CA2234941A1 - Delivery of biologically active polypeptides - Google Patents

Delivery of biologically active polypeptides

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Publication number
CA2234941A1
CA2234941A1 CA002234941A CA2234941A CA2234941A1 CA 2234941 A1 CA2234941 A1 CA 2234941A1 CA 002234941 A CA002234941 A CA 002234941A CA 2234941 A CA2234941 A CA 2234941A CA 2234941 A1 CA2234941 A1 CA 2234941A1
Authority
CA
Canada
Prior art keywords
biologically active
invasive
active polypeptides
nucleic acid
bacterium
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.)
Granted
Application number
CA002234941A
Other languages
French (fr)
Other versions
CA2234941C (en
Inventor
Lothar Steidler
Erik Remaut
Jeremy Mark Wells
Richard William Falla Le Page
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.)
Intrexon Actobiotics NV
Original Assignee
Cambridge University Technical Services Limited
Lothar Steidler
Erik Remaut
Jeremy Mark Wells
Richard William Falla Le Page
Actogenix Nv
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 Cambridge University Technical Services Limited, Lothar Steidler, Erik Remaut, Jeremy Mark Wells, Richard William Falla Le Page, Actogenix Nv filed Critical Cambridge University Technical Services Limited
Publication of CA2234941A1 publication Critical patent/CA2234941A1/en
Application granted granted Critical
Publication of CA2234941C publication Critical patent/CA2234941C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/55—IL-2
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • 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
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5412—IL-6
    • 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, e.g. protozoa; 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
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • 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
    • 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
    • C12N15/746—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for lactic acid bacteria (Streptococcus; Lactococcus; Lactobacillus; Pediococcus; Enterococcus; Leuconostoc; Propionibacterium; Bifidobacterium; Sporolactobacillus)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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

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

Abstract

The present invention relates to a use of non-invasive or non--pathogenic bacterium for delivering a polypeptide to a subject in need thereof, especially a Gram-positive bacterium, which expresses said polypeptide in situ. The invention further relates to pharmaceutical formulations comprising said bacterium and to methods for producing the pharmaceutical formulations.

Claims (54)

