CA2944402A1 - Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein - Google Patents
Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein Download PDFInfo
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- CA2944402A1 CA2944402A1 CA2944402A CA2944402A CA2944402A1 CA 2944402 A1 CA2944402 A1 CA 2944402A1 CA 2944402 A CA2944402 A CA 2944402A CA 2944402 A CA2944402 A CA 2944402A CA 2944402 A1 CA2944402 A1 CA 2944402A1
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| US201462023373P | 2014-07-11 | 2014-07-11 | |
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| PCT/IB2015/052524 WO2015155694A1 (en) | 2014-04-08 | 2015-04-08 | Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein |
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| AU2013211874B2 (en) | 2012-01-27 | 2017-11-02 | Prothena Biosciences Limited | Humanized antibodies that recognize alpha-synuclein |
| UA118441C2 (uk) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| US10513555B2 (en) | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
| CN109476728A (zh) * | 2016-07-14 | 2019-03-15 | 生命北极公司 | 脑部递送蛋白 |
| EP3583124A1 (en) | 2017-02-17 | 2019-12-25 | Bristol-Myers Squibb Company | Antibodies to alpha-synuclein and uses thereof |
| EP3725806A4 (en) * | 2017-12-14 | 2022-03-30 | ABL Bio Inc. | BISPECIFIC ANTIBODIES AGAINST A-SYN/IGF1R AND ASSOCIATED USE |
| GB201720975D0 (en) | 2017-12-15 | 2018-01-31 | Ucb Biopharma Sprl | Anti-alpha synuclein antibodies |
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| CN112312922B (zh) * | 2018-06-21 | 2025-04-11 | 诺和诺德股份有限公司 | 用于治疗肥胖症的新型化合物 |
| SG11202101273VA (en) * | 2018-08-16 | 2021-03-30 | Denali Therapeutics Inc | Engineered bispecific proteins |
| TWI734279B (zh) * | 2018-12-14 | 2021-07-21 | 美商美國禮來大藥廠 | 抗α-突觸核蛋白抗體及其用途 |
| US20200385461A1 (en) * | 2019-04-05 | 2020-12-10 | B-Portal Biologics, Inc. | Fusion constructs and uses thereof |
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| JP2022531177A (ja) * | 2019-04-29 | 2022-07-06 | トーマス・ジェファーソン・ユニバーシティ | 神経変性障害を治療するための方法 |
| EP4185612A4 (en) | 2020-07-23 | 2024-12-25 | Othair Prothena Limited | Anti-abeta antibodies |
| MX2023003008A (es) * | 2020-09-18 | 2023-04-10 | Othair Prothena Ltd | Vacuna de multiples epitopos para el tratamiento de la enfermedad de alzheimer. |
| WO2025054419A1 (en) * | 2023-09-08 | 2025-03-13 | California Institute Of Technology | Compositions for transport of therapeutic cargos using antibody binders targeting ca-iv |
Family Cites Families (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1575961A (en) | 1977-09-07 | 1980-10-01 | Sekisui Chemical Co Ltd | Foamable compositions and their use in preparing foams |
| DE3133101A1 (de) | 1981-08-21 | 1983-03-10 | Hoechst Ag, 6000 Frankfurt | Verfahren zur entfernung von katalysatorresten aus polyolefinen |
| 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 |
| DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2, Inc., Danville, Calif. | Geänderte antikörper. |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
| 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 |
| ATE139258T1 (de) | 1990-01-12 | 1996-06-15 | Cell Genesys Inc | Erzeugung xenogener antikörper |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| DK0585287T3 (da) | 1990-07-10 | 2000-04-17 | Cambridge Antibody Tech | Fremgangsmåde til fremstilling af specifikke bindingsparelementer |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| 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 |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| AU8507191A (en) | 1990-08-29 | 1992-03-30 | 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 |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | 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 |
| US5858657A (en) | 1992-05-15 | 1999-01-12 | Medical Research Council | Methods for producing members of specific binding pairs |
| US5871907A (en) | 1991-05-15 | 1999-02-16 | Medical Research Council | Methods for producing members of specific binding pairs |
| EP0940468A1 (en) | 1991-06-14 | 1999-09-08 | Genentech, Inc. | Humanized antibody variable domain |
| WO1993001222A1 (fr) | 1991-07-03 | 1993-01-21 | Kanebo, Ltd. | Elastomere de polyurethane thermoplastique, procede et dispositif de production, et fibre elastique realisee a partir de cet elastomere |
