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    Transgenic mouse expressing arctic mutation E693G
    1.
    发明授权
    Transgenic mouse expressing arctic mutation E693G 失效
    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。

    N-Terminal Truncated Protofibrils/Oligomers for Use in Therapeutic and Diagnostic Methods for Alzheimer's Disease and Related Disorders
    2.
    发明申请
    N-Terminal Truncated Protofibrils/Oligomers for Use in Therapeutic and Diagnostic Methods for Alzheimer's Disease and Related Disorders 审中-公开
    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。

    Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof
    4.
    发明授权
    Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof 有权
    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。

    ANTIBODIES SPECIFIC FOR SOLUBLE AMYLOID BETA PEPTIDE PROTOFIBRILS AND USES THEREOF
    8.
    发明申请
    ANTIBODIES SPECIFIC FOR SOLUBLE AMYLOID BETA PEPTIDE PROTOFIBRILS AND USES THEREOF 有权
    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。

    Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof
    9.
    发明授权
    Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof 有权
    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。

    Antibodies Specific For Soluble Amyloid Beta Peptide Protofibrils and Uses Thereof
    10.
    发明申请
    Antibodies Specific For Soluble Amyloid Beta Peptide Protofibrils and Uses Thereof 有权
    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。