1. A method of delivering one or more biologically active polypeptides which comprises administering to a subject a non-invasive or non-pathogenic bacterium which expresses said one or more polypeptides.
2. A method of delivering one or more antigens which comprises administering to a subject a non-invasive or non-pathogenic bacterium which expresses said one or more antigens.
3. A method of delivering one or more antigens and/or one or more biologically active polypeptides which comprises administering to a subject a non-invasive or non-pathogenic bacterium which expresses both said one or more antigens and said one or more heterologous biologically active polypeptides.
4. A method as claimed in claim 1 or claim 3 wherein the one or more biologically active polypeptides is/are heterologous to the bacterium.
5. A method as claimed in claim 4 wherein at least one of the heterologous polypeptides is derived from a eukaryote or its virus.
6. A method as claimed in claim 4 wherein at least one of the heterologous polypeptides is derived from a prokaryote or its virus or from a virus homologous to the bacterial species.
7. A method as claimed in any one of claims 1 to 6 wherein the bacterium is a-Gram-positive bacterium.
8. A method as claimed in claim 7 wherein the Gram-positive bacterium is Listeria innocua, Staphylococcus xylosus, Staphylococcus carnosus, Streptococcus gordoni, a Lactococcus species or a Lactobacillus species.
9. A method as claimed in claim 8 wherein the Gram-positive bacterium is Lactococcus lactis.
10. A method as claimed in claim 7 wherein the bacterium is an attenuated strain of a Gram-positive pathogenic bacterium.
11. A method as claimed in claim 10 wherein the bacterium is Listeria monocytogenes.
12. A method as claimed in any one of claims 5 to 11 wherein the one or more biologically active polypeptides is/are one(s) which is/are capable of functioning locally or systemically,eg is a polypeptide capable of exerting endocrine activities affecting local or whole-body metabolism.
13. A method as claimed in any one of claims 5 to 11 wherein the one or more biologically active polypeptides is/are one(s) which is/are capable of the regulation of the activities of cells belonging to the immunohaemopoeitic system.
14. A method as claimed in any one of claims 5 to 11 wherein the one or more biologically active polypeptides is/are one(s) which is/are capable of affecting the viability, growth and differentiation of a variety of normal or neoplastic cells in the body or affecting the immune regulation or induction of acute phase inflammatory responses to injury and infection.
15. A method as claimed in any one of claims 5 to 11 wherein the one or more biologically active polypeptides is/are one(s) which is/are capable of enhancing or inducing resistance to infection of cells and tissues mediated by chemokines acting on their target cell receptors, or the proliferation of epithelial cells or the promotion of wound healing.
16. A method as claimed in any one of claims 5 to 11 wherein the one or more biologically active polypeptides modulates the expression or production of substances by cells in the body.
17. A method as claimed in any one of claims 12 to 16 wherein the one or more biologically active polypeptides is/are insulin, growth hormone, prolactin, calcitonin, luteinising hormone, parathyroid hormone, somatostatin, thyroid stimulating hormone or vasoactive intestinal polypeptide.
18. A method as claimed in any one of claims 12 to 16 wherein the one or more biologically active polypeptides is/are a structural group 1 cytokine adopting an antiparallel 4.alpha. helical bundle structure such as IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-11, IL-12, IL-13, GM-CSF, M-CSF, SCF, IFN-.gamma., EPO, G-CSF, LIF, OSM, CNTF, GH, PRL or IFN.alpha./.beta..
19. A method as claimed in any one of claims 12 to 16 wherein the one or more biologically active polypeptides is/are a structural group 2 cytokine which are often cell-surface asociated, form symetric homotrimers and the subunits take up the conformation of .beta.-jelly roll described for certain viral coat proteins such as the TNF family of cytokines, eg TNF.alpha., TNF.beta., CD40, CD27 or FAS ligands, the IL-1 family of cytokines, the fibroblast growth factor family, the platelet derived growth factors, transforming growth factor .beta. and nerve growth factors.
20. A method as claimed in any one of claims 12 to 16 wherein the one or more biologically active polypeptides is/are a structural group 3 cytokine comprising short chain .alpha./.beta. molecules, which are produced as large transmembrane pre-cursor molecules which each contain at least one EGF domain in the extracellular region, eg the epidermal growth factor family of cytokines, the chemokines characterised by their possession of amino acid sequences grouped around conserved cysteine residues (the C-C or C-X-C chemokine subgroups) or the insulin related cytokines.
21. A method as claimed in any one of claims 12 to 16 wherein the one or more biologically active polypeptides is/are a structural group 4 cytokine which exhibit mosaic structures such as the heregulins or neuregulins composed of different domains, eg EGF, immunoglobulin-like and kringle domains.
22. A method as claimed in any one of claims 12 to 16 wherein the one or more biologically active polypeptides is/are a receptor or antagonist for biologically active polypeptides as defined in any one of claims 10 to 19.
23. A method of regulating the survival, growth, differentiation, effector functions or susceptibility to infection of cells or tissues which comprises administering to a subject a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11.
24. A method of boosting an immune response against tumour cells or an infection colonising a mucosal surface or adjacent or distant tissue which comprises administering to a subject a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11.
