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1. 发明申请

WO2012150321A1 AN ANTIBODY SPECIFICALLY BINDING TO INSULIN-LIKE GROWTH FACTOR-1 审中-公开
标题翻译：抗胰岛素特异性结合胰岛素样生长因子-1
公开(公告)号：WO2012150321A1
公开(公告)日：2012-11-08
申请号：PCT/EP2012/058208
申请日：2012-05-04
申请人： ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , ANDRES, Herbert , DUEFEL, Hartmut , GERG, Michael , KOWALEWSKY, Frank , SCHOLZ, Christian , SCHRAEML, Michael
发明人： ANDRES, Herbert , DUEFEL, Hartmut , GERG, Michael , KOWALEWSKY, Frank , SCHOLZ, Christian , SCHRAEML, Michael
IPC分类号： C07K16/22
CPC分类号： C07K16/22 , C07K14/475 , C07K14/65 , C07K16/1203 , C07K16/40 , C07K2317/34 , C07K2317/565 , C07K2317/92 , C07K2319/00 , C07K2319/21 , C07K2319/22 , C07K2319/23 , C07K2319/24 , C07K2319/35 , C07K2319/41 , C07K2319/43 , C12N9/90 , C12Y502/01008 , G01N33/573 , G01N33/74 , G01N2333/99
摘要： The present invention relates to an isolated antibody that specifically binds to an epitope comprised in the stretch of amino acids ranging from amino acid 76 to amino acid 84 as known for human insulin-like growth factor-1 precursor (SEQ ID NO:1). The novel antibodies are of great utility since they allow for the sensitive and specific detection of insulin-like growth factor-1 even in the presence of high excess concentration of the closely related insulin-like growth factor-2. Detection of insulin-like growth factor-1 is e.g. possible in a bodily fluid sample.
摘要翻译：本发明涉及一种分离的抗体，其特异性结合包含在人类胰岛素样生长因子-1前体（SEQ ID NO：1）已知的范围从氨基酸76至氨基酸84的氨基酸区段中的表位。新型抗体具有很大的实用性，因为即使在密切相关的胰岛素样生长因子-2的高浓度过量的情况下，它们也允许胰岛素样生长因子-1的敏感和特异性检测。胰岛素样生长因子-1的检测是例如。可能在体液样品中。

2. 发明申请

WO2012085069A3 DETECTION OF A POLYPEPTIDE DIMER BY A BIVALENT BINDING AGENT 审中-公开
标题翻译：通过双重结合剂检测多肽二聚体
公开(公告)号：WO2012085069A3
公开(公告)日：2012-08-16
申请号：PCT/EP2011073567
申请日：2011-12-21
申请人： ROCHE DIAGNOSTICS GMBH , HOFFMANN LA ROCHE , GERG MICHAEL , HEINDL DIETER , MERTENS ALFRED , RUTZ CHRISTOPH , SCHRAEML MICHAEL , SOUKUPOVA MONIKA , SUSTMANN CLAUDIO , TACKE MICHAEL , VAN DIECK JAN
发明人： GERG MICHAEL , HEINDL DIETER , MERTENS ALFRED , RUTZ CHRISTOPH , SCHRAEML MICHAEL , SOUKUPOVA MONIKA , SUSTMANN CLAUDIO , TACKE MICHAEL , VAN DIECK JAN
IPC分类号： G01N33/68 , C07K16/46
CPC分类号： C07K16/468 , C07K16/18 , C07K16/2863 , C07K16/32 , C07K16/44 , C07K2317/31 , C07K2317/34 , C07K2317/55 , C07K2317/92 , C07K2317/94 , G01N33/6857
摘要： The present invention relates to a bivalent binding agent capable of binding a polypeptide dimer the binding agent consisting of two monovalent binders that are linked to each other via a linker, wherein the first monovalent binder binds to an epitope of a first target polypeptide comprised in said dimer, wherein the second monovalent binder binds to an epitope of a second target polypeptide comprised in said dimer, wherein each monovalent binder has a Kdiss in the range of 5x10-3/sec to 10-4/sec, and wherein the bivalent binding agent has a Kdiss of 3x10-5/sec or less. A method of making such bivalent binding agent and the use of such bivalent agent in histological staining procedures are also disclosed.
摘要翻译：本发明涉及能够结合多肽二聚体的二价结合剂，所述结合剂由通过连接体相互连接的两个单价键合物组成，其中所述第一单价键结合物与包含在所述第一靶多肽中的第一靶多肽的表位结合二聚体，其中所述第二单价键合物与包含在所述二聚体中的第二靶多肽的表位结合，其中每个单价粘合剂的Kdiss在5×10 -3 /秒至10 -4 /秒的范围内，并且其中所述二价结合剂 Kdiss为3x10-5 / sec以下。还公开了制备这种二价结合剂的方法和这种二价试剂在组织学染色方法中的用途。

