DK2542575T3 - Ekspression af monoklonale antistoffer i tetrahymena - Google Patents
Ekspression af monoklonale antistoffer i tetrahymena Download PDFInfo
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- DK2542575T3 DK2542575T3 DK11707394.0T DK11707394T DK2542575T3 DK 2542575 T3 DK2542575 T3 DK 2542575T3 DK 11707394 T DK11707394 T DK 11707394T DK 2542575 T3 DK2542575 T3 DK 2542575T3
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Claims (10)
- EKSPRESSION AF MONOKLONALE ANTISTOFFER ITETRAHYMENA Patentkrav1. System til heterolog ekspression af et monoklonalt antistof (mAb) eller et antigenbindende fragment eller derivat deraf, hvilket system omfatter a) mindst én ciliat-værtscelle og b) inkorporeret i ciliat-værtscellen mindst ét heterologt nukleinsyremolekyle, der koder for det monoklonale antistof eller et antigenbindende fragment eller derivat deraf, og hvilket system yderligere omfatter en signalsekvens, der er operabelt koblet til nukleinsyremolekylet, hvor signalsekvensen forårsager sekretion af det monoklonale antistof eller fragmentet deraf, der kodes af nukleinsyremolekylet, ud i det ekstracellulære medium, hvor ciliaten er et medlem af familien Tetrahymenidae, og hvor det antigenbindende derivat er mindst én udvalgt fra gruppen, der består af • scFv eller • bi-, tri- eller højere specifikke antistofkonstruktioner.
- 2. System ifølge krav 1, hvor det monoklonale antistof (mAb) eller et antigenbindende fragment eller derivat deraf har en N-glycanstruktur, der er i det væsentlige fucosefri.
- 3. System ifølge krav 1 eller 2, hvor det monoklonale antistof (mAb) eller et antigenbindende fragment eller derivat deraf har mindst én effekt udvalgt fra gruppen, der består af • forøget antistofafhængig cellulær cytotoksicitet (ADCC), • forøget komplementafhængig cytotoksicitet (CDC), • forøget antistofafhængig apoptose, • forøget antistofafhængig opsonisering eller en forlænget halveringstid i serum.
- 4. System til heterolog ekspression af et monoklonalt antistof (mAb) eller et antigenbindende fragment eller derivat deraf, hvilket system omfatter en ciliat- værtscelle, der er opnået ved konjugation af mindst to ciliat-værtsceller ifølge systemet i krav 1, hvor ciliaten er et medlem af familien Tetrahymenidae.
- 5. Ciliat-værtscelle, der er transficeret med mindst én vektor, der omfatter mindst ét nukleinsyremolekyle, der koder for et monoklonalt antistof (mAb) eller et antigenbindende fragment eller derivat deraf ifølge krav 4, eller er opnået ved konjugation af mindst to ciliat-værtsceller ifølge systemet i krav 1, hvor ciliaten er et medlem af familien Tetrahymenidae.
- 6. Bibliotek, der omfatter mindst to ciliat-værtsceller ifølge krav 5 eller mindst to systemer ifølge krav 5, hvor hver værtscelle har inkorporeret mindst ét heterologt nukleinsyremolekyle, der koder for et antistof eller et antigenbindende fragment eller derivat deraf, fortrinsvis i form af en vektor, og hvor mindst to ciliater er udvalgt på en sådan måde, at de kan konjugere med hinanden, og ciliaten er et medlem af familien Tetrahymenidae.
- 7. Monoklonalt antistof (mAb), der dannes med et system ifølge et hvilket som helst af kravene 1-4 eller med en ciliat-værtscelle ifølge krav 5, hvor ciliaten er et medlem af familien Tetrahymenidae, hvilket antistof eller antigenbindende fragment eller derivat yderligere binder til mindst ét af målene, der er anført i tabel 1 (ADCC) eller 3 (ikke-ADCC).
- 8. Monoklonalt antistof ifølge krav 7, som har mindst ét træk udvalgt fra gruppen, der består af • forøget ADCC, CDC og/eller antistofafhængig apoptose, • forlænget halveringstid i serum og/eller • bi, tri- eller multispecificitet.