25. A method of modulating the type of immune response (antibody versus cell-mediated) against a pathogenic infectious agent which comprises administering to a subject a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11.
26. A method of modulating the infiltration of normal tissues with inflammatory or tumour cells which comprises administering to a subject a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11.
27. A method of controlling the rate of growth, rate of invasion or survival of tumour cells which comprises administering to a subject a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11.
28. A method of inducing apoptosis in tumour cells which comprises administering to a subject a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11.
29. A method as claimed in any one of claims 23 to 28 modified by any one or more of the features of claims 12 to 22
30. A method of downregulating an immune response which comprises administering to a subject a non-invasive or non-pathogenic bacterium which expresses a biologically active polypeptide.
31. A method of treating an allergic autoimmune or other immune dysregulative disease state, which comprises administering to a subject a non-invasive or non-pathogenic bacterium which expresses a biologically active polypeptide.
32. A method as claimed in claim 30 or claim 31 modified by any one or more of the features of claims 7 to 22.
33. A pharmaceutical formulation comprising a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11, optionally together with one or more pharmaceutically acceptable excipients, adjuvants, carriers, or the like.
34. A pharmaceutical formulation as claimed in claim 33 which is a vaccine formulation.
35. A pharmaceutical formulation as claimed in claim 33 or claim 34 modified by any one or more of the features of claims 12 to 22.
36. A method of producing a pharmaceutical formulation as defined in any one of claims 33 to 35 which comprises the step of admixing one or more non-invasive or non-pathogenic bacteria as defined in any one of claims 1 to 11 with one or more pharmaceutically acceptable carriers.
37. Nucleic acid comprising one or more coding sequences for one or more biologically active polypeptides and one or more coding sequences for one or more antigens wherein each coding sequence is under the control of a promoter for expression in a non-invasive or non-pathogenic bacterium.
38. Nucleic acid as claimed in claim 37 modified by one or more of the features of claims 7 to 22.
39. Nucleic acid as claimed in claim 37 or claim 38 which comprises one or more nucleic acid constructs in which the nucleic acid encoding the one or more biologically active polypeptides and/or the nucleic acid encoding the one or more antigens are under the control of appropriate regulatory sequences.
40. Nucleic acid as claimed in claim 39 wherein the appropriate regulatory sequences are selected from promoter sequences, terminator fragments, enhancer sequences and marker genes.
41. Nucleic acid as claimed in claim 39 or claim 40 wherein the one or more nucleic acid constructs comprise an artificial operon capable of generating a polycistronic RNA transcript.
42. Nucleic acid as claimed in any one of claims 37 to 41 wherein the promoter is a Lactococcal promoter for use in Lactococcus lactis.
43. Nucleic acid as claimed in any one of claims 37 to 42 which further comprises a secretory signal sequence, upstream of the coding sequence(s) for the one or more biologically active polypeptides.
44. Nucleic acid as claimed in claim 43 wherein the secretory signal sequence is the .alpha.-amylase secretion leader of Bacillus amyloliquefaciens, the secretion leader of the Staphylokinase enzyme, leader sequences for other Bacillus enzymes or S-layer proteins or the leader sequence of the Lactococcal protein Usp45.
45. Nucleic acid as claimed in any one of claims 37 to 44 wherein the antigen(s) is/are antigen(s) capable of eliciting a protective immune response.
46. Nucleic acid as claimed in any one of claims 37 to 44 wherein the antigen(s) is/are ones where a protective immune response is accelerated, amplified or rendered of longer duration in the presence of one or more coexpressed biologically active polypeptides as defined in any one of claims 12 to 22.
47. The use of nucleic acid as defined in any one of claims 37 to 46 in the transformation of a non-invasive or non-pathogenic bacterium, eg Lactococcus lactis.
48. A method of generating a bacterium as defined in any one of claims 1 to 11 comprising the step of introducing into a non-invasive or non-pathogenic bacterial host cell nucleic acid as defined in any one of claims 37 to 46.
49. A non-invasive or non-pathogenic bacterium expressing (i) one or more heterologous biologically active polypeptides and (ii) one or more antigens.
50. A non-invasive or non-pathogenic bacterium as claimed in claim 49 modified by any one or more of the features of claims 7 to 22.
51. A non-invasive or non-pathogenic bacterium as claimed in claim 49 or claim 50 which comprises nucleic acid as defined in any one claims 37 to 46.
52. A non-invasive or non-pathogenic bacterium as defined in any one of claims 49 to 51 for use in medicine.
53. The use of a non-invasive or non-pathogenic bacterium as defined in any one of claims 1 to 11 or one which comprises nucleic acid as defined in any one of claims 37 to 46 in the manufacture of an agent for the delivery of one or more biologically active polypeptides and/or one or more antigens.
54. The use as claimed in claim 53 modified by any one or more of the features of claims 23 to 32.
CA2234941A 1995-10-20 1996-10-21 Delivery of biologically active polypeptides Expired - Lifetime CA2234941C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9521568.7A GB9521568D0 (en) 1995-10-20 1995-10-20 Delivery of biologically active polypeptides
GB9521568.7 1995-10-20
PCT/GB1996/002580 WO1997014806A2 (en) 1995-10-20 1996-10-21 Delivery of biologically active polypeptides

