ATE78055T1 - Verfahren zur herstellung von proteinen und transformierten zellen und dna-konstruktionen zur korrektur von mankos und wirtszellen sowie deren herstellung und verwendung. - Google Patents

Verfahren zur herstellung von proteinen und transformierten zellen und dna-konstruktionen zur korrektur von mankos und wirtszellen sowie deren herstellung und verwendung.

Info

Publication number
ATE78055T1
ATE78055T1 AT85303702T AT85303702T ATE78055T1 AT E78055 T1 ATE78055 T1 AT E78055T1 AT 85303702 T AT85303702 T AT 85303702T AT 85303702 T AT85303702 T AT 85303702T AT E78055 T1 ATE78055 T1 AT E78055T1
Authority
AT
Austria
Prior art keywords
production
methods
proteins
cells
host cells
Prior art date
Application number
AT85303702T
Other languages
English (en)
Inventor
Glenn Kawasaki
Leslie Bell
Original Assignee
Zymogenetics 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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27087316&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ATE78055(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Zymogenetics Inc filed Critical Zymogenetics Inc
Application granted granted Critical
Publication of ATE78055T1 publication Critical patent/ATE78055T1/de

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
    • C07K14/39—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts
    • C07K14/395—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts from Saccharomyces
    • 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
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/49—Platelet-derived growth factor [PDGF]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8125—Alpha-1-antitrypsin
    • 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
    • C12N15/64—General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host
    • 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
    • C12N15/67—General methods for enhancing the expression
    • 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
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • 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
    • C12N9/90—Isomerases (5.)
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/10022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/11011—Alpharetrovirus, e.g. avian leucosis virus
    • C12N2740/11022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Mycology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Virology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
AT85303702T 1984-05-25 1985-05-24 Verfahren zur herstellung von proteinen und transformierten zellen und dna-konstruktionen zur korrektur von mankos und wirtszellen sowie deren herstellung und verwendung. ATE78055T1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US61473484A 1984-05-25 1984-05-25
US73411985A 1985-05-15 1985-05-15
EP85303702A EP0171142B2 (de) 1984-05-25 1985-05-24 Verfahren zur Herstellung von Proteinen und transformierten Zellen und DNA-Konstruktionen zur Korrektur von Mankos und Wirtszellen sowie deren Herstellung und Verwendung

Publications (1)

Publication Number Publication Date
ATE78055T1 true ATE78055T1 (de) 1992-07-15

Family

ID=27087316

Family Applications (1)

Application Number Title Priority Date Filing Date
AT85303702T ATE78055T1 (de) 1984-05-25 1985-05-24 Verfahren zur herstellung von proteinen und transformierten zellen und dna-konstruktionen zur korrektur von mankos und wirtszellen sowie deren herstellung und verwendung.

Country Status (8)

