WO1998006746A2 - Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same - Google Patents

Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same Download PDF

Info

Publication number
WO1998006746A2
WO1998006746A2 PCT/US1997/012868 US9712868W WO9806746A2 WO 1998006746 A2 WO1998006746 A2 WO 1998006746A2 US 9712868 W US9712868 W US 9712868W WO 9806746 A2 WO9806746 A2 WO 9806746A2
Authority
WO
WIPO (PCT)
Prior art keywords
melanoma
cell line
antigens
cells
melanoma cell
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.)
Ceased
Application number
PCT/US1997/012868
Other languages
English (en)
French (fr)
Other versions
WO1998006746A3 (en
Inventor
Drew M. Pardoll
Elizabeth M. Jaffee
Adam Adler
Suzanne L. Topalian
Steven A. Rosenberg
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.)
Johns Hopkins University
US Department of Health and Human Services
Original Assignee
Johns Hopkins University
US Department of Health and Human Services
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 Johns Hopkins University, US Department of Health and Human Services filed Critical Johns Hopkins University
Priority to DE69731756T priority Critical patent/DE69731756T2/de
Priority to CA2263503A priority patent/CA2263503C/en
Priority to JP50973298A priority patent/JP2001517206A/ja
Priority to AU38899/97A priority patent/AU3889997A/en
Priority to AT97936164T priority patent/ATE283069T1/de
Priority to EP97936164A priority patent/EP0929318B1/en
Publication of WO1998006746A2 publication Critical patent/WO1998006746A2/en
Publication of WO1998006746A3 publication Critical patent/WO1998006746A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/0005Vertebrate antigens
    • A61K39/0011Cancer antigens
    • A61K39/00119Melanoma antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515Animal cells
    • A61K2039/5152Tumor cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515Animal cells
    • A61K2039/5156Animal cells expressing foreign proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55522Cytokines; Lymphokines; Interferons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • the present invention provides a method of treating cancer using such cell lines, and, in particular, provides a method of treating melanoma, which does not rely on use of autologous or MHC-matched tumor cells, and that avoids the difficulties and shortcomings associated with such use.
  • the medium can contain various additional factors as necessary, e.g., when required for the growth of the melanoma cells, or for maintenance of the melanoma cells in an undifferentiatedstate.
  • the medium and medium components are readily available, and can be obtained, for instance, from commercial suppliers.
  • the tumor cell cultures can be fed and recultured as necessary, e.g., typically every 1 to 10 days.
  • the tumor cells also can be subjected to differential trypsinization to remove other cells (e.g., stromal cells) that can overgrow the primary tumor cultures. Also, suppression of fibroblast overgrowth can be achieved by supplementingthe culture medium with cholera toxin (e.g., lO ng/ml).
  • a cytokine includes, but is not restricted to, such proteins as interferons, interleukins (e.g., IL- 1 to IL- 17), tumor necrosis factor (TNF), erythropoietin(EPO), macrophage colony stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophagecolony stimulating factor (GM-CSF).
  • interferons e.g., IL- 1 to IL- 17
  • TNF tumor necrosis factor
  • EPO erythropoietin
  • M-CSF macrophage colony stimulating factor
  • G-CSF granulocyte colony stimulating factor
  • GM-CSF granulocyte-macrophagecolony stimulating factor
  • the cytokine is GM-CSF.
  • Appropriate viral vectors include, but are not limited to simian virus 40, bovine papilloma virus, Epstein-Barr virus, adenovirus, herpes virus, vaccinia virus, Moloney murine leukemia virus, Harvey murine sarcoma virus, and Rous sarcoma virus.
  • a coding sequence is "operably linked" to a promoter (e.g., when both the coding sequence and the promoter together constitute a native or recombinant cytokine gene) when the promoter is capable of directing transcription of the coding sequence.
  • cytokine "gene” or “coding sequence” includes cytokine genomic or cDNA sequences, greater and lesser sequences and mutations thereof, whether isolated from nature or synthesized in whole or in part, as long as the gene or coding sequence is capable of expressing or capable of being expressed into a protein having the characteristic function of the cytokine, i.e., the ability to stimulate the host immune response.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US1997/012868 1996-08-16 1997-08-04 Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same Ceased WO1998006746A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
DE69731756T DE69731756T2 (de) 1996-08-16 1997-08-04 Melanomzellinien, welche immundominante melanomantigene teilen und verfahren zu deren anwendung
CA2263503A CA2263503C (en) 1996-08-16 1997-08-04 Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same
JP50973298A JP2001517206A (ja) 1996-08-16 1997-08-04 免疫優性な共有黒色腫抗原を発現する黒色腫細胞株およびその使用方法
AU38899/97A AU3889997A (en) 1996-08-16 1997-08-04 Melanoma cell lines expressing shared immunodominant melanoma antigens nd methods of using same
AT97936164T ATE283069T1 (de) 1996-08-16 1997-08-04 Melanomzellinien, welche immundominante melanomantigene teilen und verfahren zu deren anwendung
EP97936164A EP0929318B1 (en) 1996-08-16 1997-08-04 Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2409896P 1996-08-16 1996-08-16
US60/024,098 1996-08-16

