JP3894795B2 - ヒト細胞株における組換え血液凝固因子の製造 - Google Patents
ヒト細胞株における組換え血液凝固因子の製造 Download PDFInfo
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| ATE489105T1 (de) | 2004-03-19 | 2010-12-15 | Baxter Int | Faktor ixa zur behandlung von blutungsstörungen |
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| DK2438931T3 (da) | 2004-09-22 | 2013-12-02 | St Jude Childrens Res Hospital | Forbedret ekspression af faktor ix i genterapivektorer |
| US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
| CN101120085B (zh) * | 2005-02-11 | 2011-06-08 | 诺和诺德医疗保健公司 | 在包含植物蛋白水解产物的无血清细胞培养液中生产多肽 |
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| EP2198870A4 (en) * | 2007-08-27 | 2011-08-03 | Univ Nagoya Nat Univ Corp | ACTIVATOR FOR BLOOD CREATION FACTOR VII PROMOTER AND ITS USE |
| RU2011110459A (ru) | 2008-08-21 | 2012-09-27 | Октафарма АГ (CH) | Рекомбинантно полученный человеческий фактор viii и ix |
| SG172789A1 (en) | 2009-02-11 | 2011-08-29 | Novozymes Biopharma Dk As | Albumin variants and conjugates |
| PT2482841T (pt) | 2009-10-02 | 2019-03-01 | Childrens Hospital Philadelphia | A presente invenção refere-se à utilização de lactonas macrocíclicas para o tratamento da demodicose, em particular em cães. |
| RU2607374C2 (ru) | 2009-10-30 | 2017-01-10 | Новозаймс Байофарма Дк А/С | Варианты альбумина |
| US10233228B2 (en) | 2010-04-09 | 2019-03-19 | Albumedix Ltd | Albumin derivatives and variants |
| BRPI1105317A2 (pt) * | 2011-01-24 | 2013-04-30 | Fundacco Hemoct De Ribeirco Preto | produÇço estÁvel e em larga escala de fviii humano em linhagem celular humana sk-hep-1 |
| EP2679681B2 (en) | 2011-02-25 | 2023-11-15 | Chugai Seiyaku Kabushiki Kaisha | FcgammaRIIB-specific FC antibody |
| CN102199607B (zh) * | 2011-03-30 | 2012-11-14 | 山西大学 | 重组人凝血因子ix小基因及其ptc突变体稳定细胞株 |
| AU2012257736B2 (en) | 2011-05-13 | 2015-12-10 | Octapharma Ag | A method of increasing the productivity of eucaryotic cells in the production of recombinant FVIII |
| TW201307563A (zh) * | 2011-05-19 | 2013-02-16 | Shire Human Genetic Therapies | 純化乙醯肝素－ｎ－硫酸酯酶之方法 |
| EP4011913A1 (en) | 2011-06-30 | 2022-06-15 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
| CN102321668A (zh) * | 2011-07-06 | 2012-01-18 | 中国人民解放军军事医学科学院野战输血研究所 | 一种表达重组人凝血因子ⅶ的方法及其专用载体 |
| JP6322411B2 (ja) | 2011-09-30 | 2018-05-09 | 中外製薬株式会社 | 複数の生理活性を有する抗原の消失を促進する抗原結合分子 |
| WO2013057219A1 (en) | 2011-10-18 | 2013-04-25 | Csl Behring Gmbh | Method for improving the stability of purified factor viii after reconstitution |
| US20140315817A1 (en) | 2011-11-18 | 2014-10-23 | Eleven Biotherapeutics, Inc. | Variant serum albumin with improved half-life and other properties |
| CN104080909A (zh) | 2011-11-30 | 2014-10-01 | 中外制药株式会社 | 包含进入细胞内以形成免疫复合体的搬运体(载体)的药物 |
| MX2014010278A (es) | 2012-03-16 | 2015-03-05 | Novozymes Biopharma Dk As | Variantes de albumina. |
| JP6254146B2 (ja) | 2012-03-27 | 2017-12-27 | エヌジーエム バイオファーマシューティカルス，インコーポレーテッド | 代謝障害を治療するための組成物および方法 |
| GB201210357D0 (en) * | 2012-06-12 | 2012-07-25 | Ucl Business Plc | Factor VIII sequences |