3. 发明申请

WO2013007667A1 AN ANTIBODY SPECIFICALLY BINDING TO NEUROPILIN-1 审中-公开
标题翻译：抗体特异性结合神经营养因子-1
公开(公告)号：WO2013007667A1
公开(公告)日：2013-01-17
申请号：PCT/EP2012/063344
申请日：2012-07-09
申请人： ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , DZIADEK, Sebastian , FLOHR, Aljoscha Michael , GERG, Michael , JARUTAT, Tiantom , SCHRAEML, Michael , TACKE, Michael
发明人： DZIADEK, Sebastian , FLOHR, Aljoscha Michael , GERG, Michael , JARUTAT, Tiantom , SCHRAEML, Michael , TACKE, Michael
IPC分类号： C07K16/28
CPC分类号： C07K16/2863 , C07K2317/34 , C07K2317/92
摘要： The present invention relates to an isolated antibody that specifically binds to the stretch of amino acids ranging from amino acid 672 to amino acid 688 as known for human neuropilin-1. The novel antibodies are of great utility since they allow for the sensitive and specific detection of neuropilin-1. Detection of neuropilin-1 is e.g. possible in a tissue sample, even when such tissue sample is a formalin-fixed paraffin embedded tissue (FFPET) sample.
摘要翻译：本发明涉及与人神经胶蛋白-1已知的氨基酸672至氨基酸688的氨基酸片段特异性结合的分离抗体。新型抗体具有很大的应用价值，因为它们可以灵敏和特异性地检测神经毡蛋白-1。神经蛋白-1的检测是例如。即使这样的组织样品是福尔马林固定的石蜡包埋组织（FFPET）样品，也可能在组织样品中。

4. 发明申请

WO2012150320A1 AMINO ACID SEQUENCE PRESENTING FUSION POLYPEPTIDE AND ITS USE 审中-公开
标题翻译：氨基酸序列显示融合多肽及其用途
公开(公告)号：WO2012150320A1
公开(公告)日：2012-11-08
申请号：PCT/EP2012/058207
申请日：2012-05-04
申请人： F. HOFFMANN-LA ROCHE AG , ANDRES, Herbert , CASAGOLDA VALLRIBERA, David , DUEFEL, Hartmut , GERG, Michael , SCHOLZ, Christian , SCHRAEML, Michael
发明人： ANDRES, Herbert , CASAGOLDA VALLRIBERA, David , DUEFEL, Hartmut , GERG, Michael , SCHOLZ, Christian , SCHRAEML, Michael
IPC分类号： C12N9/90 , C07K14/195 , C07K14/415 , C07K14/47 , C07K16/22
CPC分类号： C07K16/22 , C07K14/475 , C07K14/65 , C07K16/1203 , C07K16/40 , C07K2317/34 , C07K2317/565 , C07K2317/92 , C07K2319/00 , C07K2319/21 , C07K2319/22 , C07K2319/23 , C07K2319/24 , C07K2319/35 , C07K2319/41 , C07K2319/43 , C12N9/90 , C12Y502/01008 , G01N33/573 , G01N33/74 , G01N2333/99
摘要： Herein is reported a fusion polypeptide according to formula (I): NH 2 -S 2 -X 1 -S 1 -COOH, wherein X 1 comprises either a random amino acid sequence or an amino acid sequence derived from a first polypeptide, S2 and S1 are non-overlapping amino acid sequences derived from a second polypeptide, and denotes a peptide bond, wherein the second polypeptide is a polypeptide with peptidyl-prolyl cis/trans-isomerase activity (PPIase activity) or is derived from the FKBP-fold domain family, wherein X 1 is inserted in place of the insert-in-flap-domain of the second polypeptide.
摘要翻译：本文报道了根据式（I）的融合多肽：NH2-S2-X1-S1-COOH，其中X1包含随机氨基酸序列或衍生自第一多肽的氨基酸序列，S2和S1不重叠衍生自第二多肽的氨基酸序列，并且表示肽键，其中第二多肽是具有肽基 - 脯氨酰顺/反异构酶活性（PPIase活性）或衍生自FKBP-折叠域家族的多肽，其中X1是插入第二多肽的插入片段结构域。

