AU782154C - DNA vaccines for pets and sport animals - Google Patents

DNA vaccines for pets and sport animals

Info

Publication number
AU782154C
AU782154C AU55405/00A AU5540500A AU782154C AU 782154 C AU782154 C AU 782154C AU 55405/00 A AU55405/00 A AU 55405/00A AU 5540500 A AU5540500 A AU 5540500A AU 782154 C AU782154 C AU 782154C
Authority
AU
Australia
Prior art keywords
pets
dna vaccines
sport animals
sport
animals
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
Application number
AU55405/00A
Other languages
English (en)
Other versions
AU782154B2 (en
AU5540500A (en
Inventor
Jean-Christophe Francis Audonnet
Simona Barzu-Le-Roux
Laurent Jean-Charles Fischer
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.)
Boehringer Ingelheim Animal Health USA Inc
Original Assignee
Merial Ltd
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
Priority claimed from FR9907604A external-priority patent/FR2794648B1/fr
Application filed by Merial Ltd filed Critical Merial Ltd
Publication of AU5540500A publication Critical patent/AU5540500A/en
Publication of AU782154B2 publication Critical patent/AU782154B2/en
Assigned to MERIAL LTD reassignment MERIAL LTD Amend patent request/document other than specification (104) Assignors: MERIAL
Application granted granted Critical
Publication of AU782154C publication Critical patent/AU782154C/en
Assigned to MERIAL, INC. reassignment MERIAL, INC. Alteration of Name(s) in Register under S187 Assignors: MERIAL LTD
Assigned to Boehringer Ingelheim Animal Health USA Inc. reassignment Boehringer Ingelheim Animal Health USA Inc. Request for Assignment Assignors: MERIAL, INC.
Anticipated expiration legal-status Critical
Expired legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • A61K39/245—Herpetoviridae, e.g. herpes simplex virus
    • A61K39/265—Infectious rhinotracheitis 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
    • 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
    • A61K39/155—Paramyxoviridae, e.g. parainfluenza virus
    • A61K39/175—Canine distemper 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
    • A61K39/245—Herpetoviridae, e.g. herpes simplex 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
    • A61K39/245—Herpetoviridae, e.g. herpes simplex virus
    • A61K39/27—Equine rhinopneumonitis virus
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/53—Colony-stimulating factor [CSF]
    • C07K14/535—Granulocyte CSF; Granulocyte-macrophage CSF
    • 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
    • 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
    • A61K2039/53—DNA (RNA) vaccination
    • 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
    • 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
    • A61K2039/70—Multivalent vaccine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16634—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16711—Varicellovirus, e.g. human herpesvirus 3, Varicella Zoster, pseudorabies
    • C12N2710/16734—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18311—Metapneumovirus, e.g. avian pneumovirus
    • C12N2760/18334—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18411—Morbillivirus, e.g. Measles virus, canine distemper
    • C12N2760/18434—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • 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
    • C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
    • C12N2760/00011—Details
    • C12N2760/18011—Paramyxoviridae
    • C12N2760/18611—Respirovirus, e.g. Bovine, human parainfluenza 1,3
    • C12N2760/18634—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)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Organic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
AU55405/00A 1999-06-10 2000-06-08 DNA vaccines for pets and sport animals Expired AU782154C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
FR9907604 1999-06-10
FR9907604A FR2794648B1 (fr) 1999-06-10 1999-06-10 Vaccins adn pour animaux de compagnie et de sport
US14449099P 1999-07-19 1999-07-19
US60/144490 1999-07-19
PCT/FR2000/001592 WO2000077043A2 (fr) 1999-06-10 2000-06-08 Vaccins adn pour animaux de compagnie et de sport

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2005202233A Division AU2005202233B2 (en) 1999-06-10 2005-05-23 DNA vaccines for pets and sport animals

Publications (3)

Publication Number Publication Date
AU5540500A AU5540500A (en) 2001-01-02
AU782154B2 AU782154B2 (en) 2005-07-07
AU782154C true AU782154C (en) 2006-02-09

Family

ID=26234993

Family Applications (1)

Application Number Title Priority Date Filing Date
AU55405/00A Expired AU782154C (en) 1999-06-10 2000-06-08 DNA vaccines for pets and sport animals

Country Status (11)

