no. 14, cytochrome P450 enzymes involved in the 1995, pages 2763-2773, XP002121213 ISSN: metabolism of a new H<+>/K<+>-ATPase 0022-2623 inhibitor KR-60436" TOXICOLOGY LETTERS, • BADAWEYE- SET AL: "Potential antineoplastics. ELSEVIER BIOMEDICAL PRESS, AMSTERDAM,, Synthesis and cytotoxicity of certain 4-chloro- NL, vol. 155, no. 1, 15 January 2005 (2005-01-15), 3-(2-chloroethyl)-2-methylquinolines and related pages 103-114, XP004673494 ISSN: 0378-4274 derivatives" EUROPEAN JOURNAL OF • HEIDEMPERGHER F ET AL: "PYRROLO3,2- MEDICINAL CHEMISTRY, EDITIONS CQUINOLINE DERIVATIVES: A NEW CLASS OF SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 32, no. KYNURENINE-3-HYDROXYLASEINHIBITORS" IL 10, October 1997 (1997-10), pages 815-822, FARMACO, ROME, IT, vol. 54, no. 3, 1999, pages XP004172152 ISSN: 0223-5234 cited in the 152-160, XP002934253 ISSN: 0014-827X application • LEACH COLIN A ET AL: "Reversible inhibitors of the gastric (H+/K+)-ATPase. 2. 1-Arylpyrrolo[3,2- c]quinolines: effect of the 4-substituent" JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 35, no. 10, 1992, pages 1845-1852,XP002184101 ISSN: 0022-2623 cited in the application 2 EP 1 945 211 B1 Description [0001] This invention relates to the use of compounds based upon the pyrrolo[3,2- c]quinoline ring system to kill clinically latent microorganisms. The invention further relates to the use of such compounds to treat microbial infections, as well 5 as, inter alia, certain of the compounds per se. [0002] The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge. [0003] Before the introduction of antibiotics, patients suffering from acute bacterial infections (e.g. tuberculosis or pneumonia) had a low chance of survival. For example, mortality from tuberculosis was around 50%. 10 [0004] Although the introduction of antibacterial agents in the 1940s and 1950s rapidly changed this picture, bacteria have responded by progressively gaining resistance to commonly used antibiotics. Now, every country in the world has antibioticresistant bacteria. Indeed, more than 70% of bacteria that give rise to hospital acquired infections in the USA resist at least one of the main antimicrobial agents that are typically used to fight infection (see Nature Reviews, Drug Discover 1, 895-910 (2002)). 15 [0005] One way of tackling the growing problem of resistant bacteria is the development of new classes of antimicrobial agents. However, until the introduction of linezolid in 2000, there had been no new class of antibiotic marketed for over 37 years. Moreover, even the development of new classes of antibiotic provides only a temporary solution, and indeed there are already reports of resistance of certain bacteria to linezolid (see Lancet 357, 1179 (2001) and Lancet 358, 207-208 (2001)). 20 [0006] In order to develop more long-term solutions to the problem of bacterial resistance, it is clear that alternative approaches are required. One such alternative approach is to minimise, as much as is possible, the opportunities that bacteria are given for developing resistance to important antibiotics. [0007] Thus, strategies that can be adopted include limiting the use of antibiotics for the treatment of non-acute infections, as well as controlling which antibiotics are fed to animals in order to promote growth. 25 [0008] However, in order to tackle the problem more effectively, it is necessary to gain an understanding of the actual mechanisms by which bacteria generate resistance to antibiotic agents. To do this requires first a consideration of how current antibiotic agents work to kill bacteria. [0009] Antimicrobial agents target essential components of bacterial metabolism. For example, theβ -lactams (e.g. penicillins and cephalosporins) inhibit cell wall synthesis, whereas other agents inhibit a diverse range of targets, such 30 as DNA gyrase (quinolones) and protein synthesis (e.g. macrolides, aminoglycosides, tetracyclines and oxazolidinones). The range of organisms against which the antimicrobial agents are effective varies, depending upon which organisms are heavily reliant upon the metabolic step(s) that is/are inhibited. Further, the effect upon bacteria can vary from a mere inhibition of growth (i.e. a bacteriostatic effect, as seen with agents such as the tetracyclines) to full killing (i.e. a bact ericidal effect, as seen, for example, with penicillin). 