DK2134360T3 - Purification of virus-like particle - Google Patents
Purification of virus-like particle Download PDFInfo
- Publication number
- DK2134360T3 DK2134360T3 DK08782762.2T DK08782762T DK2134360T3 DK 2134360 T3 DK2134360 T3 DK 2134360T3 DK 08782762 T DK08782762 T DK 08782762T DK 2134360 T3 DK2134360 T3 DK 2134360T3
- Authority
- DK
- Denmark
- Prior art keywords
- vlps
- chromatography
- chromatographic
- vlp
- norovirus
- Prior art date
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- A—HUMAN NECESSITIES
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/20—Pills, tablets, discs, rods
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- 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
- A61P37/04—Immunostimulants
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/18—Ion-exchange chromatography
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- 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
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- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
- C12N7/02—Recovery or purification
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- 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
- C12N2770/16011—Caliciviridae
- C12N2770/16023—Virus like particles [VLP]
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- 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
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- C12N2770/16034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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- 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
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Landscapes
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- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US90682107P | 2007-03-14 | 2007-03-14 | |
| PCT/US2008/057072 WO2008113011A2 (en) | 2007-03-14 | 2008-03-14 | Virus like particle purification |
Publications (1)
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| DK2134360T3 true DK2134360T3 (en) | 2016-02-22 |
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| DK08782762.2T DK2134360T3 (en) | 2007-03-14 | 2008-03-14 | Purification of virus-like particle |
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| Country | Link |
|---|---|
| US (4) | US8481693B2 (https=) |
| EP (1) | EP2134360B1 (https=) |
| JP (4) | JP5284290B2 (https=) |
| KR (3) | KR101576219B1 (https=) |
| AU (1) | AU2008224877B2 (https=) |
| CA (1) | CA2683977C (https=) |
| DK (1) | DK2134360T3 (https=) |
| ES (1) | ES2559421T3 (https=) |
| HU (1) | HUE028605T2 (https=) |
| PL (1) | PL2134360T3 (https=) |
| SG (2) | SG10201701988TA (https=) |
| WO (1) | WO2008113011A2 (https=) |
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| EP2066354B1 (en) | 2006-09-29 | 2013-04-17 | Ligocyte Pharmaceuticals, Inc. | Norovirus vaccine formulations |
| WO2008113011A2 (en) | 2007-03-14 | 2008-09-18 | Ligocyte Pharmaceuticals, Inc. | Virus like particle purification |
| CN104740624B (zh) | 2007-09-18 | 2018-04-24 | 武田疫苗股份有限公司 | 赋予针对诺如病毒的保护性免疫应答的疫苗 |
| US20100266636A1 (en) | 2007-09-18 | 2010-10-21 | Ligocyte Pharmaceuticals, Inc. | Method of conferring a protective immune response to norovirus |
| KR20180000341A (ko) | 2009-06-16 | 2018-01-02 | 젠자임 코포레이션 | 재조합 ａａｖ 벡터에 대한 개선된 정제 방법 |
| WO2011000058A1 (en) * | 2009-07-03 | 2011-01-06 | The University Of Queensland | A method of preparation of a biological particulate structure |
| US20110142863A1 (en) * | 2009-12-16 | 2011-06-16 | Millipore Corporation | Flow through purification processes for large biomolecules |
| WO2011088225A1 (en) | 2010-01-15 | 2011-07-21 | Bio-Rad Laboratories, Inc. | Surface neutralization of apatite |
| BR112012026095A2 (pt) * | 2010-04-14 | 2015-09-15 | Emd Millipore Corp | métodos de produção de estoques de vírus de alta pureza e altos títulos e métodos de uso dos mesmos. |
