WO1998051318A1 - Pharmaceutical composition and diagnostic kit directed to a heterologeneous pathogenic organism in a host - Google Patents
Pharmaceutical composition and diagnostic kit directed to a heterologeneous pathogenic organism in a host Download PDFInfo
- Publication number
- WO1998051318A1 WO1998051318A1 PCT/EP1998/002871 EP9802871W WO9851318A1 WO 1998051318 A1 WO1998051318 A1 WO 1998051318A1 EP 9802871 W EP9802871 W EP 9802871W WO 9851318 A1 WO9851318 A1 WO 9851318A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- self
- pathogenic organism
- heterologeneous
- infections
- Prior art date
Links
Classifications
-
- 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
-
- 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
- C12N2795/00032—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to a pharmaceutical composition comprising a self- replicating agent directed to a heterologeneous pathogenic organism in a host, and to a process for its preparation. Further, the present invention relates to a diagnostic kit comprising the self-replicating agent.
- the technical problem underlying the present invention is to provide a new system for the treatment of diseases caused by pathogenic organisms and for the diagnosis of said diseases and the detection of said pathogenic organisms.
- a pharmaceutical composition comprising a self-replicating agent directed to a heterologeneous pathogenic organism in a host, and optionally a pharmaceutically acceptable carrier and/or diluent, wherein the self-replicating agent is capable of growth-inhibiting and/or destroying the heterologeneous pathogenic organism without substantial toxicity to the host.
- a diagnostic kit comprising a self-replicating agent directed to a heterologenous pathogenic organism, wherein the self-replicating agent contains at least one detectable marker gene.
- the aim of the invention is the infection of the respective pathogenic organism by the self-replicating agent, eventually leading to the destruction or inhibition of the pathogenic organism.
- This can be achieved by e.g. virulent as well as temperate viruses.
- Lytic strains of viruses would be of advantage with respect to a spread through the pathogenic population which would enable the use of low titer pharmaceutical compositions which would potentate themself in case of infectability of the pathogenic cells.
- the initial infection of the pathogenic host organism might be done by use of naked DNA, RNA (e.g. virions), especially encapsulated nucleic acids such as viruses (e.g. eucaryotic viruses and bacteriophages), or specific systems carrying said self replicating agent.
- Such specific systems may be microsomes and liposomes or invasive bacteria which are already infected with said self replicating agent.
- Such preinfected invasive bacteria can be used for combatting infections caused by invasive pathogens such as Listeria.
- a further aim of the invention is the infection of a pathogenic organism by the self-replicating agent, whereby the pathogenic organism can be detected via the marker gene contained in the self-replicating agent upon infection.
- the term "marker gene” means any nucleotide sequence which is introduced into the genetic material of the self-replicating agent using recombinant DNA techniques, and which can be detected upon infection of the pathogenic organism using known techniques such as PCR, enzymatic methods such as measuring the luminescence, fluorescence and/or immunologic methods. Examples of marker genes are the gene encoding luciferase, chloramphenicolacetyltransferase (CAT) and green fluorescent protein (GFP) .
- CAT chloramphenicolacetyltransferase
- GFP green fluorescent protein
- self-replicating . agent includes, agents, preferably of viral origin such as eukaryotic viruses or bacteriophages, directed specifically to the heterologeneous pathogenic organism.
- the self-replicating agent may be of natural origin such as naturally occurring eukaryotic viruses or bacteriophages, or may contain at least one nucleotide sequence obtained by recombinant DNA technique, such as a marker gene.
- self-replicating infectious agents are naturally occurring viruses, viroids or bacteriophages such as Listeria phages A51 1 , B054, or Klebsiella phages K1 1 and Klebsiella pneumoniae bacteriophage or Staphylococcus phage group II as well as viruses infecting eukaryotic cells such as yeast L-A virus, ScVLI , ScVLa, K1 and K2 killervirus, or genetically modified versions thereof.
- the self-replication of the self-replicating agent is supported by the heterologeneous pathogenic organism.
- Chlamydia phages such as Chp 1 (Storey et al., Gen. Virol. 70, 1 989, 1 321 -1 327; Bacon et al., Vet. Rec. 1 1 9, 1 986, 61 8-620), Bacillus phages such as phi 20 from the Strain Sterne 34 F7 (Inal and Karunakaran, Curr. Microbiol. 32, 1 996, 1 71 -1 75), CP 54 (Mol. Mikro- biol., Virosol. 1 37, 1 989, 1 4-1 9) and Tg l3 ant (Mol. Gen. Mikrobiol.