35 [0010] Bacteria have been growing on Earth for more than 3 billion years and, in that time, have needed to respond to vast numbers of environmental stresses. It is therefore perhaps not surprising that bacteria have developed a seemingly inexhaustible variety of mechanisms by which they can respond to the metabolic stresses imposed upon them by antibiotic agents. Indeed, mechanisms by which the bacteria can generate resistance include strategies as diverse as inactivation of the drug, modification of the site of action, modification of the permeability of the cell wall, overproduction of the targe t 40 enzyme and bypass of the inhibited steps. [0011] Nevertheless, the rate of resistance emerges to a particular agent has been observed to vary widely, depending upon factors such as the agent’s mechanism of action, whether the agent’s mode of killing is time- or concentration- dependent, the potency against the population of bacteria and the magnitude and duration of the available serum concentration. 45 [0012] It has been proposed (see Science 264, 388-393 (1994)) that agents that target single enzymes (e.g. rifampicin) are the most prone to the development of resistance. Further, the longer that suboptimal levels of antimicrobial agent are in contact with the bacteria, the more likely the emergence of resistance. [0013] Moreover, it is now known that many bacterial infections include sub-populations of bacteria that arepheno- typically resistant to antimicrobials (see, for example: J. Antimicrob. Chemother. 4, 395-404 (1988); J. Med. Microbiol. 50 38, 197-202 (1993); J. Bacteriol. 182, 1794-1801 (2000);ibid. 182, 6358-6365 (2000); ibid. 183, 6746-6751 (2001); FEMS Microbiol. Lett. 202, 59-65 (2001); and Trends in Microbiology 13, 34-40 (2005)). There appear to be several types of such phenotypically resistant bacteria, including persisters, stationary-phase bacteria, as well as those in the depths of biofilms.
Load more

Recommended publications
  • The Role of Nanobiosensors in Therapeutic Drug Monitoring
    Journal of Personalized Medicine Review Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring Vivian Garzón 1, Rosa-Helena Bustos 2 and Daniel G. Pinacho 2,* 1 PhD Biosciences Program, Universidad de La Sabana, Chía 140013, Colombia; [email protected] 2 Therapeutical Evidence Group, Clinical Pharmacology, Universidad de La Sabana, Chía 140013, Colombia; [email protected] * Correspondence: [email protected]; Tel.: +57-1-8615555 (ext. 23309) Received: 21 August 2020; Accepted: 7 September 2020; Published: 25 September 2020 Abstract: Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine. Keywords: biosensors; therapeutic drug monitoring (TDM), antibiotic; personalized medicine 1. Introduction The discovery of antibiotics (AB) ushered in a new era of progress in controlling bacterial infections in human health, agriculture, and livestock [1] However, the use of AB has been challenged due to the appearance of multi-resistant bacteria (MDR), which have increased significantly in recent years due to AB mismanagement and have become a global public health problem [2].
    [Show full text]
  • Review Electrochemical Immunosensors for Antibiotics
    Review Electrochemical Immunosensors for Antibiotic Detection Aleksandra Pollap and Jolanta Kochana * Department of Analytical Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-12-6862-416 Received: 27 March 2019; Accepted: 25 April 2019; Published: 1 May 2019 Abstract: Antibiotics are an important class of drugs destined for treatment of bacterial diseases. Misuses and overuses of antibiotics observed over the last decade have led to global problems of bacterial resistance against antibiotics (ABR). One of the crucial actions taken towards limiting the spread of antibiotics and controlling this dangerous phenomenon is the sensitive and accurate determination of antibiotics residues in body fluids, food products, and animals, as well as monitoring their presence in the environment. Immunosensors, a group of biosensors, can be considered an attractive tool because of their simplicity, rapid action, low-cost analysis, and especially, the unique selectivity arising from harnessing the antigen–antibody interaction that is the basis of immunosensor functioning. Herein, we present the recent achievements in the field of electrochemical immunosensors designed to determination of antibiotics. Keywords: antibiotic; immunosensor; antibody; electrochemical; immunoassay; antibacterial resistance 1. Introduction In recent years, a rapid development of analytical methods employing biosensors has been observed. A biosensor is a small analytical device that consists of a bioreceptor and a transducer. The role of a bioreceptor is the recognition of the target analyte, while a transducer converts the biological signal, produced by the bioreceptor and depending on the concentration of analyte molecules, into a measured signal, e.g., electrical, thermal, or optical [1].
