+

WO2001025410A3 - SONDES DE DIAGNOSTIC ET AGENTS THERAPEUTIQUES DESTINES A CIBLER uPA ET uPAR - Google Patents

SONDES DE DIAGNOSTIC ET AGENTS THERAPEUTIQUES DESTINES A CIBLER uPA ET uPAR Download PDF

Info

Publication number
WO2001025410A3
WO2001025410A3 PCT/US2000/026502 US0026502W WO0125410A3 WO 2001025410 A3 WO2001025410 A3 WO 2001025410A3 US 0026502 W US0026502 W US 0026502W WO 0125410 A3 WO0125410 A3 WO 0125410A3
Authority
WO
WIPO (PCT)
Prior art keywords
upa
residues
peptide
terminal fragment
upar
Prior art date
Application number
PCT/US2000/026502
Other languages
English (en)
Other versions
WO2001025410A2 (fr
Inventor
Andrew P Mazar
Terence R Jones
Original Assignee
Angstrom Pharmaceuticals Inc
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 Angstrom Pharmaceuticals Inc filed Critical Angstrom Pharmaceuticals Inc
Priority to JP2001528564A priority Critical patent/JP2003528035A/ja
Priority to CA002406882A priority patent/CA2406882A1/fr
Priority to AU79868/00A priority patent/AU780730B2/en
Priority to EP00970496A priority patent/EP1218496A2/fr
Publication of WO2001025410A2 publication Critical patent/WO2001025410A2/fr
Publication of WO2001025410A3 publication Critical patent/WO2001025410A3/fr

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6456Plasminogen activators
    • C12N9/6459Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00Preparations for testing in vivo
    • A61K49/001Preparation for luminescence or biological staining
    • A61K49/006Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04Organic compounds
    • A61K51/08Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81Protease inhibitors
    • C07K14/8107Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811Serine protease (E.C. 3.4.21) inhibitors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6456Plasminogen activators
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21069Protein C activated (3.4.21.69)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Optics & Photonics (AREA)
  • Biophysics (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne une protéine ou un peptide destinés à cibler uPAR, qui est marqué(e) pour le diagnostic ou la thérapie et qui est utilisé(e) dans des procédés de diagnostic de thérapie. La protéine marquée ou le peptide marqué présente, de préférence, les propriétés suivantes: il/elle comprend au moins 38 restes d'acide aminé, dont les restes 13-30 du site de liaison à uPAR de uPA; il/elle est en compétition avec DFP-uPa marqué pour se lier à une cellule ou une molécule qui présente un site de liaison à uPA, et possède une valeur IC50 d'environ 10nM ou moins; et il n'est pas une protéine hybride dans laquelle le peptide uPA est fusionné avec une autre protéine ou un autre peptide non-uPA. Les molécules préférées sont uPA, scuPA, tcuPA, un fragment N-terminal de uPA, correspondant aux restes 1-135, un fragment N-terminal de uPA, correspondant aux restes 1-143, un fragment N-terminal de uPA, des restes 1-43 ; ou un fragment N-terminal de uPA, correspondant aux restes 4-43. Les marqueurs qui peuvent être détectés comprennent un radionucléide, un agent imageable par TEP, un agent imageable IRM, un agent fluorescent, un fluorogène, un chromophore, un chromogène, un agent phosphorescent, un chimiluminescent ou un bioluminescent. Les procédés selon la présente invention sont utilisés afin d'inhiber la migration cellulaire, l'invasion cellulaire, la prolifération cellulaire ou l'angiogenèse ou afin de produire l'apoptose, de préférence pour traiter un patient ayant une maladie ou un état pathologique liés à une migration cellulaire, une invasion cellulaire, une prolifération cellulaire ou une angiogenèse non désirées.
PCT/US2000/026502 1999-10-01 2000-09-27 SONDES DE DIAGNOSTIC ET AGENTS THERAPEUTIQUES DESTINES A CIBLER uPA ET uPAR WO2001025410A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2001528564A JP2003528035A (ja) 1999-10-01 2000-09-27 uPAおよびuPARを標的化する診断プロ−ブおよび治療薬
CA002406882A CA2406882A1 (fr) 1999-10-01 2000-09-27 Sondes de diagnostic et agents therapeutiques destines a cibler upa et upar
AU79868/00A AU780730B2 (en) 1999-10-01 2000-09-27 Diagnostic probes and therapeutics targeting uPA and uPAR
EP00970496A EP1218496A2 (fr) 1999-10-01 2000-09-27 SONDES DE DIAGNOSTIC ET AGENTS THERAPEUTIQUES DESTINES A CIBLER uPA ET uPAR

