EP1180937A1 - Souches de bacteriophages utiles pour sauver des patients infectes par enterococcus faecium resistant a la vancomycine - Google Patents

Souches de bacteriophages utiles pour sauver des patients infectes par enterococcus faecium resistant a la vancomycine

Info

Publication number
EP1180937A1
EP1180937A1 EP00931911A EP00931911A EP1180937A1 EP 1180937 A1 EP1180937 A1 EP 1180937A1 EP 00931911 A EP00931911 A EP 00931911A EP 00931911 A EP00931911 A EP 00931911A EP 1180937 A1 EP1180937 A1 EP 1180937A1
Authority
EP
European Patent Office
Prior art keywords
phage
enterococcus faecium
vancomycin
enb6
pta
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00931911A
Other languages
German (de)
English (en)
Other versions
EP1180937A4 (fr
Inventor
Carl R. National Inst. of Mental Health MERRIL
Richard M. Carlton
Sankar Adhya
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
National Institutes of Health NIH
Exponential Biotherapies Inc
Original Assignee
National Institutes of Health NIH
Exponential Biotherapies Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National Institutes of Health NIH, Exponential Biotherapies Inc filed Critical National Institutes of Health NIH
Publication of EP1180937A1 publication Critical patent/EP1180937A1/fr
Publication of EP1180937A4 publication Critical patent/EP1180937A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
    • A61K39/092—Streptococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2795/00—Bacteriophages
    • C12N2795/00011—Details
    • C12N2795/10011—Details dsDNA Bacteriophages
    • C12N2795/10311—Siphoviridae
    • C12N2795/10332—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent

Definitions

  • MDR Enterococcus faecium
  • MDR multidrug resistant
  • Synercid® recently entered the market as a treatment for vancomycin-resistant bacteria, including VREF.
  • MDR bacteria are so efficient at resisting newer antibiotics (even those to which
  • efflux pump can transport out many classes of drugs; and a mutation in the
  • ribosomal subunit targeted by antibiotics can defeat several classes of drugs.
  • Bacte ophage (phage) therapy offers one such alternative.
  • phage strains for example ENB6
  • phages tend to be rapidly cleared from the systemic circulation by the filtering action
  • the technique also selects for those mutants that retain their ability to lyse the target
  • phage stains that attack VREF hosts have
  • Phage strains were grown by standard techniques known in the art,
  • the ENB6 genome contains at least 120 kb of DNA as determined by
  • nucleotide sequence has been defined at 99% confidence, while 24.7 kb has been defined at a lower level of confidence. The remaining amount is presently
  • ENB6 nucleotide sequences have been compared to all genes and
  • Figure 2 is an electron microscopic picture of phage ENB6.
  • the routes of administration include but are not limited to: oral, aerosol or
  • intrathecal intraperitoneal, intrathecal, vaginal, rectal, topical, lumbar puncture, intrathecal,
  • the free phage could be in lyophilized form and be
  • administration is contemplated to be in the range of about 10 3 to about 10 13
  • the phage are Table 2. Proteins screened by PCR amplification of ENB6 DNA.
  • the present invention will be particularly useful in treating critically ill
  • ENB6 ATCC # PTA-40
  • ENB13 ATCC # PTA-39
  • Figures 3 and 4 show the results of a dose-finding study.
  • CRMEN44 is 1 x 10 9 CFU, when injected I. P. into one month-old balb/c
  • PFU plaque forming units PFU
  • the non-parametric rating scale for observable signs of illness is as follows:
  • Phage administered as a control did not produce any detectable symptoms in the
  • Phage ENB6 rescues animals from an otherwise-fatal dose of VREF, a bacterial
  • Figures 5 and 6 show the results of delay in the treatment of a fulminant
  • VREF are orders-of-magnitude lower than the concentrations achieved here, so it

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)

Abstract

la présente invention concerne l'utilisation de bactériophages spécifiques, appelés ENB6 et ENB13, qui tuent nombre d'isolats cliniques de Enterococcus faecium résistant à la vancomycine et de Enterococcus faecium sensible à la vancomycine. Le génome d'une des souches de ces bactériophages, ENB6 à été partiellement séquencé, et il apparaît qu'il ne contient pas de séquences nucléotidiques correspondant à des gènes à virulence bactérienne connus et à une cassette présentant une résistance à la vancomycine. Son efficacité qui a permis de sauver des souris de bactériémie dont l'issue aurait en d'autres circonstances été fatale, est présentée dans ce dossier.
EP00931911A 1999-05-13 2000-05-12 Souches de bacteriophages utiles pour sauver des patients infectes par enterococcus faecium resistant a la vancomycine Withdrawn EP1180937A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US13405599P 1999-05-13 1999-05-13
US134055P 1999-05-13
PCT/US2000/006718 WO2000069269A1 (fr) 1999-05-13 2000-05-12 Souches de bacteriophages utiles pour sauver des patients infectes par enterococcus faecium resistant a la vancomycine

Publications (2)

Publication Number Publication Date
EP1180937A1 true EP1180937A1 (fr) 2002-02-27
EP1180937A4 EP1180937A4 (fr) 2004-08-04