- Trichonomas-RNA virus (Wang and Wang, PNAS 83, 1 986, 7956-7960), Gardiavirus (GLV) (Wang et al., PNAS 90, 1 993, 8595-8599), Leishmania-dsRNA virus L V ⁇ and LRV 2 ., (Widmer and Dooley, Nucleic Acids Res. 23, 1 995, 2300-2304), and Cryptosporidium- dsRNA virus (Khramtsov et al., Mol. Microbiol. 26, 1 997, 289-300).
- heterologeneous pathogenic organism means any organism, i.e. an eukaryotic or prokaryotic organism, which is capable of infecting a host, and thereby causing a disorder in the host during the course of infection.
- Such heterologeneous pathogenic organisms include Listeriae, Klebsiellae, Streptococci, Staphylococci, Pneumococci, Moraxellae, Legionellae, Vibrio, Edwardsiellae, Yersiniae, Escherichiae, Haemophilus influenza, Proteus, Heliobacter, Salmonael- la, Chlamydia, Aeromonas salmonicida, Renibacterium salmoninarum, Candida albicans, Leishmania, Trichomonas vaginalis, Giardia lamblia, Cryptosporidium parvum, Plasmodium falciparum, Entamoeba histolytica, Pneumocystis carinii, Tryanosama rhodesiense/gambiense, Trypanosoma cruzi, and bacteriological weapons such as Bacillus anthracis.
- bacteria such as Listeria monocytogenesor, Klebsiella (K.) ozaenae, K. rhinoscleromatis scleromatis and K. pneumoniae, Staphylococcus aureus, Yersinia ruckeri, Renibacterium salmoni- naram, Vibrio anguillarum, Vibrio cholerae, Vibrio salmonicida, Vibrio viscosus, Edwardsiella ictalari, or fungi such as the yeast Candida albicans, or protozoa such as Leishmania.
- bacteria such as Listeria monocytogenesor, Klebsiella (K.) ozaenae, K. rhinoscleromatis scleromatis and K. pneumoniae, Staphylococcus aureus, Yersinia ruckeri, Renibacterium salmoni- naram, Vibrio anguillarum, Vibrio cholerae, Vibrio salmonicida,
- heterologenous pathogenic organisms are Chlamydia such as Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci, Moraxella catarrhalis, Salmonella enteritides.
- host includes vertebrates such as birds, fishes and mammals, preferably humans.
- the carrier and/or diluent may be in solid or liquid form, and do not exhibit any specific restriction, but should be stabilizing and/or protecting the self-replicating agent, and should have substantially no toxicity for the host.
- the pharmaceutical composition according to the present invention may be used for the treatment of e.g. bacterial, fungal or protozoal infections of the lung such as pneumonia, infections of skin such as eczema, acne, furunkel-boiis, nasal or throat infections, eye infections, infections of internal organs, ear infections or wound infections, in e.g. vertebrates such as mammals preferably in man.
- the invention may be used for the treatment of circulating microorganisms in the circulatory systems such as the blood stream or lymphatic circulation, by use of e.g. infusions.
- the composition according to the present invention can be used for disinfection of e.g.
- the pharmaceutical composition according to the present invention can be applied to a patient without any specific restricton regarding the amount of the self-replicating agent due to its substantial non-toxicity for the host.
- the pharmaceutical composition contains a dosage of 10 3 -10 9 phages/application.
- the formulation of the pharmaceutical composition according to the present invention does not exhibit any specific restriction, and may be prepared e.g. in the form of tablets, suppositories, ointments, solutions, or retarded release- formulations.
- the pharmaceutical composition according to the present invention can be applied e.g. by way of inhalation, topically, orally, systemically, dependent on the formulation, to a patient suffering from an infection disease caused by a heterologeneous pathogenic microorganism.
- the formulation of the pharmaceutical composition can be achieved mixing the self-replicating agents in liquid or solid form with suitable carriers.
- the final mixture can be applied in form of a topically cream, inhalation of a powder or mist, application of suppositories, ointments, infusion solutions, ear drops or eye drops or nose drops or sprays, or using a tape containing said mixture for topical applications.