5. 发明申请

WO2012085113A1 BINDING AGENT 审中-公开
标题翻译：绑定代理
公开(公告)号：WO2012085113A1
公开(公告)日：2012-06-28
申请号：PCT/EP2011/073633
申请日：2011-12-21
申请人： ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , GALLUSSER, Andreas , HEINDL, Dieter , SCHRAEML, Michael , SEIDEL, Christoph , VON DER ELTZ, Herbert
发明人： GALLUSSER, Andreas , HEINDL, Dieter , SCHRAEML, Michael , SEIDEL, Christoph , VON DER ELTZ, Herbert
IPC分类号： C07K16/00 , C07K16/18
CPC分类号： C07K19/00 , C07K16/18 , C07K16/2863 , C07K16/32 , C07K2317/31 , C07K2317/34 , C07K2317/55 , C07K2317/626 , C07K2317/92 , C07K2317/94
摘要： The present invention relates to a binding agent of the FormulaA - a':a - S- b:b' - B:X(n), wherein A as well as B is a monovalent binder, wherein a':a as well as b:b' is a binding pair wherein a' and a do not interfere with the binding of b to b' and vice versa, wherein S is a spacer of at least 1 nm in length, wherein :X denotes a functional moiety bound either covalently or via a binding pair to at least one of a', a, b, b' or S, wherein (n) is an integer and at least 1, wherein - represents a covalent bond, and wherein the linker a - S - b has a length of 6 to 100 nm. Also disclosed are a method of producing such binding agent and certain uses thereof.
摘要翻译：本发明涉及式A-a'：a-S-b：b'-B：X（n）的结合剂，其中A以及B是单价粘合剂，其中a： b：b'是一个结合对，其中a'和a不干扰b与b'的结合，反之亦然，其中S是长度至少为1nm的间隔物，其中：X表示与共价或经由与a'，a，b，b'或S中的至少一个的结合对，其中（n）为整数且至少为1，其中 - 表示共价键，并且其中所述连接体a-S- b的长度为6〜100nm。还公开了生产这种结合剂及其某些用途的方法。

