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1. 发明申请

US20120100129A1 N-Terminal Truncated Protofibrils/Oligomers for Use in Therapeutic and Diagnostic Methods for Alzheimer's Disease and Related Disorders 审中-公开
标题翻译：用于阿尔茨海默病和相关疾病的治疗和诊断方法的N-末端截断的原原纤维/低聚物
公开(公告)号：US20120100129A1
公开(公告)日：2012-04-26
申请号：US13379523
申请日：2010-06-29
申请人： Pär Gellerfors , Lars Lannfelt , Linda Söderberg , Karin Tegerstedt
发明人： Pär Gellerfors , Lars Lannfelt , Linda Söderberg , Karin Tegerstedt
IPC分类号： A61K39/395 , A61P25/28 , G01N33/53 , A61K39/00 , C07K16/18
CPC分类号： C07K16/18 , A61K38/00 , C07K14/4711 , C07K2317/30
摘要： A vaccine for delaying onset of or for treatment of Alzheimer's disease or an Alzheimer-related disorder in an individual comprises a therapeutically effective amount of a physiologically acceptable protofibril/oligomer comprising N-terminal truncated Aβ. An antibody for delaying an onset of or for treatment of Alzheimer's disease or an Alzheimer-related disorder in an individual binds one or more truncated AO protofibrils/oligomers, but exhibits no or substantially no cross-reactivity with full length Aβ monomers, and optionally said antibody shows cross-reactivity to N-terminal truncated Aβ monomers. Methods for delaying an onset of or for treatment of Alzheimer's disease or an Alzheimer-related disorder employ the vaccine or antibody. Methods of detecting soluble N-terminal truncated amyloid-beta (Aβ) protofibrils/oligomers and N-terminal truncated Aβ monomers employ the antibody.
摘要翻译：用于延迟个体中阿尔茨海默病或阿尔茨海默氏病相关疾病发作或治疗的疫苗包含治疗有效量的包含N-末端截短的A＆bgr的生理上可接受的原纤维/寡聚体。用于延迟个体中阿尔茨海默病或阿尔茨海默病相关病症的发作或治疗的抗体结合一个或多个截短的AO原纤维/寡聚体，但与全长A＆bgr不显示或基本上没有交叉反应性; 单体和任选地所述抗体显示与N-末端截短的A＆bgr的交叉反应性; 单体。用于延迟阿尔茨海默病或阿尔茨海默病相关疾病的发作或治疗的方法使用疫苗或抗体。检测可溶性N-末端截短淀粉样蛋白-β（A＆bgr）原原纤维/寡聚体和N-末端截短的A＆Bgr的方法; 单体使用抗体。

2. 发明申请

US20110052498A1 Antibodies and Vaccines for Use in Therapeutic and Diagnostic Methods for Alpha-Synuclein-Related Disorders 有权
标题翻译：用于α-突触核蛋白相关疾病的治疗和诊断方法的抗体和疫苗
公开(公告)号：US20110052498A1
公开(公告)日：2011-03-03
申请号：US12990226
申请日：2009-04-28
申请人： Lars Lannfelt , Joakim Bergström , Martin Ingelsson , Pär Gellerfors
发明人： Lars Lannfelt , Joakim Bergström , Martin Ingelsson , Pär Gellerfors
IPC分类号： A61K49/00 , A61K39/395 , G01N33/53 , C07K16/18 , A61P25/28 , A61P25/18
CPC分类号： A61K51/1018 , A61K38/1709 , C07K16/18 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , Y10S530/839
摘要： A vaccine for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble α-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the α-synuclein. An antibody for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual binds soluble α-synuclein. Methods for delaying an onset of for treatment or for prevention of an α-synuclein-related disorder employ the vaccine or antibody. Methods of detecting α-synuclein oligomers employ the antibody.
摘要翻译：用于延迟个体中α-突触核蛋白相关病症的发作或治疗的疫苗包含治疗有效量的分离的稳定的可溶性α-突触核蛋白寡聚体，其具有比非可溶性聚集形式低的形成速率，稳定的α-突触核蛋白的寡聚物。用于延迟个体中α-突触核蛋白相关病症的发作或治疗的抗体结合可溶性α-突触核蛋白。用于延迟治疗或预防α-突触核蛋白相关病症的方法使用疫苗或抗体。 α-突触核蛋白寡聚物检测方法采用抗体。

