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1. 发明申请

WO2012143379A1 METHOD AND CONSTRUCTS FOR THE PH DEPENDENT PASSAGE OF THE BLOOD-BRAIN-BARRIER 审中-公开
标题翻译：血脑屏障的PH依赖性通气的方法和结构
公开(公告)号：WO2012143379A1
公开(公告)日：2012-10-26
申请号：PCT/EP2012/057051
申请日：2012-04-18
申请人： ROCHE GLYCART AG , BOHRMANN, Bernd , FRESKGARD, Per-Ola , HUGENMATTER, Adrian , KOPETZKI, Erhard , MOESSNER, Ekkehard , NIEWOEHNER, Jens , SADE, Hadassah Sumum , UMANA, Pablo
发明人： BOHRMANN, Bernd , FRESKGARD, Per-Ola , HUGENMATTER, Adrian , KOPETZKI, Erhard , MOESSNER, Ekkehard , NIEWOEHNER, Jens , SADE, Hadassah Sumum , UMANA, Pablo
IPC分类号： C07K16/28
CPC分类号： C07K16/2881 , A61K2039/54 , C07K2317/77 , C07K2317/92 , C07K2317/94 , C07K2319/00 , C07K2319/30
摘要： Herein is reported a fusion polypeptide comprising i) at least one binding site, e.g. which comprises an antibody heavy chain variable domain and an antibody light chain variable domain, and which binds to an internalizing cell surface receptor, and ii) at least one pharmaceutically active compound, whereby the EC 50 -value of the binding pair that binds to an internalizing cell surface receptor determined at pH 5.5 is higher than the EC 50 -value of the same binding pair determined at pH 7.4 and its use for delivering a pharmaceutically active compound across the blood-brain-barrier.
摘要翻译：本文报道了融合多肽，其包含i）至少一个结合位点，其包含抗体重链可变结构域和抗体轻链可变结构域，并结合内化细胞表面受体，和ii）至少一种药学活性化合物，其中结合对的EC 50值与内化在pH5.5下测定的细胞表面受体高于在pH7.4下测定的相同结合对的EC50值，以及用于在血脑屏障上递送药物活性化合物的用途。

2. 发明申请

WO2008148492A1 NEUROFILAMENTAL PROTEINS AS BIOMARKER FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译：神经元蛋白作为ALZHEIMER病的生物标志物
公开(公告)号：WO2008148492A1
公开(公告)日：2008-12-11
申请号：PCT/EP2008004237
申请日：2008-05-28
申请人： HOFFMANN LA ROCHE , BERNDT PETER , BOHRMANN BERND
发明人： BERNDT PETER , BOHRMANN BERND
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2800/2821 , G01N2800/56
摘要： The present invention relates to a method for assessing Alzheimer's disease in vitro comprising measuring in a sample (e.g. body fluid) the level of one or more proteins of the group consisting of Neurofilament triplet M protein and Alpha-internexin, or a variant thereof, wherein an altered level of said one or more proteins, or a variant thereof, is indicative that said individual suffers from Alzheimer's Disease. Furthermore, the present invention relates to a method for monitoring the progression of the Alzheimer's disease in vitro comprising measuring in a sample (e.g. body fluid) the level of one or more proteins of the group consisting of Neurofilament triplet M protein and Alpha- internexin, or a variant thereof, wherein an altered level of said one or more proteins, or a variant thereof, compared with an earlier measurement of the level of said one or more proteins, or a variant thereof, is indicative for the progression of Alzheimer's disease.
摘要翻译：本发明涉及一种体外评估阿尔茨海默病的方法，包括在样品（例如体液）中测量由神经丝三联体M蛋白和α-内啡肽组成的组中的一种或多种蛋白质或其变体的水平，其中所述一种或多种蛋白质或其变体的改变水平表明所述个体患有阿尔茨海默氏病。此外，本发明涉及用于监测体外阿尔茨海默病进展的方法，包括在样品（例如体液）中测量由神经丝三联体M蛋白和α-内啡肽组成的组中的一种或多种蛋白质的水平，或其变体，其中所述一种或多种蛋白质或其变体的改变水平与早期测量所述一种或多种蛋白质或其变体的水平相比较，其指示阿尔茨海默氏病的进展。

