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WO1998006861A3 - Administration d'antigenes tolerogeniques via des plantes comestibles ou des produits derives de plantes - Google Patents

Administration d'antigenes tolerogeniques via des plantes comestibles ou des produits derives de plantes Download PDF

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Publication number
WO1998006861A3
WO1998006861A3 PCT/US1997/013634 US9713634W WO9806861A3 WO 1998006861 A3 WO1998006861 A3 WO 1998006861A3 US 9713634 W US9713634 W US 9713634W WO 9806861 A3 WO9806861 A3 WO 9806861A3
Authority
WO
WIPO (PCT)
Prior art keywords
delivery
plant
derived products
edible plants
antigens via
Prior art date
Application number
PCT/US1997/013634
Other languages
English (en)
Other versions
WO1998006861A2 (fr
Inventor
Lisa M Welter
Original Assignee
Agrivax Inc
Lisa M Welter
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 Agrivax Inc, Lisa M Welter filed Critical Agrivax Inc
Priority to CA002263730A priority Critical patent/CA2263730A1/fr
Priority to EP97935275A priority patent/EP0939826A2/fr
Priority to AU38254/97A priority patent/AU3825497A/en
Publication of WO1998006861A2 publication Critical patent/WO1998006861A2/fr
Publication of WO1998006861A3 publication Critical patent/WO1998006861A3/fr

Links

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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
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C07K14/43513—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae
    • C07K14/43531—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae from mites
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K39/0005—Vertebrate antigens
    • A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
    • 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
    • A61K39/35—Allergens
    • 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
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C07K14/43563—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects
    • C07K14/43572—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from insects from bees
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
    • 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
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70539—MHC-molecules, e.g. HLA-molecules
    • 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
    • C07K14/70567—Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
    • 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
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8201—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation
    • C12N15/8206—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation by physical or chemical, i.e. non-biological, means, e.g. electroporation, PEG mediated
    • C12N15/8207—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation by physical or chemical, i.e. non-biological, means, e.g. electroporation, PEG mediated by mechanical means, e.g. microinjection, particle bombardment, silicon whiskers
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
    • C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
    • C12N15/8257—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
    • C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
    • C12N15/8257—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon
    • C12N15/8258—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits for the production of primary gene products, e.g. pharmaceutical products, interferon for the production of oral vaccines (antigens) or immunoglobulins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Insects & Arthropods (AREA)
  • Plant Pathology (AREA)
  • Mycology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Rheumatology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Diabetes (AREA)

Abstract

L'invention concerne l'expression d'auto-antigènes et d'allergènes dans des plantes transgéniques et les plantes, ou des produits qui en sont dérivés, utilisées sous forme de produits alimentaires ou de boissons pour prévenir ou traiter des maladies auto-immunitaires ou des réactions allergiques.
PCT/US1997/013634 1996-08-15 1997-08-05 Administration d'antigenes tolerogeniques via des plantes comestibles ou des produits derives de plantes WO1998006861A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CA002263730A CA2263730A1 (fr) 1996-08-15 1997-08-05 Administration d'antigenes tolerogeniques via des plantes comestibles ou des produits derives de plantes
EP97935275A EP0939826A2 (fr) 1996-08-15 1997-08-05 Administration d'antigenes tolerogeniques via des plantes comestibles ou des produits derives de plantes
AU38254/97A AU3825497A (en) 1996-08-15 1997-08-05 Delivery of tolerogenic antigens via edible plants or plant-derived products

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2397396P 1996-08-15 1996-08-15
US60/023,973 1996-08-15

Publications (2)

Publication Number Publication Date
WO1998006861A2 WO1998006861A2 (fr) 1998-02-19
WO1998006861A3 true WO1998006861A3 (fr) 1998-05-14

Family

ID=21818189

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/013634 WO1998006861A2 (fr) 1996-08-15 1997-08-05 Administration d'antigenes tolerogeniques via des plantes comestibles ou des produits derives de plantes

Country Status (4)

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EP (1) EP0939826A2 (fr)
AU (1) AU3825497A (fr)
CA (1) CA2263730A1 (fr)
WO (1) WO1998006861A2 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2757874B1 (fr) * 1996-12-17 2003-04-25 Biocem Collagenes recombinants et proteines derivees produits par les plantes, leurs procedes d'obtention et leurs utilisations
FR2759857B1 (fr) * 1997-02-27 1999-04-30 Biocem Nouvelles utilisations de la sterilite male chez les plantes
DE19834909A1 (de) * 1998-08-03 2000-02-17 Mpb Cologne Gmbh Molecular Pla Faserproteine und ihre Herstellung
CA2344269A1 (fr) * 1998-10-07 2000-04-13 Syngenta Participations Ag Proteines vegetales a action therapeutique
US20020009452A1 (en) * 1999-02-10 2002-01-24 Michael Caplan Method for altering undesirable immune responses to polypeptides
WO2001077353A2 (fr) * 2000-04-05 2001-10-18 Syngenta Participations Ag Proteines therapeutiquement actives dans des vegetaux
FR2841906B1 (fr) * 2002-07-05 2006-08-18 Stallergenes Sa Molecule d'acide nucleique codant une preproproteine d'allergene d'un acarien du genre dermatophagoides ou euroglyphus et son utilisation pour la production dudit allergene dans les plantes
AU2004222243A1 (en) * 2003-03-18 2004-09-30 Rutgers, The State University Improved plant transformation