| DE102010046817A1 (de) * | 2010-09-28 | 2012-03-29 | Sartorius Stedim Biotech Gmbh | Verfahren zur Abtrennung von Viren aus einem Kontaminanten enthaltenden flüssigen Medium |
| FI122520B (fi) * | 2010-10-15 | 2012-03-15 | Vesna Blazevic | Noroviruksen kapsidi ja rotaviruksen VP6-proteiini käytettäväksi yhdistelmärokotteena |
| EP2670704B1 (en) | 2011-02-02 | 2018-12-12 | Bio-Rad Laboratories, Inc. | Apatite surface neutralization with alkali solutions |
| EP4112074A1 (en) * | 2011-07-11 | 2023-01-04 | Takeda Vaccines, Inc. | Parenteral norovirus vaccine formulations |
| EP2554664A1 (de) * | 2011-08-02 | 2013-02-06 | Life Science Inkubator | Verfahren zur Aufreinigung von Virus-ähnlichen Partikeln (VLP) |
| US9517261B2 (en) * | 2011-12-30 | 2016-12-13 | Deutsches Krebsforschungszentrum | Second generation virus-like particles (VLP) from Epstein-Barr viruses for vaccination purposes |
| US9815695B2 (en) | 2012-05-30 | 2017-11-14 | Bio-Rad Laboratories, Inc. | In situ restoration of apatite-based chromatography resins |
| JOP20130186B1 (ar) * | 2012-06-22 | 2021-08-17 | Takeda Vaccines Montana Inc | تنقية الجزيئات الشبيهة بالفيروسات |
| EP2958995A4 (en) * | 2013-02-22 | 2016-11-23 | Agency Science Tech & Res | CHROMATOGRAPHIC CLEANING OF VIRUS PREPARATIONS WITH NEGATIVELY LOADED PARTICLES |
| JP2015015931A (ja) * | 2013-07-12 | 2015-01-29 | 株式会社Ｕｍｎファーマ | ウイルス様粒子を含む培養物の製造方法 |
| JP6479305B2 (ja) * | 2013-07-12 | 2019-03-06 | 株式会社Ｕｍｎファーマ | ウイルス様粒子の精製方法 |
| JP2015017065A (ja) * | 2013-07-12 | 2015-01-29 | 株式会社Ｕｍｎファーマ | ノロウイルスのウイルス様粒子を含む医薬組成物 |
| CN106103720A (zh) | 2013-10-03 | 2016-11-09 | 武田疫苗股份有限公司 | 自细胞系检测和除去弹状病毒的方法 |
| CN105407917B (zh) | 2014-06-23 | 2021-07-06 | 生物辐射实验室股份有限公司 | 磷灰石原位恢复 |
| US9802822B2 (en) | 2014-06-23 | 2017-10-31 | Bio-Rad Laboratories, Inc. | Apatite pretreatment |
| CN107603959A (zh) * | 2017-08-30 | 2018-01-19 | 四川大学 | 提高缓冲液盐离子浓度纯化病毒的方法 |
| TWI816721B (zh) * | 2017-12-07 | 2023-10-01 | 德商Ｅｍｐ生物科技公司 | 應用徑向技術色層分析術的系統及方法 |
| JP6704074B2 (ja) * | 2019-02-04 | 2020-06-03 | 株式会社Ｕｍｎファーマ | ウイルス様粒子の精製方法 |
| WO2021002257A1 (ja) * | 2019-07-04 | 2021-01-07 | 株式会社カネカ | ウイルスまたはウイルス様粒子の精製方法 |
| KR20230056661A (ko) * | 2020-08-28 | 2023-04-27 | 가부시키가이샤 가네카 | 유용 물질의 정제 방법 |
| AU2022217587A1 (en) * | 2021-02-02 | 2023-08-17 | C. I. TAKIRON Corporation | Solar power generation system and reflector for solar power generation system |
| US20240238401A1 (en) | 2021-05-21 | 2024-07-18 | Takeda Vaccines, Inc. | Solid composition, freeze-drying method and glass vial |
| WO2025077800A1 (en) * | 2023-10-12 | 2025-04-17 | Chengdu Kanghua Biological Products Co., Ltd. | Purification of norovirus virus-like particles (vlps) |
| WO2025077807A1 (en) * | 2023-10-12 | 2025-04-17 | Chengdu Kanghua Biological Products Co., Ltd. | Methods for obtaining high-purity norovirus virus-like particles (vlps) |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2833106B2 (ja) | 1990-02-21 | 1998-12-09 | 株式会社島津製作所 | 液体クロマトグラフ |
| WO1994026087A2 (en) | 1993-05-14 | 1994-11-24 | Connor Kim C O | Recombinant protein production and insect cell culture and process |
| ATE328068T1 (de) * | 1994-05-16 | 2006-06-15 | Merck & Co Inc | Papillomavirus vakzine |
| AR004464A1 (es) * | 1994-11-14 | 1998-12-16 | Merck Sharp & Dohme | Un metodo para producir una proteina de capside de papilomavirus |
| JP3316325B2 (ja) | 1994-12-20 | 2002-08-19 | 富士シリシア化学株式会社 | ビール安定化処理用シリカゲル及びその製造方法並びにビールの安定化処理方法 |
| US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
| CA2269097C (en) | 1996-11-08 | 2007-01-09 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Synthesis and purification of hepatitis c virus-like particles |
| EP1015561B1 (en) | 1997-09-05 | 2006-07-19 | Medimmune, Inc. | In vitro method for disassembly/reassembly of papillomavirus virus-like particles (vlps) |
| DE19823814A1 (de) | 1998-05-27 | 1999-12-02 | Octapharma Ag Ziegelbruecke | Verfahren zur Trennung und/oder Isolierung von Plasmaproteinen mit annularer Chromatographie |
