[go: up one dir, main page]

WO1999061467A3 - Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale - Google Patents

Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale Download PDF

Info

Publication number
WO1999061467A3
WO1999061467A3 PCT/CA1999/000461 CA9900461W WO9961467A3 WO 1999061467 A3 WO1999061467 A3 WO 1999061467A3 CA 9900461 W CA9900461 W CA 9900461W WO 9961467 A3 WO9961467 A3 WO 9961467A3
Authority
WO
WIPO (PCT)
Prior art keywords
pest
binding
knock
cell proliferation
protein tyrosine
Prior art date
Application number
PCT/CA1999/000461
Other languages
English (en)
Other versions
WO1999061467A2 (fr
Inventor
Michel L Tremblay
Jean-Francois Cote
Alexandre Angers-Lousteau
Alain Charest
Original Assignee
Univ Mcgill
Michel L Tremblay
Cote Jean Francois
Angers Lousteau Alexandre
Alain Charest
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 Univ Mcgill, Michel L Tremblay, Cote Jean Francois, Angers Lousteau Alexandre, Alain Charest filed Critical Univ Mcgill
Priority to AU39229/99A priority Critical patent/AU3922999A/en
Priority to EP99922004A priority patent/EP1077997A2/fr
Priority to JP2000550871A priority patent/JP2002516338A/ja
Priority to CA002329157A priority patent/CA2329157A1/fr
Publication of WO1999061467A2 publication Critical patent/WO1999061467A2/fr
Publication of WO1999061467A3 publication Critical patent/WO1999061467A3/fr

Links

Classifications

    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/42—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving phosphatase
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

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

Abstract

La présente invention concerne des agents ou des composés capables d'entraver la liaison de tyrosine-phosphatase PEST avec des domaines de protéines de signalisation intervenant dans la migration cellulaire, l'adhésion focale et/ou la prolifération cellulaire, notamment la p130cas et la paxilline. Ces agents peuvent être tirés de séquences minimales figurant dans des études de liaison. La PTP-PEST est une phophatase conservée essentielle pour le développement de l'embryon. Des cellules invalidées (PTP-PEST -/-) perpétuées à partir d'embryons nuls sont déficientes en ce qui concerne la migration cellulaire, l'adhésion focale et la prolifération. Dans ces conditions, tout agent capable d'entraver l'activité de PEST dans un tissu malade cible est considéré comme agent thérapeutique potentiel pour le traitement de toute maladie possédant les composantes étiologiques suivantes: prolifération cellulaire, cancer, métastase, inflammation et angiogenèse. L'invention concerne également un procédé permettant de trouver de véritables substrats pour des enzymes, à savoir des phosphatases et combiner des techniques d'invalidation de ciblage de gènes et des techniques de piégeage de substrats avec l'aide d'un enzyme mutant vis-à-vis d'un substrat, mais capable de se lier à ce substrat. La technique d'invalidation de ciblage de gènes fait intervenir moins d'artefacts que d'autres techniques (faisant appel par exemple à des composés de vanadate) caractérisées par une augmentation artificielle non spécifique du niveau d'hyperphosphorilation.
PCT/CA1999/000461 1998-05-21 1999-05-21 Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale WO1999061467A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU39229/99A AU3922999A (en) 1998-05-21 1999-05-21 Agents interfering with the binding of protein tyrosine phosphatase pest to domains of signalling proteins as inhibitors of cell migration and/or of focal adhesion
EP99922004A EP1077997A2 (fr) 1998-05-21 1999-05-21 Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale
JP2000550871A JP2002516338A (ja) 1998-05-21 1999-05-21 タンパク質チロシンホスファターゼｐｅｓｔのシグナルタンパク質への結合に干渉する、細胞移動及び／又はフォーカルアドヒージョンの阻害剤としての薬剤
CA002329157A CA2329157A1 (fr) 1998-05-21 1999-05-21 Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CA2,238,654 1998-05-21
CA2238654 1998-05-21
US11199398P 1998-12-11 1998-12-11
US60/111,993 1998-12-11

Publications (2)

Publication Number Publication Date
WO1999061467A2 WO1999061467A2 (fr) 1999-12-02
WO1999061467A3 true WO1999061467A3 (fr) 2000-05-18

Family

ID=25680245

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA1999/000461 WO1999061467A2 (fr) 1998-05-21 1999-05-21 Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale

Country Status (4)

Country Link
EP (1) EP1077997A2 (fr)
JP (1) JP2002516338A (fr)
AU (1) AU3922999A (fr)
WO (1) WO1999061467A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8957159B2 (en) 2002-10-15 2015-02-17 Exxonmobil Chemical Patents Inc. Multiple catalyst system for olefin polymerization and polymers produced therefrom

