ES2173300T3 - Vacunas de virus vivos prrs de baja patogenicidad y metodos para su preparacion. - Google Patents

Vacunas de virus vivos prrs de baja patogenicidad y metodos para su preparacion.

Info

Publication number
ES2173300T3
ES2173300T3 ES96922508T ES96922508T ES2173300T3 ES 2173300 T3 ES2173300 T3 ES 2173300T3 ES 96922508 T ES96922508 T ES 96922508T ES 96922508 T ES96922508 T ES 96922508T ES 2173300 T3 ES2173300 T3 ES 2173300T3
Authority
ES
Spain
Prior art keywords
vaccines
living
preparation
methods
low pathogenicity
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.)
Expired - Lifetime
Application number
ES96922508T
Other languages
English (en)
Inventor
Han Soo Joo
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.)
University of Minnesota Twin Cities
University of Minnesota System
Original Assignee
University of Minnesota Twin Cities
University of Minnesota System
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 University of Minnesota Twin Cities, University of Minnesota System filed Critical University of Minnesota Twin Cities
Application granted granted Critical
Publication of ES2173300T3 publication Critical patent/ES2173300T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A61K39/12—Viral antigens
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • 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
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/525—Virus
    • A61K2039/5254—Virus avirulent or attenuated
    • 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
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • A61K2039/541—Mucosal route
    • A61K2039/543—Mucosal route intranasal
    • 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
    • A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552—Veterinary vaccine
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/10011—Arteriviridae
    • C12N2770/10034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

SE APORTAN VACUNAS PRRS VIVAS O VIVAS MODIFICADAS PARA SU ADMINISTRACION A CERDOS, QUE POSEEN BAJA VIRULENCIA Y CONFIEREN INMUNIDAD EFECTIVA CONTRA PRRS. LAS VACUNAS PREFERIDAS INCLUYEN AISLADOS DE VIRUS CON UN PROMEDIO DE DIAMETROS DE PLACA DE MENOS DE UNOS 2 MM Y BAJA PATOGENICIDAD. UNA VACUNA PREFERIDA INCLUYE UNA CEPA DE PEQUEÑO DIAMETRO DE PLACA, ATCC ACCESION NO. VR2509. LAS VACUNAS DE LA INVENCION PUEDEN ADMINISTRARSE A HEMBRAS CRIANDO O A CERDAS PRIMIPARAS Y A LECHONES DESTETADOS, Y ES EFECTIVA PARA INMUNIZAR AL CERDO TANTO CONTRA LA FORMA RESPIRATORIA COMO REPRODUCTIVA DE LA ENFERMEDAD.
ES96922508T 1995-06-21 1996-06-19 Vacunas de virus vivos prrs de baja patogenicidad y metodos para su preparacion. Expired - Lifetime ES2173300T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US08/493,265 US5690940A (en) 1995-06-21 1995-06-21 Low pathogencity PRRS live virus vaccines and methods of preparation thereof

Publications (1)

Publication Number Publication Date
ES2173300T3 true ES2173300T3 (es) 2002-10-16

Family

ID=23959539

Family Applications (1)

Application Number Title Priority Date Filing Date
ES96922508T Expired - Lifetime ES2173300T3 (es) 1995-06-21 1996-06-19 Vacunas de virus vivos prrs de baja patogenicidad y metodos para su preparacion.

Country Status (20)

Country Link
US (1) US5690940A (es)
EP (1) EP0833661B1 (es)
JP (1) JP4709094B2 (es)
KR (1) KR100444809B1 (es)
CN (1) CN1126569C (es)
AT (1) ATE215384T1 (es)
AU (1) AU703084B2 (es)
BR (1) BR9608648A (es)
CA (1) CA2225388C (es)
CZ (1) CZ291611B6 (es)
DE (1) DE69620402T2 (es)
DK (1) DK0833661T3 (es)
ES (1) ES2173300T3 (es)
HU (1) HU227754B1 (es)
PL (1) PL184231B1 (es)
PT (1) PT833661E (es)
RU (1) RU2192887C2 (es)
SK (1) SK281024B6 (es)
UA (1) UA47433C2 (es)
WO (1) WO1997000696A1 (es)