Country Link
US (2) US5527668A (de)
EP (1) EP0171142B2 (de)
JP (2) JP2543497B2 (de)
AT (1) ATE78055T1 (de)
AU (1) AU600885B2 (de)
CA (1) CA1285505C (de)
DE (1) DE3586304T3 (de)
DK (1) DK175105B1 (de)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU600885B2 (en) * 1984-05-25 1990-08-30 Zymogenetics Inc. Stable DNA constructs
US5723292A (en) * 1984-05-25 1998-03-03 Zymogenetics, Inc. Stable DNA constructs
EP0487116B1 (de) * 1984-10-12 1999-12-29 ZymoGenetics, Inc. Von Blutplättchen abstammende biologisch aktive Analoga eines Wachstumsfaktors in eukaryotischen Zellen
US4801542A (en) * 1984-10-12 1989-01-31 Zymogenetics, Inc. Expression of biologically active PDGF analogs in eucaryotic cells
DK594084A (da) * 1984-12-12 1986-06-13 Novo Industri As Fremgangsmaade til stabilisering af extra-chromosomale elementer i bakterier under dyrkning
US4935349A (en) * 1986-01-17 1990-06-19 Zymogenetics, Inc. Expression of higher eucaryotic genes in aspergillus
EP0251579A3 (de) * 1986-06-24 1989-03-22 Enterovax Research Pty. Ltd. Markiersystem ohne Antibiotika
US5474982A (en) * 1986-08-13 1995-12-12 Zymogenetics, Inc. PDGF analogs and methods of use
ATE131532T1 (de) * 1986-08-13 1995-12-15 Zymogenetics Inc Expression von biologisch-aktiven pdgf-analogen in eukaryotischen zellen
EP0284044B1 (de) * 1987-03-23 1994-03-23 Zymogenetics, Inc. Hohe Proteinsyntheserate in Hefe
IL87737A (en) 1987-09-11 1993-08-18 Genentech Inc Method for culturing polypeptide factor dependent vertebrate recombinant cells
US5135854A (en) * 1987-10-29 1992-08-04 Zymogenetics, Inc. Methods of regulating protein glycosylation
WO1989006694A1 (en) * 1988-01-15 1989-07-27 Trustees Of The University Of Pennsylvania Process for selection of proteinaceous substances which mimic growth-inducing molecules
US6004776A (en) * 1989-07-07 1999-12-21 Unilever Patent Holdings, B.V. Process for preparing a protein by a fungus transformed by multicopy integration of an expression vector
DK0778348T3 (da) * 1989-07-07 2000-12-04 Unilever Nv Fremgangsmåde til fremstilling af et protein ved anvendelse af en svamp transformeret ved multikopi-integration af en ekspr
US5759833A (en) * 1994-05-27 1998-06-02 Cubist Pharmaceuticals, Inc. Human isoleucyl-tRNA synthetase proteins, nucleic acids and tester strains comprising same
GB2318732A (en) 1996-11-01 1998-05-06 Johnson & Johnson Medical Wound healing compositions containing alpha-1-antitrypsin
US6406921B1 (en) * 1998-07-14 2002-06-18 Zyomyx, Incorporated Protein arrays for high-throughput screening
US20020119579A1 (en) * 1998-07-14 2002-08-29 Peter Wagner Arrays devices and methods of use thereof
US6576478B1 (en) * 1998-07-14 2003-06-10 Zyomyx, Inc. Microdevices for high-throughput screening of biomolecules
US6897073B2 (en) * 1998-07-14 2005-05-24 Zyomyx, Inc. Non-specific binding resistant protein arrays and methods for making the same
ATE474930T1 (de) 1999-12-29 2010-08-15 Novo Nordisk As Verfahren zur herstellung von insulinvorläufern und analogen von insulinvorläufern mit verbesserter fermentationsausbeute in hefe
US7009045B2 (en) * 2000-07-14 2006-03-07 Archer-Daniels-Midland Company Transformation systems for flavinogenic yeast
WO2002094871A1 (en) 2001-05-24 2002-11-28 Human Dna Technology Inc Novel keratinocyte growth factor-2 analogue in hair follicle
US7176278B2 (en) 2001-08-30 2007-02-13 Biorexis Technology, Inc. Modified transferrin fusion proteins
DK2314629T4 (da) 2002-07-18 2023-02-06 Merus Nv Rekombinant produktion af blandinger af antistoffer
USRE47770E1 (en) 2002-07-18 2019-12-17 Merus N.V. Recombinant production of mixtures of antibodies
CA2527694C (en) 2003-05-30 2015-07-14 Hendricus Renerus Jacobus Mattheus Hoogenboom Fab library for the preparation of anti vegf and anti rabies virus fabs
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
EP1687428A1 (de) 2003-11-14 2006-08-09 Novo Nordisk A/S Verfahren zur herstellung von acyliertem insulin
CN1902226A (zh) 2003-12-03 2007-01-24 诺和诺德公司 单链胰岛素
WO2006067511A1 (en) * 2004-12-23 2006-06-29 Novozymes Delta Limited Gene expression technique
JP2006067883A (ja) * 2004-09-01 2006-03-16 Kao Corp 組換えバチルス属細菌
IL165484A0 (en) * 2004-11-30 2006-01-15 Applied Research Systems Production of proteins
US9056921B2 (en) 2005-08-16 2015-06-16 Novo Nordisk A/S Method for making mature insulin polypeptides
ATE482977T1 (de) 2006-02-27 2010-10-15 Novo Nordisk As Insulinderivate
CA2658654A1 (en) 2006-07-24 2008-01-31 Biorexis Pharmaceutical Corporation Exendin fusion proteins
JP5503968B2 (ja) 2006-09-27 2014-05-28 ノボ・ノルデイスク・エー／エス 成熟インスリンポリペプチドの作製方法
US8822639B2 (en) 2006-12-12 2014-09-02 Biorexis Pharmaceutical Corporation Transferrin fusion protein libraries
JP5710253B2 (ja) 2007-08-13 2015-04-30 ノボ・ノルデイスク・エー／エス 速効型インスリンアナログ
MX2010001645A (es) 2007-08-15 2010-03-10 Novo Nordisk As Analogos de insulina con una porcion de acil y alquilenglicol.
ES2526924T3 (es) 2007-08-15 2015-01-16 Novo Nordisk A/S Insulinas con una fracción acilo que comprende unidades repetitivas de aminoácidos que contienen alquilenglicol
JP5850848B2 (ja) 2009-11-25 2016-02-03 ノヴォ ノルディスク アー／エス ポリペプチドの製造方法
CN102791730A (zh) 2010-01-22 2012-11-21 诺沃—诺迪斯克有限公司 低度o-糖基化的fgf21的制备方法
KR102171431B1 (ko) 2012-04-20 2020-10-30 메뤼스 엔.페. Ig-유사 분자의 제조방법 및 제조수단
CN105308067B (zh) 2013-06-07 2020-07-24 诺和诺德股份有限公司 制备成熟胰岛素多肽的方法
KR102277898B1 (ko) 2014-07-03 2021-07-15 삼성전자주식회사 산물 생산능이 향상된 효모 및 그를 이용한 산물을 생산하는 방법
AR133774A1 (es) 2023-09-11 2025-10-29 Novo Nordisk As Anticuerpos de dominio anti-il-6

