JP7330164B2 - アミロイドベータに対する抗体 - Google Patents
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- JP7330164B2 JP7330164B2 JP2020502655A JP2020502655A JP7330164B2 JP 7330164 B2 JP7330164 B2 JP 7330164B2 JP 2020502655 A JP2020502655 A JP 2020502655A JP 2020502655 A JP2020502655 A JP 2020502655A JP 7330164 B2 JP7330164 B2 JP 7330164B2
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- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
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| US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008520553A (ja) | 2004-10-25 | 2008-06-19 | メルク・アンド・カンパニー・インコーポレーテッド | 抗ａｄｄｌ抗体およびこの使用 |
| JP2008524247A (ja) | 2004-12-15 | 2008-07-10 | エラン ファーマ インターナショナル リミテッド | 認知の改善における使用のためのアミロイドβ抗体 |
| WO2017079833A1 (en) | 2015-11-09 | 2017-05-18 | The University Of British Columbia | Epitopes in amyloid beta mid-region and conformationally-selective antibodies thereto |
| US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
| JP2019533426A (ja) | 2016-07-18 | 2019-11-21 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | アミロイドベータに対する抗体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| 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 |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5837672A (en) | 1992-07-10 | 1998-11-17 | Athena Neurosciences, Inc. | Methods and compositions for the detection of soluble β-amyloid peptide |
| US5766846A (en) | 1992-07-10 | 1998-06-16 | Athena Neurosciences | Methods of screening for compounds which inhibit soluble β-amyloid peptide production |
| US5735814A (en) | 1996-04-30 | 1998-04-07 | Medtronic, Inc. | Techniques of treating neurodegenerative disorders by brain infusion |
| US6436708B1 (en) | 1997-04-17 | 2002-08-20 | Paola Leone | Delivery system for gene therapy to the brain |
| US7012061B1 (en) | 1998-10-19 | 2006-03-14 | New York University | Method for increasing the permeability of the blood brain barrier |
| KR100767146B1 (ko) | 2000-02-24 | 2007-10-15 | 워싱톤 유니버시티 | Ａβ 펩티드를 격리시키는 인간화 항체 |
| US20040192898A1 (en) | 2001-08-17 | 2004-09-30 | Jia Audrey Yunhua | Anti-abeta antibodies |
| AR038568A1 (es) | 2002-02-20 | 2005-01-19 | Hoffmann La Roche | Anticuerpos anti-a beta y su uso |
| DE602004027348D1 (de) | 2003-02-10 | 2010-07-08 | Applied Molecular Evolution | Abeta-bindende moleküle |
| CN1562050A (zh) | 2004-03-24 | 2005-01-12 | 中国海洋大学 | 褐藻酸寡糖在抗痴呆、抗糖尿病中的应用 |
| US20060129126A1 (en) | 2004-11-19 | 2006-06-15 | Kaplitt Michael G | Infusion device and method for infusing material into the brain of a patient |
| AR052051A1 (es) | 2004-12-15 | 2007-02-28 | Neuralab Ltd | Anticuerpos ab humanizados usados en mejorar la cognicion |
| CA2609980C (en) | 2005-05-27 | 2015-10-13 | Queen's University At Kingston | Treatment of protein folding disorders |
| BRPI0619605B8 (pt) | 2005-12-12 | 2021-05-25 | Hoffmann La Roche | composições compreendendo moléculas de anticorpos contra amilóide beta4 com glicosilação na região variável, usos das mesmas, método de preparação de uma molécula de anticorpo, e kit |
| ES2535641T3 (es) | 2007-01-18 | 2015-05-13 | Eli Lilly & Company | Amiloide beta Fab pegilado |
| RU2542967C2 (ru) | 2007-10-05 | 2015-02-27 | Дженентек, Инк. | Применение антитела против амилоида бета при глазных заболеваниях |
| AU2008345022B2 (en) | 2007-12-28 | 2014-11-06 | Prothena Biosciences Limited | Treatment and prophylaxis of amyloidosis |
| WO2009149487A2 (en) | 2008-06-12 | 2009-12-17 | Affiris Ag | Compounds for treating symptoms associated with parkinson's disease |
| AT506820B1 (de) | 2008-06-12 | 2011-07-15 | Affiris Forschungs Und Entwicklungs Gmbh | Vakzine gegen alzheimer-krankheit |
| RU2603008C2 (ru) | 2010-04-16 | 2016-11-20 | Ац Иммуне С.А. | Новые соединения для лечения заболеваний, связанных с амилоидными или амилоидоподобными белками |
| SG10202111808WA (en) * | 2015-08-11 | 2021-11-29 | Novartis Ag | 5-bromo-2,6-di-(1h-pyrazol-1-yl)pyrimidin-4-amine for use in the treatment of cancer |
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- 2018-07-18 WO PCT/CA2018/050875 patent/WO2019014768A1/en not_active Ceased
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008520553A (ja) | 2004-10-25 | 2008-06-19 | メルク・アンド・カンパニー・インコーポレーテッド | 抗ａｄｄｌ抗体およびこの使用 |
| JP2008524247A (ja) | 2004-12-15 | 2008-07-10 | エラン ファーマ インターナショナル リミテッド | 認知の改善における使用のためのアミロイドβ抗体 |
| WO2017079833A1 (en) | 2015-11-09 | 2017-05-18 | The University Of British Columbia | Epitopes in amyloid beta mid-region and conformationally-selective antibodies thereto |
| JP2019533426A (ja) | 2016-07-18 | 2019-11-21 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | アミロイドベータに対する抗体 |
| US20180125920A1 (en) | 2016-11-09 | 2018-05-10 | The University Of British Columbia | Methods for preventing and treating A-beta oligomer-associated and/or -induced diseases and conditions |
Non-Patent Citations (1)
| Title |
|---|
| Nature (2016) Vol.537, pp.50-56, METHODS, Extended Data Figure 1-7 and Table 1-4 |
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| JP2020533955A (ja) | 2020-11-26 |
| EP3574020A4 (en) | 2020-03-25 |
| ES2984844T3 (es) | 2024-10-31 |
| EP3574020A1 (en) | 2019-12-04 |
| JP2023086132A (ja) | 2023-06-21 |
| CA3070085A1 (en) | 2019-01-24 |
| EP3574020B1 (en) | 2024-05-15 |
| WO2019014768A1 (en) | 2019-01-24 |
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