DOCSLIB.ORG

WO 2018/213641 Al 22 November 2018 (22.11.2018) W !P O PCT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2018/213641 Al 22 November 2018 (22.11.2018) W !P O PCT (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2018/213641 Al 22 November 2018 (22.11.2018) W !P O PCT (51) International Patent Classification: TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, C12Q 1/68 (2018.01) G01N 33/531 (2006.01) KM, ML, MR, NE, SN, TD, TG). G I 24/08 (2006.01) Published: (21) International Application Number: — with international search report (Art. 21(3)) PCT/US20 18/033278 — before the expiration of the time limit for amending the (22) International Filing Date: claims and to be republished in the event of receipt of 17 May 2018 (17.05.2018) amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/507,642 17 May 2017 (17.05.2017) US (71) Applicant: T2 BIOSYSTEMS, INC. [US/US]; 101 Hartwell Avenue, Lexington, MA 02421 (US). (72) Inventors: MANNING, Brendan, John; 25 Adams Street, Arlington, MA 02474 (US). SNYDER, Jessica, Lee; 46 Thorndike Street, Arlington, MA 02474 (US). CHANG, Benjamin, Nguyen; 1Porter Cirlce, Cambridge, MA 02 140 (US). HIGA, Trissha, Ritsue; 365 Faneuil Street, Apt 5, Brighton, MA (US). SHIVERS, Robert, Patrick; 232 Common Street, Watertown, MA 02472 (US). WONG, Yin Shan, Cathy; 30 Burso Avenue, Maiden, MA 02148 (US). LOWERY, Thomas, Jay; 123 Winter Street, Belmont, MA 02478 (US). VED, Urvi; 325 Speen Street, Apartment 8 11, Natick, MA 01760 (US). GAMERO, Daniel; 101 Hartwell Avenue, Lexington, MA 02421 (US). (74) Agent: ELBING, Karen, L.; Clark & Elbing LLP, 101 Federal Street, 15th Floor, Boston, MA 021 10 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 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, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (54) Title: NMR METHODS AND SYSTEMS FOR THE RAPID DETECTION OF CANDIDA SPECIES (57) Abstract: The invention features methods, systems, and panels for rapid detection of Candida species (e.g., Candida auris, Candida lusitaniae, Candida haemulonii, Candida duobushaemulonii, and Candida pseudohaemulonii) in biological samples (e.g., whole blood) and environmental samples (e.g., environmental swabs, e.g., surface swabs), and for diagnosis and monitoring of diseases, including Candidiasis and sepsis. NMR METHODS AND SYSTEMS FOR THE RAPID DETECTION OF CANDIDA SPECIES SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 17 , 201 8 , is named 5071 3-1 18W02_Sequence_Listing_5. 17.1 8_ST25 and is 12,346 bytes in size. FIELD OF THE INVENTION The invention features methods, panels, and systems for detecting Candida auris and other Candida species and for diagnosing and treating diseases. BACKGROUND OF THE INVENTION Candida auris is now recognized worldwide as a virulent pathogen that is difficult to manage, resulting in high mortality rates. The majority of Candida auris isolates have exhibited resistance to one or more antifungal agents. Nosocomial infections caused by Candida auris are growing due to the increasing rate of colonization and environmental causes. The diagnostic tests available for the identification of Candida auris are limited to date. Additionally, microbiological cultures and subsequent identification of Candida species typically require 2-5 days, and have a sensitivity of approximately 50%. Accurate diagnosis of a Candida auris infection is also hampered by misidentification of C. auris as other species, commonly Candida haemulonii and Saccharomyces cerevisiae. Thus, there remains a need for rapid and sensitive methods, preferably requiring minimal or no sample preparation , for detecting the presence of Candida auris and other Candida species analytes for diagnosis and monitoring of diseases, including Candidiasis, Candidemia, and sepsis. SUMMARY OF THE INVENTION The invention features methods, panels, and systems for detecting Candida auris and other Candida species (e.g. , Candida lusitaniae, Candida haemulonii, Candida duobushaemulonii, and Candida pseudohaemulonii), and diagnosing and treating diseases, including Candidiasis, Candidemia, and sepsis. In a first aspect, the invention features a method for detecting the presence of a Candida species in a biological or environmental sample, wherein the Candida species is Candida auris, the method including : (a) providing