CA2974993A1 - Anti-transthyretin antibodies - Google Patents
Anti-transthyretin antibodies Download PDFInfo
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- CA2974993A1 CA2974993A1 CA2974993A CA2974993A CA2974993A1 CA 2974993 A1 CA2974993 A1 CA 2974993A1 CA 2974993 A CA2974993 A CA 2974993A CA 2974993 A CA2974993 A CA 2974993A CA 2974993 A1 CA2974993 A1 CA 2974993A1
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Classifications
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Landscapes
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| US10633433B2 (en) | 2015-01-28 | 2020-04-28 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| US9879080B2 (en) | 2015-01-28 | 2018-01-30 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| US10464999B2 (en) | 2015-01-28 | 2019-11-05 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| WO2018007924A2 (en) * | 2016-07-02 | 2018-01-11 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| WO2019070901A1 (en) | 2017-10-04 | 2019-04-11 | Amgen Inc. | IMMUNOGLOBULIN FUSIONS OF TRANSTHYRETIN |
| WO2019071205A1 (en) * | 2017-10-06 | 2019-04-11 | Prothena Biosciences Limited | ANTI-TRANSTHYRETIN ANTIBODY |
| CN111757730A (zh) | 2017-10-06 | 2020-10-09 | 普罗塞纳生物科学有限公司 | 检测甲状腺素运载蛋白的方法 |
| BR112020010483A2 (pt) * | 2017-11-29 | 2020-10-20 | Prothena Biosciences Limited | formulação liofilizada de um anticorpo monoclonal contra transtirretina |
| WO2020003172A1 (en) | 2018-06-26 | 2020-01-02 | Mor Research Applications | Transthyretin antibodies and uses thereof |
| CN111018976B (zh) * | 2018-10-10 | 2022-04-01 | 东莞市朋志生物科技有限公司 | 一种抗人心肌肌钙蛋白i的重组抗体 |
| ES2989499T3 (es) * | 2018-11-09 | 2024-11-26 | Neurimmune Ag | Modelo de roedor de xenoinjerto de amiloide derivado de paciente |
| CN116751295A (zh) * | 2019-06-04 | 2023-09-15 | 江苏恒瑞医药股份有限公司 | 能结合胸腺基质淋巴细胞生成素的抗体及其应用 |
| CA3140208A1 (en) * | 2019-07-08 | 2021-01-14 | Amgen Inc. | Multispecific transthyretin immunoglobulin fusions |
| US20230235048A1 (en) | 2020-06-24 | 2023-07-27 | Andriani IOANNOU | Antibodies recognizing sortilin |
| CN118059229A (zh) * | 2020-10-14 | 2024-05-24 | 维里迪安治疗公司 | 用于治疗甲状腺眼病的组合物和方法 |
| CA3200767A1 (en) * | 2020-12-03 | 2022-06-09 | Zhiwan WANG | Anti-tslp antibody pharmaceutical composition and use thereof |
| CN117603360A (zh) * | 2020-12-16 | 2024-02-27 | 美勒斯公司 | 用于治疗癌症的多特异性抗体 |
| CN117916599A (zh) | 2021-09-07 | 2024-04-19 | 美国西门子医学诊断股份有限公司 | 生物标记物组合物及其使用方法 |
| CN116804186B (zh) * | 2023-07-05 | 2023-12-22 | 中国兽医药品监察所 | 一种抗鸡传染性贫血病毒单克隆抗体杂交瘤细胞株、单克隆抗体、试剂或试剂盒及其应用 |
| WO2025125544A1 (en) | 2023-12-15 | 2025-06-19 | Novo Nordisk A/S | Stable liquid formulations |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH652145A5 (de) | 1982-01-22 | 1985-10-31 | Sandoz Ag | Verfahren zur in vitro-herstellung von hybridomen welche humane monoklonale antikoerper erzeugen. |
| US4634666A (en) | 1984-01-06 | 1987-01-06 | The Board Of Trustees Of The Leland Stanford Junior University | Human-murine hybridoma fusion partner |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| EP0279582A3 (en) | 1987-02-17 | 1989-10-18 | Pharming B.V. | Dna sequences to target proteins to the mammary gland for efficient secretion |
| EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5633076A (en) | 1989-12-01 | 1997-05-27 | Pharming Bv | Method of producing a transgenic bovine or transgenic bovine embryo |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| ATE356869T1 (de) | 1990-01-12 | 2007-04-15 | Amgen Fremont Inc | Bildung von xenogenen antikörpern |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| ES2139598T3 (es) | 1990-07-10 | 2000-02-16 | Medical Res Council | Procedimientos para la produccion de miembros de parejas de union especifica. |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| CA2089661C (en) | 1990-08-29 | 2007-04-03 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5858657A (en) | 1992-05-15 | 1999-01-12 | Medical Research Council | Methods for producing members of specific binding pairs |