3. 发明申请

WO2008148489A1 NEUROCHONDRIN-1 AS BIOMARKER FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译： NEUROCHONDRIN-1作为ALZHEIMER疾病的生物标志物
公开(公告)号：WO2008148489A1
公开(公告)日：2008-12-11
申请号：PCT/EP2008/004234
申请日：2008-05-28
申请人： F. HOFFMANN-LA ROCHE AG , BERNDT, Peter , BOHRMANN, Bernd
发明人： BERNDT, Peter , BOHRMANN, Bernd
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2333/4703 , G01N2800/2821
摘要： The present invention relates to a method for assessing Alzheimer's disease in vitro comprising measuring the level of Neurochondrin-1, or a variant thereof in a sample collected from an individual (e.g. body fluid), wherein an altered level of said protein, or a variant thereof, is indicative that said individual suffers from Alzheimer's disease. Furthermore, the present invention relates to a method for monitoring the progression of the Alzheimer's disease in vitro comprising measuring the level of Neurochondrin-1, or a variant thereof in a sample collected from an individual (e.g. body fluid), wherein an altered level of Neurochondrin-1, or a variant thereof, compared with an earlier measurement of level of Neurochondrin-1, or a variant thereof, is indicative for the progression of Alzheimer's disease.
摘要翻译：本发明涉及一种体外评估阿尔茨海默病的方法，包括测量从个体（例如体液）收集的样品中的神经软骨蛋白-1或其变体的水平，其中所述蛋白质的水平或变体表明所述个体患有阿尔茨海默氏病。此外，本发明涉及一种用于监测体外阿尔茨海默病进展的方法，包括测量从个体（例如体液）收集的样品中的神经软骨素-1或其变体的水平，其中改变的神经软骨蛋白-1或其变体与先前测量的神经软骨素-1水平或其变体相比较，表明阿尔茨海默病的进展。

4. 发明申请

WO2009056257A1 QUADRUPLE TRANSGENIC NON-HUMAN ANIMAL 审中-公开
标题翻译：四分子转基因非人类动物
公开(公告)号：WO2009056257A1
公开(公告)日：2009-05-07
申请号：PCT/EP2008/008971
申请日：2008-10-23
申请人： F. HOFFMANN-LA ROCHE AG , BOHRMANN, Bernd , IGLESIAS, Antonio , LOETSCHER, Hansruedi
发明人： BOHRMANN, Bernd , IGLESIAS, Antonio , LOETSCHER, Hansruedi
IPC分类号： C12N15/85
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/052 , A01K2217/15 , A01K2217/206 , A01K2227/105 , A01K2267/0312 , C07K14/4711 , C07K16/18
摘要： The present invention relates to a transgenic non-human animal whose genome comprises a) a first transgenic DNA sequence encoding a human APP Swedish or a human APP London protein, wherein said first transgenic DNA sequence is operably linked to a first promoter; b) a second transgenic DNA sequence encoding a human Presenilin 2 protein comprising a N141I substitution, wherein said second transgenic DNA sequence is operably linked to a second promoter; c) a third transgenic DNA sequence encoding a light chain of a antibody directed against the amyloid peptide, wherein said third transgenic DNA sequence is operably linked to a third promoter and; d) a forth transgenic DNA sequence encoding a heavy chain of said antibody, wherein said forth transgenic is operably linked to the third promoter or to a forth promoter, and methods for producing said animal.
摘要翻译：本发明涉及一种转基因非人动物，其基因组包含a）编码人APP瑞典人或人APP伦敦蛋白的第一转基因DNA序列，其中所述第一转基因DNA序列与第一启动子可操作地连接; b）编码包含N141I取代的人类早老素2蛋白的第二转基因DNA序列，其中所述第二转基因DNA序列可操作地连接到第二启动子; c）编码针对淀粉样蛋白肽的抗体的轻链的第三转基因DNA序列，其中所述第三转基因DNA序列可操作地连接到第三启动子; d）编码所述抗体重链的第四个转基因DNA序列，其中所述第四个转基因可操作地连接到第三个启动子或第四个启动子，以及用于产生所述动物的方法。