- a preferred embodiment of the present invention is a formulation as a phage- lyophilisate to be used in a powder inhalator such as the inhalator disclosed in US-patent 5,673,685.
- phage-lyophilisates may be used for the treatment of diseases caused by Klebsiella, Pneumococcus, Staphylococcus, Legionella, Haemophilus influenza, and Moraxella catarrhalis.
- the pharmaceutical composition of the present invention is formulated for topical applications using a substrate such as a bandage (e.g. Tegasorb, 3M) or a tape.
- Such bandages or tapes may be used for the treatment of diseases caused by Klebsiella, Staphylococcus, Streptococcus and Listeria.
- the pharmaceutical composition of the present invention is formulated for oral application using e.g. gelatine capsules in gastric juice- resistant or non-resistant form.
- gelatine capsules may be used for the treatment of diseases caused by Chlamydia, Staphylococcus, Streptococcus, urinary tract infectious agents such as E. coli, Staphylococcus saprophyticus, Proteus mirabiles, Klebsiella and Heliobacter pylori.
- the self-replicating agent preferably the recombinant phage contained in the diagnostic kit according to the present invention can be used for detecting a pathogenic organism in samples derived from living organisms such as a smear, tissue, blood, urine, stool or sputum from a patient, or in samples derived from e.g. soil, air, water or other areas such as fish ponds for fish farming and/or poultry coops for e.g.
- the pathogenic organism contained in the sample will be infected with the recombinant phage having a suitable marker gene such as the gene encoding luciferase, chloramphenicolacetyltransferase (CAT) and green flourescent protein (GFP) upon infection the marker gene will be expressed and can be detected with known methods such as measuring the luminescence generated by the expressed luciferase.
- a suitable marker gene such as the gene encoding luciferase, chloramphenicolacetyltransferase (CAT) and green flourescent protein (GFP)
- pathogenic organisms to be detected are as listed above.
- Preferred examples of pathogenic organisms are Chlamydia such as Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci, Pneumococci, Haemophilus influenza, Staphylococci such as St. aureus, Moraxellae such as M. catarrhalis, Legionellae, Streptococci, Salmonellae such as Salmonella enteritides, Aeromo- nas salmonicida, and bacteriological weapons such as Bacillus anthracis.
- the self-replicating agent can be admixed with any suitable carrier and/or diluent in solid or liquid form, but preferably should stabilize and/or protect the self-replicating agent.
- a further subject of the present invention is a process for the preparation of the above mentioned pharmaceutical composition, comprising the steps of:
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98930692A EP0983077A1 (en) | 1997-05-15 | 1998-05-15 | Pharmaceutical composition and diagnostic kit directed to a heterologeneous pathogenic organism in a host |
CA002289610A CA2289610A1 (en) | 1997-05-15 | 1998-05-15 | Pharmaceutical composition and diagnostic kit directed to a heterologeneous pathogenic organism in a host |
AU81043/98A AU8104398A (en) | 1997-05-15 | 1998-05-15 | Pharmaceutical composition and diagnostic kit directed to a heterologeneous pathogenic organism in a host |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97107945 | 1997-05-15 | ||
EP97107945.4 | 1997-05-15 | ||
EP97114873 | 1997-08-27 | ||
EP97114873.9 | 1997-08-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998051318A1 true WO1998051318A1 (en) | 1998-11-19 |
Family
ID=26145448
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1998/002871 WO1998051318A1 (en) | 1997-05-15 | 1998-05-15 | Pharmaceutical composition and diagnostic kit directed to a heterologeneous pathogenic organism in a host |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0983077A1 (en) |
AU (1) | AU8104398A (en) |
CA (1) | CA2289610A1 (en) |
