DK2467489T3 - Baculovirus-baseret produktion af biofarmaceutiske midler frie for forurenende baculovirale virioner - Google Patents
Baculovirus-baseret produktion af biofarmaceutiske midler frie for forurenende baculovirale virioner Download PDFInfo
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- DK2467489T3 DK2467489T3 DK10743083.7T DK10743083T DK2467489T3 DK 2467489 T3 DK2467489 T3 DK 2467489T3 DK 10743083 T DK10743083 T DK 10743083T DK 2467489 T3 DK2467489 T3 DK 2467489T3
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Claims (9)
1. Fremgangsmåde til fremstillingen af et biofarmaceutisk produkt, omfattende: (a) inficere en biofarmaceutisk-producerende insektcelle med mindst ét baculovirus, idet det mindst ene baculovirus omfattende et genom der koder for det biofarmaceutiske produkt, og (b) opretholde den biofarmaceutisk-producerende insektcelle under betingelser så at det biofarmaceutiske produkt fremstilles, hvor genomet af det mindst ene baculovirus er mangelfuldt for vp80 eller hvor den biofarmaceutisk-producerende insektcelle omfatter et ekspressionskontrolsystem der tillader aktiveringen af vp80.
2. Fremgangsmåden ifølge krav 1, hvor - vp80 er gjort mangelfuldt i genomet ved hjælp af nukleotidsubstitution, insertion eller deletion; eller - hvor den biofarmaceutisk-producerende insektcelle er en rekombinant insektcelle omfattende et konstrukt der udtrykker dsRNA der er specifik for vp80, dsRNA'et udtrykkes eventuelt under en inducerbar promotor.
3. Fremgangsmåden ifølge krav 1 eller 2, hvor det mindst ene baculovirus fremstilles før trin (a) i en baculovirus-producerende celle der udtrykker en komplementerende kopi af vp80.
4. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 3, hvor mangelfuldheden eller inaktivering af vp80 ikke påvirker meget sen ekspression fra baculovirus i sammenligning med meget sen ekspression fra vild-type baculovirus.
5. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 4, hvor det biofarmaceutiske produkt er et rekombinant protein, et rekombinant virus eller en virus-lignende partikel.
6. Fremgangsmåden ifølge krav 5, hvor the biofarmaceutisk produkt er et rekombinant AAV.
7. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 6, hvor det biofarmaceutiske produkt kodes af mindst ét gen indført i det rekombinante baculovirusgenom under kontrollen af polyhedrin eller plO promotor.
8. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 7, hvor det mindst ene baculovirus er afledt fra AcMNPV eller BmNPV.
9. Anvendelse af et baculovirus-insektcellesystem til fremstillingen af et biofarmaceutisk produkt hvor baculovirus-insektcellesystemet omfatter en baculovirus-producerende insektcelle inficeret med mindst ét rekombinant baculovirus, hvor: - den, eller hvert, rekombinante baculovirus omfatter et baculovirusgenom der koder for det biofarmaceutiske produkt, eller mindst én komponent af det biofarmaceutiske produkt, og - den, eller de, rekombinante baculovirale genom er mangelfuldt for vp80, eller den baculovirus-producerende insektcelle omfatter et ekspressionskontrolsystem der tillader aktiveringen af vp80.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09305761A EP2292781A1 (en) | 2009-08-17 | 2009-08-17 | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
| PCT/EP2010/061456 WO2011020710A2 (en) | 2009-08-17 | 2010-08-05 | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
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| DK15168775.3T DK2933336T3 (da) | 2009-08-17 | 2010-08-05 | Baculovirus-baseret produktion af biofarmaceutika frie for forurenende baculovirale virioner |