| US5209485A (en) | 1991-09-23 | 1993-05-11 | Lisco, Inc. | Restricted flight golf ball |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5208362A (en) | 1992-02-27 | 1993-05-04 | Ethyl Corporation | Process for stabilizing organophosphorus compounds |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| DE69330523D1 (de) | 1992-08-21 | 2001-09-06 | Vrije Universiteit Brussel Bru | Immunoglobuline ohne leichte ketten |
| DK0672142T3 (da) | 1992-12-04 | 2001-06-18 | Medical Res Council | Multivalente og multispecifikke bindingsproteiner samt fremstilling og anvendelse af disse |
| 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 |
| BR0007956A (pt) | 1999-02-05 | 2002-04-09 | Samsung Electronics Co Ltd | Método de recuperação de textura por imagem e equipamento para essa finalidade, e meio legìvel por computador |
| EP1409654B1 (en) | 1999-06-16 | 2008-08-20 | Boston Biomedical Research Institute | Immunological control of beta-amyloid levels in vivo |
| AU2002211352A1 (en) | 2000-10-23 | 2002-05-06 | Dow Global Technologies Inc. | Propylene polymer foams |
| PE20020574A1 (es) | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
| US6583190B2 (en) | 2000-12-27 | 2003-06-24 | Sealed Air Corporation (U.S.) | Expandable composition, blowing agent, and process for extruded thermoplastic foams |
| KR100456392B1 (ko) | 2001-02-01 | 2004-11-10 | 미쓰이 가가쿠 가부시키가이샤 | 올레핀계 엘라스토머 가교발포체용 엘라스토머 조성물 및그의 용도 |
| US6881557B2 (en) | 2001-07-12 | 2005-04-19 | Arrowsmith Technologies Llp | Super humanized antibodies |
| WO2004039234A2 (en) | 2002-05-13 | 2004-05-13 | Alexion Pharmaceuticals, Inc. | Humanized antibodies against the venezuelan equine encephalitis virus |
| US20080014194A1 (en) | 2003-10-31 | 2008-01-17 | Elan Pharmaceuticals, Inc. | Prevention and Treatment of Synucleinopathic and Amyloidogenic Disease |
| US9034337B2 (en) | 2003-10-31 | 2015-05-19 | Prothena Biosciences Limited | Treatment and delay of outset of synucleinopathic and amyloidogenic disease |
| TW200509968A (en) | 2002-11-01 | 2005-03-16 | Elan Pharm Inc | Prevention and treatment of synucleinopathic disease |
| US8506959B2 (en) * | 2002-11-01 | 2013-08-13 | Neotope Biosciences Limited | Prevention and treatment of synucleinopathic and amyloidogenic disease |
| JP4344325B2 (ja) | 2002-11-29 | 2009-10-14 | 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 | 新規なネオマイシンホスホトランスフェラーゼ遺伝子及び高生産組換え細胞の選抜方法 |
| US7358331B2 (en) | 2003-05-19 | 2008-04-15 | Elan Pharmaceuticals, Inc. | Truncated fragments of alpha-synuclein in Lewy body disease |
| DE10338531A1 (de) | 2003-08-19 | 2005-04-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Reklonierung von Produktionszellen |
| WO2005047860A2 (en) | 2003-11-08 | 2005-05-26 | Elan Pharmaceuticals, Inc. | Antibodies to alpha-synuclein |
| AU2004297616B2 (en) | 2003-12-04 | 2008-12-18 | Xencor, Inc. | Methods of generating variant proteins with increased host string content and compositions thereof |
| JP2006089637A (ja) | 2004-09-24 | 2006-04-06 | Kaneka Corp | ポリプロピレン系樹脂発泡シートの製造方法 |
| KR101235658B1 (ko) | 2004-11-10 | 2013-02-21 | 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 | Ｃｈｏ 세포에 대한 세포 뱅킹 전략을 최적화하기 위한 유동 세포측정 분석의 용도 |
| US7179873B2 (en) | 2005-01-26 | 2007-02-20 | Fina Technology, Inc. | Branched ionomers |
| WO2007011907A2 (en) | 2005-07-19 | 2007-01-25 | University Of Rochester | Alpha-synuclein antibodies and methods related thereto |
| CN101351476B (zh) | 2005-12-12 | 2013-04-03 | 豪夫迈·罗氏有限公司 | 抗体可变区的糖基化 |
| US8148085B2 (en) | 2006-05-15 | 2012-04-03 | Sea Lane Biotechnologies, Llc | Donor specific antibody libraries |
| TWI551607B (zh) | 2006-07-14 | 2016-10-01 | Ａｃ免疫公司 | 人類化抗體 |
| US20080124760A1 (en) | 2006-07-26 | 2008-05-29 | Barbara Enenkel | Regulatory Nucleic Acid Elements |
| JP5558834B2 (ja) | 2007-02-23 | 2014-07-23 | ヤンセン アルツハイマー イミュノセラピー | シヌクレイノパチーおよびアミロイド形成疾患（ａｍｙｌｏｉｄｏｇｅｎｉｃｄｉｓｅａｓｅ）の予防および処置 |
| EP2064242A1 (en) | 2007-02-23 | 2009-06-03 | Schering Corporation | Engineered anti-il-23p19 antibodies |
| KR20100015363A (ko) | 2007-03-02 | 2010-02-12 | 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 | 단백질 생산의 개선 |