    [Show full text]
  • Derivatives of Clavulanic Acid, Process for Their Preparation And
    Europaisches Patentamt © ê European Patent Office © Publication number: 0 003 254 Office européen des brevets Bl © EUROPEAN PATENT SPECIFICATION (45) Date of publication of patent spécification: 28.03.84 © Int. ci.3: C 07 D 498/04, A 61 K 31/42, @ Application number: 78300762.8 A 61 K 31/43, @ Date offiling: 07.12.78 A 61 K 31/545 //(C07D498/04, 263/00, 205/00), (A6 1 K3 1 /43, 3 1/42), (A61K3 1/545, 31/42) (54) Derivatives of clavulanic acid, process for their préparation and compositions containing them. (§) Priority: 26.01 .78 GB 312978 @ Proprietor: BEECHAM GROUP PLC Beecham House Great West Road Brentford Middlesex (GB) (43) Date of publication of application: 08.08.79 Bulletin 79/1 6 @ Inventor: Gasson, Brian Charles 9, Clarence Walk (45) Publication of the grant of the patent: Redhill Surrey (GB) 28.03.84 Bulletin 84/13 © Représentative: Hesketh, Alan, Dr. et al, (84) Designated Contracting States: European Patent Attorney Beecham BE CH DEFRGBITNL Pharmaceuticals Great Burgh Yew Tree Bottom Road Epsom, Surrey, KT18 5XQ (GB) (56) Références cited: BE - A - 847 046 The file contains technical information submitted after the application was filed and not included in this spécification Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid.
    [Show full text]
  • National Antibiotic Consumption for Human Use in Sierra Leone (2017–2019): a Cross-Sectional Study
    Tropical Medicine and Infectious Disease Article National Antibiotic Consumption for Human Use in Sierra Leone (2017–2019): A Cross-Sectional Study Joseph Sam Kanu 1,2,* , Mohammed Khogali 3, Katrina Hann 4 , Wenjing Tao 5, Shuwary Barlatt 6,7, James Komeh 6, Joy Johnson 6, Mohamed Sesay 6, Mohamed Alex Vandi 8, Hannock Tweya 9, Collins Timire 10, Onome Thomas Abiri 6,11 , Fawzi Thomas 6, Ahmed Sankoh-Hughes 12, Bailah Molleh 4, Anna Maruta 13 and Anthony D. Harries 10,14 1 National Disease Surveillance Programme, Sierra Leone National Public Health Emergency Operations Centre, Ministry of Health and Sanitation, Cockerill, Wilkinson Road, Freetown, Sierra Leone 2 Department of Community Health, Faculty of Clinical Sciences, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone 3 Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, 1211 Geneva, Switzerland; [email protected] 4 Sustainable Health Systems, Freetown, Sierra Leone; [email protected] (K.H.); [email protected] (B.M.) 5 Unit for Antibiotics and Infection Control, Public Health Agency of Sweden, Folkhalsomyndigheten, SE-171 82 Stockholm, Sweden; [email protected] 6 Pharmacy Board of Sierra Leone, Central Medical Stores, New England Ville, Freetown, Sierra Leone; [email protected] (S.B.); [email protected] (J.K.); [email protected] (J.J.); [email protected] (M.S.); [email protected] (O.T.A.); [email protected] (F.T.) Citation: Kanu, J.S.; Khogali, M.; 7 Department of Pharmaceutics and Clinical Pharmacy & Therapeutics, Faculty of Pharmaceutical Sciences, Hann, K.; Tao, W.; Barlatt, S.; Komeh, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown 0000, Sierra Leone 8 J.; Johnson, J.; Sesay, M.; Vandi, M.A.; Directorate of Health Security & Emergencies, Ministry of Health and Sanitation, Sierra Leone National Tweya, H.; et al.
    [Show full text]
  • Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
    International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1.
    [Show full text]
  • Dissertation
    DISSERTATION FOLATE PATHWAY INHIBITOR RESISTANCE MECHANISMS IN BURKHOLDERIA PSEUDOMALLEI Submitted by Nicole L. Podnecky Department of Microbiology, Immunology and Pathology In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Fall 2013 Doctoral Committee: Advisor: Herbert P. Schweizer Steven W. Dow Richard A. Slayden Laurie A. Stargell ABSTRACT FOLATE PATHWAY INHIBITOR RESISTANCE MECHANISMS IN BURKHOLDERIA PSEUDOMALLEI Antimicrobials are invaluable tools used to facilitate the treatment of infectious diseases. Their use has saved millions of lives since their introduction in the early 1900’s. Unfortunately, due to the increased incidence and dispersal of antimicrobial resistance determinants, many of these drugs are no longer efficacious. This greatly limits the options available for treatment of serious bacterial infections, including melioidosis, which is caused by Burkholderia pseudomallei, a Gram-negative saprophyte. This organism is intrinsically resistant to many antimicrobials. Additionally, there have been reports of B. pseudomallei isolates resistant to several of the antimicrobials currently used for treatment, including the trimethoprim and sulfamethoxazole combination, co-trimoxazole. The overarching goal of this project was to identify and characterize mechanisms of trimethoprim and sulfamethoxazole resistance in clinical and environmental isolates, as well as in laboratory induced mutants. Prior to these studies, very little work has been done to identify and characterize the mechanisms by which B. pseudomallei strains are or could become resistant to folate-pathway inhibitors, specifically trimethoprim and sulfamethoxazole. During the initial phases of these studies, we determined the antimicrobial susceptibilities of a large collection of clinical and environmental isolates from Thailand and Australia (n = 65).