6. 发明申请

WO2012085069A2 DETECTION OF A POLYPEPTIDE DIMER BY A BIVALENT BINDING AGENT 审中-公开
标题翻译：用二元结合剂检测多肽二聚体
公开(公告)号：WO2012085069A2
公开(公告)日：2012-06-28
申请号：PCT/EP2011/073567
申请日：2011-12-21
申请人： ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , GERG, Michael , HEINDL, Dieter , MERTENS, Alfred , RUTZ, Christoph , SCHRAEML, Michael , SOUKUPOVA, Monika , SUSTMANN, Claudio , TACKE, Michael , VAN DIECK, Jan
发明人： GERG, Michael , HEINDL, Dieter , MERTENS, Alfred , RUTZ, Christoph , SCHRAEML, Michael , SOUKUPOVA, Monika , SUSTMANN, Claudio , TACKE, Michael , VAN DIECK, Jan
IPC分类号： G01N33/68 , C07K16/46
CPC分类号： C07K16/468 , C07K16/18 , C07K16/2863 , C07K16/32 , C07K16/44 , C07K2317/31 , C07K2317/34 , C07K2317/55 , C07K2317/92 , C07K2317/94 , G01N33/6857
摘要： The present invention relates to a bivalent binding agent capable of binding a polypeptide dimer the binding agent consisting of two monovalent binders that are linked to each other via a linker, wherein the first monovalent binder binds to an epitope of a first target polypeptide comprised in said dimer, wherein the second monovalent binder binds to an epitope of a second target polypeptide comprised in said dimer, wherein each monovalent binder has a Kdiss in the range of 5x10 -3 /sec to 10 -4 /sec, and wherein the bivalent binding agent has a Kdiss of 3x10 -5 /sec or less. A method of making such bivalent binding agent and the use of such bivalent agent in histological staining procedures are also disclosed.
摘要翻译：本发明涉及能够结合多肽二聚体的二价结合剂，所述结合剂由两个经由接头彼此连接的单价结合剂组成，其中所述第一单价结合剂结合表位的所述二聚体中包含的第一靶多肽，其中所述第二单价结合剂结合包含在所述二聚体中的第二靶多肽的表位，其中每个单价结合剂具有5×10 -3至5×10 -5的Kdiss。 /秒至10-4 /秒，并且其中二价结合剂具有3×10 -5秒/秒或更小的Kdiss。还公开了制造这种二价结合剂的方法和这种二价试剂在组织学染色过程中的用途。

7. 发明申请

WO2011023623A1 VELOCITY FACTOR 审中-公开
标题翻译：速度因素
公开(公告)号：WO2011023623A1
公开(公告)日：2011-03-03
申请号：PCT/EP2010/062115
申请日：2010-08-19
申请人： F. HOFFMANN-LA ROCHE AG , SCHRAEML, Michael , VON PROFF, Leopold
发明人： SCHRAEML, Michael , VON PROFF, Leopold
IPC分类号： C07K16/00 , A61K39/395
CPC分类号： G01N33/557 , C07K16/00 , C07K16/461 , C07K2317/24 , C07K2317/90 , C07K2317/92 , C07K2317/94 , G01N33/6854
摘要： The current invention is directed to the velocity factor. Based on the velocity factor antibodies can be classified, i.e. antibodies can be characterized on their binding properties as e.g. entropic or enthalpic antigen binder. A velocity factor based classification does not require detailed thermodynamic determinations and/or calculations. The velocity factor is the ratio of the antigen-antibody complex association rate constants ka determined at 37 °C and 13 °C. As only two experimental determinations are required to calculate the velocity factor this is a fast and high-throughput suited method.
摘要翻译：本发明涉及速度因子。基于速度因子，可以对抗体进行分类，即可以将抗体的结合特性表征为例如抗体。熵或焓抗原结合物。基于速度因子的分类不需要详细的热力学测定和/或计算。速度因子是在37℃和13℃下测定的抗原 - 抗体复合物缔合速率常数ka的比率。由于只需要两个实验测定来计算速度因子，因此这是一种快速且高通量的适合方法。