| MX2009010179A (es) | 2007-03-22 | 2010-03-15 | Imclone Llc | Formulaciones estables de anticuerpo. |
| NZ580553A (en) | 2007-03-22 | 2012-05-25 | Genentech Inc | Apoptotic anti- ige antibodies binding the membrane-bound ige |
| EP2031064A1 (de) | 2007-08-29 | 2009-03-04 | Boehringer Ingelheim Pharma GmbH & Co. KG | Verfahren zur Steigerung von Proteintitern |
| EA028356B1 (ru) | 2007-12-28 | 2017-11-30 | Протена Байосайенсиз Лимитед | Лечение и профилактика амилоидоза |
| AU2009232353B2 (en) | 2008-04-05 | 2015-04-30 | Single Cell Technology, Inc. | Method of screening single cells for the production of biologically active agents |
| LT2282758T (lt) | 2008-04-29 | 2019-03-12 | Bioarctic Ab | Antikūnai ir vakcinos, skirti su alfa sinukleinu susijusių sutrikimų gydymo ir diagnostiniams metodams |
| US20120276019A1 (en) | 2008-07-25 | 2012-11-01 | Diamedica Inc. | Tissue kallikrein for the treatment of parkinson's disease |
| DE102008048129A1 (de) | 2008-09-20 | 2010-04-22 | Lfk-Lenkflugkörpersysteme Gmbh | Flugkörper mit zumindest einem Bremsfallschirm sowie Befestigungsvorrichtung zur Befestigung eines Bremsfallschirms an einem Flugkörper |
| PE20110926A1 (es) | 2008-09-26 | 2011-12-29 | Roche Glycart Ag | Anticuerpos biespecificos anti-egfr/anti-igf-1r |
| CN102227440A (zh) | 2008-09-30 | 2011-10-26 | 雅培制药有限公司 | 改良的抗体文库 |
| CN102272327B (zh) | 2008-11-07 | 2015-11-25 | 赛昆塔公司 | 通过序列分析监测状况的方法 |
| CA2746778C (en) | 2008-12-19 | 2019-04-23 | University Of Zurich | Human anti-alpha-synuclein autoantibodies |
| CN102369215B (zh) | 2009-04-02 | 2015-01-21 | 罗切格利卡特公司 | 包含全长抗体和单链Fab片段的多特异性抗体 |
| WO2011025826A1 (en) | 2009-08-26 | 2011-03-03 | Research Development Foundation | Methods for creating antibody libraries |
| US20130116413A1 (en) | 2009-12-29 | 2013-05-09 | Dr. Reddy's Laboratories, Inc. | Purification of proteins |
| KR102188544B1 (ko) | 2010-11-30 | 2020-12-08 | 제넨테크, 인크. | 저친화도 혈액-뇌 장벽 수용체 항체 및 그의 용도 |
| US8741298B2 (en) | 2011-02-07 | 2014-06-03 | Neotope Biosciences Limited | APOE immunotherapy |
| US20120220730A1 (en) | 2011-02-24 | 2012-08-30 | Fina Technology, Inc. | High Melt Strength Polypropylene and Methods of Making Same |
| WO2012160536A1 (en) | 2011-05-26 | 2012-11-29 | Dr Reddy's Laboratories Limited | Antibody purification |
| US8715449B2 (en) | 2011-06-17 | 2014-05-06 | Berry Plastics Corporation | Process for forming an insulated container having artwork |
| US9845327B2 (en) | 2011-06-22 | 2017-12-19 | The General Hospital Corporation | Treatment of proteinopathies |
| US9045615B2 (en) | 2011-08-24 | 2015-06-02 | Fina Technology, Inc. | Metal carboxylate additives for thermoplastics |
| US20130063945A1 (en) | 2011-09-12 | 2013-03-14 | Chaun-Choung Technology Corp. | Bulb-type led lamp having replaceable light source module |
| CN107880123A (zh) | 2011-10-28 | 2018-04-06 | 普罗典娜生物科学有限公司 | 识别α‑突触核蛋白的人源化抗体 |
| KR102259829B1 (ko) | 2011-10-31 | 2021-06-03 | 제넨테크, 인크. | 항체 제제 |
| US8829114B2 (en) | 2011-11-29 | 2014-09-09 | Fina Technology, Inc. | Preparation of metallic comonomers for polystyrene |
| AU2013211874B2 (en) | 2012-01-27 | 2017-11-02 | Prothena Biosciences Limited | Humanized antibodies that recognize alpha-synuclein |
| HUE045144T2 (hu) | 2012-08-29 | 2019-12-30 | Hoffmann La Roche | Véragygát-shuttle |
| US8925815B2 (en) | 2012-09-05 | 2015-01-06 | Symbol Technologies, Inc. | Checkout system for and method of preventing a customer-operated accessory reader facing a bagging area from imaging targets on products passed through a clerk-operated workstation to the bagging area |
| UA118441C2 (uk) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Антитіло, що розпізнає альфа-синуклеїн |
| US10513555B2 (en) | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
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- 2015-04-08 US US15/129,676 patent/US10562973B2/en active Active
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2020
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| US20200299397A1 (en) | 2020-09-24 |
| JP2017514515A (ja) | 2017-06-08 |
| US10562973B2 (en) | 2020-02-18 |
| JP6744856B2 (ja) | 2020-08-19 |
| WO2015155694A1 (en) | 2015-10-15 |
| US20170174777A1 (en) | 2017-06-22 |
| EP3129051A1 (en) | 2017-02-15 |
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