Country Link
EP (1) EP1185662B1 (https=)
JP (1) JP2003502345A (https=)
KR (1) KR100768114B1 (https=)
AR (1) AR024334A1 (https=)
AU (1) AU782154C (https=)
BR (1) BR0011732B1 (https=)
CA (1) CA2375320C (https=)
CZ (1) CZ20014392A3 (https=)
NZ (1) NZ515993A (https=)
PL (1) PL210451B1 (https=)
WO (1) WO2000077043A2 (https=)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2804028B1 (fr) * 2000-01-21 2004-06-04 Merial Sas Vaccins adn ameliores pour animaux de rente
FR2823222B1 (fr) 2001-04-06 2004-02-06 Merial Sas Vaccin contre le virus de la fievre du nil
FR2825280B1 (fr) * 2001-06-01 2005-04-15 Merial Sas Vaccination contre le virus de l'immunodeficience feline
WO2005049794A2 (en) 2003-11-13 2005-06-02 University Of Georgia Research Foundation, Inc. Methods of characterizing infectious bursal disease virus
RS51324B (sr) 2005-04-25 2010-12-31 Merial Ltd. Vakcine protiv nipah virusa
EP1954308B1 (en) * 2005-09-16 2011-09-07 Merial Ltd. Stabilizers for freeze-dried vaccines
US7682619B2 (en) 2006-04-06 2010-03-23 Cornell Research Foundation, Inc. Canine influenza virus
US7862821B2 (en) 2006-06-01 2011-01-04 Merial Limited Recombinant vaccine against bluetongue virus
US8877206B2 (en) 2007-03-22 2014-11-04 Pds Biotechnology Corporation Stimulation of an immune response by cationic lipids
EP2276495B1 (en) 2008-04-17 2018-11-21 PDS Biotechnology Corporation Stimulation of an immune response by enantiomers of cationic lipids
EP3756684A1 (en) 2009-05-22 2020-12-30 Genocea Biosciences, Inc. Vaccines against herpes simplex virus type 2: compositions and methods for eliciting an immune response
US20130197612A1 (en) * 2010-02-26 2013-08-01 Jack W. Lasersohn Electromagnetic Radiation Therapy
JP6055776B2 (ja) 2010-11-24 2016-12-27 ジェノセア バイオサイエンシーズ， インコーポレイテッド 単純ヘルペスウイルス２型に対するワクチン：免疫応答を誘発する組成物及び方法
AU2012340712B2 (en) 2011-11-23 2017-09-14 Genocea Biosciences, Inc. Nucleic acid vaccines against Herpes Simplex Virus type 2: compositions and methods for eliciting an immune response
CA2876656C (en) * 2012-06-15 2023-09-26 Pds Biotechnology Corporation Cationic lipid vaccine compositions and methods of use
CN113144188A (zh) 2012-09-21 2021-07-23 Pds生物科技公司 改进的疫苗组合物和使用方法
CN104164409A (zh) * 2014-07-18 2014-11-26 中国人民解放军军事医学科学院军事兽医研究所 含有犬gmcsf基因的重组犬瘟热病毒及其制备方法
CN104958283A (zh) * 2015-06-02 2015-10-07 北京盛大康成医疗技术有限公司 弱碱性皮肤粘膜清洗消毒组合物及其制造方法和用途
CA3005251A1 (en) 2015-11-13 2017-05-18 Pds Biotechnology Corporation Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy
KR101694676B1 (ko) 2015-12-10 2017-01-10 우진 비앤지 주식회사 말 선역 질병원인 국내 분리 스트렙토코커스 이콰이 균주 및 이를 포함하는 백신
US10350288B2 (en) 2016-09-28 2019-07-16 Genocea Biosciences, Inc. Methods and compositions for treating herpes
WO2019113200A1 (en) 2017-12-05 2019-06-13 Pds Biotechnology Corporation Methods and compositions comprising cationic lipids for stimulating type 1 interferon genes
US20220054616A1 (en) 2019-01-04 2022-02-24 Boehringer Ingelheim Animal Health USA Inc. Attenuated Bordetella Bronchiseptica Strains, Oral Vaccines Containing the Attenuated Strains, and Methods of Making & Use Thereof
IL291968A (en) * 2019-10-09 2022-06-01 Mayo Found Medical Education & Res Rabies megaloglutin virus and fusion polypeptides

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AU1131200A (en) * 1998-10-23 2000-05-15 Heska Corporation Cationic lipid-mediated enhancement of nucleic acid immunization of cats

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JPH11504631A (ja) * 1995-04-25 1999-04-27 バイカル インコーポレイテッド Ｄｎａ／脂質複合体の単一バイアル製剤
ES2109189B1 (es) * 1996-03-14 1998-05-16 Iberica Cyanamid Vectores basados en genomas virales defectivos recombinantes y su empleo en la formulacion de vacunas.
EP0954582A1 (en) * 1996-04-29 1999-11-10 Andreas Prof. Zurbriggen Polynucleotide vaccine against canine distemper
FR2751226B1 (fr) * 1996-07-19 1998-11-27 Rhone Merieux Formule de vaccin polynucleotidique contre les pathologies du cheval
FR2751223B1 (fr) * 1996-07-19 1998-12-04 Rhone Merieux Formule de vaccin polynucleotidique felin
FR2751227B1 (fr) * 1996-07-19 1998-11-27 Rhone Merieux Formule de vaccin polynucleotidique contre les pathologies canines, notamment les pathologies respiratoires et digestives
WO1998040499A1 (en) * 1997-03-10 1998-09-17 Heather Lynn Davis Gene delivery to mucosal epithelium for immunization or therapeutic purposes

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Publication number Priority date Publication date Assignee Title
AU1131200A (en) * 1998-10-23 2000-05-15 Heska Corporation Cationic lipid-mediated enhancement of nucleic acid immunization of cats

Non-Patent Citations (2)

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KLAVINSKIS ET AL. THE JOURNAL OF IMMU. (1999) 162(1) 254-262 *
OKADA ET AL. THE JOURNAL OF IMMUN. (1997) 159 3638-3647 *

Also Published As

Publication number Publication date
JP2003502345A (ja) 2003-01-21
CA2375320A1 (en) 2000-12-21
BR0011732B1 (pt) 2014-02-04
WO2000077043A3 (fr) 2001-07-19
PL210451B1 (pl) 2012-01-31
PL352212A1 (en) 2003-08-11
AU782154B2 (en) 2005-07-07
AU5540500A (en) 2001-01-02
KR100768114B1 (ko) 2007-10-17
EP1185662A2 (fr) 2002-03-13
WO2000077043A2 (fr) 2000-12-21
CA2375320C (en) 2013-02-19
CZ20014392A3 (cs) 2002-06-12
BR0011732A (pt) 2002-03-05
KR20020012271A (ko) 2002-02-15
NZ515993A (en) 2004-04-30
EP1185662B1 (fr) 2011-03-02
AR024334A1 (es) 2002-10-02

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Legal Events

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PC Assignment registered

Owner name: BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC.

Free format text: FORMER OWNER(S): MERIAL, INC.

MK14 Patent ceased section 143(a) (annual fees not paid) or expired