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    METHODS AND COMPOSITIONS TO TREAT AND DETECT MISFOLDED-SOD1 MEDIATED DISEASES
    4.
    发明申请
    METHODS AND COMPOSITIONS TO TREAT AND DETECT MISFOLDED-SOD1 MEDIATED DISEASES 审中-公开
    治疗和检测MISDOLD-SOD1介导的疾病的方法和组合

    公开(公告)号：WO2007098607A1

    公开(公告)日：2007-09-07

    申请号：PCT/CA2007/000346

    申请日：2007-03-05

    Applicant: AMORFIX LIFE SCIENCES LTD. ,  UNIVERSITY HEALTH NETWORK ,  CASHMAN, Neil, R. ,  CHAKRABARTTY, Avijit ,  RAKHIT, Rishi ,  OSTERMAN, Joachim, Bernhard

    Inventor： CASHMAN, Neil, R. ,  CHAKRABARTTY, Avijit ,  RAKHIT, Rishi ,  OSTERMAN, Joachim, Bernhard

    IPC: C12N15/53 ,  A61K31/7088 ,  A61K38/44 ,  A61K39/00 ,  A61K39/395 ,  A61K48/00 ,  A61P25/28 ,  C07K16/40 ,  C12N5/12 ,  C12N9/02 ,  G01N33/573

    CPC classification number: C07K16/40 ,  A01K2267/0312 ,  A01K2267/0318 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/0005 ,  A61K39/0007 ,  A61K48/005 ,  A61K2039/505 ,  A61K2039/53 ,  A61K2039/575 ,  C07K2317/24 ,  C07K2317/76 ,  C07K2317/92 ,  C12N9/0089 ,  G01N33/573 ,  G01N33/6896 ,  G01N2333/90283 ,  G01N2800/2828

    Abstract: The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

    Abstract translation: 本发明提供了在需要治疗的受试者中治疗由错误折叠形式的超氧化物歧化酶（SOD）介导的医学病症，疾病或病症的方法。 所述方法任选包括向受试者施用包含药学上可接受的载体和选自（1）选择性结合SOD的错误折叠形式的外源性抗体或其片段的组合物，和/或（2）引起生产的免疫原 选择性结合SOD的错误折叠形式的内源性抗体，和/或（3）编码（1）或（2）的核酸序列。 在某些实施方案中，本发明提供了使用肌萎缩性疾病特异性表位治疗疾病如阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的方法，以及包括这些表位的组合物。 本发明还提供结合单体或错折叠的SOD1，而不是在天然同二聚体SOD1的分子表面上的抗体。 此外，本发明包括在受试者中诊断阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的方法。 此外，本发明提供了鉴定用于治疗或预防阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的物质以及使用本发明的结合蛋白的试剂盒的方法。

    METHODS OF DIAGNOSING ALS
    6.
    发明申请
    METHODS OF DIAGNOSING ALS 有权
    诊断方法ALS

    公开(公告)号：US20140335538A1

    公开(公告)日：2014-11-13

    申请号：US14448584

    申请日：2014-07-31

    Applicant: Amorfix Life Sciences Ltd.

    Inventor： Neil Cashman

    IPC: G01N33/68 ,  G01N33/58 ,  C07K16/40

    CPC classification number: G01N33/6896 ,  A61K38/00 ,  C07K16/18 ,  C07K16/40 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/624 ,  C07K2317/626 ,  G01N33/58 ,  G01N33/581 ,  G01N33/68 ,  G01N33/6845 ,  G01N2333/90283 ,  G01N2800/28 ,  G01N2800/2828

    Abstract: The invention relates to an epitope protection assay for use in diagnosis, prognosis and therapeutic intervention in diseases, for example, involving polypeptide aggregation, such as prion infections. The methods of the invention first block accessible polypeptide target epitope with a blocking agent. After denaturation of the polypeptide, a detecting agent is used to detect protein with target epitope that was inaccessible during contact with the blocking agent. The invention also relates to novel amyotrophic lateral sclerosis-specific epitopes and their uses to make antibodies, and to the novel antibodies and uses thereof.