    [Show full text]
  • Cytosolic Selection Systems to Study Protein Stability
    Cytosolic Selection Systems To Study Protein Stability Ajamaluddin Malik,* Antje Mueller-Schickert, James C. A. Bardwell Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA Here we describe biosensors that provide readouts for protein stability in the cytosolic compartment of prokaryotes. These bio- sensors consist of tripartite sandwich fusions that link the in vitro stability or aggregation susceptibility of guest proteins to the in vivo resistance of host cells to the antibiotics kanamycin, spectinomycin, and nourseothricin. These selectable markers confer Downloaded from antibiotic resistance in a wide range of hosts and are easily quantifiable. We show that mutations within guest proteins that af- fect their stability alter the antibiotic resistances of the cells expressing the biosensors in a manner that is related to the in vitro stabilities of the mutant guest proteins. In addition, we find that polyglutamine tracts of increasing length are associated with an increased tendency to form amyloids in vivo and, in our sandwich fusion system, with decreased resistance to aminoglycoside antibiotics. We demonstrate that our approach allows the in vivo analysis of protein stability in the cytosolic compartment with- out the need for prior structural and functional knowledge. http://jb.asm.org/ rotein folding has been intensely studied in vitro, providing us sion number WP_004614937). To eliminate expression of the toxic CcdB Pwith a detailed understanding of this process. However, the product present on this plasmid, we introduced a stop codon (TAA) by simplified conditions typically used in vitro (i.e., the use of single mutating the tyrosine at amino acid position 5 of the ccdB gene.
    [Show full text]
  • 9-20-08 Referral
    Comparative studies with antibiotics: Why should we change the rules? Paul M. Tulkens, MD, PhD Cellular and Molecular Pharmacology & Centre for Clinical Pharmacy Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 1 What its all about ? • We are in real need of novel antibiotics… but … most clinical studies with new compounds aim at equivalence or non-inferiority, failing to meet clinicians’ expectations and regulatory requirements for novelty. In parallel, safety issues are becoming an increasingly worrying hurdle for manufacturers Pricing make antibiotic unattractive • What are the possible solutions ? 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 2 The antibiotic crisis * * A pictorial view using 4 paintings of Van Gogh (who stayed briefly in Belgium when moving from Holland to France) and with selected Belgian and International data… 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 3 Are antibiotics following a path to madness ? discovery in soil bacteria and fungi 1928 - … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 4 Are antibiotics following a path to madness ? and then we all saw the blooming tree of semi- synthetic and totally synthetic antibiotics 1950 – 1980 … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 5 Are antibiotics following a path to madness ? and the US General Surgeon told us that the fight was over 1970 … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 6 Are antibiotics following a path to madness ? But… 2012 … 10-10-2012 Late Phase Leaders Forum, Vienna, Austria 7 Extent of resistance of P.
    [Show full text]
  • An Updated Review of Iclaprim
    Open Forum Infectious Diseases REVIEW ARTICLE An Updated Review of Iclaprim: A Potent and Rapidly Bactericidal Antibiotic for the Treatment of Skin and Skin Structure Infections and Nosocomial Pneumonia Caused by Gram-Positive Including Multidrug-Resistant Bacteria David B. Huang,1 Catherine D. Strader,3 James S. MacDonald,3 Mark VanArendonk,2 Richard Peck,4 and Thomas Holland5 1Motif BioSciences, New York, New York; Rutgers New Jersey Medical School, 2Vermeer Pharma, Morristown, New Jersey, 3Synergy Partners R&D Solutions, Chester, New Jersey; 4Hemex, Liestal, Switzerland, 5Duke University Medical Center, Durham, North Carolina New antibiotics are needed because of the increased morbidity and mortality associated with multidrug-resistant bacteria. Iclaprim, a bacterial dihydrofolate reductase inhibitor, not currently approved, is being studied for the treatment of skin infections and noso- comial pneumonia caused by Gram-positve bacteria, including multidrug-resistant bacteria. Iclaprim showed noninferiority at –10% to linezolid in 1 of 2 phase 3 studies for the treatment of complicated skin and skin structure infections with a weight-based dose (0.8 mg/kg) but did not show noninferiority at –10% to linezolid in a second phase 3 study. More recently, iclaprim has shown noninferiority at –10% to vancomycin in 2 phase 3 studies for the treatment of acute bacterial skin and skin structure infections with an optimized fixed dose (80 mg). A phase 3 study for the treatment of hospital-acquired bacterial and ventilator-associated bacterial pneumonia is upcoming. If, as anticipated, iclaprim becomes available for the treatment of skin and skin structure infections, it will serve as an alternative to current antibiotics for treatment of severe infections.