3. 发明授权

US08404459B2 Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof 有权
标题翻译：可溶性淀粉样蛋白β原型原纤维特异性抗体及其用途
公开(公告)号：US08404459B2
公开(公告)日：2013-03-26
申请号：US13336520
申请日：2011-12-23
申请人： Pär Gellerfors , Lars Lannfelt
发明人： Pär Gellerfors , Lars Lannfelt
IPC分类号： G01N33/53 , G01N33/542 , G01N33/567
CPC分类号： C07K16/18 , C07K14/4711 , C07K2317/24 , G01N2800/2821 , G01N2800/387
摘要： The invention pertains to a method of measuring Aβ protofibrils in a sample. The method includes the steps of (a) providing a labeled monoclonal antibody or fragment thereof that binds wildtype Aβ 42/40 protofibril and Aβ42/40 Arc protofibril and has no or little cross-reactivity to Aβ 42/40 monomers with an agent that generates a measurable signal, (b) contacting said labeled antibody or fragment thereof with the fluid or tissue having or suspected of comprising Aβ protofibrils, and (c) measuring the amount of protofibrils bound to the antibody by measuring the signal generated by the agent.
摘要翻译：本发明涉及一种测量A＆bgr的方法; 样品中的原纤维。该方法包括以下步骤：（a）提供结合野生型A和bgr的标记的单克隆抗体或其片段; 42/40原纤维和A＆bgr; 42/40弧原纤维，对A＆bgr没有或几乎没有交叉反应性; 42/40单体，其具有产生可测量信号的试剂，（b）使所述标记的抗体或其片段与具有或怀疑包含A＆bgr的流体或组织接触; 原纤维，（c）通过测量由该药剂产生的信号来测量与抗体结合的原纤维的量。

4. 发明授权

US08809506B2 Antibodies and vaccines for use in therapeutic and diagnostic methods for α-synuclein-related disorders 有权
标题翻译：用于α-突触核蛋白相关疾病的治疗和诊断方法的抗体和疫苗
公开(公告)号：US08809506B2
公开(公告)日：2014-08-19
申请号：US12990226
申请日：2009-04-28
申请人： Lars Lannfelt , Joakim Bergström , Martin Ingelsson , Pär Gellerfors
发明人： Lars Lannfelt , Joakim Bergström , Martin Ingelsson , Pär Gellerfors
IPC分类号： A61K39/395 , C07K16/18 , G01N33/567 , A61K38/17 , G01N33/68
CPC分类号： A61K51/1018 , A61K38/1709 , C07K16/18 , C07K2317/92 , G01N33/6896 , G01N2333/4709 , Y10S530/839
摘要： A vaccine for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual comprises a therapeutically effective amount of isolated stabilized soluble α-synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized oligomer of the α-synuclein. An antibody for delaying an onset of or for treatment of an α-synuclein-related disorder in an individual binds soluble α-synuclein. Methods for delaying an onset of for treatment or for prevention of an α-synuclein-related disorder employ the vaccine or antibody. Methods of detecting α-synuclein oligomers employ the antibody.
摘要翻译：用于延迟个体中α-突触核蛋白相关病症的发作或治疗的疫苗包含治疗有效量的分离的稳定的可溶性α-突触核蛋白寡聚体，其具有比非可溶性聚集形式低的形成速率，稳定的α-突触核蛋白的寡聚物。用于延迟个体中α-突触核蛋白相关病症的发作或治疗的抗体结合可溶性α-突触核蛋白。用于延迟治疗或预防α-突触核蛋白相关病症的方法使用疫苗或抗体。 α-突触核蛋白寡聚物检测方法采用抗体。

5. 发明授权

US08025878B2 Protofibril selective antibodies and the use thereof 有权
标题翻译：原始纤维选择性抗体及其用途
公开(公告)号：US08025878B2
公开(公告)日：2011-09-27
申请号：US12294207
申请日：2007-03-23
申请人： Pär Gellerfors , Lars Lannfelt , Dag Sehlin , Frida Ekholm Pettersson , Hillevi Englund
发明人： Pär Gellerfors , Lars Lannfelt , Dag Sehlin , Frida Ekholm Pettersson , Hillevi Englund
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： G01N33/6896 , A61K2039/505 , C07K16/18 , C07K16/465 , C07K2317/24 , C07K2317/565 , G01N2333/4709 , G01N2800/2814 , G01N2800/387
摘要： The present invention pertains to the prevention, treatment and diagnosis of neurodegenerative diseases, in particular Alzheimer's disease, and other similar disease. More specifically to high affinity antibodies selective for amyloid beta protein (Aβ) in its protofibril conformation and of IgG class and IgG1 or IgG4 subclass or combinations thereof or mutations thereof, retaining high Fc receptor binding and low C1(C1q) binding, effective in clearance of Aβ protofibrils and with reduce risk of inflammation.
摘要翻译：本发明涉及神经变性疾病，特别是阿尔茨海默氏病和其他类似疾病的预防，治疗和诊断。更具体地，涉及其原始原纤维构象中的淀粉样蛋白β蛋白（A＆bgr）和IgG类和IgG1或IgG4亚类或其组合或其突变选择性的高亲和力抗体，保持高Fc受体结合和低C1（C1q）结合，有效地清关A＆BGR 原纤维，并减少炎症的风险。