Publications (2)

Publication Number Publication Date
CA2234941A1 true CA2234941A1 (en) 1997-04-24
CA2234941C CA2234941C (en) 2010-09-21

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ID=10782670

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CA2234941A Expired - Lifetime CA2234941C (en) 1995-10-20 1996-10-21 Delivery of biologically active polypeptides

Country Status (17)

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US (2) US6605286B2 (en)
EP (1) EP0871748B1 (en)
JP (2) JP2000508162A (en)
KR (1) KR19990064308A (en)
CN (1) CN1195860C (en)
AT (1) ATE435294T1 (en)
AU (1) AU7315496A (en)
BR (1) BR9610929A (en)
CA (1) CA2234941C (en)
DE (1) DE69637961D1 (en)
DK (1) DK0871748T3 (en)
ES (1) ES2328751T3 (en)
GB (1) GB9521568D0 (en)
NO (1) NO328224B1 (en)
NZ (1) NZ320418A (en)
WO (1) WO1997014806A2 (en)
ZA (1) ZA968806B (en)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9521568D0 (en) * 1995-10-20 1995-12-20 Lynxvale Ltd Delivery of biologically active polypeptides
WO1999007839A2 (en) * 1997-08-05 1999-02-18 Vlaams Interuniversitair Instituut Voor Biotechnologie Immunoprotective influenza antigen and its use in vaccination
US6080849A (en) * 1997-09-10 2000-06-27 Vion Pharmaceuticals, Inc. Genetically modified tumor-targeted bacteria with reduced virulence
CN1253551C (en) * 1997-09-10 2006-04-26 维昂药品公司 Genetically modified tumor-targeted bacteria with reduced virulence
EP1123314B1 (en) * 1998-10-20 2004-02-18 Vlaams Interuniversitair Instituut voor Biotechnologie vzw. Use of a cytokine-producing lactococcus strain to treat colitis
FR2791998B1 (en) * 1999-04-07 2001-06-08 Agronomique Inst Nat Rech MODIFIED LACTOCOCCUS EXPRESSING CATALASE AND USES THEREOF
ATE342983T1 (en) 1999-07-05 2006-11-15 Vlaams Interuniv Inst Biotech PROVISION OF PEPTIDES WITH CLOVER LEAF STRUCTURE
US6962696B1 (en) * 1999-10-04 2005-11-08 Vion Pharmaceuticals Inc. Compositions and methods for tumor-targeted delivery of effector molecules
DE60227498D1 (en) 2001-03-23 2008-08-21 Advanced Bionutrition Corp DISTRIBUTION OF AGENTS FOR THE CONTROL OF AFFECTS IN AQUACULTURE USING BIOACTIVE PROTEINS CONTAINING YEAST
US7780961B2 (en) 2001-05-03 2010-08-24 Actogenix N.V. Self-containing Lactococcus strain
EP1513545B1 (en) 2002-06-19 2008-03-19 Actogenix N.V. Methods and means to promote gut absorption
CA2489142C (en) * 2002-06-20 2013-11-26 Paul Francis Mckee Distributed computer
US20050129711A1 (en) * 2002-11-14 2005-06-16 Janakiraman Ramachandran Incapacitated whole-cell immunogenic bacterial compositions produced by recombinant expression
WO2004046346A2 (en) * 2002-11-15 2004-06-03 Vib Vzw Self-containing lactobacillus strain
GB0230331D0 (en) * 2002-12-31 2003-02-05 British Telecomm Method and apparatus for operating a computer network
CA2515298C (en) * 2003-02-06 2014-04-08 Cerus Corporation Modified free-living microbes, vaccine compositions and methods of use thereof
EP1592441B1 (en) * 2003-02-06 2012-04-11 Aduro Biotech Listeria attenuated for entry into non-phagocytic cells, vaccines comprising the listeria, and methods of use thereof
US7695725B2 (en) 2003-02-06 2010-04-13 Aduro Biotech Modified free-living microbes, vaccine compositions and methods of use thereof