    Abstract translation: 本发明涉及用于疾病的诊断，预后和治疗干预的表位保护测定法，例如涉及多肽聚集，例如朊病毒感染。 本发明的方法首先用阻断剂阻断可获得的多肽靶抗原表位。 在多肽变性后，使用检测试剂检测在与阻断剂接触期间不能接近的靶抗原表位的蛋白质。 本发明还涉及新颖的肌萎缩性侧索硬化特异性表位及其用于制备抗体及其新型抗体及其用途的用途。

    Methods and Compositions to Treat and Detect Misfolded-SOD1 Mediated DIseases
    8.
    发明申请
    Methods and Compositions to Treat and Detect Misfolded-SOD1 Mediated DIseases 有权
    治疗和检测错误折叠的SOD1介导的细胞因子的方法和组合物

    公开(公告)号：US20140348822A1

    公开(公告)日：2014-11-27

    申请号：US14300858

    申请日：2014-06-10

    Applicant: Amorfix Life Sciences Ltd.

    Inventor： Neil R. Cashman ,  Avijit Chakrabartty ,  Rishi Rakhit ,  Joachim Bernhard Ostermann

    IPC: C07K16/40 ,  G01N33/573 ,  G01N33/68 ,  A61K39/00

    CPC classification number: C07K16/40 ,  A01K2267/0312 ,  A01K2267/0318 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/0005 ,  A61K39/0007 ,  A61K48/005 ,  A61K2039/505 ,  A61K2039/53 ,  A61K2039/575 ,  C07K2317/24 ,  C07K2317/76 ,  C07K2317/92 ,  C12N9/0089 ,  G01N33/573 ,  G01N33/6896 ,  G01N2333/90283 ,  G01N2800/2828

    Abstract: The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

    Abstract translation: 本发明提供了在需要治疗的受试者中治疗由错误折叠形式的超氧化物歧化酶（SOD）介导的医学病症，疾病或病症的方法。 所述方法任选地包括向受试者施用包含药学上可接受的载体和选自（1）选择性结合SOD的错误折叠形式的外源性抗体或其片段的组合物，和/或（2）引起生产的免疫原 选择性结合SOD的错误折叠形式的内源性抗体，和/或（3）编码（1）或（2）的核酸序列。 在某些实施方案中，本发明提供了使用肌萎缩性疾病特异性表位治疗疾病如阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的方法，以及包括这些表位的组合物。 本发明还提供结合单体或错折叠的SOD1，而不是在天然同二聚体SOD1的分子表面上的抗体。 此外，本发明包括在受试者中诊断阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的方法。 此外，本发明提供了鉴定用于治疗或预防阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的物质的方法以及使用本发明的结合蛋白的试剂盒。

    METHODS AND COMPOSITIONS TO TREAT AND DETECT MISFOLDED-SOD1 MEDIATED DISEASES
    9.
    发明申请
    METHODS AND COMPOSITIONS TO TREAT AND DETECT MISFOLDED-SOD1 MEDIATED DISEASES 审中-公开
    治疗和检测MISDOLD-SOD1介导的疾病的方法和组合

    公开(公告)号：WO2007098607A8

    公开(公告)日：2016-10-27

    申请号：PCT/CA2007000346

    申请日：2007-03-05

    Applicant: AMORFIX LIFE SCIENCES LTD ,  UNIV HEALTH NETWORK ,  CASHMAN NEIL R ,  CHAKRABARTTY AVIJIT ,  RAKHIT RISHI ,  OSTERMAN JOACHIM BERNHARD

    Inventor： CASHMAN NEIL R ,  CHAKRABARTTY AVIJIT ,  RAKHIT RISHI ,  OSTERMAN JOACHIM BERNHARD

    IPC: C12N15/53 ,  A61K31/7088 ,  A61K38/44 ,  A61K39/00 ,  A61K39/395 ,  A61K48/00 ,  A61P25/28 ,  C07K16/40 ,  C12N5/12 ,  C12N9/02 ,  G01N33/573