Publications (2)

Publication Number Publication Date
WO1998006746A2 true WO1998006746A2 (en) 1998-02-19
WO1998006746A3 WO1998006746A3 (en) 1998-05-07

Family

ID=21818860

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/012868 Ceased WO1998006746A2 (en) 1996-08-16 1997-08-04 Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same

Country Status (8)

Country Link
US (1) US6187306B1 (https=)
EP (1) EP0929318B1 (https=)
JP (5) JP2001517206A (https=)
AT (1) ATE283069T1 (https=)
AU (1) AU3889997A (https=)
CA (1) CA2263503C (https=)
DE (1) DE69731756T2 (https=)
WO (1) WO1998006746A2 (https=)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999006544A1 (en) * 1997-07-29 1999-02-11 The Immune Response Corporation Membrane-bound cytokine compositions and methods of modulating an immune response using same
WO1999047178A1 (en) * 1998-03-20 1999-09-23 Genzyme Corporation Novel complementing receptor-ligand pairs and adoptive immunotherapy using same
WO2000047757A1 (de) * 1999-02-10 2000-08-17 Medigene Ag Verfahren zur herstellung eines rekombinanten adeno-assoziierten virus, geeignete mittel hierzu sowie verwendung zur herstellung eines arzneimittels
US6277368B1 (en) 1996-07-25 2001-08-21 The Regents Of The University Of California Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokine
EP0932411A4 (en) * 1996-02-09 2001-09-26 Ludwig Inst Cancer Res COMPOSITIONS CONTAINING IMMUNOGENIC MOLECULES AND GRANULOCYTE MACROPHONE COLONY STIMULATION FACTOR AS ADJUVANT
WO2001098464A3 (en) * 2000-06-22 2002-04-18 Aventis Pasteur Continuous adherent melanocyte cell line
EP1100546A4 (en) * 1998-07-28 2002-08-14 Rappaport Family Inst For Res DNA VACCINES ENCODING CYTOKIN AND ITS USE FOR INDUCING PROTECTIVE IMMUNITY AGAINST MULTIPLE SCLEROSIS
CN101861163B (zh) * 2007-04-11 2013-06-12 国家科学和技术研究委员会(Conicet) 用于治疗黑素瘤的细胞系、含有它们的组合物、制备所述组合物的方法以及治疗方法