    [Show full text]
  • Identification of Leishmania Donovani Inhibitors from Pathogen Box Compounds of Medicine for Malaria Venture
    bioRxiv preprint doi: https://doi.org/10.1101/716134; this version posted July 26, 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. Identification of Leishmania donovani inhibitors from pathogen box compounds of Medicine for Malaria Venture Markos Tadele1¶, Solomon M. Abay2¶*, Eyasu Makonnen2,4, Asrat Hailu3 1 Ethiopian institute of agricultural research, Animal health research program, Holetta, Ethiopia 2Department of Pharmacology and clinical pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia 3Department of Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia 4Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT Africa), College of Health Sciences, Addis Ababa University * Corresponding author Email: [email protected], [email protected] ¶ These authors contributed equally to this work. Author Contributions Conceptualization and design the experiment: MT, SMA, EM, AH Investigation: MT, SMA, AH Data analysis: MT, SMA Funding acquisition and reagents contribution: SMA, AH Supervision: SMA, EM, AH Writing – original draft: MT Writing – review & editing: MT, SMA, EM, AH 1 | P a g e bioRxiv preprint doi: https://doi.org/10.1101/716134; this version posted July 26, 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.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin Et Al
    US 201201.15729A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin et al. (43) Pub. Date: May 10, 2012 (54) PROCESS FOR FORMING FILMS, FIBERS, Publication Classification AND BEADS FROM CHITNOUS BOMASS (51) Int. Cl (75) Inventors: Ying Qin, Tuscaloosa, AL (US); AOIN 25/00 (2006.01) Robin D. Rogers, Tuscaloosa, AL A6II 47/36 (2006.01) AL(US); (US) Daniel T. Daly, Tuscaloosa, tish 9.8 (2006.01)C (52) U.S. Cl. ............ 504/358:536/20: 514/777; 426/658 (73) Assignee: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF 57 ABSTRACT ALABAMA, Tuscaloosa, AL (US) (57) Disclosed is a process for forming films, fibers, and beads (21) Appl. No.: 13/375,245 comprising a chitinous mass, for example, chitin, chitosan obtained from one or more biomasses. The disclosed process (22) PCT Filed: Jun. 1, 2010 can be used to prepare films, fibers, and beads comprising only polymers, i.e., chitin, obtained from a suitable biomass, (86). PCT No.: PCT/US 10/36904 or the films, fibers, and beads can comprise a mixture of polymers obtained from a suitable biomass and a naturally S3712). (4) (c)(1), Date: Jan. 26, 2012 occurring and/or synthetic polymer. Disclosed herein are the (2), (4) Date: an. AO. films, fibers, and beads obtained from the disclosed process. O O This Abstract is presented solely to aid in searching the sub Related U.S. Application Data ject matter disclosed herein and is not intended to define, (60)60) Provisional applicationpp No. 61/182,833,sy- - - s filed on Jun.
    [Show full text]
  • AMEG Categorisation of Antibiotics
    12 December 2019 EMA/CVMP/CHMP/682198/2017 Committee for Medicinal Products for Veterinary use (CVMP) Committee for Medicinal Products for Human Use (CHMP) Categorisation of antibiotics in the European Union Answer to the request from the European Commission for updating the scientific advice on the impact on public health and animal health of the use of antibiotics in animals Agreed by the Antimicrobial Advice ad hoc Expert Group (AMEG) 29 October 2018 Adopted by the CVMP for release for consultation 24 January 2019 Adopted by the CHMP for release for consultation 31 January 2019 Start of public consultation 5 February 2019 End of consultation (deadline for comments) 30 April 2019 Agreed by the Antimicrobial Advice ad hoc Expert Group (AMEG) 19 November 2019 Adopted by the CVMP 5 December 2019 Adopted by the CHMP 12 December 2019 Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged. Categorisation of antibiotics in the European Union Table of Contents 1. Summary assessment and recommendations .......................................... 3 2. Introduction ............................................................................................ 7 2.1. Background ........................................................................................................
    [Show full text]