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69201441T3 (de) 1991-06-06 2008-12-04 Boehringer Ingelheim Vetmedica Gmbh Erreger der mysteriösen schweinekrankheit,impfstoff-zusammensetzungen und diagnose kits.
US5866401A (en) * 1996-03-01 1999-02-02 Schering Corporation Porcine reproductive and respiratory syndrome vaccine
EE04741B1 (et) * 1996-03-01 2006-12-15 Schering Corporation Sigade sigimis- ja hingamissündroomi vaktsiin
US20040224327A1 (en) * 1996-10-30 2004-11-11 Meulenberg Johanna Jacoba Maria Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof
EP0839912A1 (en) * 1996-10-30 1998-05-06 Instituut Voor Dierhouderij En Diergezondheid (Id-Dlo) Infectious clones of RNA viruses and vaccines and diagnostic assays derived thereof
EP1882696A3 (en) 1997-05-06 2008-03-05 Boehringer Ingelheim Vetmedica Gmbh PRRSV antigenic sites identifying peptide sequences of PRRS virus for use in vaccines or diagnostic assays
CA2366072C (en) * 1999-03-08 2007-07-10 Id-Lelystad, Instituut Voor Dierhouderij En Diergezondheid B.V. Prrsv vaccines
MXPA01010681A (es) * 1999-04-22 2003-08-20 Us Agriculture Vacuna de sindrome respiratorio y reproductiva porcina a base de ja-142 aislado.
SG83740A1 (en) * 1999-08-10 2001-10-16 Inst Of Molecular Agrobiology An attenuated porcine reproductive and respiratory syndrome virus strain and methods of use
RU2007101725A (ru) * 2004-06-18 2008-07-27 Риджентс Оф Дзе Юниверсити Оф Миннесота (Us) Идентификация инфицированных вирусом и вакцинированных вирусом организмов
US7632636B2 (en) * 2004-09-21 2009-12-15 Boehringer Ingelheim Vetmedica, Inc. Porcine reproductive and respiratory syndrome isolates and methods of use
CA2894069C (en) 2005-06-24 2019-02-26 Regents Of The University Of Minnesota Prrs viruses, infectious clones, mutants thereof, and methods of use
US7241582B2 (en) 2005-07-05 2007-07-10 Mj Biologics, Inc. Diagnostic test kits
RU2316346C2 (ru) * 2006-02-20 2008-02-10 Федеральное государственное учреждение "Федеральный центр охраны здоровья животных" (ФГУ "ВНИИЗЖ") Вакцина против репродуктивно-респираторного синдрома свиней эмульсионная инактивированная
ES2389748T3 (es) * 2007-06-25 2012-10-31 South Dakota State University Virus del síndrome reproductivo y respiratorio porcino de tipo 1 norteamericano recombinante y métodos de uso
KR101653177B1 (ko) * 2008-08-25 2016-09-01 베링거잉겔하임베트메디카인코퍼레이티드 고병원성 돼지 생식기 및 호흡기 증후군(ｈｐ ｐｒｒｓ)에 대한 백신
US8762067B2 (en) 2008-10-31 2014-06-24 The Invention Science Fund I, Llc Methods and systems for ablation or abrasion with frozen particles and comparing tissue surface ablation or abrasion data to clinical outcome data
US20100111857A1 (en) 2008-10-31 2010-05-06 Boyden Edward S Compositions and methods for surface abrasion with frozen particles
US9050070B2 (en) 2008-10-31 2015-06-09 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8545857B2 (en) 2008-10-31 2013-10-01 The Invention Science Fund I, Llc Compositions and methods for administering compartmentalized frozen particles
US8731841B2 (en) 2008-10-31 2014-05-20 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8409376B2 (en) 2008-10-31 2013-04-02 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8551505B2 (en) 2008-10-31 2013-10-08 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8731840B2 (en) 2008-10-31 2014-05-20 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US9060934B2 (en) 2008-10-31 2015-06-23 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8788211B2 (en) 2008-10-31 2014-07-22 The Invention Science Fund I, Llc Method and system for comparing tissue ablation or abrasion data to data related to administration of a frozen particle composition
US8858912B2 (en) 2008-10-31 2014-10-14 The Invention Science Fund I, Llc Frozen compositions and methods for piercing a substrate