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9810040D0 (en) * 1998-05-11 1998-07-08 Univ Nottingham Blood borne tumour markers
GB9827228D0 (en) * 1998-12-10 1999-02-03 Univ Nottingham Cancer detection method and reagents
US20030232399A1 (en) * 2000-06-14 2003-12-18 Robertson John Forsyth Russell Cancer detection methods and reagents
US20050201993A1 (en) * 2002-10-09 2005-09-15 Link Charles J.Jr. Antitumor vaccination using allogeneic tumor cells expressing alpha (1,3)-galactosyltransferase
CN1756568A (zh) * 2002-10-09 2006-04-05 衣阿华中央卫生系统 使用表达α(1,3)-半乳糖基转移酶的同种异型肿瘤细胞的抗肿瘤免疫
GB2395270B (en) * 2002-11-14 2006-08-16 Univ Nottingham Tumour marker proteins and uses thereof
US20050136035A1 (en) * 2003-06-03 2005-06-23 Derek Ko Cell specific replication-competent viral vectors comprising a self processing peptide cleavage site
WO2005017149A1 (en) * 2003-06-03 2005-02-24 Cell Genesys, Inc. Compositions and methods for enhanced expression of recombinant polypeptides from a single vector using a peptide cleavage site
US20050186178A1 (en) * 2003-08-28 2005-08-25 Ennist David L. Oncolytic adenoviral vectors encoding GM-CSF
GB2426581A (en) * 2005-05-27 2006-11-29 Univ Nottingham Immunoassay methods
SI1889059T1 (sl) 2005-05-27 2009-12-31 Oncimmune Ltd Izboljšani imunotestni postopek
WO2007123737A2 (en) 2006-03-30 2007-11-01 University Of California Methods and compositions for localized secretion of anti-ctla-4 antibodies
US7919079B2 (en) 2006-03-31 2011-04-05 Biosante Pharmaceuticals, Inc. Cancer immunotherapy compositions and methods of use
CN101632020B (zh) 2006-09-13 2013-11-27 昂西免疫有限公司 改进的免疫测定方法
US7998486B2 (en) 2006-10-25 2011-08-16 Newlink Genetics Corporation Enhanced immunogenicity of tumor associated antigens by addition of alphaGal epitopes
GB0725239D0 (en) * 2007-12-24 2008-02-06 Oncimmune Ltd Calibrator for autoantibody assay
EP2492300B1 (en) * 2009-10-23 2018-10-03 Dow Corning Toray Co., Ltd. Novel organopolysiloxane copolymer
GB2592821B (en) 2015-07-31 2022-01-12 Univ Minnesota Modified cells and methods of therapy
CN110520530A (zh) 2016-10-18 2019-11-29 明尼苏达大学董事会 肿瘤浸润性淋巴细胞和治疗方法
KR20240024328A (ko) 2016-11-22 2024-02-23 알로플렉스 바이오테라퓨틱스 동종이형 종양 세포 백신
EP3645021A4 (en) 2017-06-30 2021-04-21 Intima Bioscience, Inc. ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4595653A (en) 1981-06-09 1986-06-17 Lee Biomolecular Research Laboratories, Inc. Process for assaying cellular immunity
US5045320A (en) 1989-03-23 1991-09-03 Medical Biology Institute Large multivalent immunogen
US5399346A (en) 1989-06-14 1995-03-21 The United States Of America As Represented By The Department Of Health And Human Services Gene therapy
CA2091346C (en) 1990-09-14 2007-04-24 Philip Frost Methods and compositions for genetic therapy and potentiation of anti-tumor immunity
US5342774A (en) 1991-05-23 1994-08-30 Ludwig Institute For Cancer Research Nucleotide sequence encoding the tumor rejection antigen precursor, MAGE-1
AU677165B2 (en) * 1991-10-04 1997-04-17 Johns Hopkins University School Of Medicine, The The regulation of systemic immune responses utilizing cytokines and antigens
US5637483A (en) * 1991-10-04 1997-06-10 Whitehead Institute For Biomedical Research Irradiated tumor cell vaccine engineered to express GM-CSF
DK0668350T4 (da) * 1994-02-16 2009-02-23 Us Gov Health & Human Serv Melanomassocieret antigen, epitoper deraf samt vacciner mod melanom
EP0756604A1 (en) * 1994-04-22 1997-02-05 THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services Melanoma antigens
US5759535A (en) * 1994-05-13 1998-06-02 Research Corporation Technologies, Inc. Immunotherapeutic strategies for the treatment of cancer