a biological or environmental sample; (b) amplifying a Candida species target nucleic acid in the biological or environmental sample; and (c) detecting the amplified nucleic acid to determine whether Candida auris is present in the biological or environmental sample, wherein (i) the presence of Candida auris in the biological or environmental sample is determined within about 5 hours (e.g., about 1, 2 , 3 , 4 , or 5 hours) from obtaining the sample or less; (ii) the presence of Candida auris is determined directly from the biological or environmental sample without a prior culturing step; and/or (iii) the Candida auris is present in the biological or environmental sample at a concentration of about 10 cells/mL of biological or environmental sample or less (e.g., about 1, 2 , 3 , 4 , 5 , 6 , 7 , 9 , or 10 cells/mL). In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida lusitaniae is present. In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida haemulonii is present. In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida duobushaemulonii is present. In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida pseudohaemulonii is present. In some embodiments, the method detects a concentration of Candida auris of 10 cells/mL of biological or environmental sample or less (e.g. , about 1, 2 , 3 , 4 , 5 , 6 , 7 , 9 , or 10 cells/mL). In some embodiments, step (a) further includes lysing Candida cells present in the biological or environmental sample. In some embodiments, the amplified Candida species target nucleic acid is detected by sequencing (e.g. , Sanger sequencing or high-throughput sequencing (e.g. , ILLUMINA® sequencing), optical, fluorescent, mass, density, magnetic, chromatographic, and/or electrochemical measurement. In some embodiments, the amplified Candida species target nucleic acid is detected by measuring the T 2 relaxation response of the biological or environmental sample or a portion thereof following contacting the biological or environmental sample or the portion thereof with magnetic particles, wherein the magnetic particles have binding moieties on their surfaces, the binding moieties operative to alter the specific aggregation of the magnetic particles in the presence of the amplified Candida species target nucleic acid. In another aspect, the invention features a method for detecting the presence of a Candida species in a biological or environmental sample, wherein the Candida species is Candida lusitaniae, the method including : (a) providing a biological or environmental sample; (b) amplifying a Candida species target nucleic acid in the biological or environmental sample; and (c) detecting the amplified nucleic acid to determine whether Candida lusitaniae is present in the biological or environmental sample, wherein (i) the presence of Candida lusitaniae in the biological or environmental sample is determined within about 5 hours from obtaining the sample or less (e.g., about 1, 2 , 3 , 4 , or 5 hours) ; (ii) the presence of Candida lusitaniae is determined directly from the biological or environmental sample without a prior culturing step; and/or (iii) the Candida lusitaniae is present in the biological or environmental sample at a concentration of about 10 cells/mL of biological or environmental sample or less (e.g., about 1, 2 , 3 , 4 , 5 , 6 , 7 , 9 , or 10 cells/mL). In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida auris is present. In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida haemulonii is present. In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida duobushaemulonii is present. In some embodiments, step (c) further includes detecting the amplified nucleic acid to determine whether Candida pseudohaemulonii is present. In some embodiments, the method detects a concentration of Candida lusitaniae of 10 cells/mL of biological or environmental sample or less (e.g., about 1, 2 , 3 , 4 , 5 , 6 , 7 , 9 , or 10 cells/mL). In some embodiments, step (a) further includes lysing Candida cells present in the biological or environmental sample. In some embodiments, the amplified Candida species target nucleic acid is detected by sequencing (e.g. , Sanger sequencing or high-throughput sequencing (e.g., ILLUMINA® sequencing), optical, fluorescent, mass, density, magnetic, chromatographic, and/or electrochemical measurement.