| WO2014008172A2 (en) * | 2012-07-03 | 2014-01-09 | Expression Therapeutics, Llc | High yield suspension cell line, system and method for making same |
| EP3404105A1 (en) | 2012-07-06 | 2018-11-21 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor viii polypeptides and uses thereof |
| CN105452290A (zh) | 2012-11-08 | 2016-03-30 | 诺维信生物制药丹麦公司 | 白蛋白变体 |
| CN105025920A (zh) * | 2013-01-24 | 2015-11-04 | 博尔托拉制药公司 | 具有因子Xa衍生物的组织因子途径抑制剂的抑制 |
| CA2908350C (en) | 2013-04-02 | 2023-08-08 | Futa Mimoto | Fc region variant |
| EP2853538A1 (en) | 2013-09-27 | 2015-04-01 | Université Pierre et Marie Curie (Paris 6) | Analogues of temporin-SHa and uses thereof |
| SG10201802098UA (en) * | 2014-07-30 | 2018-04-27 | Ngm Biopharmaceuticals Inc | Compositions and methods of use for treating metabolic disorders |
| CN115043945A (zh) | 2014-10-31 | 2022-09-13 | Ngm生物制药有限公司 | 用于治疗代谢病症的组合物和方法 |
| GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
| MY181199A (en) | 2014-12-19 | 2020-12-21 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
| BR102015012334A2 (pt) | 2015-05-27 | 2016-11-29 | Fundação Hemoct De Ribeirão Preto Fundherp | processo de produção do fator vii de coagulação sanguínea e fator vii de coagulação sanguínea |
| WO2016198499A1 (en) | 2015-06-09 | 2016-12-15 | Glycotope Gmbh | IMPROVED METHOD FOR PRODUCTION OF γ-CARBOXYLATED POLYPEPTIDES |
| CA2989966C (en) | 2015-08-20 | 2024-04-30 | Albumedix A/S | Albumin variants and conjugates |
| CN105219739A (zh) * | 2015-09-21 | 2016-01-06 | 北京神源德生物科技有限公司 | 重组单纯疱疹病毒及它感染和制备它的宿主细胞以及它们的应用 |
| WO2017110981A1 (en) | 2015-12-25 | 2017-06-29 | Chugai Seiyaku Kabushiki Kaisha | Anti-myostatin antibodies and methods of use |
| KR102450833B1 (ko) | 2016-04-15 | 2022-10-05 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | 혈우병 a 치료용 유전자 요법 |
| JP6527643B2 (ja) | 2016-08-05 | 2019-06-05 | 中外製薬株式会社 | Ｉｌ−８関連疾患の治療用又は予防用組成物 |
| WO2018210771A1 (en) | 2017-05-17 | 2018-11-22 | Octapharma Ag | Method for the production of a recombinant target protein |
| EP3710589A4 (en) | 2017-11-14 | 2021-11-10 | Chugai Seiyaku Kabushiki Kaisha | ANTI-C1S ANTIBODIES AND METHOD OF USING |
| WO2020020364A1 (zh) * | 2018-07-26 | 2020-01-30 | 正大天晴药业集团南京顺欣制药有限公司 | 一种制备重组人凝血因子ⅷ的方法 |
| SG10202106830VA (en) | 2018-08-10 | 2021-08-30 | Chugai Pharmaceutical Co Ltd | Anti-cd137 antigen-binding molecule and utilization thereof |
| US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
| GB201813528D0 (en) | 2018-08-20 | 2018-10-03 | Ucl Business Plc | Factor IX encoding nucleotides |
| AU2019366942B2 (en) | 2018-10-23 | 2025-10-30 | The Children's Hospital Of Philadelphia | Compositions and methods for modulating factor VIII function |
| CA3137649A1 (en) | 2019-05-15 | 2020-11-19 | Chugai Seiyaku Kabushiki Kaisha | An antigen-binding molecule, a pharmaceutical composition, and a method |
| CA3221235A1 (en) | 2021-06-11 | 2022-12-15 | Ali Ladram | Short antimicrobial peptides |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI86885C (fi) * | 1984-04-20 | 1992-10-26 | Genentech Inc | Foerfarande foer framstaellning av human rekombinantfaktor viii och nukleinsyrasekvenser och vektorer anvaend daertill |