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4237224A (en) * 1974-11-04 1980-12-02 Board Of Trustees Of The Leland Stanford Jr. University Process for producing biologically functional molecular chimeras
JPS55156591A (en) * 1979-05-23 1980-12-05 Ajinomoto Co Inc Method for stabilizing property of bacteria containing plasmid
JPS6048322B2 (ja) * 1980-08-25 1985-10-26 松下電工株式会社 セメント系無機材料の押出成形方法
US4506013A (en) * 1980-10-03 1985-03-19 Eli Lilly And Company Stabilizing and selecting recombinant DNA host cells
DE3279270D1 (en) * 1981-09-02 1989-01-12 Biogen Nv Amplified expression of dna sequences
CA1198069A (en) * 1982-06-08 1985-12-17 David H. Gelfand Temperature sensitive multicopy plasmids
GB2125047B (en) * 1982-08-09 1986-02-19 Ciba Geigy Ag Yeast hybrid vectors and their use for the production of polypeptides
CA1209501A (en) * 1982-09-16 1986-08-12 Nikos Panayotatos Expression vector
GB8407498D0 (en) * 1984-03-22 1984-05-02 Biogen Nv High copy number expression vectors
US4931373A (en) * 1984-05-25 1990-06-05 Zymogenetics, Inc. Stable DNA constructs for expression of α-1 antitrypsin
AU600885B2 (en) * 1984-05-25 1990-08-30 Zymogenetics Inc. Stable DNA constructs

Also Published As

Publication number Publication date
US5700643A (en) 1997-12-23
US5527668A (en) 1996-06-18
AU4279485A (en) 1985-11-28
AU600885B2 (en) 1990-08-30
EP0171142B2 (de) 2004-09-01
DE3586304T3 (de) 2005-02-17
JP2543497B2 (ja) 1996-10-16
EP0171142A1 (de) 1986-02-12
DK175105B1 (da) 2004-06-01
JPS6156092A (ja) 1986-03-20
EP0171142B1 (de) 1992-07-08
JPH0767685A (ja) 1995-03-14
CA1285505C (en) 1991-07-02
DE3586304D1 (de) 1992-08-13
DE3586304T2 (de) 1992-12-10
JP2704115B2 (ja) 1998-01-26
DK235085D0 (da) 1985-05-24
DK235085A (da) 1985-11-26

