ATE404582T1 - Immunogene zusammensetzungen, die replikonvektoren des venezolanischen pferdeencephalitisvirus und paramyxovirus- proteinantigene enthalten - Google Patents
Immunogene zusammensetzungen, die replikonvektoren des venezolanischen pferdeencephalitisvirus und paramyxovirus- proteinantigene enthaltenInfo
- Publication number
- ATE404582T1 ATE404582T1 AT04776196T AT04776196T ATE404582T1 AT E404582 T1 ATE404582 T1 AT E404582T1 AT 04776196 T AT04776196 T AT 04776196T AT 04776196 T AT04776196 T AT 04776196T AT E404582 T1 ATE404582 T1 AT E404582T1
- Authority
- AT
- Austria
- Prior art keywords
- blebs
- immunogenic compositions
- venuezolan
- enchalitis
- equinovirus
- Prior art date
Links
- 230000002163 immunogen Effects 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 title abstract 2
- 241000700605 Viruses Species 0.000 title 1
- 239000000427 antigen Substances 0.000 title 1
- 102000036639 antigens Human genes 0.000 title 1
- 108091007433 antigens Proteins 0.000 title 1
- 108700010867 paramyxovirus proteins Proteins 0.000 title 1
- 239000013598 vector Substances 0.000 title 1
- 208000002352 blister Diseases 0.000 abstract 4
- 230000000799 fusogenic effect Effects 0.000 abstract 2
- 239000002245 particle Substances 0.000 abstract 2
- 241000712003 Human respirovirus 3 Species 0.000 abstract 1
- 241000124008 Mammalia Species 0.000 abstract 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 abstract 1
- 108010059722 Viral Fusion Proteins Proteins 0.000 abstract 1
- 230000000120 cytopathologic effect Effects 0.000 abstract 1
- 230000002950 deficient Effects 0.000 abstract 1
- 230000003053 immunization Effects 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 230000010076 replication Effects 0.000 abstract 1
- 239000006228 supernatant Substances 0.000 abstract 1
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
-
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
- C07K14/08—RNA viruses
- C07K14/18—Togaviridae; Flaviviridae
-
- 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
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- A61K2039/5256—Virus expressing foreign proteins
-
- 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
-
- 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
- C12N2760/18511—Pneumovirus, e.g. human respiratory syncytial virus
- C12N2760/18522—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
- 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
- C12N2760/18622—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
- 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
-
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36122—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
- 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
- C12N2770/36011—Togaviridae
- C12N2770/36111—Alphavirus, e.g. Sindbis virus, VEE, EEE, WEE, Semliki
- C12N2770/36141—Use of virus, viral particle or viral elements as a vector
- C12N2770/36143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Plant Pathology (AREA)
- Communicable Diseases (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47613703P | 2003-06-05 | 2003-06-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE404582T1 true ATE404582T1 (de) | 2008-08-15 |
Family
ID=34193021
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT04776196T ATE404582T1 (de) | 2003-06-05 | 2004-06-02 | Immunogene zusammensetzungen, die replikonvektoren des venezolanischen pferdeencephalitisvirus und paramyxovirus- proteinantigene enthalten |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US7541038B2 (de) |
| EP (1) | EP1629004B1 (de) |
| JP (1) | JP2007534295A (de) |
| KR (1) | KR20060017635A (de) |
| CN (1) | CN1798760A (de) |
| AT (1) | ATE404582T1 (de) |