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990008161A1 (fr) * 1989-01-12 1990-07-26 The Blood Center Of Southeastern Wisconsin Modulation par peptides mediateurs de la reconnaissance d'antigenes par les lymphocytes t, utilises comme moyens d'affectation de reactions immunitaires
WO1992006708A1 (fr) * 1990-10-15 1992-04-30 Brigham And Women's Hospital Traitement de maladies auto-immunes par administration orale d'auto-antigenes
WO1994020135A1 (fr) * 1993-03-04 1994-09-15 Edible Vaccines Inc. Vaccins exprimes dans des plantes
WO1995008347A1 (fr) * 1993-09-21 1995-03-30 London Health Association Procedes et produits destines a la regulation de reponses immunes chez les mammiferes
WO1995027500A1 (fr) * 1994-04-08 1995-10-19 Brigham And Women's Hospital TRAITEMENT DE MALADIES AUTO-IMMUNES AVEC DES AGENTS D'INDUCTION DE TOLERANCE ET/OU DES CYTOKINES DE RENFORCEMENT DES Th2 ADMINISTRES PAR VOIE ORALE
WO1995028424A1 (fr) * 1994-04-14 1995-10-26 Immulogic Pharmaceutical Corporation Formulations pharmaceutiques a base de peptides utiles pour traiter l'allergie aux acariens detriticoles
WO1995030435A2 (fr) * 1994-05-10 1995-11-16 Immulogic Pharmaceutical Corporation Compositions et traitement de la sclerose en plaques
WO1996012737A2 (fr) * 1994-10-25 1996-05-02 Immulogic Pharmaceutical Corporation Compositions et traitement pour la sclerose en plaques
WO1996040229A1 (fr) * 1995-06-07 1996-12-19 Thomas Jefferson University Vaccins synthetises a l'aide de plantes transgeniques

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990008161A1 (fr) * 1989-01-12 1990-07-26 The Blood Center Of Southeastern Wisconsin Modulation par peptides mediateurs de la reconnaissance d'antigenes par les lymphocytes t, utilises comme moyens d'affectation de reactions immunitaires
WO1992006708A1 (fr) * 1990-10-15 1992-04-30 Brigham And Women's Hospital Traitement de maladies auto-immunes par administration orale d'auto-antigenes
WO1994020135A1 (fr) * 1993-03-04 1994-09-15 Edible Vaccines Inc. Vaccins exprimes dans des plantes
WO1995008347A1 (fr) * 1993-09-21 1995-03-30 London Health Association Procedes et produits destines a la regulation de reponses immunes chez les mammiferes
WO1995027500A1 (fr) * 1994-04-08 1995-10-19 Brigham And Women's Hospital TRAITEMENT DE MALADIES AUTO-IMMUNES AVEC DES AGENTS D'INDUCTION DE TOLERANCE ET/OU DES CYTOKINES DE RENFORCEMENT DES Th2 ADMINISTRES PAR VOIE ORALE
WO1995028424A1 (fr) * 1994-04-14 1995-10-26 Immulogic Pharmaceutical Corporation Formulations pharmaceutiques a base de peptides utiles pour traiter l'allergie aux acariens detriticoles
WO1995030435A2 (fr) * 1994-05-10 1995-11-16 Immulogic Pharmaceutical Corporation Compositions et traitement de la sclerose en plaques
WO1996012737A2 (fr) * 1994-10-25 1996-05-02 Immulogic Pharmaceutical Corporation Compositions et traitement pour la sclerose en plaques
WO1996040229A1 (fr) * 1995-06-07 1996-12-19 Thomas Jefferson University Vaccins synthetises a l'aide de plantes transgeniques

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BRINER, T.J., ET AL.: "PERIPHERAL T-CELL TOLERANCE INDUCED IN NAIVE AND PRIMED MICE BY SUBCUTANEOUS INJECTION OF PEPTIDES FROM MAJOR CAT ALLERGEN FEL d1", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE USA, vol. 90, August 1993 (1993-08-01), pages 7608 - 7612, XP002056822 *
GRIFFITH I J ET AL: "EXPRESSION AND GENOMIC STRUCTURE OF THE GENES ENCODING FDI, THE MAJOR ALLERGEN FROM THE DOMESTIC CAT", GENE, vol. 113, 1992, pages 263 - 268, XP002033869 *
MA, S.-W., ET AL.: "TRANSGENIC PLANTS EXPRESSING AUTOANTIGENS FED TO MICE TO INDUCE ORAL IMMUNE TOLERANCE", NATURE MEDICINE, vol. 3, no. 7, July 1997 (1997-07-01), pages 793 - 796, XP002056824 *
MASON H S ET AL: "TRANSGENIC PLANTS AS VACCINE PRODUCTION SYSTEMS", TRENDS IN BIOTECHNOLOGY, vol. 13, no. 9, September 1995 (1995-09-01), pages 388 - 392, XP002024035 *
MUELLER U ET AL: "SUCCESFUL IMMUNOTHERAPY WITH T-CELL EPITOPES OF BEE VENOM PHOSPHOLIPASE A2 (PLA) IN PATIENTS WITH BEE VENOM (BV) ALLERGY", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 97, no. 1, PART 03, January 1996 (1996-01-01), pages 426, XP002035179 *
SAYEGH, M.H., ET AL .: "INDUCTION OF IMMUNITY AND ORAL TOLERANCE WITH POLYMORPHIC CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX ALLOPEPTIDES IN THE RAT", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE USA, vol. 89, August 1992 (1992-08-01), pages 7762 - 7766, XP002056823 *

Also Published As

Publication number Publication date
WO1998006861A2 (fr) 1998-02-19
AU3825497A (en) 1998-03-06
CA2263730A1 (fr) 1998-02-19
EP0939826A2 (fr) 1999-09-08

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