Load more

Recommended publications
  • Topical and Systemic Antifungal Therapy for Chronic Rhinosinusitis (Protocol)
    CORE Metadata, citation and similar papers at core.ac.uk Provided by University of East Anglia digital repository Cochrane Database of Systematic Reviews Topical and systemic antifungal therapy for chronic rhinosinusitis (Protocol) Head K, Sacks PL, Chong LY, Hopkins C, Philpott C Head K, Sacks PL, Chong LY, Hopkins C, Philpott C. Topical and systemic antifungal therapy for chronic rhinosinusitis. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD012453. DOI: 10.1002/14651858.CD012453. www.cochranelibrary.com Topical and systemic antifungal therapy for chronic rhinosinusitis (Protocol) Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 BACKGROUND .................................... 1 OBJECTIVES ..................................... 3 METHODS ...................................... 3 ACKNOWLEDGEMENTS . 8 REFERENCES ..................................... 9 APPENDICES ..................................... 10 CONTRIBUTIONSOFAUTHORS . 25 DECLARATIONSOFINTEREST . 26 SOURCESOFSUPPORT . 26 NOTES........................................ 26 Topical and systemic antifungal therapy for chronic rhinosinusitis (Protocol) i Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Protocol] Topical and systemic antifungal therapy for chronic rhinosinusitis Karen Head1, Peta-Lee Sacks2, Lee Yee Chong1, Claire Hopkins3, Carl Philpott4 1UK Cochrane Centre,
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • Pharmaceuticals As Environmental Contaminants
    PharmaceuticalsPharmaceuticals asas EnvironmentalEnvironmental Contaminants:Contaminants: anan OverviewOverview ofof thethe ScienceScience Christian G. Daughton, Ph.D. Chief, Environmental Chemistry Branch Environmental Sciences Division National Exposure Research Laboratory Office of Research and Development Environmental Protection Agency Las Vegas, Nevada 89119 [email protected] Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Why and how do drugs contaminate the environment? What might it all mean? How do we prevent it? Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada This talk presents only a cursory overview of some of the many science issues surrounding the topic of pharmaceuticals as environmental contaminants Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada A Clarification We sometimes loosely (but incorrectly) refer to drugs, medicines, medications, or pharmaceuticals as being the substances that contaminant the environment. The actual environmental contaminants, however, are the active pharmaceutical ingredients – APIs. These terms are all often used interchangeably Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Office of Research and Development Available: http://www.epa.gov/nerlesd1/chemistry/pharma/image/drawing.pdfNational
    [Show full text]
  • Evaluation of Vaginal Antifungal Formulations in Vivo R. J. MCRIPLEY P
    Postgrad Med J: first published as 10.1136/pgmj.55.647.648 on 1 September 1979. Downloaded from Postgraduate Medical Journal (September 1979) 55, 648-652 Evaluation of vaginal antifungal formulations in vivo R. J. MCRIPLEY P. J. ERHARD Ph.D. B.S. R. A. SCHWIND R. R. WHITNEY B.S. B.A. The Squibb Institute for Medical Research, Princeton, New Jersey, U.S.A. Summary employed to establish the experimental infection. Relatively simple and rapid procedures have been Inocula for infection were prepared by harvesting developed for evaluating the local efficacy of vaginal the growth from Sabouraud's dextrose agar slants antifungal agents in vivo in a vaginal candidiasis model of C. albicans obtained after 24-48 hr incubation at in ovariectomized rats. The results of this investigation 37°C and making suspensions containing 10s colony- indicate that the model and methods described are forming units (CFU)/ml. quite suitable for screening potential antifungal sub- Protected by copyright. stances and for assessing the chemotherapeutic Establishment of the experimental infection effectiveness ofnew antifungal agents and formulations Rats were pretreated with 0.5 mg of progesterone before carrying out clinical studies. and 0.5 mg of oestradiol valerate administered sub- cutaneously to induce oestrus. Confirmation of Introduction oestrus was made by microscopic examination of Vaginal candidiasis is a common and chronic ailment vaginal smears. Beginning 2 days after hormonal in women of child-bearing age. The incidence of this treatment, rats were inoculated intravaginally on 2 vaginal infection has increased considerably in successive days with 107 CFU of C. albicans con- recent years with the more frequent use of anti- tained in a 0.1 ml inoculum.
    [Show full text]
  • Natamycin As an Allowed Nonsynthetic Substance
    Technology Sciences Group Inc. 712 Fifth St., Suite A Davis, CA 95616 Direct: (530) 601-5064 Fax: (530) 757-1299 E-Mail: [email protected] Jacob S. Moore Regulatory Consultant September 1, 2016 USDA/AMS/NOP, Standards Division 1400 Independence Ave. SW Room 2648-So., Ag Stop 0268 Washington, DC 20250-0268 Attention: Lisa Brines, PhD National List Manager RE: National Organic Program Petition for Classification of Natamycin as an Allowed Nonsynthetic Substance Dear Dr. Brines: Technology Sciences Group Inc., on behalf of DSM Food Specialties B.V., submits the enclosed petition for classification of natamycin as an allowed nonsynthetic substance. Natamycin is a naturally-occurring compound produced by fermentation of Streptomyces natalensis. As natamycin is known to the National Organic Program and National Organic Standards Board, the petitioner requests that a focused Technical Report be issued to complement the work previously done and resolve the classification status of the petitioned substance. Please contact me with any questions or concerns. Jacob S. Moore TITLE Petition for Classification of Natamycin as an Allowed Nonsynthetic Substance in Organic Crop Production AUTHOR Technology Sciences Group Inc. DATE September 1, 2016 Page 1 of 212 Natamycin Allowed Nonsynthetic Petition – National Organic Program – September 1, 2016 Table of Contents Item A—Indicate which section or sections the petitioned substance will be included on and/or removed from the National List. .................................................................................................................................
