DK2771471T3 - CONSTRUCTION - Google Patents
CONSTRUCTION Download PDFInfo
- Publication number
- DK2771471T3 DK2771471T3 DK12778779.4T DK12778779T DK2771471T3 DK 2771471 T3 DK2771471 T3 DK 2771471T3 DK 12778779 T DK12778779 T DK 12778779T DK 2771471 T3 DK2771471 T3 DK 2771471T3
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- DK
- Denmark
- Prior art keywords
- vector
- aadc
- dopamine
- linker
- dopa
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- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/027—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a retrovirus
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/48—Vector systems having a special element relevant for transcription regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE
-
- 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
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
- C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US201161552581P | 2011-10-28 | 2011-10-28 | |
| GBGB1118636.8A GB201118636D0 (en) | 2011-10-28 | 2011-10-28 | Nucleotide sequence |
| PCT/GB2012/052668 WO2013061076A1 (en) | 2011-10-28 | 2012-10-26 | Construct |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2771471T3 true DK2771471T3 (en) | 2017-08-21 |
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| DK12778779.4T DK2771471T3 (en) | 2011-10-28 | 2012-10-26 | CONSTRUCTION |
| DK17161437.3T DK3219801T3 (da) | 2011-10-28 | 2012-10-26 | Konstruktion |
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| Application Number | Title | Priority Date | Filing Date |
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| DK17161437.3T DK3219801T3 (da) | 2011-10-28 | 2012-10-26 | Konstruktion |
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| US (1) | US11279954B2 (OSRAM) |
| EP (2) | EP3219801B1 (OSRAM) |
| JP (1) | JP6296987B2 (OSRAM) |
| CN (2) | CN107523581B (OSRAM) |
| AU (1) | AU2012328166B2 (OSRAM) |
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| DK (2) | DK2771471T3 (OSRAM) |
| ES (2) | ES2857003T3 (OSRAM) |
| GB (1) | GB201118636D0 (OSRAM) |
| PL (2) | PL3219801T3 (OSRAM) |
| WO (1) | WO2013061076A1 (OSRAM) |
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| GB201322798D0 (en) | 2013-12-20 | 2014-02-05 | Oxford Biomedica Ltd | Production system |
| SG11201703148TA (en) | 2014-11-05 | 2017-05-30 | Voyager Therapeutics Inc | Aadc polynucleotides for the treatment of parkinson's disease |
| WO2017021359A1 (en) * | 2015-08-03 | 2017-02-09 | Myodopa Limited | Systemic synthesis and regulation of l-dopa |
| GB2562774A (en) * | 2017-05-25 | 2018-11-28 | Mcdonald Michael | Genetic construct |
| JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
| EP3794126A1 (en) | 2018-05-15 | 2021-03-24 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of parkinson's disease |
| CN116024271A (zh) * | 2018-05-31 | 2023-04-28 | 康霖生物科技（杭州）有限公司 | 一种用于中枢神经系统疾病治疗的基因序列构建体 |
| AU2019346655B2 (en) | 2018-09-28 | 2025-03-13 | Voyager Therapeutics, Inc. | Frataxin expression constructs having engineered promoters and methods of use thereof |
| EP3937985A1 (en) * | 2019-03-10 | 2022-01-19 | Sio Gene Therapies Inc. | Gene therapy compositions and methods for treating parkinson's disease |
| CN109971729B (zh) * | 2019-04-19 | 2021-07-16 | 上海信致医药科技有限公司 | 一种酶组合物 |
| GB2587319A (en) | 2019-08-12 | 2021-03-31 | Healing Genes Llc | Genetic construct |
| CN118360338A (zh) * | 2020-03-13 | 2024-07-19 | 康霖生物科技（杭州）有限公司 | 一种核酸构建体 |
| GB2601752A (en) | 2020-12-08 | 2022-06-15 | Maavrx Ltd | Expression vector |
| EP4448774A1 (en) | 2021-12-17 | 2024-10-23 | Imperial College Innovations Limited | Rna construct |
| CN114317610B (zh) * | 2022-01-27 | 2024-07-02 | 上海本导基因技术有限公司 | 一种适用于帕金森疾病基因治疗的慢病毒载体 |
| CN117106825B (zh) * | 2023-08-28 | 2024-11-01 | 康霖生物科技（杭州）有限公司 | 用于治疗帕金森病的基因治疗载体及其用途 |
| CN118389675B (zh) * | 2024-05-27 | 2025-06-27 | 南方医科大学珠江医院 | 芳香族氨基酸脱羧酶作为标志物在肝性脑病的检测产品中的应用 |
Family Cites Families (27)
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| US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| DE4006630A1 (de) | 1990-03-03 | 1991-09-12 | Behringwerke Ag | Humane monoklonale antikoerper gegen tollwutviren, ihre herstellung und verwendung |
