EA020979B1 - ПЭГИЛИРОВАННЫЕ Fab-ФРАГМЕНТЫ АНТИТЕЛ К ПЕПТИДУ Aβ - Google Patents
ПЭГИЛИРОВАННЫЕ Fab-ФРАГМЕНТЫ АНТИТЕЛ К ПЕПТИДУ Aβ Download PDFInfo
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- EA020979B1 EA020979B1 EA200970694A EA200970694A EA020979B1 EA 020979 B1 EA020979 B1 EA 020979B1 EA 200970694 A EA200970694 A EA 200970694A EA 200970694 A EA200970694 A EA 200970694A EA 020979 B1 EA020979 B1 EA 020979B1
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Landscapes
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Applications Claiming Priority (2)
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| US88543907P | 2007-01-18 | 2007-01-18 | |
| PCT/US2008/050554 WO2008088983A1 (en) | 2007-01-18 | 2008-01-09 | PEGYLATED Aβ FAB |
Publications (2)
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| EA200970694A1 EA200970694A1 (ru) | 2010-02-26 |
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| KR101784231B1 (ko) | 2008-06-20 | 2017-11-08 | 노파르티스 아게 | 응집이 감소된 면역글로불린 |
| PL2310970T3 (pl) | 2008-06-20 | 2013-10-31 | Novartis Ag | Metody identyfikacji w białkach regionów wiązania makrocząsteczek i regionów podatności na agregację i zastosowanie tych metod |
| PL2896404T3 (pl) | 2009-06-04 | 2017-12-29 | Novartis Ag | Sposoby identyfikacji miejsc koniugacji IgG |
| MX2012009460A (es) | 2010-03-03 | 2012-09-12 | Boehringer Ingelheim Int | Polipeptidos biparatopicos de union abeta. |
| JP6231263B2 (ja) * | 2012-07-17 | 2017-11-15 | 株式会社島津製作所 | アフィニティ支持体及びそれを用いた物質の捕捉方法 |
| US10431325B2 (en) | 2012-08-03 | 2019-10-01 | Novartis Ag | Methods to identify amino acid residues involved in macromolecular binding and uses therefor |
| WO2015036553A1 (en) * | 2013-09-16 | 2015-03-19 | Novo Nordisk Health Care Ag | Thiol functionalized polymers |
| KR20150133576A (ko) | 2014-05-20 | 2015-11-30 | 삼성전자주식회사 | 화학적 개질된 표적화 단백질 및 그의 이용 |
| WO2017079833A1 (en) | 2015-11-09 | 2017-05-18 | The University Of British Columbia | Epitopes in amyloid beta mid-region and conformationally-selective antibodies thereto |
| WO2017079835A1 (en) | 2015-11-09 | 2017-05-18 | The University Of British Columbia | Amyloid beta epitopes and antibodies thereto |
| HK1259325A1 (zh) | 2015-11-09 | 2019-11-29 | 英属哥伦比亚大学 | 淀粉样蛋白β中的N-末端表位及其构象选择性抗体 |
| TWI735600B (zh) | 2016-07-01 | 2021-08-11 | 美商美國禮來大藥廠 | 抗－N3pGlu類澱粉β肽抗體及其用途 |
| WO2018014126A1 (en) | 2016-07-18 | 2018-01-25 | The University Of British Columbia | Antibodies to amyloid beta |
| CN109562167A (zh) | 2016-08-09 | 2019-04-02 | 伊莱利利公司 | 联合治疗 |
| 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 |
| US12286469B2 (en) | 2017-07-18 | 2025-04-29 | The University Of British Columbia | Humanized antibodies binding to amyloid-beta (A-beta) |
| JP7330164B2 (ja) | 2017-07-18 | 2023-08-21 | 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 |
| WO2019023247A1 (en) | 2017-07-25 | 2019-01-31 | Immutics, Inc. | TREATMENT OF CANCER BY BLOCKING THE INTERACTION OF TIM-3 AND ITS LIGAND |
| WO2019134039A1 (en) * | 2018-01-04 | 2019-07-11 | Septa Therapeutics, Inc. | Septapeptides associated with neurodegeneracy |
| JP2022523333A (ja) | 2019-01-30 | 2022-04-22 | トゥルーバインディング，インコーポレイテッド | 抗ｇａｌ３抗体およびその使用 |
| EP4157338A4 (en) | 2020-05-26 | 2024-11-13 | TrueBinding, Inc. | METHOD FOR TREATING INFLAMMATORY DISEASES BY GALECTIN-3 BLOCKING |
| TW202300518A (zh) | 2021-03-12 | 2023-01-01 | 美商美國禮來大藥廠 | 抗N3pGlu類澱粉β抗體及其用途 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004071408A2 (en) * | 2003-02-10 | 2004-08-26 | Applied Molecular Evolution, Inc. | Aβ BINDING MOLECULES |
| WO2006040153A2 (en) * | 2004-10-13 | 2006-04-20 | Ablynx N.V. | Single domain camelide anti -amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenarative neural diseases such as alzheimer's disease |