WO (1) | WO1998051318A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002076483A2 (en) * | 2001-03-28 | 2002-10-03 | Danelia Nodar A | Bacteriophage preparation |
US6479280B1 (en) | 1999-09-24 | 2002-11-12 | Vlaams Interuniversitair Institutuut Voor Biotechnologie Vzw | Recombinant phages capable of entering host cells via specific interaction with an artificial receptor |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4957686A (en) * | 1990-02-06 | 1990-09-18 | Norris Alan H | Use of bacteriophages to inhibit dental caries |
EP0403292A2 (en) * | 1989-06-14 | 1990-12-19 | Microbial Developments Limited | Ruminant feedstuff additives |
EP0414304A2 (en) * | 1989-08-21 | 1991-02-27 | Unilever N.V. | Aqueous antibacterial compositions comprising surfactant and bacteriophage |
SU1685998A1 (en) * | 1989-10-11 | 1991-10-23 | Научно-Производственное Объединение "Бактериофаг" Тбилисского Научно-Исследовательского Института Вакцин И Сывороток | Strain of bacteriophage enterobacter aerogenes for diagnostication, prophylaxis and treatment infection, induced by enterobacter aerogenes |
WO1995027043A1 (en) * | 1994-04-05 | 1995-10-12 | Exponential Biotherapies, Inc. | Antibacterial therapy with genotypically modified bacteriophage |
-
1998
- 1998-05-15 EP EP98930692A patent/EP0983077A1/en not_active Withdrawn
- 1998-05-15 WO PCT/EP1998/002871 patent/WO1998051318A1/en not_active Application Discontinuation
- 1998-05-15 AU AU81043/98A patent/AU8104398A/en not_active Abandoned
- 1998-05-15 CA CA002289610A patent/CA2289610A1/en not_active Abandoned
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0403292A2 (en) * | 1989-06-14 | 1990-12-19 | Microbial Developments Limited | Ruminant feedstuff additives |
EP0414304A2 (en) * | 1989-08-21 | 1991-02-27 | Unilever N.V. | Aqueous antibacterial compositions comprising surfactant and bacteriophage |
SU1685998A1 (en) * | 1989-10-11 | 1991-10-23 | Научно-Производственное Объединение "Бактериофаг" Тбилисского Научно-Исследовательского Института Вакцин И Сывороток | Strain of bacteriophage enterobacter aerogenes for diagnostication, prophylaxis and treatment infection, induced by enterobacter aerogenes |
US4957686A (en) * | 1990-02-06 | 1990-09-18 | Norris Alan H | Use of bacteriophages to inhibit dental caries |
WO1995027043A1 (en) * | 1994-04-05 | 1995-10-12 | Exponential Biotherapies, Inc. | Antibacterial therapy with genotypically modified bacteriophage |
Non-Patent Citations (5)
Title |
---|
DATABASE WPI Section Ch Week 9239, Derwent World Patents Index; Class B04, AN 92-321600, XP002036010 * |
LOESSNER M J ET AL: "Construction of luciferase reporter bacteriophage A511::luxAB for rapid and sensitive detection of viable Listeria cells.", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, (1996 APR) 62 (4) 1133-40, XP002079442 * |
MERRIL C R ET AL: "Long-circulating bacteriophage as antibacterial agents.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 93 (8). 1996. 3188-3192, XP002044135 * |
SMITH H W ET AL: "SUCCESSFUL TREATMENT OF EXPERIMENTAL ESCHERICHIA COLI INFECTIONS IN MICE USING PHAGE: ITS GENERAL SUPERIORITY OVER ANTIBIOTICS", JOURNAL OF GENERAL MICROBIOLOGY, vol. 128, no. PART 02, February 1982 (1982-02-01), pages 307 - 318, XP002036009 * |
SMITH H W ET AL: "THE CONTROL OF EXPERIMENTAL ESCHERICHIA COLI DIARRHOEA IN CALVES BY MEANS OF BACTERIOPHAGES", JOURNAL OF GENERAL MICROBIOLOGY, vol. 133, no. PART 05, May 1987 (1987-05-01), pages 1111 - 1126, XP002036008 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6479280B1 (en) | 1999-09-24 | 2002-11-12 | Vlaams Interuniversitair Institutuut Voor Biotechnologie Vzw | Recombinant phages capable of entering host cells via specific interaction with an artificial receptor |
WO2002076483A2 (en) * | 2001-03-28 | 2002-10-03 | Danelia Nodar A | Bacteriophage preparation |
WO2002076483A3 (en) * | 2001-03-28 | 2003-05-01 | Nodar A Danelia | Bacteriophage preparation |
Also Published As
Publication number | Publication date |
---|---|
AU8104398A (en) | 1998-12-08 |
CA2289610A1 (en) | 1998-11-19 |
EP0983077A1 (en) | 2000-03-08 |
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