- 9. Fremgangsmåde til fremstilling af mindst ét monoklonalt antistof (mAb) eller et antigenbindende fragment eller derivat deraf i en ciliat-værtscelle, hvilken fremgangsmåde omfatter trinene a) transfektion af mindst to forskellige ciliat-værtsceller med mindst ét nukleinsyremolekyle, der koder for et antistof eller et fragment eller derivat deraf, eller fortrinsvis med mindst én vektor, der omfatter mindst ét nukleinsyremolekyle, der koder for et monoklonalt antistof (mAb) eller et antigenbindende fragment eller derivat deraf, b) konjugering af de to ciliat-værtsceller eller afkom deraf til opnåelse af mindst én ciliat-celle, der bærer mindst to forskellige nukleinsyremolekyler, der koder for mindst to forskellige antistoffer eller fragmenter eller derivater deraf, og c) dyrkning af den således dannede ciliat-celle under betingelser, der åbner mulighed for ekspression af et protein, hvor ciliaten er et medlem af familien Te tra hym enidae.
- 10. Monoklonalt antistof (mAb), der er dannet ved en fremgangsmåde ifølge krav 9, hvor ciliaten er et medlem af familien Tetrahymenidae, hvilket antistof eller antigenbindende fragment eller derivat yderligere binder til mindst ét af målene anført i tabel 1 (ADCC) eller 3 (ikke-ADCC).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB1003701.8A GB201003701D0 (en) | 2010-03-05 | 2010-03-05 | System for the expression of a protein |
| PCT/EP2011/053129 WO2011107520A1 (en) | 2010-03-05 | 2011-03-02 | Expression of monoclonal antibodies in ciliate host cells |
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| DK2542575T3 true DK2542575T3 (da) | 2017-01-23 |
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| GB201003701D0 (en) | 2010-03-05 | 2010-04-21 | Cilian Ag | System for the expression of a protein |
| RU2518739C1 (ru) * | 2013-01-31 | 2014-06-10 | Федеральное бюджетное учреждение науки "Московский научно-исследовательский институт эпидемиологии и микробиологии им. Г.Н. Габричевского" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека | Способ определения функциональной активности комплемента человека, лабораторных, домашних, сельскохозяйственных животных, птиц и земноводных |
| MX362922B (es) * | 2013-03-26 | 2019-02-25 | Coherus Biosciences Inc | Método de producción de proteínas. |
| US9732154B2 (en) | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
| US9603927B2 (en) | 2014-02-28 | 2017-03-28 | Janssen Biotech, Inc. | Combination therapies with anti-CD38 antibodies |
| BR112017004614A2 (pt) | 2014-09-09 | 2018-02-27 | Janssen Biotech, Inc. | terapias de combinação com anticorpos anti-cd38 |
| EA202092609A1 (ru) | 2014-12-04 | 2021-10-29 | Янссен Байотек, Инк. | Антитела к cd38 для лечения острого миелолейкоза |
| CN108136218B (zh) | 2015-05-20 | 2022-12-13 | 詹森生物科技公司 | 用于治疗轻链淀粉样变性及其它cd38阳性血液恶性肿瘤的抗cd38抗体 |
| NZ777133A (en) | 2015-06-22 | 2025-05-02 | Janssen Biotech Inc | Combination therapies for heme malignancies with anti-cd38 antibodies and survivin inhibitors |
| US20170044265A1 (en) | 2015-06-24 | 2017-02-16 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| CN105200004A (zh) * | 2015-09-30 | 2015-12-30 | 中国科学技术大学 | 交联后的四膜虫小核的分离纯化方法 |
| EP3156417A1 (en) * | 2015-10-13 | 2017-04-19 | Affimed GmbH | Multivalent fv antibodies |
| RS61651B1 (sr) | 2015-11-03 | 2021-04-29 | Janssen Biotech Inc | Potkožne formulacije anti-cd38 antitela i njihova upotreba |
| US10781261B2 (en) | 2015-11-03 | 2020-09-22 | Janssen Biotech, Inc. | Subcutaneous formulations of anti-CD38 antibodies and their uses |
| CN110959012A (zh) * | 2017-06-05 | 2020-04-03 | 詹森生物科技公司 | 工程化表面电荷用于产生双特异性抗体的方法 |
| JP2021502961A (ja) | 2017-10-31 | 2021-02-04 | ヤンセン バイオテツク,インコーポレーテツド | 高リスク多発性骨髄腫の治療方法 |
| EP3917564A4 (en) * | 2019-02-01 | 2022-12-21 | NovaRock Biotherapeutics, Ltd. | ANTI-CLAUDINE 18 ANTIBODIES AND THEIR METHODS OF USE |
| WO2024251839A1 (en) | 2023-06-05 | 2024-12-12 | Pure Biologics Spólka Akcyjna | Anti-garp antibodies and methods of use |