    CPC classification number: C07K16/40 ,  A01K2267/0312 ,  A01K2267/0318 ,  A61K31/7088 ,  A61K31/713 ,  A61K39/0005 ,  A61K39/0007 ,  A61K48/005 ,  A61K2039/505 ,  A61K2039/53 ,  A61K2039/575 ,  C07K2317/24 ,  C07K2317/76 ,  C07K2317/92 ,  C12N9/0089 ,  G01N33/573 ,  G01N33/6896 ,  G01N2333/90283 ,  G01N2800/2828

    Abstract: The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

    Abstract translation: 本发明提供了在需要治疗的受试者中治疗由错误折叠形式的超氧化物歧化酶（SOD）介导的医学病症，疾病或病症的方法。 所述方法任选包括向受试者施用包含药学上可接受的载体和选自（1）选择性结合SOD的错误折叠形式的外源性抗体或其片段的组合物，和/或（2）引起生产的免疫原 选择性结合SOD的错误折叠形式的内源性抗体，和/或（3）编码（1）或（2）的核酸序列。 在某些实施方案中，本发明提供了使用肌萎缩性疾病特异性表位治疗疾病如阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的方法，以及包括这些表位的组合物。 本发明还提供结合单体或错折叠的SOD1，而不是在天然同二聚体SOD1的分子表面上的抗体。 此外，本发明包括在受试者中诊断阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的方法。 此外，本发明提供了鉴定用于治疗或预防阿尔茨海默病，帕金森病或肌萎缩性侧索硬化的物质以及使用本发明的结合蛋白的试剂盒的方法。

    DETECTION OF PROTEIN AGGREGATES
    10.
    发明申请
    DETECTION OF PROTEIN AGGREGATES 审中-公开
    检测蛋白质聚集体

    公开(公告)号：WO2010003227A1

    公开(公告)日：2010-01-14

    申请号：PCT/CA2009/000930

    申请日：2009-07-08

    Applicant: AMORFIX LIFE SCIENCES LTD. ,  LEHTO, Marty ,  BEG, Steve, Hrvoje ,  KUS, Bart ,  PLAWINSKI, Ewa ,  CHAI, Viengthong ,  CASHMAN, Neil, Roy

    Inventor： LEHTO, Marty ,  BEG, Steve, Hrvoje ,  KUS, Bart ,  PLAWINSKI, Ewa ,  CHAI, Viengthong ,  CASHMAN, Neil, Roy

    IPC: G01N33/53 ,  G01N33/543 ,  G01N33/68 ,  G01N33/84

    CPC classification number: G01N33/6896 ,  G01N33/84

    Abstract: Provided are methods and kits useful to detect the presence of an aggregated form of a target protein in a sample that may also contain the target protein in non-aggregated form. The assay entails treating the sample to elevate the pH thereof to a value of at least about 12, thereby to alter epitopes accessible on the target protein without causing hydrolysis of the target protein. The treated sample is then neutralized and the neutralized sample is treated by dissociation to release target protein within the aggregate. Released target protein is then incubated with an agent that binds selectively to an epitope protected from pH elevation. The formation of a binding agent:target protein complex reveals the presence of aggregated protein in the original sample. The assay is useful to detect prion aggregates, to diagnose sheep scrapie and human CJD, and aggregated forms of other proteins of clinical interest.

    Abstract translation: 提供了可用于检测样品中聚集形式的靶蛋白的存在的方法和试剂盒，其还可以以非聚集形式含有靶蛋白。 该测定需要处理样品将其升高至至少约12的值，从而改变靶蛋白上可接近的表位，而不引起靶蛋白的水解。 然后将经处理的样品中和，并通过解离处理中和的样品以释放聚集体内的靶蛋白。 然后将释放的靶蛋白与选择性结合到不受pH升高保护的表位的试剂进行温育。 结合剂的形成：靶蛋白复合物显示原始样品中聚集的蛋白质的存在。 该测定法可用于检测朊病毒聚集体，诊断绵羊瘙痒病和人类CJD，以及临床感兴趣的其他蛋白质的聚集形式。

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