5. 发明申请

WO2007140976A3 ENZYMES AS BIOMARKER FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译： ENZYMES作为ALZHEIMER疾病的生物标记
公开(公告)号：WO2007140976A3
公开(公告)日：2008-02-07
申请号：PCT/EP2007004949
申请日：2007-06-04
申请人： HOFFMANN LA ROCHE , BERNTENIS NIKOLAOS , BOHRMANN BERND , GUENTERT ANDREAS , MUELLER BERND
发明人： BERNTENIS NIKOLAOS , BOHRMANN BERND , GUENTERT ANDREAS , MUELLER BERND
IPC分类号： G01N33/68
CPC分类号： C12Q1/28 , C12Q1/48 , G01N2333/91177 , G01N2800/2821
摘要： The present invention relates to a method for assessing Alzheimer's Disease in vitro comprising measuring in a body fluid sample the level of Peroxiredoxin 5 or Microsomal glutathione S-transferase 3 (MGST-3), or a variant thereof, wherein a decreased level of one of said proteins is indicative that said individual suffers from Alzheimer's Disease.
摘要翻译：本发明涉及体外评估阿尔茨海默病的方法，其包括在体液样品中测量过氧化还原毒素5或微粒体型谷胱甘肽S-转移酶3（MGST-3）或其变体的水平，其中，所述蛋白质表明所述个体患有阿尔茨海默氏病。

6. 发明申请

WO2007140971A2 CELL ADHESION PROTEINS AS BIOMARKER FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译：细胞粘附蛋白作为ALZHEIMER病的生物标记
公开(公告)号：WO2007140971A2
公开(公告)日：2007-12-13
申请号：PCT/EP2007/004944
申请日：2007-06-04
申请人： F. HOFFMANN-LA ROCHE AG , BERNTENIS, Nikolaos , BOHRMANN, Bernd , GUENTERT, Andreas , MUELLER, Bernd
发明人： BERNTENIS, Nikolaos , BOHRMANN, Bernd , GUENTERT, Andreas , MUELLER, Bernd
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2800/2821
摘要： The present invention relates to a method for assessing Alzheimer's Disease in vitro comprising measuring in a body fluid sample the level of one or more proteins of the group consisting of Myelin-associated glycoprotein precursor (MAG), Claudin-11, Contactin associated protein 1 precursor, Myelin oligodendrocyte glycoprotein precursor I (MOG), Contactin 1 precursor and Contactin 2 precursor, or a variant thereof, wherein an altered level of one of said proteins is indicative that said individual suffers from Alzheimer's Disease.
摘要翻译：本发明涉及一种体外评估阿尔茨海默氏病的方法，其包括在体液样品中测量由髓磷脂相关糖蛋白前体（MAG），紧密连接蛋白-11，接触蛋白相关蛋白1前体的一种或多种蛋白质的水平，髓鞘少突胶质细胞糖蛋白前体I（MOG），接触蛋白1前体和接触蛋白2前体或其变体，其中所述蛋白质之一的水平改变表明所述个体患有阿尔茨海默氏病。

