RU2716977C2 - Новые селективные векторы и способы селекции эукариотических клеток-хозяев - Google Patents
Новые селективные векторы и способы селекции эукариотических клеток-хозяев Download PDFInfo
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- RU2716977C2 RU2716977C2 RU2016106270A RU2016106270A RU2716977C2 RU 2716977 C2 RU2716977 C2 RU 2716977C2 RU 2016106270 A RU2016106270 A RU 2016106270A RU 2016106270 A RU2016106270 A RU 2016106270A RU 2716977 C2 RU2716977 C2 RU 2716977C2
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- folate receptor
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| DK2401377T3 (en) | 2009-02-27 | 2016-08-29 | Novartis Ag | Expression vector system comprising two selection markers |
| PT3027646T (pt) | 2013-07-31 | 2018-10-16 | Novartis Ag | Novos vetores e métodos de seleção de células hospedeiras eucarióticas |
| IL258538B2 (en) * | 2015-10-09 | 2023-04-01 | Genzyme Corp | Early isolation after the infection of cells (epic) for the production of biological material |
| EP3521435A1 (en) | 2018-02-06 | 2019-08-07 | Bayer AG | A high stringency selection system for protein expression in proline-auxotrophic cells |
| US20210356377A1 (en) * | 2018-09-07 | 2021-11-18 | Medimmune, Llc | Methods Of Cell Selection |
| MX2022003192A (es) | 2019-09-18 | 2022-04-11 | Novartis Ag | Proteinas de fusion nkg2d y sus usos. |
| JP2023550459A (ja) | 2020-11-23 | 2023-12-01 | ノバルティス アーゲー | 抗体構築物の発現技術 |
| JP2024517711A (ja) | 2021-04-29 | 2024-04-23 | ノバルティス アーゲー | 高シアル酸付加細胞 |
| CN118510902A (zh) * | 2021-12-21 | 2024-08-16 | Absci公司 | 用于鉴定具有增加的可溶性靶蛋白表达的菌株的FolA选择测定 |
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| WO2009080759A1 (en) * | 2007-12-21 | 2009-07-02 | Novartis Ag | Organic compounds |
| WO2010097240A1 (en) * | 2009-02-27 | 2010-09-02 | Novartis Ag | Expression vector system comprising two selection markers |
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| US4771036A (en) | 1986-02-10 | 1988-09-13 | Trustees Of Columbia University In The City Of New York | Method and ophthalmic composition for the prevention and reversal of cataracts |
| JP2585532B2 (ja) | 1986-05-10 | 1997-02-26 | 三井東圧化学株式会社 | 動物細胞の形質転換体及びそれを得る方法並びにその形質転換体を用いてｔ−ＰＡを生産する方法 |
| EP0557459B1 (en) | 1990-11-13 | 1997-10-22 | Immunex Corporation | Bifunctional selectable fusion genes |
| JP3438889B2 (ja) | 1991-03-29 | 2003-08-18 | ジェネンテク，インコーポレイテッド | 所望のタンパク質を高レベルに発現させる組換え宿主細胞の選別法 |
| WO1994028143A1 (en) | 1993-05-21 | 1994-12-08 | Targeted Genetics Corporation | Bifunctional selectable fusion genes based on the cytosine deaminase (cd) gene |
| US5439808A (en) | 1993-07-23 | 1995-08-08 | North American Vaccine, Inc. | Method for the high level expression, purification and refolding of the outer membrane group B porin proteins from Neisseria meningitidis |
| US5830698A (en) | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| US6106825A (en) | 1997-05-07 | 2000-08-22 | University Of Florida | Entomopoxvirus-vertebrate gene delivery vector and method |
| FR2784030B1 (fr) | 1998-10-02 | 2002-12-20 | Inst Nat Sante Rech Med | Utilisation de bloqueurs des canaux calciques et/ou cgmp-dependants pour le traitement de pathologies de la retine |
| FR2823221B1 (fr) | 2001-04-06 | 2004-04-02 | Univ Pasteur | Sequences associees a la degenerescence retinienne et applications |
| DE10256083A1 (de) | 2002-11-29 | 2004-08-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Expressionsvektor, Verfahren zur Herstellung von heterologen Genprodukten und Selektionsverfahren für hochproduzierende rekombinante Zellen |
| US7384744B2 (en) | 2002-11-29 | 2008-06-10 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | Expression vector, methods for the production of heterologous gene products and for the selection of recombinant cells producing high levels of such products |
| BRPI0408246A (pt) | 2003-03-11 | 2006-03-01 | Applied Research Systems | vetores de expressão que compreendem o promotor ie2 do mcmv |
| US20070224635A1 (en) | 2004-01-30 | 2007-09-27 | Maxygen Holdings, Ltd. | Regulated Stop Codon Readthrough |
| US20060275794A1 (en) | 2005-03-07 | 2006-12-07 | Invitrogen Corporation | Collections of matched biological reagents and methods for identifying matched reagents |
| CN101389763B (zh) | 2006-02-21 | 2013-01-23 | 科罗迈吉尼科斯公司 | 高水平表达蛋白质的宿主细胞的选择 |
| BRPI0712073B8 (pt) | 2006-05-17 | 2021-05-25 | Hoffmann La Roche | ácido nucléico para produção de um polipeptídio ou proteína heteróloga |
| ES2784926T3 (es) | 2007-12-21 | 2020-10-02 | Novartis Ag | Vector de expresión de mamífero |
| RU2528858C2 (ru) | 2008-08-28 | 2014-09-20 | Новартис Аг | Дисплей на поверхности клеток полипептидных изоформ на основе прочитывания терминирующего кодона |
| WO2010029130A1 (en) | 2008-09-10 | 2010-03-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Neuronal viability factor and use thereof |
| SG173457A1 (en) | 2009-02-27 | 2011-09-29 | Novartis Ag | Methods for selecting eukaryotic cells expressing a heterologous protein |
| CN102030754B (zh) * | 2009-09-28 | 2013-07-10 | 中国科学院微生物研究所 | 非病毒载体及其制备方法与应用 |
| PT3027646T (pt) | 2013-07-31 | 2018-10-16 | Novartis Ag | Novos vetores e métodos de seleção de células hospedeiras eucarióticas |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009080759A1 (en) * | 2007-12-21 | 2009-07-02 | Novartis Ag | Organic compounds |
| WO2010097240A1 (en) * | 2009-02-27 | 2010-09-02 | Novartis Ag | Expression vector system comprising two selection markers |
Non-Patent Citations (4)
| Title |
|---|
| GRAPP M. et al., Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency, Brain, 2012, V. 135. N. 7. p. 2022-2031 * |
| MAZIARZ K.M. at al., Complete Mapping of Divergent Amino Acids Responsible for Differential Ligand Binding of Folate Receptors α and β, The Journal of Biologival Chemistry, 1999, V. 274, N. 16, p.11086-11091. * |
| MAZIARZ K.M. at al., Complete Mapping of Divergent Amino Acids Responsible for Differential Ligand Binding of Folate Receptors α and β, The Journal of Biologival Chemistry, 1999, V. 274, N. 16, p.11086-11091. GRAPP M. et al., Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport deficiency, Brain, 2012, V. 135. N. 7. p. 2022-2031. * |
| ЛЕСОВАЯ Е. А. et al., Терапия раковых заболеваний при помощи направленной активации комплемента, Российский биотерапевтический журнал, 2008. Т. 7, N. 3, с.13-18. * |
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