US9072688B2 (en) 2008-10-31 2015-07-07 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US8725420B2 (en) 2008-10-31 2014-05-13 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8603494B2 (en) 2008-10-31 2013-12-10 The Invention Science Fund I, Llc Compositions and methods for administering compartmentalized frozen particles
US8721583B2 (en) 2008-10-31 2014-05-13 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US9072799B2 (en) 2008-10-31 2015-07-07 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US8414356B2 (en) 2008-10-31 2013-04-09 The Invention Science Fund I, Llc Systems, devices, and methods for making or administering frozen particles
US8613937B2 (en) 2008-10-31 2013-12-24 The Invention Science Fund I, Llc Compositions and methods for biological remodeling with frozen particle compositions
US9060931B2 (en) 2008-10-31 2015-06-23 The Invention Science Fund I, Llc Compositions and methods for delivery of frozen particle adhesives
US8545855B2 (en) 2008-10-31 2013-10-01 The Invention Science Fund I, Llc Compositions and methods for surface abrasion with frozen particles
US20100111835A1 (en) * 2008-10-31 2010-05-06 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Compositions and methods for therapeutic delivery with frozen particles
US8603495B2 (en) 2008-10-31 2013-12-10 The Invention Science Fund I, Llc Compositions and methods for biological remodeling with frozen particle compositions
US8793075B2 (en) 2008-10-31 2014-07-29 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US9060926B2 (en) 2008-10-31 2015-06-23 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
US9050251B2 (en) 2008-10-31 2015-06-09 The Invention Science Fund I, Llc Compositions and methods for delivery of frozen particle adhesives
US9050317B2 (en) 2008-10-31 2015-06-09 The Invention Science Fund I, Llc Compositions and methods for therapeutic delivery with frozen particles
AR078253A1 (es) * 2009-09-02 2011-10-26 Boehringer Ingelheim Vetmed Metodos para reducir la actividad antivirica en composiciones pcv-2 y composiciones pcv-2 con mejor inmunogenicidad
US8263677B2 (en) 2009-09-08 2012-09-11 Creative Nail Design, Inc. Removable color gel basecoat for artificial nail coatings and methods therefore
US8492454B2 (en) * 2009-10-05 2013-07-23 Creative Nail Design, Inc. Removable color layer for artificial nail coatings and methods therefore
US8541482B2 (en) * 2009-10-05 2013-09-24 Creative Nail Design, Inc. Removable multilayer nail coating system and methods therefore
ES2550258T3 (es) 2011-02-17 2015-11-05 Boehringer Ingelheim Vetmedica Gmbh Nueva cepa del PRRSV europea
SG192821A1 (en) 2011-02-17 2013-09-30 Boehringer Ingelheim Vetmed Commercial scale process for production of prrsv
AU2011361736A1 (en) 2011-03-07 2013-05-02 Creative Nail Design, Inc. Compositions and methods for UV-curable cosmetic nail coatings
KR101281361B1 (ko) 2011-07-18 2013-07-02 서울대학교산학협력단 북미형 돼지 생식기 호흡기 증후군 바이러스 예방 백신 조성물 및 이를 포함하는 혼합백신 조성물
EP2737059A1 (en) 2011-07-29 2014-06-04 Boehringer Ingelheim Vetmedica GmbH Novel prrs virus inducing type i interferon in susceptible cells
US9187731B2 (en) 2011-07-29 2015-11-17 Boehringer Ingelheim Vetmedica Gmbh PRRS virus inducing type I interferon in susceptible cells
WO2014089117A1 (en) 2012-12-07 2014-06-12 The Board Of Trustees Of The University Of Illinois Porcine reproductive and respiratory syndrome virus compositions and uses thereof
WO2014150822A2 (en) 2013-03-15 2014-09-25 Boehringer Ingelheim Vetmedica, Inc. Porcine reproductive and respiratory syndrome virus, compositions, vaccine and methods of use
US10279031B2 (en) 2016-05-11 2019-05-07 Phibro Animal Health Corporation Composition comprising antigens and a mucosal adjuvant and a method for using