EP1599170B1 (en) * 2003-02-21 2013-01-16 Hasumi Llc (Dba Shukokai International) Human lymphocyte vaccine adjuvant
US20070298012A1 (en) * 2003-12-16 2007-12-27 Ivan King Compositions and Methods for Tumor-Targeted Delivery of Effector Molecules
GB0412655D0 (en) * 2004-06-07 2004-07-07 British Telecomm Distributed storage network
US9200249B2 (en) 2004-08-20 2015-12-01 Actogenix N.V. Method to improve Lactococcus preservation
ATE511848T1 (en) 2004-08-25 2011-06-15 Us Gov Health & Human Serv LIVE MICROBIAL MICROBICIDES
KR20070057864A (en) 2004-08-26 2007-06-07 더 유니버시티 오브 웨스턴 온타리오 Pharmaceutical compositions comprising inhibitors of iron transport, and method of identifying iron transport inhibitors, fn staphylococcus aureus
EP1871868A2 (en) 2005-04-15 2008-01-02 North Carolina State University Methods and compositions to modulate adhesion and stress tolerance in bacteria
BRPI0615593A2 (en) * 2005-08-30 2011-05-24 Commw Scient And Ind Reseaech Organisation bacterial release of biologically active polypeptides
JP5049973B2 (en) * 2005-08-30 2012-10-17 アクトジェニックス・エヌブイ Anti-TNFα producing lactic acid bacteria for the treatment of chronic enterocolitis
CA2631598C (en) 2005-11-29 2017-06-27 Actogenix Nv Induction of mucosal tolerance to antigens
US8734823B2 (en) * 2005-12-14 2014-05-27 The Invention Science Fund I, Llc Device including altered microorganisms, and methods and systems of use
US8278094B2 (en) 2005-12-14 2012-10-02 The Invention Science Fund I, Llc Bone semi-permeable device
US20110182859A1 (en) * 2010-01-22 2011-07-28 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Compositions and methods for therapeutic delivery with microorganisms
US20110172826A1 (en) * 2005-12-14 2011-07-14 Amodei Dario G Device including altered microorganisms, and methods and systems of use
US8682619B2 (en) * 2005-12-14 2014-03-25 The Invention Science Fund I, Llc Device including altered microorganisms, and methods and systems of use
JP2009535380A (en) 2006-05-02 2009-10-01 アクトジェニックス・エヌブイ Microbial intestinal delivery of obesity-related peptides
US20080124355A1 (en) 2006-09-22 2008-05-29 David Gordon Bermudes Live bacterial vaccines for viral infection prophylaxis or treatment
US20100303777A1 (en) * 2006-12-14 2010-12-02 Actogenix N.V. Delivery of binding molecules to induce immunomodulation
US8759088B2 (en) 2007-01-12 2014-06-24 Actogenix N.V. Lactococcus promoters and uses thereof
JP2010516269A (en) 2007-01-25 2010-05-20 アクトジェニックス・エヌブイ Treatment of immune diseases by mucosal delivery of antigen
EP2344626B1 (en) 2008-09-29 2017-03-29 Intrexon Actobiotics NV Reduced colonization of microbes at the mucosa
US8241623B1 (en) 2009-02-09 2012-08-14 David Bermudes Protease sensitivity expression system
KR101821417B1 (en) 2009-04-30 2018-01-23 인트랙슨 액토바이오틱스 엔.브이. Cryoprotectants for freeze drying of lactic acid bacteria
EP2275527A1 (en) 2009-07-17 2011-01-19 ActoGeniX NV Animal component-free culture medium for bacterial fermentation
EP3192873A1 (en) 2009-09-29 2017-07-19 Intrexon Actobiotics NV Lactobacillus and streptococcus promoters and uses thereof