| DK10743083.7T DK2467489T3 (da) | 2009-08-17 | 2010-08-05 | Baculovirus-baseret produktion af biofarmaceutiske midler frie for forurenende baculovirale virioner |
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| DK15168775.3T DK2933336T3 (da) | 2009-08-17 | 2010-08-05 | Baculovirus-baseret produktion af biofarmaceutika frie for forurenende baculovirale virioner |
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| US (4) | US8993317B2 (da) |
| EP (4) | EP2292781A1 (da) |
| CN (1) | CN102686732A (da) |
| CA (2) | CA3050271A1 (da) |
| DK (3) | DK3187589T3 (da) |
| ES (3) | ES2542740T3 (da) |
| HU (1) | HUE025056T2 (da) |
| PL (2) | PL2467489T3 (da) |
| PT (3) | PT2467489E (da) |
| WO (1) | WO2011020710A2 (da) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2292781A1 (en) | 2009-08-17 | 2011-03-09 | Genethon | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
| EP2737070A1 (en) * | 2011-07-27 | 2014-06-04 | GBiotech SARL | Production of recombinant protein in insect cells using a baculovirus expression system |
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| EP3448874A4 (en) | 2016-04-29 | 2020-04-22 | Voyager Therapeutics, Inc. | COMPOSITIONS FOR TREATING A DISEASE |
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| BR112018073472A2 (pt) | 2016-05-18 | 2019-08-27 | Voyager Therapeutics, Inc. | composições e métodos de tratamento da doença de huntington |
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| CA3061652A1 (en) | 2017-05-05 | 2018-11-08 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (als) |
| JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
| CN111132626B (zh) | 2017-07-17 | 2024-01-30 | 沃雅戈治疗公司 | 轨迹阵列引导系统 |
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| TWI904068B (zh) | 2017-08-09 | 2025-11-11 | 美商生物化學醫療公司 | 核酸分子及其用途 |
| AU2018338728B2 (en) | 2017-09-29 | 2025-01-02 | Centre National De La Recherche Scientifique (Cnrs) | Rescue of central and peripheral neurological phenotype of Friedreich's Ataxia by intravenous delivery |
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| US20200237799A1 (en) | 2017-10-16 | 2020-07-30 | Voyager Therapeutics, Inc. | Treatment of amyotrophic lateral sclerosis (als) |
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| AU2019268330A1 (en) | 2018-05-15 | 2020-11-26 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of Parkinson's disease |
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| CN108823176B (zh) * | 2018-07-20 | 2021-09-28 | 山西大学 | 一种重组杆状病毒及其构建方法和应用 |
| WO2020033863A1 (en) | 2018-08-09 | 2020-02-13 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof for non-viral gene therapy |
| CN108998455B (zh) * | 2018-08-13 | 2021-03-16 | 西南大学 | 家蚕核型多角体病毒诱导型39k启动子及其重组载体和应用 |
| EP3856762A1 (en) | 2018-09-28 | 2021-08-04 | Voyager Therapeutics, Inc. | Frataxin expression constructs having engineered promoters and methods of use thereof |
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| SG11202110607WA (en) | 2019-04-01 | 2021-10-28 | Tenaya Therapeutics Inc | Adeno-associated virus with engineered capsid |
| AU2020302861A1 (en) * | 2019-06-26 | 2022-02-24 | Virovek, Inc. | Baculovirus expression system |
| IL292297A (en) | 2019-10-17 | 2022-06-01 | Stridebio Inc | Adeno-associated viral vectors for treatment of niemann-pick disease type c |
| CN110940807A (zh) * | 2019-11-08 | 2020-03-31 | 江苏科技大学 | 研究家蚕基因抑制BmNPV DNA复制相关基因的表达的方法 |
| CA3189878A1 (en) | 2020-08-19 | 2022-02-24 | Colin O'BANION | Adeno-associated virus vectors for treatment of rett syndrome |