6. 发明授权

US09034334B2 Protofibril selective antibodies and the use thereof 有权
标题翻译：原始纤维选择性抗体及其用途
公开(公告)号：US09034334B2
公开(公告)日：2015-05-19
申请号：US13219012
申请日：2011-08-26
申请人： Pär Gellerfors , Lars Lannfelt , Dag Sehlin , Frida Ekholm Pettersson , Hillevi Englund
发明人： Pär Gellerfors , Lars Lannfelt , Dag Sehlin , Frida Ekholm Pettersson , Hillevi Englund
IPC分类号： A61K39/00 , A61K39/395 , G01N33/68 , C07K16/18 , C07K16/46
CPC分类号： G01N33/6896 , A61K2039/505 , C07K16/18 , C07K16/465 , C07K2317/24 , C07K2317/565 , G01N2333/4709 , G01N2800/2814 , G01N2800/387
摘要： The invention relates to an isolated antibody, or fragment thereof, having high affinity for human Aβ protofibrils. The invention further relates to compositions that include the antibody, or a fragment thereof, and a pharmaceutically acceptable buffer. The invention further relates to a method of preventing or treating Alzheimer's disease, which includes the step of administering to a patient having or suspected of having Alzheimer's disease such an antibody, or fragment thereof or a composition that includes the antibody or a fragment thereof.
摘要翻译：本发明涉及对人A＆bgr具有高亲和力的分离的抗体或其片段; 原纤维。本发明还涉及包含抗体或其片段和药学上可接受的缓冲液的组合物。本发明还涉及一种预防或治疗阿尔茨海默病的方法，其包括对具有或疑似患有阿尔茨海默病的患者或其片段或包含该抗体或其片段的组合物的患者给药的步骤。

7. 发明申请

US20120230912A1 ANTIBODIES SPECIFIC FOR SOLUBLE AMYLOID BETA PEPTIDE PROTOFIBRILS AND USES THEREOF 有权
标题翻译：可溶性淀粉样蛋白抗原肽抗原特异性抗体及其用途
公开(公告)号：US20120230912A1
公开(公告)日：2012-09-13
申请号：US13336520
申请日：2011-12-23
申请人： Pär Gellerfors , Lars Lannfelt
发明人： Pär Gellerfors , Lars Lannfelt
IPC分类号： G01N33/577 , A61K49/00 , A61K51/10
CPC分类号： C07K16/18 , C07K14/4711 , C07K2317/24 , G01N2800/2821 , G01N2800/387
摘要： The invention pertains to a method of measuring Aβ protofibrils in a sample. The method includes the steps of (a) providing a labeled monoclonal antibody or fragment thereof that binds wildtype Aβ 42/40 protofibril and Aβ42/40 Arc protofibril and has no or little cross-reactivity to Aβ 42/40 monomers with an agent that generates a measurable signal, (b) contacting said labeled antibody or fragment thereof with the fluid or tissue having or suspected of comprising Aβ protofibrils, and (c) measuring the amount of protofibrils bound to the antibody by measuring the signal generated by the agent.
摘要翻译：本发明涉及一种测量A＆bgr的方法; 样品中的原纤维。该方法包括以下步骤：（a）提供结合野生型A和bgr的标记的单克隆抗体或其片段; 42/40原纤维和A＆bgr; 42/40弧原纤维，对A＆bgr没有或几乎没有交叉反应性; 42/40单体，其具有产生可测量信号的试剂，（b）使所述标记的抗体或其片段与具有或怀疑包含A＆bgr的流体或组织接触; 原纤维，（c）通过测量由该药剂产生的信号来测量与抗体结合的原纤维的量。