| US20060257396A1 (en) * | 2004-12-15 | 2006-11-16 | Jacobsen Jack S | Abeta antibodies for use in improving cognition |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US5278049A (en) * | 1986-06-03 | 1994-01-11 | Incyte Pharmaceuticals, Inc. | Recombinant molecule encoding human protease nexin |
| US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5753624A (en) * | 1990-04-27 | 1998-05-19 | Milkhaus Laboratory, Inc. | Materials and methods for treatment of plaquing disease |
| US5445090A (en) | 1991-07-25 | 1995-08-29 | Mim Industries, Inc. | Interchangeable clamp for use in a sewing machine |
| 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 |
| CA2115900A1 (en) | 1993-02-22 | 1994-08-23 | Gerald W. Becker | Pharmaceutical screens and antibodies |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| AU692237B2 (en) * | 1994-02-03 | 1998-06-04 | Picower Institute For Medical Research, The | Compositions and methods for advanced glycosylation endproduct-mediated modulation of amyloidosis |
| US5668651A (en) * | 1994-03-18 | 1997-09-16 | Sharp Kabushiki Kaisha | Polymer-wall LCD having liquid crystal molecules having a plane-symmetrical bend orientation |
| US6114133A (en) * | 1994-11-14 | 2000-09-05 | Elan Pharmaceuticals, Inc. | Methods for aiding in the diagnosis of Alzheimer's disease by measuring amyloid-β peptide (x-≧41) |
| US5688651A (en) | 1994-12-16 | 1997-11-18 | Ramot University Authority For Applied Research And Development Ltd. | Prevention of protein aggregation |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5786180A (en) | 1995-02-14 | 1998-07-28 | Bayer Corporation | Monoclonal antibody 369.2B specific for β A4 peptide |
| US6214966B1 (en) | 1996-09-26 | 2001-04-10 | Shearwater Corporation | Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution |
| US20040121415A1 (en) * | 1996-12-10 | 2004-06-24 | King David John | Monovalent antibody fragments |
| US6218506B1 (en) | 1997-02-05 | 2001-04-17 | Northwestern University | Amyloid β protein (globular assembly and uses thereof) |
| US6413940B1 (en) | 1997-02-07 | 2002-07-02 | Nymox Corporation | Pharmaceutically active agents that impede the formation of amyloid by impeding the genesis of DMS |
| US20020086847A1 (en) * | 1997-04-09 | 2002-07-04 | Mindset Biopharmaceuticals (Usa) | Recombinant antibodies specific for beta-amyloid ends, DNA encoding and methods of use thereof |
| DK0994728T3 (da) | 1997-04-09 | 2008-12-01 | Intellect Neurosciences Inc | Rekombinante antistoffer, som er specifikke for beta-amyloide ender, DNA, der koder derfor, samt fremgangsmåder til anvendelse heraf |
| US6787319B2 (en) * | 1997-04-16 | 2004-09-07 | American Home Products Corp. | β-amyloid peptide-binding proteins and polynucleotides encoding the same |
| US6227999B1 (en) | 1997-07-09 | 2001-05-08 | Transmisiones Tsp, S.A. De C.V. | Method and apparatus for operating a clutch in an automated mechanical transmission |
| IT1293511B1 (it) | 1997-07-30 | 1999-03-01 | Gentili Ist Spa | Anticorpi monoclonali catalitici ad attivita' proteasica per la lisi selettiva della componente proteica di placche e aggregati correlati |
| EP0996736A1 (en) * | 1997-08-11 | 2000-05-03 | Chiron Corporation | Methods for genetically modifying t cells |
| US6448369B1 (en) | 1997-11-06 | 2002-09-10 | Shearwater Corporation | Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation |
| TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US7964192B1 (en) * | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| ATE268609T1 (de) | 1998-03-12 | 2004-06-15 | Nektar Therapeutics Al Corp | Polyethylenglycolderivate mit benachbarten reaktiven gruppen |
| CA2325600A1 (en) | 1998-05-21 | 1999-11-25 | The University Of Tennessee Research Corporation | Methods for amyloid removal using anti-amyloid antibodies |