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15701299P 1999-10-01 1999-10-01
US60/157,012 1999-10-01

Publications (2)

Publication Number Publication Date
WO2001025410A2 WO2001025410A2 (fr) 2001-04-12
WO2001025410A3 true WO2001025410A3 (fr) 2002-01-10

Family

ID=22562008

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/026502 WO2001025410A2 (fr) 1999-10-01 2000-09-27 SONDES DE DIAGNOSTIC ET AGENTS THERAPEUTIQUES DESTINES A CIBLER uPA ET uPAR

Country Status (5)

Country Link
EP (1) EP1218496A2 (fr)
JP (1) JP2003528035A (fr)
AU (1) AU780730B2 (fr)
CA (1) CA2406882A1 (fr)
WO (1) WO2001025410A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111462491A (zh) * 2019-12-10 2020-07-28 北京航空航天大学 一种基于匝道控制的高速公路合流区交通冲突预警方法

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002076486A2 (fr) 2001-02-05 2002-10-03 Innoventus Project Ab Glycoproteine riche en histidine
TWI240632B (en) 2001-07-30 2005-10-01 Epix Medical Inc Purified peptides for peptide-based multimeric targeted contrast agents
WO2004099780A1 (fr) * 2003-05-06 2004-11-18 Rigshospitalet Dosages immunologiques pour la detection de formes de recepteur d'urokinase
US6987270B2 (en) 2003-05-07 2006-01-17 General Electric Company Method to account for event losses due to positron range in positron emission tomography and assay of positron-emitting isotopes
KR101248350B1 (ko) 2004-09-29 2013-04-01 지이 헬스케어 에이에스 uPAR 영상화제
US20070190068A1 (en) * 2005-10-10 2007-08-16 Richard Hart uPAR-binding molecule-drug conjugates and uses thereof
NZ569818A (en) * 2005-12-16 2012-07-27 Catherine M Shachaf Diagnostic system for the detection and diagnosis of skin cancer
WO2013118165A1 (fr) * 2012-02-07 2013-08-15 Jcr Pharmaceuticals Co., Ltd. Agents pharmaceutiques liés par fusion à l'atf pour une biodisponibilité améliorée
CN104768573B (zh) 2012-05-08 2017-08-29 Trt创新有限责任公司 用于位点特异性uPAR靶向的177‑Lu标记肽
HUE046326T2 (hu) 2012-12-03 2020-03-30 Curasight Aps Pozitront emittáló radionukliddal jelölt peptidek humán uPAR PET-tel történõ leképezésére
US11633363B2 (en) 2017-09-27 2023-04-25 Emory University Fusion proteins having a toxin and cancer marker, nanoparticles, and uses related thereto

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990012091A1 (fr) * 1989-04-07 1990-10-18 Cancerforskningsfondet Af 1989 Recepteur de l'activateur du plasminogene du type urokinase
WO1998021230A1 (fr) * 1996-11-12 1998-05-22 Angstrom Pharmaceuticals, Inc. Peptides cycliques se fixant a un recepteur de l'activateur de plasminogene de type urokinase
EP0890638A2 (fr) * 1996-01-08 1999-01-13 Nissin Food Products Co., Ltd. Inhibiteur de metastases cancereuses
WO1999048509A1 (fr) * 1998-03-23 1999-09-30 Rabbani Shafaat A Utilisation du recepteur des activateurs du plasminogene d'urokinase comme cible pour le depistage des metastases

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990012091A1 (fr) * 1989-04-07 1990-10-18 Cancerforskningsfondet Af 1989 Recepteur de l'activateur du plasminogene du type urokinase
EP0890638A2 (fr) * 1996-01-08 1999-01-13 Nissin Food Products Co., Ltd. Inhibiteur de metastases cancereuses
WO1998021230A1 (fr) * 1996-11-12 1998-05-22 Angstrom Pharmaceuticals, Inc. Peptides cycliques se fixant a un recepteur de l'activateur de plasminogene de type urokinase
WO1999048509A1 (fr) * 1998-03-23 1999-09-30 Rabbani Shafaat A Utilisation du recepteur des activateurs du plasminogene d'urokinase comme cible pour le depistage des metastases