8. 发明授权

US08106164B2 Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof 有权
标题翻译：可溶性淀粉样蛋白β原型原纤维特异性抗体及其用途
公开(公告)号：US08106164B2
公开(公告)日：2012-01-31
申请号：US11570995
申请日：2005-06-21
申请人： Pär Gellerfors , Lars Lannfelt
发明人： Pär Gellerfors , Lars Lannfelt
IPC分类号： C07K16/00 , A61K39/35
CPC分类号： C07K16/18 , C07K14/4711 , C07K2317/24 , G01N2800/2821 , G01N2800/387
摘要： The invention pertains to the development of antibodies that specifically bind amyloid beta protein (Abeta) in its protofibril conformation. The invention also comprises methods of using anti-Abeta protofibril antibodies to diagnose or treat Alzheimer's disease, Down's syndrome Lewybody dementia, vascular dementia, and other neurodegenerative disorders. Furthermore, the invention pertains to the use of anti-Abeta protofibril antibodies to screen and identify substances that will modulate protofibril activity or formation in vitro or in vivo. The invention also pertains to methods for synthesising pure Abeta protofibril antigens as well as to a method for stabilising Abeta protofibrils antigens as well as to a method for stabilising Abeta protofibrils.
摘要翻译：本发明涉及在其原纤维构象中特异性结合淀粉样β蛋白（Abeta）的抗体的开发。本发明还包括使用抗Abeta原纤维抗体来诊断或治疗阿尔茨海默病，唐氏综合征Lewybody痴呆，血管性痴呆和其他神经变性疾病的方法。此外，本发明涉及抗Aβ原原纤维抗体在体外或体内筛选和鉴定将调节原纤维活性或形成的物质的用途。本发明还涉及用于合成纯Abeta原纤维抗原的方法以及稳定Abeta原纤维抗原的方法以及用于稳定Abeta原纤维的方法。

9. 发明授权

US07709695B1 Transgenic mouse expressing arctic mutation E693G 失效
标题翻译：转基因小鼠表达北极突变E693G
公开(公告)号：US07709695B1
公开(公告)日：2010-05-04
申请号：US10593639
申请日：2005-03-17
申请人： Lars Nilsson , Lars Lannfelt , Pär Gellerfors
发明人： Lars Nilsson , Lars Lannfelt , Pär Gellerfors
IPC分类号： G01N33/00 , A01K67/033
CPC分类号： C07K14/4711 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0312 , C12N15/8509
摘要： A transgenic non-human animal expressing at least one transgene including a DNA sequence encoding a heterologous Amyloid Precursor Protein (APP) including at least the Arctic mutation (E693G) and a further AD (Alzheimer's disease) pathogenic mutation or a further transgene affecting AD pathogenesis, which results in increased amounts of intracellular soluble A aggregates, including A peptides. The method of producing the transgenic animal, and methods of screening for therapeutic or diagnostic agents useful in treatment or diagnosis of Alzheimer's disease are also disclosed.
摘要翻译：表达至少一个转基因的转基因非人动物，其包含编码异源淀粉样蛋白前体蛋白（APP）的DNA序列，所述DNA序列至少包括北极突变（E693G）和另外的AD（阿尔茨海默氏病）致病突变或进一步影响AD发病机制的转基因，其导致增加量的细胞内可溶性A聚集体，包括A肽。还公开了生产转基因动物的方法，以及筛选用于治疗或诊断阿尔茨海默病的治疗或诊断剂的方法。

10. 发明申请

US20090155246A1 Antibodies Specific For Soluble Amyloid Beta Peptide Protofibrils and Uses Thereof 有权
标题翻译：特异于可溶性淀粉样β肽原原纤维的抗体及其用途
公开(公告)号：US20090155246A1
公开(公告)日：2009-06-18
申请号：US11570995
申请日：2005-06-21
申请人： Pär Gellerfors , Lars Lannfelt
发明人： Pär Gellerfors , Lars Lannfelt
IPC分类号： A61K39/395 , C07K16/18 , G01N33/53 , C12Q1/68
CPC分类号： C07K16/18 , C07K14/4711 , C07K2317/24 , G01N2800/2821 , G01N2800/387
摘要： The invention pertains to the development of antibodies that specifically bind amyloid beta protein (Abeta) in its protofibril conformation. The invention also comprises methods of using anti-Abeta protofibril antibodies to diagnose or treat Alzheimer's disease, Down's syndrome Lewybody dementia, vascular dementia, and other neurodegenerative disorders. Furthermore, the invention pertains to the use of anti-Abeta protofibril antibodies to screen and identify substances that will modulate protofibril activity or formation in vitro or in vivo. The invention also pertains to methods for synthesising pure Abeta protofibril antigens as well as to a method for stabilising Abeta protofibrils antigens as well as to a method for stabilising Abeta protofibrils.
摘要翻译：本发明涉及在其原纤维构象中特异性结合淀粉样β蛋白（Abeta）的抗体的开发。本发明还包括使用抗Abeta原纤维抗体来诊断或治疗阿尔茨海默病，唐氏综合征Lewybody痴呆，血管性痴呆和其他神经变性疾病的方法。此外，本发明涉及抗Aβ原原纤维抗体在体外或体内筛选和鉴定将调节原纤维活性或形成的物质的用途。本发明还涉及用于合成纯Abeta原纤维抗原的方法以及稳定Abeta原纤维抗原的方法以及用于稳定Abeta原纤维的方法。

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