CA3083199A1 - Anti-alpha-synuclein antibodies - Google Patents
Anti-alpha-synuclein antibodies Download PDFInfo
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- CA3083199A1 CA3083199A1 CA3083199A CA3083199A CA3083199A1 CA 3083199 A1 CA3083199 A1 CA 3083199A1 CA 3083199 A CA3083199 A CA 3083199A CA 3083199 A CA3083199 A CA 3083199A CA 3083199 A1 CA3083199 A1 CA 3083199A1
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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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| US7674599B2 (en) | 2003-11-08 | 2010-03-09 | Elan Pharmaceuticals, Inc. | Methods of using antibodies to detect alpha-synuclein in fluid samples |
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| WO2007021255A1 (en) | 2005-08-09 | 2007-02-22 | Elan Pharmaceuticals, Inc. | Antibodies to alpha-synuclein |
| PL2583978T3 (pl) | 2007-02-23 | 2016-07-29 | Prothena Biosciences Ltd Co | Profilaktyka i leczenie chorób synukleinopatycznych i amyloidogennych |
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| LT3067066T (lt) * | 2007-02-23 | 2019-06-25 | Prothena Biosciences Limited | Sinukleopatinių ir amiloidogeninių ligų prevencija ir gydymas |
| LT2282758T (lt) | 2008-04-29 | 2019-03-12 | Bioarctic Ab | Antikūnai ir vakcinos, skirti su alfa sinukleinu susijusių sutrikimų gydymo ir diagnostiniams metodams |
| PT2370466E (pt) | 2008-12-19 | 2015-09-21 | Univ Zuerich | Autoanticorpos humanos anti-alfa-sinucleína |
| US8609097B2 (en) * | 2009-06-10 | 2013-12-17 | Hoffmann-La Roche Inc. | Use of an anti-Tau pS422 antibody for the treatment of brain diseases |
| RU2555526C2 (ru) * | 2010-02-26 | 2015-07-10 | Байоарктик Ньюросайенс Аб | Антитела, связывающиеся с протофибриллами, и их применение в методах терапии и диагностики болезни паркинсона, деменции, ассоциированной с образованием диффузных телец леви, и других альфа-синуклеинопатий |
| EP2366714A1 (en) | 2010-03-03 | 2011-09-21 | Dr. Rentschler Holding GmbH & Co. KG | Naturally occuring autoantibodies against alpha-synuclein that inhibit the aggregation and cytotoxicity of alpha-synuclein |
| EP2635906A4 (en) | 2010-11-05 | 2014-04-02 | Univ Brandeis | Ice inhibiting compounds and uses thereof |
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| KR102086061B1 (ko) | 2012-01-27 | 2020-03-11 | 프로테나 바이오사이언시즈 리미티드 | 알파-시누클레인을 인식하는 인간화된 항체 |
| ES2856272T3 (es) | 2012-05-30 | 2021-09-27 | Chugai Pharmaceutical Co Ltd | Molécula de unión a antígenos para eliminar antígenos agregados |
| UA118441C2 (uk) * | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| US9534044B2 (en) | 2013-02-28 | 2017-01-03 | United Arab Emirates University | Alpha-synuclein antibodies and uses thereof |
| WO2015051159A1 (en) | 2013-10-02 | 2015-04-09 | The Rockefeller University | Amyloid protofibril antibodies and methods of use thereof |
| EP3071974A2 (en) | 2013-11-19 | 2016-09-28 | Prothena Biosciences Limited | Monitoring immunotherapy of lewy body disease from constipation symptoms |
| PL3071597T3 (pl) | 2013-11-21 | 2020-11-30 | F.Hoffmann-La Roche Ag | Przeciwciała przeciwko alfa-synukleinie i sposoby stosowania |
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| US10155030B2 (en) | 2014-05-23 | 2018-12-18 | University Of South Florida | Methods, antibodies, and vaccines utilizing epitopes of alpha synuclein for treatment of parkinsons disease |
| GB201411320D0 (en) | 2014-06-25 | 2014-08-06 | Ucb Biopharma Sprl | Antibody construct |
| JP6980953B2 (ja) | 2014-09-11 | 2021-12-15 | ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム | ミスフォールディングタンパク質の検出 |
| WO2016040905A1 (en) | 2014-09-11 | 2016-03-17 | Board Of Regents Of The University Of Texas System | Detection of misfolded alpha synuclein protein |
| WO2016040903A1 (en) | 2014-09-11 | 2016-03-17 | Board Of Regents Of The University Of Texas System | Detection of misfolded amyloid beta protein |
| JP2017536102A (ja) | 2014-10-16 | 2017-12-07 | ジェネンテック， インコーポレイテッド | 抗アルファ−シヌクレイン抗体及び使用方法 |
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| CA2994518C (en) | 2015-08-25 | 2025-05-06 | Prothena Biosciences Limited | METHODS FOR DETECTING PHOSPHORYLATED ALPHA-SYNUCLEIN |
| AU2016361350B2 (en) | 2015-11-23 | 2023-04-06 | Sangamo Therapeutics, Inc. | Methods and compositions for engineering immunity |
| US10766954B2 (en) | 2016-04-06 | 2020-09-08 | Imago Pharmaceuticals, Inc. | Therapeutic antibodies for treatment of neurodegeneration |
| EA038358B1 (ru) | 2016-06-02 | 2021-08-13 | Медиммун Лимитед | Антитела к альфа-синуклеину и их применение |
| GB201611840D0 (en) | 2016-07-07 | 2016-08-24 | Univ Court Of The Univ Of Edinburgh The | Alpha-synuclein detection assay |
| US20190194324A1 (en) | 2016-08-23 | 2019-06-27 | The Johns Hopkins University | THERAPEUTIC USES OF LAG3 THE (alpha)-SYNUCLEIN TRANSMISSION RECEPTOR |
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| US20190315846A1 (en) | 2016-12-12 | 2019-10-17 | The Michael J. Fox Foundation For Parkinson's Research | Antibodies to Human Alpha-Synuclein |
| ES3008133T3 (en) | 2016-12-16 | 2025-03-21 | H Lundbeck As | Agents, uses and methods |
| US10364286B2 (en) | 2016-12-22 | 2019-07-30 | H. Lundbeck A/S | Monoclonal anti-alpha-synuclein antibodies for preventing tau aggregation |
| AU2018206279B2 (en) | 2017-01-06 | 2020-09-03 | Abl Bio Inc. | Anti-alpha-syn antibody and use thereof |
| ES2970504T3 (es) | 2017-01-09 | 2024-05-29 | California Inst Of Techn | Uso de la microbiota intestinal en el diagnóstico de la enfermedad de Parkinson |
| US11142570B2 (en) * | 2017-02-17 | 2021-10-12 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
| JOP20190227A1 (ar) | 2017-03-31 | 2019-09-30 | Biogen Int Neuroscience Gmbh | تركيبات وطرق لعلاج اعتلالات السينوكلين |
| CN110869763B (zh) | 2017-05-16 | 2022-07-29 | 安培里翁公司 | 错误折叠tau蛋白质的检测 |
| WO2018237338A1 (en) | 2017-06-23 | 2018-12-27 | Denali Therapeutics Inc. | Anti-alpha-synuclein antibodies and methods of use thereof |
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