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2684792A (en) * 1991-10-14 1993-05-21 Akzo Nobel N.V. Porcine reproductive respiratory syndrome vaccine and diagnostic
US5695766A (en) * 1992-10-30 1997-12-09 Iowa State University Research Foundation Highly virulent porcine reproductive and respiratory syndrome viruses which produce lesions in pigs and vaccines that protect pigs against said syndrome
KR100374295B1 (ko) * 1993-02-08 2003-12-24 바이엘 코포레이션 돼지생식및호흡증후군바이러스의생육방법과백신에서그의용도
ES2074950B1 (es) * 1993-09-17 1996-03-16 Iberica Cyanamid Vacuna para la prevencion de la enfermedad reproductiva y respiratoria de la cerda.

Also Published As

Publication number Publication date
CZ412797A3 (cs) 1998-05-13
MX9710149A (es) 1998-07-31
DE69620402T2 (de) 2002-11-07
EP0833661A1 (en) 1998-04-08
HU227754B1 (en) 2012-02-28
BR9608648A (pt) 1999-12-07
ATE215384T1 (de) 2002-04-15
HUP9903169A3 (en) 2001-06-28
JP3954101B2 (ja) 2007-08-08
SK165797A3 (en) 1998-05-06
US5690940A (en) 1997-11-25
PL184231B1 (pl) 2002-09-30
EP0833661B1 (en) 2002-04-03
WO1997000696A1 (en) 1997-01-09
JP2006306894A (ja) 2006-11-09
CN1126569C (zh) 2003-11-05
AU6336196A (en) 1997-01-22
RU2192887C2 (ru) 2002-11-20
KR19990022848A (ko) 1999-03-25
HUP9903169A2 (hu) 2000-01-28
JP4709094B2 (ja) 2011-06-22
CZ291611B6 (cs) 2003-04-16
DE69620402D1 (de) 2002-05-08
PL324204A1 (en) 1998-05-11
HK1016870A1 (en) 1999-11-12
CN1188417A (zh) 1998-07-22
CA2225388A1 (en) 1997-01-09
JPH11509087A (ja) 1999-08-17
AU703084B2 (en) 1999-03-18
UA47433C2 (uk) 2002-07-15
PT833661E (pt) 2002-08-30
EP0833661A4 (en) 1998-10-21
CA2225388C (en) 2010-03-23
KR100444809B1 (ko) 2004-11-06
SK281024B6 (sk) 2000-11-07
DK0833661T3 (da) 2002-05-06

Similar Documents

Publication Publication Date Title
ES2173300T3 (es) Vacunas de virus vivos prrs de baja patogenicidad y metodos para su preparacion.
CO5611162A2 (es) Metodos para prevenir enfermedades reproductivas en el ganado vacuno
ES2065303T5 (es) Procedimiento de diagnosis y vacuna especifica.
ES2170234T3 (es) Vacuna contra el virus prrs (sindrome reproductor y respiratorio porcino).
NZ323973A (en) Vaccine compositions for intranasal administration comprising chitosan and use thereof
TNSN05059A1 (fr) Vaccin pour des infections du systeme respiratoire et du systeme reproducteur chez les bovins
ES2192582T3 (es) Composicion de vaccineo, conteniendo quitina, parcialmente deacetilado.
ES2118815T3 (es) Virus de la seudorrabia, s-prv-155, atenuado y obtenido por ingenieria genetica y sus usos.
PT1326635E (pt) Composicao farmaceutica para imunizacao contra a sida
ES2074950B1 (es) Vacuna para la prevencion de la enfermedad reproductiva y respiratoria de la cerda.
Levine et al. Vaccines and vaccination in historical perspective
ES2035818T3 (es) Mutantes de delecion de la timidin-kinasa del virus del herpes bovino-1, vacunas contra la rinotraqueitis bovina infecciosa que los contienen y metodos para su produccion y uso.
CY1107188T1 (el) Εμβολιο ε. coli πτηνου για την προστασια εναντι κολοβακτηριωσης
ES2070266T3 (es) Vacuna contra la infeccion por escherichia coli.
BR0317544A (pt) Uso de uma composição que compreende vlps de hpv 16 e hpv 18, e, métodos para induzir uma resposta imune contra um ou mais do grupo de tipos de hpv oncogênicos, para prevenir infecção e/ou doença causada por um ou mais do grupo de tipos de hpv oncogênicos, para prevenir a infecção de uma população de pacientes por um ou mais tipos de hpv, uso de uma mistura de vlps de hpv 16 e hpv18, e, composição de vacina
ES2155129T3 (es) Vacunacion in ovo contra la coccidiosis.
Ruitenberg et al. A prime-boost immunization strategy with DNA and recombinant baculovirus-expressed protein enhances protective immunogenicity of glycoprotein D of equine herpesvirus 1 in naı̈ve and infection-primed mice
CO5090882A1 (es) Nueva vacuna y procedimiento de uso des transmitidas sexualmente
CL2022002832A1 (es) Vacuna inactivada para sars-cov-2 y preparación de la misma
ES2127761T3 (es) Vacuna contra la dermatomicosis.
AU6383296A (en) Multivalent bovine coronavirus vaccine and method of treating bovine coronavirus infection
NZ505538A (en) A vaccine comprising immunogenic acyl glyceryl phosphatidylinositol manno-oligosaccharide (PIM); and the use of PIM for inducing an immune response in a patient effective in the prevention or treatment of Th2-mediated diseases or disorders such as asthma
ES2098788T3 (es) Nueva bacteria que provoca enfermedades en las aves y vacuna derivada de esta bacteria.
AR037020A1 (es) Vacuna contra pasteurella trehalosi y/o mannheimia haemolytica, nueva enfermedad bacteriana de las aves de corral del tracto respiratorio superior y tracto reproductor.
AR027558A1 (es) Proteccion in ovo contra bronquitis infecciosa

Legal Events

Date Code Title Description
FG2A Definitive protection

Ref document number: 833661

Country of ref document: ES