Similar Documents

Publication Publication Date Title
ATE78055T1 (de) Verfahren zur herstellung von proteinen und transformierten zellen und dna-konstruktionen zur korrektur von mankos und wirtszellen sowie deren herstellung und verwendung.
EP0174367A4 (de) Menge und verfahren zur herstellung rekombinierter erzeugnisse in grosser ausbeute.
DE3851289D1 (de) Verfahren zur Züchtung rekombinanter Zellen.
DE3888561D1 (de) Hohe Proteinsyntheserate in Hefe.
ATE123065T1 (de) Proteine und deren herstellung.
BR8200191A (pt) Celula viva renina preprorrenina prorrenina processo para obter expressao de preporrenina prorrenina e renina gene de prorrenina preprorrenina e renina e coli material dna recombinador saccharomyces cerevisiae polipetidio processo para exprimir um gene
ATE209679T1 (de) Proteine mit faktor viii aktivität, verfahren zu deren herstellung unter verwendung von genetisch modifizierten zellen und diese enthaltende zusammensetzungen
ATE140960T1 (de) Verfahren zur herstellung von zellen, die stabil integrierte fremde dns mit hoher kopiezahl enthalten, durch dieses verfahren hergestellte zellen und verwendung dieser zellen zur herstellung von durch diese fremde dns kodierten polypeptiden
ES8800343A1 (es) Un metodo para producir una proteina que contiene actividad biologica para coagulacion de sangre, mediada por factor viia
IL68366A (en) Process for expressing a gene encoding a protein comprising the enzymatic portion of human urokinase in a microorganism or cell culture
AU682140B2 (en) Multidrug resistance gene
DE69935978D1 (de) Kulturmedium zur kultivierung tierischer zellen und verfahren zur herstellung von proteinen durch dessen verwendung
DE69636899D1 (de) Wirtszelle, die reduzierte mengen einer metalloprotease exprimiert und methoden zur verwendung dieser wirtszelle zur proteinproduktion
ATE93272T1 (de) Expression von protein c.
PT80542B (pt) Processo de tecnologia genetica para a preparacao de interleucina-2 humana
EP0155832A3 (de) Stabile Proteine, Verfahren zu deren Herstellung, dieselben kodierende Plasmide und andere DNS, diese Plasmide enthaltende Zellkulturen
WO2000006713A3 (en) Methods for recombinant protein production in mammalian cells comprising co-expression with fetuin
ATE451469T1 (de) In vivo-verfahren zur herstellung von proteinen, die nicht-konventionelle aminosäuren enthalten
IE881779L (en) Dna fragments, containing a lactic acid bacterium-specific¹regulator region for the expression of genes coding for¹normally heterologous proteins, recombinant plasmids based¹on such dna fragments, lactic acid bacteria which contain¹these recombinant plasmids and the heterologous proteins and¹products prepared with the aid of the above microorganisms
DE69917294D1 (de) Verfahren zur herstellung von heterologen polypeptiden in transformierten hefezellen
AU1321988A (en) The cloning of malaria-specific dna sequences: isolation of the gene for the 140 kd protein
WO2000052133A3 (en) Hansenula polymorpha mutants and process for the preparation of recombinant proteins using the same
DE58909205D1 (de) Expressionsvektor und Verfahren zur regulierbaren Herstellung von Proteinen in Eukaryonten.
ATE113314T1 (de) Genetisch modifizierte milchsäurebakterien und ihre verwendung bei der herstellung von käse und rekombinanten plasmiden.
DE69923595D1 (de) Herstellung von proteinen

Legal Events

Date Code Title Description
EELA Cancelled due to lapse of time
UEP Publication of translation of european patent specification

Ref document number: 0171142

Country of ref document: EP