7. 发明申请

WO2007068429A1 ANTIBODIES AGAINST AMYLOID BETA 4 WITH GLYCOSYLATED IN THE VARIABLE REGION 审中-公开
标题翻译：抗变态反应体系中抗糖蛋白β4
公开(公告)号：WO2007068429A1
公开(公告)日：2007-06-21
申请号：PCT/EP2006/011914
申请日：2006-12-11
申请人： F. HOFFMANN-LA ROCHE AG , LOETSCHER, Hansruedi , HUBER, Walter , SCHUHBAUER, Diana , WEYER, Karl , BROCKHAUS, Manfred , BOHRMANN, Bernd , KOLL, Hans , SCHAUBMAR, Andreas , LANG, Kurt
发明人： LOETSCHER, Hansruedi , HUBER, Walter , SCHUHBAUER, Diana , WEYER, Karl , BROCKHAUS, Manfred , BOHRMANN, Bernd , KOLL, Hans , SCHAUBMAR, Andreas , LANG, Kurt
IPC分类号： C07K16/18 , A61K39/395 , A61P25/28
CPC分类号： A61K39/3955 , A61K2039/505 , C07K16/18 , C07K2317/41 , C07K2317/56 , C07K2317/77
摘要： The present invention relates to a purified antibody molecule preparation being characterized in that at least one antigen binding site comprises a glycosylated asparagine (Asn) in the variable region of the heavy chain (V H ). More specifically, a pharmaceutical and a diagnostic composition comprising said antibody molecule and antibody mixtures are provided which is/are capable of specifically recognizing the β-A4 peptide/Aβ4. The present invention relates in particular to a mixture of antibodies comprising one or two glycosylated antigen binding sites with a glycosylated asparagine (Asn) in the variable region of the heavy chain, i.e. mixtures of isoforms of antibodies which comprise a glycosylated Asn in the variable region of the heavy chain (V H ). Also disclosed are compositions or antibody preparations comprising the specifically glycosylated antibody isoforms. Furthermore, the pharmaceutical and diagnostic uses for these antibodies are provided. The antibody isoforms may for example be used in the pharmaceutical intervention of amyloidogenesis or amyloid-plaque formation and/or in the diagnosis of the same.
摘要翻译：本发明涉及纯化抗体分子制剂，其特征在于至少一个抗原结合位点包含重链可变区（V H H H）中的糖基化天冬酰胺（Asn）。更具体地，提供了包含所述抗体分子和抗体混合物的药物和诊断组合物，其能够特异性识别β-A4肽/Aβ。本发明特别涉及包含一个或两个糖基化抗原结合位点与重链可变区中的糖基化天冬酰胺（Asn）的抗体的混合物，即包含可变区中的糖基化Asn的抗体同种型的混合物的重链（V H H）。还公开了包含特异性糖基化抗体同种型的组合物或抗体制剂。此外，提供了这些抗体的药物和诊断用途。抗体同种型可以例如用于淀粉样变形或淀粉样蛋白斑形成的药物干预和/或其诊断。

8. 发明申请

WO2003070760A2 ANTI-Aβ ANTIBODIES AND THEIR USE 审中-公开
标题翻译：抗Aβ抗体及其用途
公开(公告)号：WO2003070760A2
公开(公告)日：2003-08-28
申请号：PCT/EP2003/001759
申请日：2003-02-20
申请人： F. HOFFMANN-LA ROCHE AG , MORPHOSYS AG , BARDROFF, Michael , BOHRMANN, Bernd , BROCKHAUS, Manfred , HUBER, Walter , KRETZSCHMAR, Titus , LÖHNING, Corinna , LOETSCHER, Hansruedi , NORDSTEDT, Christer , ROTHE, Christine
发明人： BARDROFF, Michael , BOHRMANN, Bernd , BROCKHAUS, Manfred , HUBER, Walter , KRETZSCHMAR, Titus , LÖHNING, Corinna , LOETSCHER, Hansruedi , NORDSTEDT, Christer , ROTHE, Christine
IPC分类号： C07K14/47
CPC分类号： C07K16/18 , A61K39/0007 , A61K2039/505 , C07K14/4711 , G01N33/6896
摘要： The present invention relates to antibody molecules capable of specifically recognizing two regions of the R-A4 peptide, wherein the first region comprises the amino acid sequence AEFRHDSGY as shown in SEQ ID NO: 1 or a fragment thereof and wherein the second region comprises the amino acid sequence VHHQKLVFFAEDVG as shown in SEQ ID NO: 2 or a fragment thereof. Furthermore, nucleic acid molecules encoding the inventive antibody molecules and vectors and hosts comprising said nucleic acid molecules are disclosed. In addition, the present invention provides for compositions, preferably pharmaceutical or diagnostic compositions, comprising the compounds of the invention as well as for specific uses of the antibody molecules, nucleic acid molecules, vectors or hosts of the invention.
摘要翻译：本发明涉及能够特异性识别R-A4肽的两个区域的抗体分子，其中第一区域包含如SEQ ID NO：1所示的氨基酸序列AEFRHDSGY或其片段，其中第二区域包含氨基酸酸序列VHHQKLVFFAEDVG，如SEQ ID NO：2所示或其片段。此外，公开了编码本发明抗体分子的核酸分子和包含所述核酸分子的载体和宿主。此外，本发明提供包含本发明化合物以及本发明的抗体分子，核酸分子，载体或宿主的特定用途的组合物，优选药物或诊断组合物。

