JP7017013B2 - 抗トランスサイレチン抗体 - Google Patents
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- JP7017013B2 JP7017013B2 JP2018568300A JP2018568300A JP7017013B2 JP 7017013 B2 JP7017013 B2 JP 7017013B2 JP 2018568300 A JP2018568300 A JP 2018568300A JP 2018568300 A JP2018568300 A JP 2018568300A JP 7017013 B2 JP7017013 B2 JP 7017013B2
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| PCT/IB2017/053991 WO2018007924A2 (en) | 2016-07-02 | 2017-06-30 | Anti-transthyretin antibodies |
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| KR20230032108A (ko) * | 2021-08-30 | 2023-03-07 | 주식회사 뉴보텍 | 노후배관 보강 및 보수를 위한 보강신축관 및 이 보강신축관을 이용한 노후배관 보수방법 |
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| 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 |
| US10633433B2 (en) | 2015-01-28 | 2020-04-28 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| BR112020006434A2 (pt) | 2017-10-06 | 2020-11-03 | Prothena Biosciences Limited | anticorpos anti-transtirretina |
| KR102581734B1 (ko) | 2017-10-06 | 2023-09-22 | 네오토프 뉴로사이언스 리미티드 | 트랜스타이레틴의 검출 방법 |
| BR112020010483A2 (pt) | 2017-11-29 | 2020-10-20 | Prothena Biosciences Limited | formulação liofilizada de um anticorpo monoclonal contra transtirretina |
| US20230183329A1 (en) | 2020-05-12 | 2023-06-15 | Neurimmune Ag | Combination therapy for ttr amyloidosis |
| EP4237005A4 (en) * | 2020-10-28 | 2024-10-09 | Novo Nordisk A/S | ANTI-TRANSTHYRETIN ANTIBODIES AND METHODS OF USE THEREOF |
| CA3239708A1 (en) | 2021-12-03 | 2023-06-08 | Aubin MICHALON | Novel potency assay for antibody-based drugs and useful means therefor |
| WO2024105062A1 (en) | 2022-11-15 | 2024-05-23 | Neurimmune Ag | Methods for treating or preventing transthyretin-mediated amyloidosis |
| WO2024240562A1 (en) | 2023-05-19 | 2024-11-28 | Neurimmune Ag | Novel immunotherapy for musculoskeletal disorders and conditions |
| WO2025238147A1 (en) | 2024-05-15 | 2025-11-20 | Neurimmune Ag | Maintenance treatment of cardiac ttr amyloidosis using anti-transthyretin antibodies |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140056904A1 (en) | 2012-08-24 | 2014-02-27 | University Health Network | Antibodies to TTR and Methods of Use |
| WO2016120811A1 (en) | 2015-01-28 | 2016-08-04 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
Family Cites Families (50)
| 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 |
| EP0832981A1 (en) | 1987-02-17 | 1998-04-01 | Pharming B.V. | DNA sequences to target proteins to the mammary gland for efficient secretion |
| JP3101690B2 (ja) | 1987-03-18 | 2000-10-23 | エス・ビィ・２・インコーポレイテッド | 変性抗体の、または変性抗体に関する改良 |
| 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 |
| SG48759A1 (en) | 1990-01-12 | 2002-07-23 | Abgenix Inc | Generation of xenogenic antibodies |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| ES2139598T3 (es) | 1990-07-10 | 2000-02-16 | Medical Res Council | Procedimientos para la produccion de miembros de parejas de union especifica. |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for 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 |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| ES2246502T3 (es) | 1990-08-29 | 2006-02-16 | Genpharm International, Inc. | Animales no humanos transgenicos capaces de producir anticuerpos heterologos. |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of 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 |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | 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 |
| JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| CA2124967C (en) | 1991-12-17 | 2008-04-08 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| CA2150262C (en) | 1992-12-04 | 2008-07-08 | Kaspar-Philipp Holliger | Multivalent and multispecific binding proteins, their manufacture and use |
| US5827690A (en) | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US5914349A (en) | 1994-01-10 | 1999-06-22 | 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 |
| CN100405399C (zh) | 1999-02-05 | 2008-07-23 | 三星电子株式会社 | 图像纹理恢复方法及其装置 |
| TWI255272B (en) | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| WO2004006955A1 (en) | 2001-07-12 | 2004-01-22 | Jefferson Foote | Super humanized antibodies |
| ES2289174T3 (es) | 2001-12-28 | 2008-02-01 | Amgen Fremont Inc. | Anticuerpos contra el antigeno muc-18. |
| 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 |
| DK1820022T3 (da) | 2004-11-10 | 2009-09-14 | Boehringer Ingelheim Pharma | Anvendelse af flow-cytometrisk analyse for at optimere cellebanks-strategier af CHO-celler |
| US8703096B2 (en) | 2006-04-21 | 2014-04-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Beta-amyloid PET imaging agents |
| US20080124760A1 (en) | 2006-07-26 | 2008-05-29 | Barbara Enenkel | Regulatory Nucleic Acid Elements |
| EP2099823B2 (en) | 2006-12-01 | 2022-02-09 | Seagen Inc. | Variant target binding agents and uses thereof |
| DK2126093T3 (da) | 2007-03-02 | 2013-01-07 | Boehringer Ingelheim Pharma | Forbedring af proteinfremstilling |
| EP2031064A1 (de) | 2007-08-29 | 2009-03-04 | Boehringer Ingelheim Pharma GmbH & Co. KG | Verfahren zur Steigerung von Proteintitern |
| JP2016514091A (ja) * | 2013-02-08 | 2016-05-19 | ミスフォールディング ダイアグノスティクス， インコーポレイテッド | トランスサイレチン抗体およびその使用 |
| TWI718121B (zh) * | 2015-01-28 | 2021-02-11 | 愛爾蘭商普羅佘納生物科技有限公司 | 抗甲狀腺素運送蛋白抗體 |
-
2017
- 2017-06-30 EP EP17746544.0A patent/EP3478716A2/en active Pending
- 2017-06-30 WO PCT/IB2017/053991 patent/WO2018007924A2/en not_active Ceased
- 2017-06-30 JP JP2018568300A patent/JP7017013B2/ja active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140056904A1 (en) | 2012-08-24 | 2014-02-27 | University Health Network | Antibodies to TTR and Methods of Use |
| WO2016120811A1 (en) | 2015-01-28 | 2016-08-04 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
Non-Patent Citations (6)
| Title |
|---|
| Amyloid, 2016.3, Vol.23, No.2, pp.86-97 |
| Human Pathology, 2011, Vol.42, pp.1259-1264 |
| JCI insight, 2016.2, Vol.1, No.2, #e85633 |
| Modern Pathology, 2015, Vol.28, pp.201-207 |
| Scientific Reports, 2016.4, Vol.6, #25080 |
| Synovial deposition of wild-typetransthyretin-derived amyloid in knee joint osteoarthritis patients，信州医誌, 2014, Vol. 62, pp.329-330 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20230032108A (ko) * | 2021-08-30 | 2023-03-07 | 주식회사 뉴보텍 | 노후배관 보강 및 보수를 위한 보강신축관 및 이 보강신축관을 이용한 노후배관 보수방법 |
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| WO2018007924A3 (en) | 2018-03-01 |
| EP3478716A2 (en) | 2019-05-08 |
| WO2018007924A2 (en) | 2018-01-11 |
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