| WO2024251787A1 (en) | 2023-06-05 | 2024-12-12 | Pure Biologics Spólka Akcyjna | Anti ror1 antibodies and method of use |
Family Cites Families (26)
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| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| AU606320B2 (en) * | 1985-11-01 | 1991-02-07 | International Genetic Engineering, Inc. | Modular assembly of antibody genes, antibodies prepared thereby and use |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
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| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| DE122004000008I1 (de) | 1991-06-14 | 2005-06-09 | Genentech Inc | Humanisierter Heregulin Antikörper. |
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| DE19626564A1 (de) | 1996-07-03 | 1998-01-08 | Hoechst Ag | Genetische Transformation von Ciliatenzellen durch Microcarrier-Bombardement mit DNA beladenen Goldpartikeln |
| AU2756100A (en) | 1999-02-04 | 2000-08-25 | Cornell Research Foundation Inc. | Diagnostic and protective antigen gene sequences of ichthyophthirius |
| US6846481B1 (en) | 1999-02-04 | 2005-01-25 | University Of Georgia Research Foundation, Inc. | Recombinant expression of heterologous nucleic acids in protozoa |
| US20010010928A1 (en) | 1999-03-26 | 2001-08-02 | Stephen M. Beverley | Protozoan expression system |
| ES2568899T3 (es) | 1999-04-09 | 2016-05-05 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de una molécula inmunofuncional |
| WO2003018749A2 (en) * | 2001-08-22 | 2003-03-06 | Shengfeng Li | Compositions and methods for generating antigen-binding units |
| WO2003078566A2 (en) | 2002-03-19 | 2003-09-25 | Cilian Ag | Dna sequences of major secreted proteins from the ciliate tetrahymena and use thereof |
| DE10214413A1 (de) * | 2002-03-30 | 2003-10-09 | Nutrinova Gmbh | Expression von rekombinanten humanen Proteinen in Tetrahymena |
| DE10214406A1 (de) | 2002-03-30 | 2003-10-09 | Nutrinova Gmbh | Verfahren und Marker zur einfachen Transformation und Selektion von rekombinanten Protisten |
| EP2330201B1 (en) * | 2003-10-22 | 2017-04-05 | Keck Graduate Institute | Methods of synthesizing heteromultimeric polypeptides in yeast using a haploid mating strategy |
| WO2007006812A1 (en) | 2005-07-13 | 2007-01-18 | Cilian Ag | Tetrahymena heat inducible promoters and their use |
| CA2616256C (en) * | 2005-07-22 | 2016-10-25 | Kyowa Hakko Kogyo Co., Ltd. | Genetically modified antibody composition |
| WO2007028106A2 (en) | 2005-08-31 | 2007-03-08 | Centocor, Inc. | Host cell lines for production of antibody constant region with enhanced effector function |
| CN101627111A (zh) * | 2005-08-31 | 2010-01-13 | 森托科尔公司 | 用于生产具有增强的效应子功能的抗体恒定区的宿主细胞系 |
| WO2010108182A2 (en) * | 2009-03-20 | 2010-09-23 | Tetragenetics, Inc. | Production of recombinant proteins in ciliates and uses thereof |
| GB201003701D0 (en) | 2010-03-05 | 2010-04-21 | Cilian Ag | System for the expression of a protein |
| WO2011116387A1 (en) * | 2010-03-19 | 2011-09-22 | Tetragenetics, Inc. | Production of aglycosylated monoclonal antibodies in ciliates |
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| US20130109593A1 (en) | 2013-05-02 |
| KR20120131201A (ko) | 2012-12-04 |
| BR112012022459A2 (pt) | 2020-09-01 |
| CA2828131C (en) | 2019-03-26 |
| JP5984680B2 (ja) | 2016-09-06 |
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| KR20180037304A (ko) | 2018-04-11 |
| BR112012022459B1 (pt) | 2023-03-07 |
| EP2542575B1 (en) | 2016-10-05 |
| WO2011107520A1 (en) | 2011-09-09 |
| KR102035439B1 (ko) | 2019-10-22 |
| CN102884078B (zh) | 2015-06-17 |
| GB201003701D0 (en) | 2010-04-21 |
| EP2542575A1 (en) | 2013-01-09 |
| PL2542575T3 (pl) | 2017-06-30 |
| JP2013520976A (ja) | 2013-06-10 |
| CA2828131A1 (en) | 2011-09-09 |
| US9963499B2 (en) | 2018-05-08 |
| ES2609787T3 (es) | 2017-04-24 |
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