8. 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。

9. 发明申请

WO2010022910A1 METHOD TO SCREEN HIGH AFFINITY ANTIBODY 审中-公开
标题翻译：筛选高亲和力抗体的方法
公开(公告)号：WO2010022910A1
公开(公告)日：2010-03-04
申请号：PCT/EP2009/006136
申请日：2009-08-25
申请人： F. HOFFMANN-LA ROCHE AG , SCHRAEML, Michael , VON PROFF, Leopold
发明人： SCHRAEML, Michael , VON PROFF, Leopold
IPC分类号： G01N21/55
CPC分类号： G01N33/6854 , C07K16/26 , G01N21/553
摘要： The current invention reports a method for producing an antibody comprising the steps of a) providing a plurality of hybridoma cells each expressing an antibody, b) determining the time dependent amount of said antibody bound to the respective antigen by surface plasmon resonance at different temperatures and different antibody concentrations, c) calculating with the time dependent amount determined in b) based on equations (II) to (XIII) at least the thermodynamic parameters (i) standard association binding entropy formula (A), (ii) standard dissociation binding entropy formula (B), (iii) standard binding entropy (ΔS°), (iv) free standard binding enthalpy (ΔG°), (v) standard dissociation free binding enthalpy formula (C), (vi) standard association free binding enthalpy formula (D), (vii) -TΔS°, (viii) dissociation rate constant k d , (ix) equilibrium binding constant K D , and (x) association rate constant k a , d) selecting a hybridoma cell producing an antibody with at least two of the following: i) a standard association binding entropy of less than 10 J/K*mol, ii) an absolute standard dissociation binding entropy of 100 J/mol*K or more, iii) an absolute standard binding entropy of 100 J/mol*K or more, e) producing an antibody by cultivating said selected cell under conditions suitable for the expression of said antibody and recovering said antibody from the cells or/and the cultivation medium.
摘要翻译：本发明报告了一种制备抗体的方法，包括以下步骤：a）提供多个表达抗体的杂交瘤细胞，b）通过在不同温度下的表面等离振子共振测定与相应抗原结合的所述抗体的时间依赖性量，不同的抗体浓度，c）基于等式（II）至（XIII），至少在热力学参数（i）标准关联结合熵公式（A），（ii）标准解离结合熵式（B），（iii）标准结合熵（ΔS°），（iv）游离标准结合焓（ΔG°），（v）标准无离子结合焓式（C），（vi）焓公式（D），（vii）-T≤S°，（viii）解离速率常数kd，（ix）平衡结合常数KD和（x）缔合速率常数ka，d）选择产生抗体的杂交瘤细胞至少有两个以下：i）小于10J / K * mol的标准缔合结合熵，ii）100J / mol * K以上的绝对标准解离结合熵，iii）绝对标准结合熵为100J / mol * K以上，e）通过在适于表达所述抗体的条件下培养所述选择的细胞并从细胞或培养基中回收所述抗体来产生抗体。

10. 发明申请

WO2012113718A1 A DIAGNOSTIC METHOD FOR TYPE II DIABETES 审中-公开
标题翻译：一种二型糖尿病的诊断方法
公开(公告)号：WO2012113718A1
公开(公告)日：2012-08-30
申请号：PCT/EP2012/052732
申请日：2012-02-17
申请人： ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , ENGEL, Alfred , HAEFLIGER, Carolina , KUBALEC, Pavel , ROESSLER, Markus , SCHRAEML, Michael , SOUKUPOVA, Monika
发明人： ENGEL, Alfred , HAEFLIGER, Carolina , KUBALEC, Pavel , ROESSLER, Markus , SCHRAEML, Michael , SOUKUPOVA, Monika
IPC分类号： C07K16/28 , G01N33/53
CPC分类号： G01N33/68 , C07K16/28 , C07K16/40 , C07K2317/34 , C07K2317/92 , G01N2800/042
摘要： The present invention relates to an in vitro method aiding in the assessment of type II diabetes (T2D). It discloses the use of the protein TMEM 27 as a marker of T2D. Furthermore, it especially relates to a method for assessing T2D from a sample, derived from an individual by measuring the protein TMEM27 in said sample in vitro. The invention further relates to antibodies against human TMEM27 protein, methods for their production, and uses thereof.
摘要翻译：本发明涉及一种辅助评估II型糖尿病（T2D）的体外方法。它公开了蛋白质TMEM 27作为T2D的标记物的用途。此外，它特别涉及通过在体外测量所述样品中的蛋白TMEM27来评估来自个体的样品的T2D的方法。本发明还涉及针对人TMEM27蛋白的抗体，其制备方法及其用途。

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