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
APPELLA E ET AL: "THE RECEPTOR-BINDING SEQUENCE OF UROKINASE", JOURNAL OF BIOLOGICAL CHEMISTRY,US,AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, vol. 262, no. 10, 5 April 1987 (1987-04-05), pages 4437 - 4440, XP000881270, ISSN: 0021-9258 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 1986, HIGGINS, D.L. ET AL.: "The incorporation of a fluorescent probe into the active sites of one- and two-chain tissue-type plasminogen activator.", XP002178460 *
PLOUG E A: "Photoaffinity labelling of the human receptor for urokinase-type plasminogen activator using a decapeptide antagonist. Evidence for a composite lignad-binding site and a short interdomain separation", BIOCHEMISTRY,US,AMERICAN CHEMICAL SOCIETY. EASTON, PA, vol. 37, no. 11, 17 March 1998 (1998-03-17), pages 3612 - 3622, XP002124882, ISSN: 0006-2960 *
See also references of EP1218496A2 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111462491A (zh) * 2019-12-10 2020-07-28 北京航空航天大学 一种基于匝道控制的高速公路合流区交通冲突预警方法
CN111462491B (zh) * 2019-12-10 2022-03-01 北京航空航天大学 一种基于匝道控制的高速公路合流区交通冲突预警方法

Also Published As

Publication number Publication date
AU780730B2 (en) 2005-04-14
JP2003528035A (ja) 2003-09-24
EP1218496A2 (fr) 2002-07-03
AU7986800A (en) 2001-05-10
CA2406882A1 (fr) 2001-04-12
WO2001025410A2 (fr) 2001-04-12

Similar Documents

Publication Publication Date Title
WO2001025410A3 (fr) SONDES DE DIAGNOSTIC ET AGENTS THERAPEUTIQUES DESTINES A CIBLER uPA ET uPAR
Wiman et al. Inactivation of tissue plasminogen activator in plasma. Demonstration of a complex with a new rapid inhibitor.
JP3419772B2 (ja) フィブリン結合ドメインポリペプチド及びその使用,並びにその製造方法
Lucas et al. The binding of human plasminogen to fibrin and fibrinogen.
US5759542A (en) Compositions and methods for the delivery of drugs by platelets for the treatment of cardiovascular and other diseases
Bennick et al. The nature of the hydroxyapatite-binding site in salivary acidic proline-rich proteins
Flannery et al. Identification of a stromelysin cleavage site within the interglobular domain of human aggrecan. Evidence for proteolysis at this site in vivo in human articular cartilage.
Wistedt et al. Identification of a plasminogen‐binding motif in PAM, a bacterial surface protein
Carballo et al. DNA and histone H1 interact with different domains of HMG 1 and 2 proteins.
US6197519B1 (en) Pancreas-derived serpin
CA2443236A1 (fr) Cathepsine derivee d'ostoclaste humain
BRPI9910394A (pt) moléculas de ligação específica para cintigrafia e conjugados contendo as mesmas
Sugo et al. Calcium binding of bovine protein S. Effect of thrombin cleavage and removal of the gamma-carboxyglutamic acid-containing region.
Garcia-Pardo et al. Primary structure of human plasma fibronectin. The 29,000-dalton NH2-terminal domain.
WO1996019580A3 (fr) Fraction proteinique de la telomerase
JPS62108821A (ja) アルフア−1−プロテイナ−ゼ阻害剤の製造方法
MX2010010759A (es) Mutantes de estreptocinasa y sus formas covalentemente modificadas.
Dewji et al. Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor.
Dwulet et al. Internal duplication and evolution of human ceruloplasmin.
Suzuki et al. In vitro poly (ADP-ribosyl) ation of seminal ribonuclease.
ATE191922T1 (de) Feststellung der wechselwirkungsstelle zwischen p21-waf und pcna und deren therapeutischen verwendungen
Medved et al. Domain structure, stability and interactions in streptokinase
Elzinga Amino acid sequence around 3-methylhistidine in rabbit skeletal muscle actin
Seibel et al. Antigenic properties of keratan sulfate: influence of antigen structure, monoclonal antibodies, and antibody valency
US6624289B1 (en) Region of factor IXa protease domain that interacts with factor VIIIa and methods therefor

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ 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 MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG 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 MZ SD SL SZ TZ 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 AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ 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 MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG 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 MZ SD SL SZ TZ 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 country code: JP

Ref document number: 2001 528564

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 79868/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2000970496

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2406882

Country of ref document: CA

WWP Wipo information: published in national office

Ref document number: 2000970496

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000970496

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务,不要输入任何密码和下载