| ES2312348T3 (es) * | 1999-06-16 | 2009-03-01 | Boston Biomedical Research Institute | Control inmunologico de niveles de beta-amiloide in vivo. |
| AU6524500A (en) | 1999-08-04 | 2001-03-05 | Northwestern University | Amyloid beta protein (globular assembly and uses thereof) |
| ATE461996T1 (de) | 1999-09-03 | 2010-04-15 | Univ Ramot | Verbindungen, zusammensetzungen und verfahren zur behandlung oder vorsorge von alzheimer erkrankung |
| US6294171B2 (en) | 1999-09-14 | 2001-09-25 | Milkhaus Laboratory, Inc. | Methods for treating disease states comprising administration of low levels of antibodies |
| DE60026073T2 (de) | 1999-12-22 | 2006-09-28 | Nektar Therapeutics Al, Corp., Huntsville | Sterisch gehinderte derivate von wasserlöslichen polymeren |
| US6413507B1 (en) | 1999-12-23 | 2002-07-02 | Shearwater Corporation | Hydrolytically degradable carbamate derivatives of poly (ethylene glycol) |
| DZ3295A1 (fr) * | 2000-02-24 | 2001-08-30 | Anticorps humanises sequestrant un peptide amyloide .beta. | |
| US20020009445A1 (en) * | 2000-07-12 | 2002-01-24 | Yansheng Du | Human beta-amyloid antibody and use thereof for treatment of alzheimer's disease |
| AU2001290638C1 (en) | 2000-09-06 | 2009-04-30 | Aventis Pharma S.A. | Methods and compositions for diseases associated with amyloidosis |
| US6436386B1 (en) | 2000-11-14 | 2002-08-20 | Shearwater Corporation | Hydroxyapatite-targeting poly (ethylene glycol) and related polymers |
| TWI255272B (en) | 2000-12-06 | 2006-05-21 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| WO2004081026A2 (en) * | 2003-06-30 | 2004-09-23 | Domantis Limited | Polypeptides |
| US20040241164A1 (en) * | 2001-08-17 | 2004-12-02 | Bales Kelly Renee | Use of antibodies having high affinity for soluble ab to treat conditions and diseases related to ass |
| JP2005503789A (ja) | 2001-08-17 | 2005-02-10 | イーライ・リリー・アンド・カンパニー | 抗Ａβ抗体 |
| EP1519740A4 (en) | 2001-08-17 | 2005-11-09 | Lilly Co Eli | FASTER IMPROVEMENT OF COGNITION IN DISEASES ASSOCIATED WITH A-BETA |
| AU2002329775C1 (en) * | 2001-08-17 | 2011-04-07 | Eli Lilly And Company | Assay method for alzheimer's disease |
| ATE381346T1 (de) | 2001-08-17 | 2008-01-15 | Univ Washington | Assayverfahren für alzheimer-krankheit |
| US7166478B2 (en) * | 2002-03-12 | 2007-01-23 | Enzo Life Sciences, Inc., C/O Enzo Biochem, Inc. | Labeling reagents and labeled targets, target labeling processes and other processes for using same in nucleic acid determinations and analyses |
| WO2003090772A1 (en) | 2002-04-25 | 2003-11-06 | Eli Lilly And Company | Method for treating anxiety and mood disorders in older subjects |
| DE60329627D1 (de) * | 2002-12-31 | 2009-11-19 | Nektar Therapeutics Al Corp | Hydrolysestabile maleimidendgruppen-enthaltende polymere |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004071408A2 (en) * | 2003-02-10 | 2004-08-26 | Applied Molecular Evolution, Inc. | Aβ BINDING MOLECULES |
| WO2006040153A2 (en) * | 2004-10-13 | 2006-04-20 | Ablynx N.V. | Single domain camelide anti -amyloid beta antibodies and polypeptides comprising the same for the treatment and diagnosis of degenarative neural diseases such as alzheimer's disease |
| US20060257396A1 (en) * | 2004-12-15 | 2006-11-16 | Jacobsen Jack S | Abeta antibodies for use in improving cognition |
Non-Patent Citations (1)
| Title |
|---|
| CHAPMAN ANDREW P.: "PEGylated antibodies and antibody fragments for improved therapy: A review", 20020617, vol. 54, no. 4, 17 June 2002 (2002-06-17), pages 531-545, XP001199533, page 532, right-hand column, paragraph 1 - page 534, right-hand column, paragraph 1 page 537, right-hand column, paragraph 3 - page 539, right-hand column, paragraph 1, page 542, left-hand column, paragraph 2 - right-hand column, paragraph 1, page 543, right-hand column, paragraph 2 * |
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