WO2003068954A3 - Mikroorganismus zur gentherapeutischen behandlung proliferativer erkrankungen - Google Patents

Mikroorganismus zur gentherapeutischen behandlung proliferativer erkrankungen Download PDF

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Publication number
WO2003068954A3
WO2003068954A3 PCT/DE2003/000470 DE0300470W WO03068954A3 WO 2003068954 A3 WO2003068954 A3 WO 2003068954A3 DE 0300470 W DE0300470 W DE 0300470W WO 03068954 A3 WO03068954 A3 WO 03068954A3
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WIPO (PCT)
Prior art keywords
microorganism
nucleotide sequence
specific
optionally
expression
Prior art date
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Ceased
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PCT/DE2003/000470
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English (en)
French (fr)
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WO2003068954A2 (de
WO2003068954A8 (de
Inventor
Werner Goebel
R Ulf Rapp
Hans-Harald Sedlacek
Joachim Fensterle
Ivaylo Gentschev
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.)
Medinnova Gesellschaft fuer Medizinische Innovationen aus Akademischer Forschung mbH,
Original Assignee
Medinnova Gesellschaft fuer Medizinische Innovationen aus Akademischer Forschung mbH,
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
Priority to MXPA04007934A priority Critical patent/MXPA04007934A/es
Priority to EP03704314A priority patent/EP1474519A2/de
Priority to KR10-2004-7012866A priority patent/KR20040103941A/ko
Priority to YU72404A priority patent/RS72404A/sr
Priority to DE2003190506 priority patent/DE10390506D2/de
Priority to NZ535310A priority patent/NZ535310A/en
Priority to HRP20040832 priority patent/HRP20040832A2/hr
Priority to BRPI0307722A priority patent/BRPI0307722A2/pt
Priority to US10/504,944 priority patent/US20050244374A1/en
Priority to CA002513198A priority patent/CA2513198A1/en
Priority to AU2003206663A priority patent/AU2003206663B2/en
Priority to JP2003568069A priority patent/JP2005517405A/ja
Application filed by Medinnova Gesellschaft fuer Medizinische Innovationen aus Akademischer Forschung mbH, filed Critical Medinnova Gesellschaft fuer Medizinische Innovationen aus Akademischer Forschung mbH,
Priority to IL16355303A priority patent/IL163553A0/xx
Publication of WO2003068954A2 publication Critical patent/WO2003068954A2/de
Publication of WO2003068954A3 publication Critical patent/WO2003068954A3/de
Anticipated expiration legal-status Critical
Priority to NO20043800A priority patent/NO20043800L/no
Publication of WO2003068954A8 publication Critical patent/WO2003068954A8/de
Ceased legal-status Critical Current

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    • 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
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01031—Beta-glucuronidase (3.2.1.31)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76—Albumins
    • C07K14/765—Serum albumin, e.g. HSA
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405—Glucanases
    • C12N9/2434—Glucanases acting on beta-1,4-glucosidic bonds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/16—Exonucleases active with either ribo- or deoxyribonucleic acids and producing 3'-phosphomonoesters (3.16)
    • C12Y301/16001—Spleen exonuclease (3.1.16.1), i.e. 5->3 exoribonuclease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Rheumatology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Pain & Pain Management (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)