    [Show full text]
  • Effect of Amphotericin B on Candida Albicans
    University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 1968 Effect of amphotericin B on Candida albicans Edward Carney The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Carney, Edward, "Effect of amphotericin B on Candida albicans" (1968). Graduate Student Theses, Dissertations, & Professional Papers. 2149. https://scholarworks.umt.edu/etd/2149 This Thesis is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. EFFECT OF AMPHOTERICIN B ON CANDIDA ALBICANS By Edward M. Carney B, S., Southern Connecticut State College, 1965 Presented in partial fulfillment of the requirements for the degree of Master of Science UNIVERSITY OF MONTANA 1968 Graduate School AUG 2 1968 Date UMI Number: EP34624 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent on the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMT UMI EP34624 Copyright 2012 by ProQuest LLC. All rights reserved. This edition of the work is protected against unauthorized copying under Title 17, United States Code. ProOuesf ProQuest LLC.
    [Show full text]
  • WO 2007/014308 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 1 February 2007 (01.02.2007) PCT WO 2007/014308 Al (51) International Patent Classification: Brook Road, Kensington, CT 06037 (US). KIM, Ha, C07D 513/04 (2006.01) A61P 33/00 (2006.01) Young [KR/US]; 87 Deepwood Drive, Cheshire, CT A61K 31/4365 (2006.01) 06410 (US). (21) International Application Number: (74) Agent: HARVATH,Leslie-anne; Cantor Colburn LLP, 55 PCT/US2006/029302 Griffin Road South, Bloomfield, CT 06002 (US). (22) International Filing Date: 27 July 2006 (27.07.2006) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (25) Filing Language: English AT,AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, (26) Publication Language: English GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, (30) Priority Data: LU, LV,LY,MA, MD, MG, MK, MN, MW, MX, MZ, NA, 60/702,811 27 July 2005 (27.07.2005) US NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, (71) Applicant (for all designated States except US): UA, UG, US, UZ, VC, VN, ZA, ZM, ZW ACHILLION PHARMACEUTICALS, INC. [US/US]; 300 George Street, New Haven, CT 0651 1 (US).
    [Show full text]
  • O'heany. According to the Criteria of Dr. Reiffen- Careful Investigation; It Certainly Merited Publica- Stein, Dr
    3. 224 CORRESPONDENCE Jan.Canad.25, Med.1969,Ass.vol. 100 O'Heany. According to the criteria of Dr. Reiffen- careful investigation; it certainly merited publica- stein, Dr. O'Heany's study would fall into Category tion; and his findings stand a good chance of holding I, a dismal fate indeed. The purpose of this letter is up in clinical practice. It would be wrong, therefore, to argue the point that Dr. O'Heany's report, al- in my view, to consider this study a poor one, which though indeed Category I ("No controls"), is far would be the case were Dr. Reiffenstein's criteria from being a study without value, and, by extension, to be applied, to the exclusion of other considera- to suggest that Dr. Reiffenstein's conclusions (which, tions. Not all studies are perfect, of course, and the of course, were not directed towards Dr. O'Heany's present study could indeed have been improved by study personally) are too simplicistic. I hope Dr. the use of a standard therapy as control, or even O'Heany will not object to my using his article had some indication been given by the author of the to illustrate my thesis (particularly since most of rate of remission seen with other treatment, for the what I have to say about it is favourable). benefit of readers who are not gynecologists. In the same conciliatory vein, let me say to Dr. Surveys such as Dr. Reiffenstein has made are Reiffenstein that I have too much respect for him, extremely interesting, but I feel they could be im- and for the aims of his student program, with which proved by the application of a broader range of I became familiar as the former Medical Director criteria, more subtle in nature.
    [Show full text]
  • Medicinal Chemistry of Modern Antibiotics
    Chemistry 259 Medicinal Chemistry of Modern Antibiotics Spring 2012 Lecture 2: History of Antibiotics Thomas Hermann Department of Chemistry & Biochemistry University of California, San Diego 03/23/2006 Southwestern College Prelude to Antibiotics: Leeuwenhoek & The Birth of Microbiology Antonie van Leeuwenhoek (Delft, 1632-1723) Bacteria in tooth plaque (1683) First to observe and describe single celled organisms which he first referred to as animalicula, and which we now know to be microorganisms (protozoa, bacteria). Prelude to Antibiotics: Pasteur, Koch & The Germ Theory of Disease Koch’s Postulates: (1890) To establish that a microorganism is the cause of a disease, it must be: 1) found in all cases of the disease. 2) isolated from the host and Louis Pasteur maintained in pure culture. (Strasbourg, 1822-1895) 3) capable of producing the Showed that some original infection, even after Robert Koch microorganisms several generations in (Berlin, 1843-1910) contaminated fermenting culture. beverages and concluded Discovered Bacillus that microorganisms infected 4) recoverable from an anthracis, Mycobacterium animals and humans as well. experimentally infected host. tuberculosis, Vibrio cholerae and developed “Koch’s Postulates". Nobel Price in Medicine 1905 for work on tuberculosis. Invention of Modern Drug Discovery: Ehrlich & The Magic Bullet Atoxyl Salvarsan (Bechamp 1859) (Compound 606, Hoechst 1910) Paul Ehrlich (Frankfurt, 1854-1915) Synthesized and screened hundreds of compounds to Salvarsan in solution eventually discover and consists of cyclic develop the first modern species (RAs)n, with chemotherapeutic agent n=3 (2) and n=5 (3) as (Salvarsan, 1909) for the the preferred sizes. treatment of syphillis Lloyd et al. (2005) Angewandte (Treponema pallidum).