| 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 |
| CA2111234C (en) | 1991-06-21 | 2002-11-26 | Manoj Chalam | Method for increasing rainout from autorefrigerated vaporous cloud containing hydrofluoric acid |
| US6001650A (en) | 1995-08-03 | 1999-12-14 | Avigen, Inc. | High-efficiency wild-type-free AAV helper functions |
| AU1073797A (en) * | 1995-11-14 | 1997-06-05 | Somatix Therapy Corporation | Joint expression of gtp cyclohydrolase and tyrosine hydroxylase |
| US5866552A (en) | 1996-09-06 | 1999-02-02 | The Trustees Of The University Of Pennsylvania | Method for expressing a gene in the absence of an immune response |
| CN1195863C (zh) | 1996-10-17 | 2005-04-06 | 牛津生物医学（英国）有限公司 | 逆转录病毒载体 |
| GB9622500D0 (en) * | 1996-10-29 | 1997-01-08 | Oxford Biomedica Ltd | Therapeutic gene |
| GB9720465D0 (en) | 1997-09-25 | 1997-11-26 | Oxford Biomedica Ltd | Dual-virus vectors |
| GB9803351D0 (en) | 1998-02-17 | 1998-04-15 | Oxford Biomedica Ltd | Anti-viral vectors |
| GB2351290A (en) | 1998-05-22 | 2000-12-27 | Oxford Biomedica Ltd | Retroviral delivery sytem |
| GB9904905D0 (en) | 1999-03-03 | 1999-04-28 | Oxford Biomedica Ltd | Cells |
| BR0012407A (pt) | 1999-07-13 | 2002-03-12 | Pellicer Carlos F | Painel para construção e uma instalação para sua fabricação |
| GB0009760D0 (en) | 2000-04-19 | 2000-06-07 | Oxford Biomedica Ltd | Method |
| GB0024550D0 (OSRAM) * | 2000-10-06 | 2000-11-22 | Oxford Biomedica Ltd | |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| EP2348119B1 (en) | 2002-02-01 | 2017-04-26 | Oxford BioMedica (UK) Limited | Multicistronic lentiviral vector |
| SE0302509D0 (sv) | 2003-09-19 | 2003-09-19 | Amersham Biosciences Ab | Matrix for separation of polyethers and method of separation |
| US7943374B2 (en) | 2005-08-21 | 2011-05-17 | Markus Hildinger | Super-size adeno-associated viral vector harboring a recombinant genome larger than 5.7 kb |
| GB0526211D0 (en) | 2005-12-22 | 2006-02-01 | Oxford Biomedica Ltd | Viral vectors |
| GB0526210D0 (en) | 2005-12-22 | 2006-02-01 | Oxford Biomedica Ltd | Vectors |
| US20090214478A1 (en) | 2008-02-21 | 2009-08-27 | Alberto Auricchio | Method of treating ocular diseases by gene therapy |
| EP2307551B1 (en) | 2008-06-18 | 2016-12-14 | Oxford BioMedica (UK) Limited | Purification of retroviral vectors |
| WO2010055290A1 (en) * | 2008-11-11 | 2010-05-20 | Oxford Biomedica (Uk) Limited | Method |
| EP2575894B1 (en) * | 2010-05-28 | 2015-02-25 | Oxford Biomedica (UK) Ltd | Delivery of lentiviral vectors to the brain |
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2012
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- 2012-10-26 EP EP17161437.3A patent/EP3219801B1/en active Active
- 2012-10-26 WO PCT/GB2012/052668 patent/WO2013061076A1/en not_active Ceased
- 2012-10-26 CA CA2849241A patent/CA2849241C/en active Active
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- 2012-10-26 PL PL17161437T patent/PL3219801T3/pl unknown
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2019
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2012328166A1 (en) | 2014-06-12 |
| JP6296987B2 (ja) | 2018-03-20 |
| EP2771471A1 (en) | 2014-09-03 |
| US11279954B2 (en) | 2022-03-22 |
| WO2013061076A1 (en) | 2013-05-02 |
| AU2012328166B2 (en) | 2018-03-08 |
| JP2014532402A (ja) | 2014-12-08 |
| GB201118636D0 (en) | 2011-12-07 |
| EP3219801B1 (en) | 2020-12-16 |
| DK3219801T3 (da) | 2021-02-22 |
| CN107523581B (zh) | 2021-08-17 |
| US20200040361A1 (en) | 2020-02-06 |
| CN107523581A (zh) | 2017-12-29 |
| PL3219801T3 (pl) | 2021-06-14 |
| ES2628419T3 (es) | 2017-08-02 |
| CA2849241C (en) | 2019-12-31 |
| EP2771471B1 (en) | 2017-05-03 |
| CA3052407A1 (en) | 2013-05-02 |
| CA2849241A1 (en) | 2013-05-02 |
| PL2771471T3 (pl) | 2017-10-31 |
| CN104011213A (zh) | 2014-08-27 |
| EP3219801A1 (en) | 2017-09-20 |
| CN104011213B (zh) | 2017-10-03 |
| CA3052407C (en) | 2020-03-31 |
| ES2857003T3 (es) | 2021-09-28 |
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