| HUP0103091A3 (en) * | 1998-08-14 | 2002-03-28 | Merck & Co Inc | Process for purifying human papillomavirus virus-like particles |
| US6349843B1 (en) | 1999-04-01 | 2002-02-26 | The Vollrath Company Llc | Pan removal ramp |
| KR100771402B1 (ko) * | 1999-06-22 | 2007-10-30 | 국립감염증연구소장이 대표하는 일본국 | Ｓｒｓｖ 검출 킷트 |
| DE10012732A1 (de) | 2000-03-18 | 2001-09-20 | Aventis Behring Gmbh | Thrombin-Zubereitungen und Verfahren zu ihrer Herstellung |
| JP2003066021A (ja) | 2001-08-28 | 2003-03-05 | Hiroshi Shionoya | 連続分取液体クロマトグラフィー装置とそれを用いる方法 |
| US20040121465A1 (en) * | 2002-02-14 | 2004-06-24 | Novavax, Inc. | Optimization of gene sequences of virus-like particles for expression in insect cells |
| WO2003102132A2 (en) | 2002-04-26 | 2003-12-11 | Genetech, Inc. | Non-affinity purification of proteins |
| US20040106184A1 (en) | 2002-08-28 | 2004-06-03 | Introgen Therapeutics Inc. | Chromatographic methods for adenovirus purification |
| WO2005032457A2 (en) * | 2003-07-21 | 2005-04-14 | Boyce Thompson Institute For Plant Research, Inc. | Vectors and methods for immunization against norwalk virus using transgenic plants |
| US7481997B1 (en) * | 2004-02-12 | 2009-01-27 | Montana State University | Snow mountain virus genome sequence, virus-like particles and methods of use |
| WO2006138514A2 (en) * | 2005-06-16 | 2006-12-28 | Children's Hospital Medical Center | Novel norovirus particle for use as an antiviral or vaccine |
| EP1736538A1 (en) * | 2005-06-21 | 2006-12-27 | Cytos Biotechnology AG | Process for the preparative purification of virus-like-particles (VLPs) |
| ES2514316T3 (es) | 2005-11-22 | 2014-10-28 | Novartis Vaccines And Diagnostics, Inc. | Partículas similares a virus (VLPs) de Norovirus y Sapovirus |
| EP1968630B1 (en) | 2005-12-29 | 2018-01-24 | Boehringer Ingelheim Vetmedica, Inc. | Multivalent pcv2 immunogenic compositions |
| EP2044198A4 (en) | 2006-07-27 | 2010-09-08 | Ligocyte Pharmaceuticals Inc | CHIMERIC INFLUENZA VIRUS TYPE PARTICLES |
| EP2066354B1 (en) * | 2006-09-29 | 2013-04-17 | Ligocyte Pharmaceuticals, Inc. | Norovirus vaccine formulations |
| US8202967B2 (en) | 2006-10-27 | 2012-06-19 | Boehringer Ingelheim Vetmedica, Inc. | H5 proteins, nucleic acid molecules and vectors encoding for those, and their medicinal use |
| WO2008113011A2 (en) | 2007-03-14 | 2008-09-18 | Ligocyte Pharmaceuticals, Inc. | Virus like particle purification |
| EP2027875A1 (en) | 2007-08-23 | 2009-02-25 | Octapharma AG | A Process for Isolation and Purification of a Target Protein free of Prion Protein (PrPSC) |
| CN104740624B (zh) | 2007-09-18 | 2018-04-24 | 武田疫苗股份有限公司 | 赋予针对诺如病毒的保护性免疫应答的疫苗 |
| WO2009080781A1 (en) | 2007-12-21 | 2009-07-02 | Cytos Biotechnology Ag | Process for clarifying cell homogenates |
| NO2324113T3 (https=) * | 2008-08-08 | 2018-07-28 | ||
| JP5683476B2 (ja) | 2008-11-03 | 2015-03-11 | タケダ ヴァクシーンズ， インコーポレイテッド | 感染因子を含まないエンベロープウイルスベースｖｌｐを単離するための改良法 |
| US8945895B2 (en) | 2009-07-31 | 2015-02-03 | Baxter International Inc. | Methods of purifying recombinant ADAMTS13 and other proteins and compositions thereof |
| CA2787666A1 (en) * | 2010-01-21 | 2011-07-28 | Ligocyte Pharmaceuticals, Inc. | Targeted heterologous antigen presentation on calicivirus virus-like particles |
| EP2619217B1 (en) | 2010-09-20 | 2016-11-09 | Bio-Rad Laboratories, Inc. | Dissociation of product-complexed contaminants in chromatography |
| FI122520B (fi) | 2010-10-15 | 2012-03-15 | Vesna Blazevic | Noroviruksen kapsidi ja rotaviruksen VP6-proteiini käytettäväksi yhdistelmärokotteena |
| CN102260651A (zh) | 2011-06-24 | 2011-11-30 | 华中科技大学同济医学院附属协和医院 | 一种纯化病毒样颗粒蛋白的方法及其应用 |
| JOP20130186B1 (ar) | 2012-06-22 | 2021-08-17 | Takeda Vaccines Montana Inc | تنقية الجزيئات الشبيهة بالفيروسات |
| JP2015015931A (ja) | 2013-07-12 | 2015-01-29 | 株式会社Ｕｍｎファーマ | ウイルス様粒子を含む培養物の製造方法 |
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