EP2343319A1 (en) 2010-01-07 2011-07-13 University of Ljubljana Genetically modified food grade microorganism for treatment of inflammatory bowel disease
US8524220B1 (en) 2010-02-09 2013-09-03 David Gordon Bermudes Protease inhibitor: protease sensitivity expression system composition and methods improving the therapeutic activity and specificity of proteins delivered by bacteria
US9597379B1 (en) 2010-02-09 2017-03-21 David Gordon Bermudes Protease inhibitor combination with therapeutic proteins including antibodies
US8771669B1 (en) 2010-02-09 2014-07-08 David Gordon Bermudes Immunization and/or treatment of parasites and infectious agents by live bacteria
JP2013530187A (en) 2010-06-17 2013-07-25 ザ ユナイテッド ステイツ オブ アメリカ アズ リプレゼンティッド バイ ザ シークレタリー デパートメント オブ ヘルス アンド ヒューマン サービシーズ Compositions and methods for treating inflammatory diseases.
CN101921725B (en) * 2010-07-27 2013-06-05 浙江大学 Converter for inhibiting hen somatostatin action through oral immunization and application thereof
JP5991650B2 (en) * 2010-08-10 2016-09-14 国立研究開発法人農業・食品産業技術総合研究機構 Porcine erysipelas expressing cytokines and delivery method of cytokines using swine erysipelas
RU2644346C2 (en) 2011-06-01 2018-02-08 Интрексон Актобиотикс Н.В. System of polycistronic expression for bacteria
ES2676707T3 (en) 2011-09-23 2018-07-24 Intrexon Actobiotics Nv Modified gram positive bacteria and their uses
DK2758513T3 (en) 2011-09-23 2018-07-23 Intrexon Actobiotics Nv MODIFIED GRAM POSITIVE BACTERIES AND APPLICATIONS THEREOF
MX2015001751A (en) 2012-08-07 2015-11-13 Topgenix Inc Topical composition comprising transformed bacteria expressing a compound of interest.
US9593339B1 (en) 2013-02-14 2017-03-14 David Gordon Bermudes Bacteria carrying bacteriophage and protease inhibitors for the treatment of disorders and methods of treatment
JP6088648B2 (en) * 2013-06-11 2017-03-01 ハウスウェルネスフーズ株式会社 Carrier that delivers substances to phagocytic cells
US10064797B2 (en) 2014-06-17 2018-09-04 TopGeniX, Inc. Topical formulations for UV protection
EP3020816A1 (en) * 2014-11-11 2016-05-18 University College Cork Bacterial mediated gene therapy
CN104476458B (en) * 2014-11-14 2016-08-17 中黔电气集团股份有限公司 A kind of low-voltage cabinet skeleton assembly or fitting table of band automatic clamping mechanism
AU2015370982B2 (en) 2014-12-23 2019-03-21 Ilya Pharma Ab Methods for wound healing
US10676723B2 (en) 2015-05-11 2020-06-09 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
CA3011331A1 (en) 2016-01-14 2017-07-20 Intrexon Actobiotics N.V. Compositions and methods for the treatment of type 1 diabetes
US11180535B1 (en) 2016-12-07 2021-11-23 David Gordon Bermudes Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria
US11129906B1 (en) 2016-12-07 2021-09-28 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
KR102015116B1 (en) * 2018-05-04 2019-10-21 (주)메디톡스 Extracellular vesicle isolated from recombinant microorganism comprising polynucleotide encoding target protein and use thereof
KR102553825B1 (en) * 2018-05-04 2023-07-13 (주)메디톡스 Extracellular vesicle isolated from recombinant microorganism comprising polynucleotide encoding target protein and use thereof
AU2019433065B2 (en) 2019-03-04 2022-08-18 Aurealis Therapeutics AG Chloride-inducible prokaryotic expression system