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0932411A4 (en) * 1996-02-09 2001-09-26 Ludwig Inst Cancer Res COMPOSITIONS CONTAINING IMMUNOGENIC MOLECULES AND GRANULOCYTE MACROPHONE COLONY STIMULATION FACTOR AS ADJUVANT
US7264820B2 (en) 1996-07-25 2007-09-04 The Regents Of The University Of California Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokline
US6277368B1 (en) 1996-07-25 2001-08-21 The Regents Of The University Of California Cancer immunotherapy using autologous tumor cells combined with cells expressing a membrane cytokine
US7364726B2 (en) 1996-07-25 2008-04-29 The Regents Of The University Of California Pharmaceutical composition for cancer treatment containing cells that express a membrane cytokine
US5891432A (en) * 1997-07-29 1999-04-06 The Immune Response Corporation Membrane-bound cytokine compositions comprising GM=CSF and methods of modulating an immune response using same
WO1999006544A1 (en) * 1997-07-29 1999-02-11 The Immune Response Corporation Membrane-bound cytokine compositions and methods of modulating an immune response using same
US6482407B2 (en) 1997-07-29 2002-11-19 The Immune Response Corporation Membrane-bound cytokine compositions comprising GM-CSF or an active fragment thereof and methods of modulating and an immune response using the same
WO1999047178A1 (en) * 1998-03-20 1999-09-23 Genzyme Corporation Novel complementing receptor-ligand pairs and adoptive immunotherapy using same
EP1100546A4 (en) * 1998-07-28 2002-08-14 Rappaport Family Inst For Res DNA VACCINES ENCODING CYTOKIN AND ITS USE FOR INDUCING PROTECTIVE IMMUNITY AGAINST MULTIPLE SCLEROSIS
WO2000047757A1 (de) * 1999-02-10 2000-08-17 Medigene Ag Verfahren zur herstellung eines rekombinanten adeno-assoziierten virus, geeignete mittel hierzu sowie verwendung zur herstellung eines arzneimittels
US6846665B1 (en) 1999-02-10 2005-01-25 Medigene Aktiengesellschaft Method of producing a recombinant adeno-associated virus, suitable means for producing the same and use thereof for producing a medicament
WO2001098464A3 (en) * 2000-06-22 2002-04-18 Aventis Pasteur Continuous adherent melanocyte cell line
US6541250B2 (en) 2000-06-22 2003-04-01 Aventis Pasteur Limited Continuous adherent melanocyte cell line
CN101861163B (zh) * 2007-04-11 2013-06-12 国家科学和技术研究委员会(Conicet) 用于治疗黑素瘤的细胞系、含有它们的组合物、制备所述组合物的方法以及治疗方法

Also Published As

Publication number Publication date
EP0929318A2 (en) 1999-07-21
WO1998006746A3 (en) 1998-05-07
JP2014012738A (ja) 2014-01-23
AU3889997A (en) 1998-03-06
CA2263503C (en) 2012-04-10
DE69731756T2 (de) 2005-12-15
US6187306B1 (en) 2001-02-13
DE69731756D1 (de) 2004-12-30
JP2008044969A (ja) 2008-02-28
JP2012001548A (ja) 2012-01-05
JP2016106137A (ja) 2016-06-16
ATE283069T1 (de) 2004-12-15
CA2263503A1 (en) 1998-02-19
JP2001517206A (ja) 2001-10-02
EP0929318B1 (en) 2004-11-24

Similar Documents

Publication Publication Date Title
EP0929318B1 (en) Melanoma cell lines expressing shared immunodominant melanoma antigens and methods of using same
US6350445B1 (en) Method of treating cancer with a tumor cell line having modified cytokine expression
EP1053301B1 (en) A universal immunomodulatory cytokine-expressing bystander cell line and related compositions and methods of manufacture and use
Reilly et al. HER-2/neu is a tumor rejection target in tolerized HER-2/neu transgenic mice
Chen et al. Experimental vaccine strategies for cancer immunotherapy
JP4723722B2 (ja) ワクチン用アジュバントとしてのmhcクラスiiリガンドの使用および癌治療におけるlag−3の使用
EP0869803B1 (en) Allogeneic paracrine cytokine tumor vaccines
AU2004237854B2 (en) Melanoma cell lines expressing shared melanoma antigens and methods of using same
US6087174A (en) Growth medium for primary pancreatic tumor cell culture
Havranek et al. Advances in prostate cancer immunotherapy
AU2008201147A1 (en) Melanoma cell lines expressing shared melanoma antigens and methods of using same
Young et al. Genetic and immunological therapy for cancer
Santin et al. Development and in vitro characterization of a GM‐CSF secreting human ovarian carcinoma tumor vaccine
WO2001032843A9 (en) Enhanced immune recognition of pathogenic cells by icsbp expression
MXPA99012024A (en) Use of mhc class ii ligands as adjuvant for vaccination and of lag-3 in cancer treatment

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT

121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2263503

Country of ref document: CA

Ref country code: CA

Ref document number: 2263503

Kind code of ref document: A

Format of ref document f/p: F

ENP Entry into the national phase

Ref country code: JP

Ref document number: 1998 509732

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1997936164

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1997936164

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 1997936164

Country of ref document: EP