| AU (1) | AU2004265232A1 (de) |
| BR (1) | BRPI0411099A (de) |
| CA (1) | CA2526146A1 (de) |
| DE (1) | DE602004015775D1 (de) |
| DK (1) | DK1629004T3 (de) |
| ES (1) | ES2311857T3 (de) |
| MX (1) | MXPA05012542A (de) |
| PL (1) | PL1629004T3 (de) |
| PT (1) | PT1629004E (de) |
| SI (1) | SI1629004T1 (de) |
| WO (1) | WO2005016961A1 (de) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI377253B (en) | 2001-04-16 | 2012-11-21 | Martek Biosciences Corp | Product and process for transformation of thraustochytriales microorganisms |
| AU2003237346A1 (en) * | 2002-05-31 | 2003-12-19 | Thomas Jefferson University | Compositions and methods for transepithelial molecular transport |
| US20090104226A1 (en) * | 2004-05-21 | 2009-04-23 | Novartis Vaccines And Diagnostics Inc. | Alphavirus Vectors for Respiratory Pathogen Vaccines |
| US20090162395A1 (en) * | 2007-09-26 | 2009-06-25 | Crowe Jr James E | Vaccine for rsv and mpv |
| ES2752196T3 (es) * | 2009-03-16 | 2020-04-03 | Dsm Ip Assets Bv | Producción de proteínas en microorganismos del filo Labyrinthulomycota |
| US20110032319A1 (en) * | 2009-08-10 | 2011-02-10 | Kornit Digital Technologies Ltd. | Digital printing device with improved pre-printing textile surface treatment |
| IN2012DN06277A (de) * | 2009-12-28 | 2015-09-25 | Dsm Ip Assets Bv | |
| EP2519636B8 (de) * | 2009-12-28 | 2017-08-09 | DSM IP Assets B.V. | Herstellung eines hämagglutinin-neuraminidase-proteins in mikroalgen |
| NZ717682A (en) * | 2012-02-16 | 2017-10-27 | Vlp Therapeutics Llc | Virus like particle composition |
| MX2019013259A (es) | 2017-05-08 | 2020-01-13 | Gritstone Oncology Inc | Vectores de neoantigeno de alfavirus. |
| EP4368702A3 (de) * | 2017-09-13 | 2024-08-14 | BioNTech SE | Verfahren zur erhöhung der rna-expression in einer zelle |
| BR112020011044A2 (pt) | 2017-12-04 | 2020-11-17 | Intervet International B.V. | vacinação com partículas de replicon e adjuvante de óleo |
| EP3735271A4 (de) | 2018-01-04 | 2022-06-15 | Iconic Therapeutics, Inc. | Anti-gewebefaktor-antikörper, antikörperarzneimittel-konjugate und verwandte verfahren |
| MX2021014525A (es) | 2019-05-30 | 2022-03-17 | Gritstone Bio Inc | Adenovirus modificados. |
| WO2021138447A1 (en) | 2019-12-31 | 2021-07-08 | Elixirgen Therapeutics, Inc. | Temperature-based transient delivery of nucleic acids and proteins to cells and tissues |
| KR20230046313A (ko) | 2020-08-06 | 2023-04-05 | 그릿스톤 바이오, 인코포레이티드 | 다중에피토프 백신 카세트 |
| CN114317563B (zh) * | 2021-12-17 | 2023-09-05 | 华南理工大学 | 提高基因表达的rna复制子及其应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4650764A (en) * | 1983-04-12 | 1987-03-17 | Wisconsin Alumni Research Foundation | Helper cell |
| US5091309A (en) * | 1986-01-16 | 1992-02-25 | Washington University | Sindbis virus vectors |
| AU611784B2 (en) * | 1988-04-22 | 1991-06-20 | Pharmacia & Upjohn Company | Chimeric glycoproteins containing immunogenic segments of human parainfluenza virus type 3 |
| US5217879A (en) * | 1989-01-12 | 1993-06-08 | Washington University | Infectious Sindbis virus vectors |
| US5185440A (en) * | 1989-06-20 | 1993-02-09 | North Carolina State University | cDNA clone coding for Venezuelan equine encephalitis virus and attenuating mutations thereof |
| US5580564A (en) * | 1990-08-15 | 1996-12-03 | Akzo Nobel N.V. | Method for modifying the cell, tissue or host tropism of microorganisms; recombinant microorganisms obtained in this way and use thereof in medicine and veterinary medicine |
| US5512421A (en) * | 1991-02-19 | 1996-04-30 | The Regents Of The University Of California | Generation, concentration and efficient transfer of VSV-G pseudotyped retroviral vectors |