| DE69230142T2 (de) | 1991-05-15 | 2000-03-09 | Cambridge Antibody Technology Ltd. | Verfahren zur herstellung von spezifischen bindungspaargliedern |
| DE122004000008I1 (de) | 1991-06-14 | 2005-06-09 | Genentech Inc | Humanisierter Heregulin Antikörper. |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| ATE199392T1 (de) | 1992-12-04 | 2001-03-15 | Medical Res Council | Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US5877218A (en) | 1994-01-10 | 1999-03-02 | Teva Pharmaceutical Industries, Ltd. | Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically active 1-aminoindan derivatives |
| US5786464C1 (en) | 1994-09-19 | 2012-04-24 | Gen Hospital Corp | Overexpression of mammalian and viral proteins |
| DE19539493A1 (de) | 1995-10-24 | 1997-04-30 | Thomae Gmbh Dr K | Starker homologer Promotor aus Hamster |
| US5834597A (en) | 1996-05-20 | 1998-11-10 | Protein Design Labs, Inc. | Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same |
| US6114148C1 (en) | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
| US5888809A (en) | 1997-05-01 | 1999-03-30 | Icos Corporation | Hamster EF-1α transcriptional regulatory DNA |
| ATE490518T1 (de) | 1999-02-05 | 2010-12-15 | Samsung Electronics Co Ltd | Verfahren und vorrichtung zum wiederauffinden von texturbildern |
| TWI255272B (en) | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| MXPA05000511A (es) | 2001-07-12 | 2005-09-30 | Jefferson Foote | Anticuepros super humanizados. |
| EP1470146B8 (en) | 2001-12-28 | 2007-09-12 | Amgen Fremont Inc. | Antibodies against the muc18 antigen |
| ES2293096T3 (es) | 2002-11-29 | 2008-03-16 | BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG | Nuevos genes de la fosfotransferasa de neomicina y procedimiento para la seleccion de celulas recombinantes de produccion elevada. |
| DE10338531A1 (de) | 2003-08-19 | 2005-04-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Reklonierung von Produktionszellen |
| JP4620739B2 (ja) | 2004-11-10 | 2011-01-26 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | Ｃｈｏ細胞に対する細胞保存戦略を最適化するためのフローサイトメトリ分析の使用 |
| WO2007124345A2 (en) | 2006-04-21 | 2007-11-01 | The Government Of The United States, As Represented By The Secretary Of Health And Human Services | Beta-amyloid pet imaging agents |
| US20080124760A1 (en) | 2006-07-26 | 2008-05-29 | Barbara Enenkel | Regulatory Nucleic Acid Elements |
| CA2699837C (en) | 2006-12-01 | 2017-06-13 | Seattle Genetics, Inc. | Variant target binding agents and uses thereof |
| JP5467415B2 (ja) | 2007-03-02 | 2014-04-09 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | タンパク質製造の改良 |
| EP2031064A1 (de) | 2007-08-29 | 2009-03-04 | Boehringer Ingelheim Pharma GmbH & Co. KG | Verfahren zur Steigerung von Proteintitern |
| JP2010195710A (ja) * | 2009-02-25 | 2010-09-09 | Kumamoto Univ | アミロイド線維形成抑制剤及びその利用 |
| US9534048B2 (en) * | 2012-08-24 | 2017-01-03 | University Health Network | Antibodies to TTR and methods of use |
| UA118441C2 (uk) * | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| US9790269B2 (en) * | 2013-02-08 | 2017-10-17 | Misfolding Diagnostics, Inc. | Transthyretin antibodies and uses thereof |
| EP3022225B1 (en) * | 2013-07-19 | 2021-09-29 | Board Of Regents Of the University Of Texas System | Transthyretin amyloid-selective and polyreactive catabodies |
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