| BR112023002395A2 (pt) * | 2020-08-23 | 2023-03-21 | Bioverativ Therapeutics Inc | Sistema de baculovírus modificado para produção aprimorada de dna com extremidades fechadas (cedna) |
| CN115698304A (zh) | 2020-10-09 | 2023-02-03 | 特纳亚治疗股份有限公司 | 亲斑蛋白-2基因疗法的方法和组合物 |
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| CA3229668A1 (en) * | 2021-08-23 | 2023-03-02 | Bioverativ Therapeutics Inc. | Baculovirus expression system |
| CN114058598B (zh) * | 2021-11-04 | 2023-04-28 | 中国科学院精密测量科学与技术创新研究院 | 新的重组杆状病毒基因组插入位点及其应用 |
| EP4508062A1 (en) | 2022-04-11 | 2025-02-19 | Tenaya Therapeutics, Inc. | Adeno-associated virus with engineered capsid |
| CN118956967A (zh) * | 2024-04-17 | 2024-11-15 | 和元生物技术（上海）股份有限公司 | 核酸分子、包含其的重组杆状病毒及其应用 |
| CN120137918B (zh) * | 2025-05-12 | 2025-09-02 | 中国林业科学研究院高原林业研究所 | 重组dsRNA-杆状病毒及其制备方法和应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4745051A (en) | 1983-05-27 | 1988-05-17 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
| EP0127839B1 (en) | 1983-05-27 | 1992-07-15 | THE TEXAS A&M UNIVERSITY SYSTEM | Method for producing a recombinant baculovirus expression vector |
| ZA848495B (en) | 1984-01-31 | 1985-09-25 | Idaho Res Found | Production of polypeptides in insect cells |
| CN1062601C (zh) * | 1992-03-24 | 2001-02-28 | 剑桥药物研究有限公司 | 病毒疫苗 |
| FR2756297B1 (fr) * | 1996-11-22 | 1999-01-08 | Centre Nat Rech Scient | Procede de production de virus recombinants |
| GB9919409D0 (en) * | 1999-08-18 | 1999-10-20 | Univ Oxford Brookes | Baculovirus expression system |
| US20040219516A1 (en) * | 2002-07-18 | 2004-11-04 | Invitrogen Corporation | Viral vectors containing recombination sites |
| WO2005072364A2 (en) * | 2004-01-27 | 2005-08-11 | University Of Florida | A modified baculovirus expression system for production of pseudotyped raav vector |
| EP2292781A1 (en) * | 2009-08-17 | 2011-03-09 | Genethon | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
-
2009
- 2009-08-17 EP EP09305761A patent/EP2292781A1/en not_active Withdrawn
-
2010
- 2010-08-05 EP EP10743083.7A patent/EP2467489B1/en not_active Not-in-force
- 2010-08-05 ES ES10743083.7T patent/ES2542740T3/es active Active
- 2010-08-05 US US13/390,806 patent/US8993317B2/en not_active Expired - Fee Related
- 2010-08-05 EP EP16205440.7A patent/EP3187589B1/en active Active
- 2010-08-05 DK DK16205440.7T patent/DK3187589T3/da active
- 2010-08-05 HU HUE10743083A patent/HUE025056T2/en unknown
- 2010-08-05 ES ES15168775.3T patent/ES2627744T3/es active Active
- 2010-08-05 PT PT107430837T patent/PT2467489E/pt unknown
- 2010-08-05 PL PL10743083T patent/PL2467489T3/pl unknown
- 2010-08-05 DK DK15168775.3T patent/DK2933336T3/da active
- 2010-08-05 WO PCT/EP2010/061456 patent/WO2011020710A2/en not_active Ceased
- 2010-08-05 PT PT151687753T patent/PT2933336T/pt unknown
- 2010-08-05 CN CN2010800456298A patent/CN102686732A/zh active Pending
- 2010-08-05 PT PT162054407T patent/PT3187589T/pt unknown
- 2010-08-05 ES ES16205440T patent/ES2787706T3/es active Active
- 2010-08-05 PL PL16205440T patent/PL3187589T3/pl unknown
- 2010-08-05 EP EP15168775.3A patent/EP2933336B1/en not_active Not-in-force
- 2010-08-05 DK DK10743083.7T patent/DK2467489T3/da active
- 2010-08-05 CA CA3050271A patent/CA3050271A1/en not_active Abandoned
- 2010-08-05 CA CA2771250A patent/CA2771250C/en not_active Expired - Fee Related
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2015
- 2015-03-27 US US14/670,459 patent/US9862934B2/en not_active Expired - Fee Related
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2017
- 2017-12-14 US US15/841,359 patent/US10428315B2/en not_active Expired - Fee Related
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