Abstract

Die Erfindung lehrt einen ummantelten Mikroorganismus, in dessen Genom folgende Komponenten eingefügt und exprimierbar sind: I) eine Nukleotidsequenz, kodierend für ein di­rekt oder indirekt, antiproliferativ oder zytotoxisch wirkendes Expressionsprodukt oder für mehrere verschiedene solcher Expressionsprodukte, II) eine Nukleotidsequenz, welche für ein Blutplasmaprotein unter der Kontrolle einer im Mikroorganismus aktivierbaren Aktivierungssequenz kod­iert oder konstitutiv aktiv ist, III) optional, eine Nuk­leotidsequenz, welche für einen zellspezifischen Liganden unter der Kontrolle einer im Mikroorganismus aktivierbaren Aktivierungssequenz kodiert oder konstitutiv aktiv ist, IV) eine Nukleotidsequenz für ein Transportsystem, welches die Expression der Expressionsprodukte der Komponenten (I) und (II) sowie optional (III) auf der Außenfläche des Mikro­organismus oder die Sekretion der Expressionsprodukte der Komponente (I) und Expression der Komponente (II) sowie op­tional (III) bewirkt und vorzugsweise konstitutiv aktiv ist, V) optional eine Nukleotidsequenz für ein Protein zur Lyse des Mikrooganismus im Cytosol von Säugerzellen und zur intrazellulären Freisetzung von Plasmiden mit zumind­est einer oder mehreren der Komponenten (I) und (VI) enthalten in dem lysierten Mikroorganismus, und VI) eine in dem Mikroorganismus aktivierbare, und/oder eine gewebezellspezifische, tumorzellspezifische, funktionsspezi­fische oder nicht zellspezifische Aktivierungssequenz zur Expression von Komponente I), wobei jede der Komponenten (I) bis (VI) einfach oder mehrfach, jeweils gleich oder ver­schieden, eingerichtet sein kann.
PCT/DE2003/000470 2002-02-14 2003-02-13 Mikroorganismus zur gentherapeutischen behandlung proliferativer erkrankungen Ceased WO2003068954A2 (de)

Priority Applications (14)

Application Number Priority Date Filing Date Title
EP03704314A EP1474519A2 (de) 2002-02-14 2003-02-13 Mikroorganismus zur gentherapeutischen behandlung proliferativer erkrankungen
KR10-2004-7012866A KR20040103941A (ko) 2002-02-14 2003-02-13 증식성 질병의 유전자 치료를 위한 미생물
YU72404A RS72404A (sr) 2002-02-14 2003-02-13 Mikroorganizam za genetsko terapeutsko lečenje proliferativnih oboljenja
DE2003190506 DE10390506D2 (de) 2002-02-14 2003-02-13 Ummantelter Mikroorganismus
NZ535310A NZ535310A (en) 2002-02-14 2003-02-13 Microorganism for genetic therapeutic treatment of proliferative diseases
HRP20040832 HRP20040832A2 (en) 2002-02-14 2003-02-13 Microorganism for genetic therapeutic treatment of proliferative diseases
BRPI0307722A BRPI0307722A2 (pt) 2002-02-14 2003-02-13 microorganismo envolvido
CA002513198A CA2513198A1 (en) 2002-02-14 2003-02-13 Microorganism for genetic therapeutic treatment of proliferative diseases
US10/504,944 US20050244374A1 (en) 2002-02-14 2003-02-13 Enveloped miroorganism
MXPA04007934A MXPA04007934A (es) 2002-02-14 2003-02-13 Microorganismo envuelto.
JP2003568069A JP2005517405A (ja) 2002-02-14 2003-02-13 増殖性疾患の遺伝子療法的治療のための微生物
AU2003206663A AU2003206663B2 (en) 2002-02-14 2003-02-13 Microorganism for genetic therapeutic treatment of proliferative diseases
IL16355303A IL163553A0 (en) 2002-02-14 2003-08-13 Microorganism for genetic therapeutic treatment ofproliferative diseases
NO20043800A NO20043800L (no) 2002-02-14 2004-09-10 Mikroorganisme for genetisk terapetuisk behandling av proliferativ sykdom

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10206325A DE10206325A1 (de) 2002-02-14 2002-02-14 Ummantelter Mikroorganismus
DE10206325.7 2002-02-14

Publications (3)

Publication Number Publication Date
WO2003068954A2 WO2003068954A2 (de) 2003-08-21
WO2003068954A3 true WO2003068954A3 (de) 2003-10-16
WO2003068954A8 WO2003068954A8 (de) 2005-10-13

Family

ID=27674670

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2003/000470 Ceased WO2003068954A2 (de) 2002-02-14 2003-02-13 Mikroorganismus zur gentherapeutischen behandlung proliferativer erkrankungen

Country Status (19)