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4874702A (en) * 1980-09-08 1989-10-17 Biogen, Inc. Vectors and methods for making such vectors and for expressive cloned genes
US5417986A (en) * 1984-03-16 1995-05-23 The United States Of America As Represented By The Secretary Of The Army Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres
US5032510A (en) * 1984-09-26 1991-07-16 Eli Lilly And Company Method for expression and secretion in bacillus
EP0176320B1 (en) * 1984-09-26 1990-07-25 Eli Lilly And Company A method for expression and secretion in bacillus
US5504005A (en) * 1987-03-02 1996-04-02 Albert Einstein College Of Medicine Of Yeshiva University Recombinant mycobacterial vaccine
US5591632A (en) * 1987-03-02 1997-01-07 Beth Israel Hospital Recombinant BCG
US5330753A (en) * 1987-04-29 1994-07-19 President And Fellows Of Harvard College Cholera vaccines
US6130082A (en) * 1988-05-05 2000-10-10 American Cyanamid Company Recombinant flagellin vaccines
US5149532A (en) * 1989-11-01 1992-09-22 Cedars Sinai Medical Center Method of vaccine or toxoid preparation and immunization by colonization with recombinant microorganisms
GB9006400D0 (en) * 1990-03-22 1990-05-23 Ciba Geigy Ag Bacterial vectors
IL99097A0 (en) * 1990-09-05 1992-07-15 Akzo Nv Haemophilus paragallinarum vaccine
CA2099841C (en) * 1991-03-05 2003-02-25 Ian G. Charles Expression of recombinant proteins in attenuated bacteria
IL103530A0 (en) * 1991-10-25 1993-03-15 Duphar Int Res Treponema hyodysenteriae vaccine
CA2130453A1 (en) * 1992-02-27 1993-09-02 Richard W. F. Le Page Heterologous gene expression in lactococcus, and the expression products threrefrom
US5455034A (en) * 1992-06-26 1995-10-03 Kansas State University Research Foundation Fusobacterium necrophorum leukotoxoid vaccine
US5837509A (en) * 1992-12-30 1998-11-17 Bioteknologisk Institut Recombinant lactic acid bacterium containing an inserted promoter and method of constructing same
IT1270123B (en) * 1994-10-05 1997-04-28 Dompe Spa PHARMACEUTICAL COMPOSITIONS CONTAINING ENGINEERED MICROORGANISMS AND THEIR USE FOR THERAPY
US5733540A (en) * 1995-03-08 1998-03-31 Lee; Peter Poon-Hang Protection from viral infection via colonization of mucosal membranes with genetically modified bacteria
US5824538A (en) * 1995-09-06 1998-10-20 The United States Of America As Represented By The Secretary Of The Army Shigella vector for delivering DNA to a mammalian cell
GB9518323D0 (en) * 1995-09-07 1995-11-08 Steidler Lothar Materials and methods relating to the attachment and display of substances on cell surfaces
GB9521568D0 (en) * 1995-10-20 1995-12-20 Lynxvale Ltd Delivery of biologically active polypeptides
JP2000510332A (en) * 1996-04-19 2000-08-15 ヘンリー エム．ジャクソン ファンデーション フォー ザ アドバンスメント オブ ミリタリー メディシン Methods of stimulating an immune response by administering a host organism expressing intimin alone or as a fusion protein with one or more other antigens
US6685943B1 (en) * 1997-01-21 2004-02-03 The Texas A&M University System Fibronectin binding protein compositions and methods of use
ATE346931T1 (en) * 1997-06-20 2006-12-15 Intervet Int Bv CLOSTRIDIUM PERFRINGENS VACCINE
US6100388A (en) * 1998-03-16 2000-08-08 Biogaia Biologies Ab Lactobacilli harboring aggregation gene as a vaccine delivery vehicle
US6190669B1 (en) * 1998-05-13 2001-02-20 University Of Maryland, Baltimore Attenuated mutants of salmonella which constitutively express the Vi antigen
EP1123314B1 (en) * 1998-10-20 2004-02-18 Vlaams Interuniversitair Instituut voor Biotechnologie vzw. Use of a cytokine-producing lactococcus strain to treat colitis
ATE449861T1 (en) * 2000-10-20 2009-12-15 Bioneer As METHOD FOR THE FERMENTATIVE PRODUCTION OF HETEROLOGUE GENE PRODUCTS IN LACTIC ACID BACTERIA
US7425449B2 (en) * 2002-04-30 2008-09-16 The Regents Of The University Of California Site specific Listeria integration vectors and methods for using the same

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