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001020021A2 (fr) * 1999-09-14 2001-03-22 Forschungszentrum Karlsruhe Gmbh Complexe a enzymes dephosphorylantes specifiques, ses effecteurs et leur procede de production
AUPR598901A0 (en) * 2001-06-28 2001-07-19 Unisearch Limited Inhibition of angiogenesis by targeting protein tyrosine phosphatases
WO2003094916A1 (fr) 2002-05-10 2003-11-20 Qlt Inc. Procedes d'utilisation de derives de thiazolidine dans le traitement du cancer ou de l'inflammation
AU2003229459A1 (en) * 2002-05-17 2003-12-02 Qlt Inc. Methods of using thiazolidinedithione derivatives
WO2005058944A2 (fr) * 2003-12-12 2005-06-30 The Government Of The United States, As Represented By The Secretary Of The Department Of Health & Human Services Peptides immunogenes de xage-1
WO2016191328A1 (fr) * 2015-05-22 2016-12-01 Allosta Pharmaceuticals Procédés pour préparer et utiliser des modèles de site de liaison pour la modulation de l'activité de la phosphatase et la détermination de la sélectivité

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995024419A1 (fr) * 1994-03-11 1995-09-14 Ariad Pharmaceuticals, Inc. Procedes et materiaux d'identification d'inhibiteurs d'interactions moleculaires induites par les domaines sh3
WO1998000552A2 (fr) * 1996-07-02 1998-01-08 President And Fellows Of Harvard College Recepteur tyrosine-phosphatase et ses emplois
WO1998004712A2 (fr) * 1996-07-25 1998-02-05 Cold Spring Harbor Laboratory Proteine-tyrosine-phosphatases de piegeage de substrats

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995024419A1 (fr) * 1994-03-11 1995-09-14 Ariad Pharmaceuticals, Inc. Procedes et materiaux d'identification d'inhibiteurs d'interactions moleculaires induites par les domaines sh3
WO1998000552A2 (fr) * 1996-07-02 1998-01-08 President And Fellows Of Harvard College Recepteur tyrosine-phosphatase et ses emplois
WO1998004712A2 (fr) * 1996-07-25 1998-02-05 Cold Spring Harbor Laboratory Proteine-tyrosine-phosphatases de piegeage de substrats

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
ANGERS-LOUSTAU A. ET AL.: "Protein tyrosine phosphatase PEST regulates focal adhesion disassembly, migration and cytokinesis in fibroblasts", JURNAL OF CELL BIOLOGY, vol. 144, no. 5, March 1999 (1999-03-01), pages 1019 - 131, XP000876950 *
CHAREST A ET AL: "MURINE PROTEIN TYROSINE PHOSPHATASE-PEST, A STABLE CYTOSOLIC PROTEIN TYROSINE PHOSPHATASE", BIOCHEMICAL JOURNAL,GB,PORTLAND PRESS, LONDON, vol. 308, no. PART 02, 1995, pages 425-432, XP000676759, ISSN: 0264-6021 *
CHAREST A. ET AL.: "Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase PEST. Evidence for exentended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 271, no. 14, 1996, pages 8424 - 8429, XP000876941 *
CÔTÉ J.F. ET AL.: "Combination of gene targeting and substrate trapping to identify substrates of protein tyrosine phosphatases using PTP-PEST as a model", BIOCHEMISTRY, vol. 37, no. 38, 22 September 1998 (1998-09-22), EASTON, PA US, pages 13128 - 13127, XP000876953 *
CÔTÉ J.F. ET AL: "Intact LIM 3 and LIM 4 domains of paxillin are required for the association to a novel polyproline region (Pro 2) of protein-tyrosine phosphatase PEST", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 29, 16 July 1999 (1999-07-16), pages 10550 - 20560, XP000876944 *
DAVIDSON D. ET AL.: "Inhibitory tyrosine protein kinase p50csk is associated with protein-tyrosine phosphatase PTP-PEST in hemopoietic and non-hemopoietic cells", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 272, no. 37, 1997, MD US, pages 23455 - 23462, XP000876942 *
DOWBENKO D. ET AL.: "Identification of a novel polyproline recognition site in the cytoskeletal associated protein, proline serine threonine phosphatase interacting protein", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, no. 2, 9 January 1998 (1998-01-09), pages 989 - 996, XP000876966 *
FAUMAN E B ET AL: "Structure and function of the protein tyrosine phosphatases", TIBS TRENDS IN BIOCHEMICAL SCIENCES,EN,ELSEVIER PUBLICATION, CAMBRIDGE, vol. 21, no. 11, 1996, pages 413-417, XP004071016, ISSN: 0968-0004 *
GARTON A J ET AL: "IDENTIFICATION OF 130CAS AS A SUBSTRATE FOR THE CYTOSOLIC PROTEIN TYROSINE PHOSPHATASE PTP-PEST", MOLECULAR AND CELLULAR BIOLOGY,US,WASHINGTON, DC, vol. 16, no. 11, 1996, pages 6408-6418, XP002051430, ISSN: 0270-7306 *
GARTON A J ET AL: "PTP-PEST: A PROTEIN TYROSINE PHOSPHATASE REGULATED BY SERINE PHOSPHORYLATION", EMBO JOURNAL,GB,OXFORD UNIVERSITY PRESS, SURREY, vol. 13, no. 16, pages 3763-3771, XP002051427, ISSN: 0261-4189 *
GARTON A.J. ET AL.: "Association of PTP-PEST with SH3 domain of p130cas: a novel mechanism of protein tyrosine phosphatase substrate recognition", ONCOGENE, vol. 15, no. 8, 1997, pages 877 - 885, XP000884055 *
LIU F ET AL: "DIRECT BINDING OF THE PROLINE-RICH REGION OF PROTEIN TYROSINE PHOSPHATASE 1B TO THE SRC HOMOLOGY 3 DOMAIN OF P130CAS", JOURNAL OF BIOLOGICAL CHEMISTRY,US,AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, vol. 271, no. 49, 1996, pages 31290-31295, XP002051433, ISSN: 0021-9258 *
SHEN Y. ET AL.: "Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, no. 11, 13 March 1998 (1998-03-13), pages 6474 - 6481, XP000876943 *
YANG Q ET AL: "CLONING AND EXPRESSION OF PTP-PEST A NOVEL, HUMAN, NONTRANSMEMBRANE PROTEIN TYROSINE PHOSPHATASE", JOURNAL OF BIOLOGICAL CHEMISTRY,US,AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, vol. 268, no. 9, 1993, pages 6622-6628, XP002034265, ISSN: 0021-9258 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8957159B2 (en) 2002-10-15 2015-02-17 Exxonmobil Chemical Patents Inc. Multiple catalyst system for olefin polymerization and polymers produced therefrom