Country Link
US (1) US20050244374A1 (de)
EP (1) EP1474519A2 (de)
JP (1) JP2005517405A (de)
KR (1) KR20040103941A (de)
CN (1) CN1646693A (de)
AU (1) AU2003206663B2 (de)
BR (1) BRPI0307722A2 (de)
CA (1) CA2513198A1 (de)
DE (2) DE10206325A1 (de)
HR (1) HRP20040832A2 (de)
IL (1) IL163553A0 (de)
MX (1) MXPA04007934A (de)
NO (1) NO20043800L (de)
NZ (1) NZ535310A (de)
PL (1) PL372901A1 (de)
RS (1) RS72404A (de)
RU (1) RU2004127459A (de)
WO (1) WO2003068954A2 (de)
ZA (1) ZA200407358B (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1781096B1 (de) * 2004-06-29 2016-02-24 AntiCancer, Inc. Prostatakarzinomselektive salmonella typhimurium auxotrophe
TWI838389B (zh) 2018-07-19 2024-04-11 美商再生元醫藥公司 雙特異性抗-BCMAｘ抗-CD3抗體及其用途
MX2021000532A (es) 2018-07-19 2021-04-12 Regeneron Pharma Receptores antigénicos quiméricos con especificidad para bcma y usos de estos.
WO2020172462A1 (en) * 2019-02-22 2020-08-27 Arizona Board Of Regents On Behalf Of Arizona State University Tumor-navigating, self-eradicating, trail-armed salmonella for precision cancer therapy

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19720761A1 (de) * 1997-05-07 1998-11-12 Schering Ag Verfahren zur Synthese und Sekretion von zur Kontrazeption geeigneter Proteine oder Proteinfragmente durch attenuierte Salmonellen oder einen anderen Gram-negativen attenuierten Impfstamm zur Erzeugung einer oralen Vakzinierung

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GENTSCHEV I ET AL: "Delivery of protein antigens and DNA by virulence-attenuated strains of Salmonella typhimurium and Listeria monocytogenes", JOURNAL OF BIOTECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 83, no. 1-2, 29 September 2000 (2000-09-29), pages 19 - 26, XP004212147, ISSN: 0168-1656 *
PAWELEK J M ET AL: "TUMOR-TARGETED SALMONELLA AS A NOVEL ANTICANCER VECTOR", CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, BALTIMORE, MD, US, vol. 57, October 1997 (1997-10-01), pages 4537 - 4544, XP002939099, ISSN: 0008-5472 *
SU G ET AL: "EXTRACELLULAR EXPORT OF SHIGA TOXIN B-SUBUNIT/HAEMOLYSIN A (C-TERMINUS) FUSION PROTEIN EXPRESSED IN SALMONELLA TYPHIMURIUM AROA-MUTANT AND STIMULATION OF B-SUBUNIT SPECIFIC ANTIBODY RESPONSES IN MICE", MICROBIAL PATHOGENESIS, ACADEMIC PRESS LIMITED, NEW YORK, NY, US, vol. 13, no. 6, December 1992 (1992-12-01), pages 465 - 476, XP000983124, ISSN: 0882-4010 *

Also Published As

Publication number Publication date
IL163553A0 (en) 2005-12-18
DE10390506D2 (de) 2005-01-13
ZA200407358B (en) 2005-11-18
NZ535310A (en) 2008-04-30
AU2003206663B2 (en) 2007-11-01
JP2005517405A (ja) 2005-06-16
BRPI0307722A2 (pt) 2017-07-04
WO2003068954A2 (de) 2003-08-21
RS72404A (sr) 2006-12-15
AU2003206663B9 (en) 2003-09-04
AU2003206663A1 (en) 2003-09-04
PL372901A1 (en) 2005-08-08
CA2513198A1 (en) 2003-08-21
CN1646693A (zh) 2005-07-27
DE10206325A1 (de) 2003-09-04
WO2003068954A8 (de) 2005-10-13
KR20040103941A (ko) 2004-12-09
EP1474519A2 (de) 2004-11-10
RU2004127459A (ru) 2005-05-10
NO20043800L (no) 2004-11-08
MXPA04007934A (es) 2005-11-23
HRP20040832A2 (en) 2004-12-31
US20050244374A1 (en) 2005-11-03

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