Family

ID=22461568

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00931911A Withdrawn EP1180937A4 (fr) 1999-05-13 2000-05-12 Souches de bacteriophages utiles pour sauver des patients infectes par enterococcus faecium resistant a la vancomycine

Country Status (5)

Country Link
EP (1) EP1180937A4 (fr)
JP (1) JP2002543816A (fr)
AU (1) AU4971900A (fr)
CA (1) CA2373486A1 (fr)
WO (1) WO2000069269A1 (fr)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1250143A2 (fr) 2000-01-11 2002-10-23 Intralytix Inc. Reduction de la colonisation bacterienne par administration de compositions bacteriophages
US6759229B2 (en) 2001-12-18 2004-07-06 President & Fellows Of Harvard College Toxin-phage bacteriocide antibiotic and uses thereof
GB0209680D0 (en) * 2002-04-27 2002-06-05 Univ Strathclyde Immobilisation and stabilisation of bacteriophage
WO2004052274A2 (fr) 2002-12-09 2004-06-24 Phage Biopharm Llc Production de compositions bacteriophages destinees a etre utilisees dans la therapie phagique
DE10342071B4 (de) * 2003-09-10 2006-01-19 Fleischmann, Wilhelm, Dr.med. Vorrichtung und Verfahren zur Applikation von Wïrkstoffen an eine Wundoberfläche
US8178087B2 (en) 2006-04-04 2012-05-15 Centre National de la Recherche Scientifique —CNRS Process of production of bacteriophage compositions and methods in phage therapy field
KR100958139B1 (ko) * 2008-03-31 2010-05-18 주식회사 인트론바이오테크놀로지 엔테로코쿠스 패칼리스 특이적 사멸능을 갖는 신규한박테리오파지
PL215522B1 (pl) 2008-09-29 2013-12-31 Inst Immunologii I Terapii Doswiadczalnej Pan Nowe szczepy bakteriofagów do leczenia zakazen bakteryjnych, zwlaszcza szczepami bakterii lekoopornych rodzaju Enterococcus
KR100988771B1 (ko) * 2008-09-29 2010-10-20 주식회사 인트론바이오테크놀로지 엔테로코쿠스 및 스트렙토코쿠스 특이적 사멸능을 갖는 신규한 리신 단백질
RU2580248C9 (ru) * 2009-02-06 2018-01-17 Текнофахе, Инвестигасао Э Десенвольвименто Эм Биотекнолохия, Са Бактериофаг, обладащий активностью против pseudomonas aeruginosa, белки бактериофага и способы их применения
WO2017177196A1 (fr) 2016-04-08 2017-10-12 The Trustees Of Princeton University Nouvelles compositions antimicrobiennes et méthodes d'utilisation
KR101957266B1 (ko) * 2017-02-22 2019-03-13 주식회사 인트론바이오테크놀로지 엔테로코쿠스 패슘에 대하여 용균력을 가지는 신규한 항균단백질 efal-2
KR101822812B1 (ko) * 2017-02-22 2018-01-29 주식회사 인트론바이오테크놀로지 신규한 엔테로코쿠스 패슘 박테리오파지 Ent-FAP-4 및 이의 엔테로코쿠스 패슘 증식 억제 용도
GB201712733D0 (en) 2017-08-08 2017-09-20 Snipr Tech Ltd Methods & cells
KR102203679B1 (ko) * 2018-12-26 2021-01-15 주식회사 옵티팜 신규한 엔테로코커스 패시움 균 특이 박테리오파지 ef44 및 이를 포함하는 항균 조성물
GB201901099D0 (en) 2019-01-27 2019-03-13 Snipr Biome Aps Methods, uses and compositions
IL309276A (en) * 2021-06-15 2024-02-01 Ferring Bv Bacteriophages against vancomycin-resistant enterococci
WO2024003301A1 (fr) 2022-06-29 2024-01-04 Snipr Biome Aps Ciblage de cellules d'e. coli

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5766892A (en) * 1994-04-05 1998-06-16 Exponential Biotherapies, Inc. Antibacterial therapy with bacteriophage genotypically modified to delay inactivation by the host defense system together with an antibiotic

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5766892A (en) * 1994-04-05 1998-06-16 Exponential Biotherapies, Inc. Antibacterial therapy with bacteriophage genotypically modified to delay inactivation by the host defense system together with an antibiotic

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ALISKY J ET AL: "BACTERIOPHAGE SHOW PROMISE AS ANTIMICROBIAL AGENTS" JOURNAL OF INFECTION, ACADEMIC PRESS, LONDON, GB, vol. 36, 1998, pages 5-15, XP000993238 ISSN: 0163-4453 *
See also references of WO0069269A1 *

Also Published As

Publication number Publication date
JP2002543816A (ja) 2002-12-24
AU4971900A (en) 2000-12-05
WO2000069269A1 (fr) 2000-11-23
CA2373486A1 (fr) 2000-11-23
WO2000069269A9 (fr) 2002-02-21
EP1180937A4 (fr) 2004-08-04

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