| US5505947A (en) * | 1994-05-27 | 1996-04-09 | The University Of North Carolina At Chapel Hill | Attenuating mutations in Venezuelan Equine Encephalitis virus |
| US5792462A (en) * | 1995-05-23 | 1998-08-11 | University Of North Carolina At Chapel Hill | Alphavirus RNA replicon systems |
| CA2309826A1 (en) * | 1997-11-14 | 1999-05-27 | Connaught Laboratories Limited | Alphavirus vectors for paramyxovirus vaccines |
| NZ505312A (en) * | 1997-12-22 | 2003-01-31 | Univ Tennesse Res Corp | Recombinant Vesicular Stomatitis virus comprising a heterologous F protein (Paramyxovirus strain SV5) and CD4 antireceptor protein |
| CN1416471A (zh) | 2000-01-28 | 2003-05-07 | 托马斯杰斐逊大学 | 重组弹状病毒作为免疫缺陷病毒的活病毒疫苗 |
| WO2001092548A2 (en) | 2000-06-01 | 2001-12-06 | St. Jude Children's Research Hospital | Vaccine and gene therapy vector and methods of use thereof |
| WO2002080983A1 (en) | 2001-04-05 | 2002-10-17 | The Uab Research Foundation | Enhanced dispersion of adenoviral vectors by fusogenic membrane glycoproteins |
| WO2002089728A2 (en) | 2001-04-20 | 2002-11-14 | Thomas Jefferson University | Recombinant rhabdoviruses as live-viral vaccines |
| US20030077251A1 (en) | 2001-05-23 | 2003-04-24 | Nicolas Escriou | Replicons derived from positive strand RNA virus genomes useful for the production of heterologous proteins |
| AU2002303330B2 (en) * | 2001-05-31 | 2008-07-24 | Novartis Vaccines And Diagnostics, Inc. | Chimeric alphavirus replicon particles |
| US20040208848A1 (en) * | 2002-12-13 | 2004-10-21 | Smith Jonathan F. | Multi-antigenic alphavirus replicon particles and methods |
-
2004
- 2004-06-02 AT AT04776196T patent/ATE404582T1/de not_active IP Right Cessation
- 2004-06-02 PL PL04776196T patent/PL1629004T3/pl unknown
- 2004-06-02 MX MXPA05012542A patent/MXPA05012542A/es active IP Right Grant
- 2004-06-02 AU AU2004265232A patent/AU2004265232A1/en not_active Abandoned
- 2004-06-02 SI SI200430895T patent/SI1629004T1/sl unknown
- 2004-06-02 KR KR1020057023359A patent/KR20060017635A/ko not_active Withdrawn
- 2004-06-02 DK DK04776196T patent/DK1629004T3/da active
- 2004-06-02 BR BRPI0411099-4A patent/BRPI0411099A/pt not_active IP Right Cessation
- 2004-06-02 JP JP2006515041A patent/JP2007534295A/ja active Pending
- 2004-06-02 PT PT04776196T patent/PT1629004E/pt unknown
- 2004-06-02 ES ES04776196T patent/ES2311857T3/es not_active Expired - Lifetime
- 2004-06-02 US US10/559,429 patent/US7541038B2/en not_active Expired - Fee Related
- 2004-06-02 CA CA002526146A patent/CA2526146A1/en not_active Abandoned
- 2004-06-02 CN CNA2004800150075A patent/CN1798760A/zh active Pending
- 2004-06-02 DE DE602004015775T patent/DE602004015775D1/de not_active Expired - Fee Related
- 2004-06-02 WO PCT/US2004/017127 patent/WO2005016961A1/en not_active Ceased
- 2004-06-02 EP EP04776196A patent/EP1629004B1/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1798760A (zh) | 2006-07-05 |
| ES2311857T3 (es) | 2009-02-16 |
| US20070128222A1 (en) | 2007-06-07 |
| DE602004015775D1 (de) | 2008-09-25 |
| WO2005016961A1 (en) | 2005-02-24 |
| PL1629004T3 (pl) | 2009-02-27 |
| SI1629004T1 (sl) | 2008-12-31 |
| CA2526146A1 (en) | 2005-02-24 |
| US7541038B2 (en) | 2009-06-02 |
| EP1629004A1 (de) | 2006-03-01 |
| JP2007534295A (ja) | 2007-11-29 |
| DK1629004T3 (da) | 2008-11-17 |
| EP1629004B1 (de) | 2008-08-13 |
| PT1629004E (pt) | 2008-11-14 |
| AU2004265232A1 (en) | 2005-02-24 |
| KR20060017635A (ko) | 2006-02-24 |
| MXPA05012542A (es) | 2006-02-08 |
| BRPI0411099A (pt) | 2006-07-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| UEP | Publication of translation of european patent specification |
Ref document number: 1629004 Country of ref document: EP |
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| REN | Ceased due to non-payment of the annual fee |