    [Show full text]
  • Common Study Protocol for Observational Database Studies WP5 – Analytic Database Studies
    Arrhythmogenic potential of drugs FP7-HEALTH-241679 http://www.aritmo-project.org/ Common Study Protocol for Observational Database Studies WP5 – Analytic Database Studies V 1.3 Draft Lead beneficiary: EMC Date: 03/01/2010 Nature: Report Dissemination level: D5.2 Report on Common Study Protocol for Observational Database Studies WP5: Conduct of Additional Observational Security: Studies. Author(s): Gianluca Trifiro’ (EMC), Giampiero Version: v1.1– 2/85 Mazzaglia (F-SIMG) Draft TABLE OF CONTENTS DOCUMENT INFOOMATION AND HISTORY ...........................................................................4 DEFINITIONS .................................................... ERRORE. IL SEGNALIBRO NON È DEFINITO. ABBREVIATIONS ......................................................................................................................6 1. BACKGROUND .................................................................................................................7 2. STUDY OBJECTIVES................................ ERRORE. IL SEGNALIBRO NON È DEFINITO. 3. METHODS ..........................................................................................................................8 3.1.STUDY DESIGN ....................................................................................................................8 3.2.DATA SOURCES ..................................................................................................................9 3.2.1. IPCI Database .....................................................................................................9
    [Show full text]
  • (10) Patent No.: US 7.659,399 B2 Bradbury Et Al
    USOO7659399B2 (12) United States Patent (10) Patent No.: US 7.659,399 B2 Bradbury et al. (45) Date of Patent: *Feb. 9, 2010 (54) 1-THIA-24A-DIAZA-CYCLOPENTAB JP O3-209367 9, 1991 NAPTHTHALENE-3,4-DIONES AND JP 10-130 149 5, 1998 RELATED COMPOUNDSAS WO WO95/298.94 11, 1995 ANT-INFECTIVE AGENTS WO WO 2005/019228 A1 3, 2005 OTHER PUBLICATIONS (75) Inventors: Barton James Bradbury, Wallingford, CT (US); Jason Allan Wiles, Hamden, Dorwald F. A. Side Reactions in Organic Synthesis, 2005, Wiley: VCH. Weinheimp. IX of Preface.* CT (US) Li, Qun et al., “Synthesis and Structure-Activity Relationships of O O 2-Pyridones: A Novel Series of Potent DNA Gyrase Inhibitors as (73) Assignee: Achillion Pharmaceuticals, Inc., New Antibacterial Agents.” J. Med. Chem. (1996) 39: 3070-3088. Haven, CT (US) Wiles, Jason A. et al., “Isothiazolopyridones: Synthesis, Structure, and Biological Activity of a New Class of Antibacterial Agents.” J. (*) Notice: Subject to any disclaimer, the term of this Med. Chem. (2006) 49: 39-42. patent is extended or adjusted under 35 Frigola, Jordi et al., “7-AZetidinylcquinolones as Antibacterial U.S.C. 154(b) by 709 days. Agents. Synthesis and Structure-Activity Relationships.” J. Med. Chem. (1993) 36: 801-810. This patent is Subject to a terminal dis- Ishiyama, Tatsuo et al., “Palladium (0)-Catalyzed Cross-Coupling claimer Reaction of Alkoxydiboron with Haloarenes: A Direct Procedure for Arylboronic Esters,” J. Org. Chem. (1995) 60:7508-7510. (21) Appl. No.: 11/326,109 (Continued) (22) Filed: Jan. 5, 2006 Primary Examiner Rita J Desai (74) Attorney, Agent, or Firm—Cantor Colburn LLP (65) Prior Publication Data (57) ABSTRACT US 2007/0129333 A1 Jun.
    [Show full text]