| JPS6171774A (ja) * | 1984-09-14 | 1986-04-12 | Sony Corp | テレビジヨンカメラ装置のビ−ム電流制御装置 |
| AU5864086A (en) * | 1985-04-22 | 1986-11-18 | Genetics Institute Inc. | High yield production of active factor ix |
| DE3785102T2 (de) * | 1986-01-03 | 1993-07-22 | Genetics Inst | Verfahren zur herstellung von faktor-viii:c-typ-proteinen. |
| US5451521A (en) * | 1986-05-29 | 1995-09-19 | Genetics Institute, Inc. | Procoagulant proteins |
| US5422260A (en) * | 1986-05-29 | 1995-06-06 | Genetics Institute, Inc. -Legal Affairs | Human factor VIII:c muteins |
| US5024939A (en) * | 1987-07-09 | 1991-06-18 | Genentech, Inc. | Transient expression system for producing recombinant protein |
| FR2638643B1 (fr) * | 1988-11-09 | 1991-04-12 | Transgene Sa | Sequence d'adn codant pour le facteur ix humain ou une proteine analogue, vecteur d'expression, cellules transformees, procede de preparation du facteur ix et produits obtenus correspondants |
| CA2135744A1 (en) * | 1989-11-17 | 1991-05-18 | Barbara Chapman | Protein complexes having factor viii:c activity and production thereof |
| SE465222C5 (sv) * | 1989-12-15 | 1998-02-10 | Pharmacia & Upjohn Ab | Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning |
| FI923347A0 (fi) * | 1990-01-26 | 1992-07-23 | Immuno Ag | Blodfaktorer producerade med rekombinant-dna-teknik och foerfarande foer expression av naemnda blodfaktorer samt i naemnda foerfarande anvaenda rekombinanta kokoppvirus. |
| US5445953A (en) * | 1991-08-26 | 1995-08-29 | Immuno Aktiengesellschaft | Direct molecular cloning of a modified poxvirus genome |
| CA2162497A1 (en) * | 1993-06-10 | 1994-12-22 | Sheila Connelly | Adenoviral vectors for treatment of hemophilia |
| EP0951544A2 (en) * | 1996-07-03 | 1999-10-27 | Chiron Corporation | Methods for administration of recombinant gene delivery vehicles for treatment of human disease |
| US6114148C1 (en) * | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
| JP2002517180A (ja) * | 1997-12-05 | 2002-06-18 | ジ・イミユーン・リスポンス・コーポレーシヨン | 増大された発現を示す新規ベクターおよび遺伝子 |
| US6358703B1 (en) * | 1998-12-10 | 2002-03-19 | Bayer Corporation | Expression system for factor VIII |
| JP2002537311A (ja) | 1999-02-19 | 2002-11-05 | オクタジーン・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | ホルモン−ホルモン受容体の複合体および核酸構築物、並びに遺伝子治療におけるそれらの使用 |
| WO2001012836A1 (en) * | 1999-08-13 | 2001-02-22 | Fred Hutchinson Cancer Research Center | Crystal of a truncated protein construct containing a coagulation factor viii c2 domain in the presence or absence of a bound ligand and methods of use thereof |
| BRPI0109494B8 (pt) * | 2000-03-22 | 2021-05-25 | Octagene Gmbh | muteína de fator viii, sequência de dna, vetor, processo para produção da muteína de fator viii, composição farmacêutica e uso da muteína do fator viii |
| WO2003009237A1 (en) * | 2001-07-18 | 2003-01-30 | Skaginn Hf. | A method and apparatus for relating information of a processed object to an operator |
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