9. 发明申请

WO2010142423A2 USE OF AN ANTI-TAU PS422 ANTIBODY FOR THE TREATMENT OF BRAIN DISEASES 审中-公开
标题翻译：使用抗谷氨酸PS422抗体治疗脑疾病
公开(公告)号：WO2010142423A2
公开(公告)日：2010-12-16
申请号：PCT/EP2010/003437
申请日：2010-06-08
申请人： F. HOFFMANN-LA ROCHE AG , BOHRMANN, Bernd , GOEPFERT, Ulrich , GRUENINGER, Fiona , HUBER, Walter , KRELL, Hans-Willi , LIFKE, Valeria , MUNDIGL, Olaf , OFFNER, Sonja , OZMEN, Laurence , SCHRAEML, Michael
发明人： BOHRMANN, Bernd , GOEPFERT, Ulrich , GRUENINGER, Fiona , HUBER, Walter , KRELL, Hans-Willi , LIFKE, Valeria , MUNDIGL, Olaf , OFFNER, Sonja , OZMEN, Laurence , SCHRAEML, Michael
IPC分类号： C07K16/18
CPC分类号： C07K16/18 , A61K2039/505 , C07K14/4711 , C07K16/3053 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C07K2319/40 , C07K2319/55
摘要： An antibody binding to Tau, phosphorylated at serine 422 (pS422), characterized in specifically binding to phosphorylated Tau fragment of SEQ ID NO: 9 and to Tau pS422, but not binding to Tau and to phosphorylated MCAK fragment of SEQ ID NO: 17 is useful in the treatment of a Tauopathy.
摘要翻译：特异性结合SEQ ID NO：9的磷酸化Tau片段和Tau pS422，但不结合Tau和SEQ ID NO：17的磷酸化MCAK片段的以丝氨酸422（pS422）磷酸化的抗体结合Tau的抗体是可用于治疗Tauopathy。

10. 发明申请

WO2008148493A3 ANNEXIN A5 AND ANNEXIN A6 AS BIOMARKTER FOR ALZHEIMER'S DISEASE 审中-公开
标题翻译：附件A5和附件A6作为阿尔茨海默病的生物标志物
公开(公告)号：WO2008148493A3
公开(公告)日：2009-02-05
申请号：PCT/EP2008004238
申请日：2008-05-28
申请人： HOFFMANN LA ROCHE , BERNDT PETER , BOHRMANN BERND
发明人： BERNDT PETER , BOHRMANN BERND
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2333/4718 , G01N2800/2821
摘要： The present invention relates to a method for assessing Alzheimer's disease in vitro comprising measuring in a sample (e.g. body fluid) the level of one or more proteins of the group consisting of Annexin A5 and Annexin A6, or a variant thereof, wherein an altered level of said one or more proteins, or a variant thereof, is indicative that said individual suffers from Alzheimer's Disease. Furthermore, the present invention relates to a method for monitoring the progression of the Alzheimer's disease in vitro comprising measuring in a sample (e.g. body fluid) the level of one or more proteins of the group consisting of Annexin A5 and Annexin A6, or a variant thereof, wherein an altered level of said one or more proteins, or a variant thereof, compared with an earlier measurement of the level of said one or more proteins, or a variant thereof, is indicative for the progression of Alzheimer's disease.
摘要翻译：本发明涉及一种体外评估阿尔茨海默病的方法，包括在样品（例如体液）中测量由Annexin A5和Annexin A6组成的组中的一种或多种蛋白质或其变体的水平，其中改变的水平的所述一种或多种蛋白质或其变体表明所述个体患有阿尔茨海默氏病。此外，本发明涉及一种用于监测体外阿尔茨海默病进展的方法，其包括在样品（例如体液）中测量由Annexin A5和Annexin A6组成的组中的一种或多种蛋白质的水平或变体其中与所述一种或多种蛋白质或其变体的水平的较早测量相比，所述一种或多种蛋白质或其变体的水平的改变指示阿尔茨海默氏病的进展。

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