Also Published As

Publication number Publication date
EP1077997A2 (fr) 2001-02-28
WO1999061467A2 (fr) 1999-12-02
JP2002516338A (ja) 2002-06-04
AU3922999A (en) 1999-12-13

Similar Documents

Publication Publication Date Title
Tabata et al. Identification of the cytosolic carboxylesterase catalyzing the 5′-deoxy-5-fluorocytidine formation from capecitabine in human liver
Bossis et al. SUMO: regulating the regulator
Mermoud et al. Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism.
Zhang et al. The gap junction-independent tumor-suppressing effect of connexin 43
Xu et al. Phosphorylation and activation of the Ca (2+)-pumping ATPase of cardiac sarcoplasmic reticulum by Ca2+/calmodulin-dependent protein kinase.
Mitchelhill et al. Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase.
Zandomeni et al. Inhibitory effect of 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole on a protein kinase.
Swope et al. Significance of the melanocortin 1 receptor in the DNA damage response of human melanocytes to ultraviolet radiation
AU666854B2 (en) ATP-dependent protease and use of inhibitors for same in the treatment of cachexia and muscle wasting
Chou et al. Proteomics study of oxidative stress and Src kinase inhibition in H9C2 cardiomyocytes: a cell model of heart ischemia–reperfusion injury and treatment
BEG et al. Regulation of liver 3-hydroxy-3-methylglutaryl-CoA reductase
Wilson et al. Ubiquitin C-terminal hydrolase 1: A novel functional marker for liver myofibroblasts and a therapeutic target in chronic liver disease
Mon et al. A role for focal adhesion kinase signaling in tumor necrosis factor-α–dependent matrix metalloproteinase-9 production in a cholangiocarcinoma cell line, CCKS1
ATE354957T1 (de) Durch trans-spaltung erhaltene therapeutische molekule
TR200002446T2 (tr) Fosfolipaz enzimlerinin inhibitörleri
Jard et al. A cyclic AMP-dependent protein kinase from frog bladder epithelial cells
Ishii et al. Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages
Connelly et al. Evidence for the activation of the multifunctional Ca2+/calmodulin-dependent protein kinase in response to hormones that increase intracellular Ca2+.
Saijo et al. Growth state and cell cycle dependent phosphorylation of DNA topoisomerase II in Swiss 3T3 cells
Acs et al. Both the catalytic and regulatory domains of protein kinase C chimeras modulate the proliferative properties of NIH 3T3 cells
WO1999061467A3 (fr) Agents interferant avec la liaison de typrosine-phosphatase pest a des domaines de proteines de signalisation en tant qu'inhibiteurs de migration cellulaire et/ou d'adhesion focale
Koo et al. PKC phosphorylation disrupts gap junctional communication at G0/S phase in clone 9 cells
Ventura et al. Bovine brain 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase. Evidence for a neural-specific isozyme.
Birnbaum et al. Phosphorylation of the oncogenic transcription factor interferon regulatory factor 2 (IRF2) in vitro and in vivo
CN1897951B (zh) h-PRUNE的酶抑制剂在制备预防和治疗过度表达h-PRUNE的肿瘤转移的药物中的应用

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN 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 US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
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): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GD GE GH GM HR HU ID IL IN 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 US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

ENP Entry into the national phase

Ref document number: 2329157

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: KR

WWE Wipo information: entry into national phase

Ref document number: 1999922004

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 39229/99

Country of ref document: AU

WWP Wipo information: published in national office

Ref document number: 1999922004

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWE Wipo information: entry into national phase

Ref document number: 09700881

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: CA

WWW Wipo information: withdrawn in national office

Ref document number: 1999922004

Country of ref document: EP