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    Method to screen high affinity antibody
    1.
    发明授权
    Method to screen high affinity antibody 有权
    筛选高亲和力抗体的方法

    公开(公告)号：US08645083B2

    公开(公告)日：2014-02-04

    申请号：US13060535

    申请日：2009-08-25

    申请人： Michael Schraeml ,  Leopold Von Proff

    发明人： Michael Schraeml ,  Leopold Von Proff

    IPC分类号： G01N31/00 ,  G01N33/48 ,  G06G7/58

    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 kd, (ix) equilibrium binding constant KD, and (x) association rate constant ka, 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子体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（DeltaG°），（v）标准无离子结合焓配方（C），（vi）标准无结合焓配方 （D），（vii）-TDeltaS°，（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 t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100 J / mol * K或更多，e）通过在适于所述抗体表达的条件下培养所述选择的细胞产生抗体，并从细胞或培养基中回收所述抗体。

    VELOCITY FACTOR
    6.
    发明申请
    VELOCITY FACTOR 有权
    速度因素

    公开(公告)号：US20120156726A1

    公开(公告)日：2012-06-21

    申请号：US13392217

    申请日：2010-08-19

    申请人： Michael Schraeml ,  Leopold Von Proff

    发明人： Michael Schraeml ,  Leopold Von Proff

    IPC分类号： C12P21/04 ,  G01N33/557

    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的比值。由于仅需要两个实验测定来计算速度因子，这是一种快速且高通量的适合方法。

    Velocity factor
    7.
    发明授权
    Velocity factor 有权
    速度系数

    公开(公告)号：US08617849B2

    公开(公告)日：2013-12-31

    申请号：US13392217

    申请日：2010-08-19

    申请人： Michael Schraeml ,  Leopold Von Proff

    发明人： Michael Schraeml ,  Leopold Von Proff

    IPC分类号： C12P21/08 ,  G01N33/557 ,  G01N33/53

    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的比值。由于仅需要两个实验测定来计算速度因子，这是一种快速且高通量的适合方法。

    Hemopexin-Like Structure as New Polypeptide-Scaffold
    8.
    发明申请
    Hemopexin-Like Structure as New Polypeptide-Scaffold 审中-公开
    新型多肽 - 支架血栓素样结构

    公开(公告)号：US20090054252A1

    公开(公告)日：2009-02-26

    申请号：US11794415

    申请日：2006-01-02

    申请人： Martin Lanzendoerfer ,  Michael Schraeml

    发明人： Martin Lanzendoerfer ,  Michael Schraeml

    IPC分类号： C40B30/04 ,  C07K14/00 ,  G01N33/00 ,  C12N15/00 ,  C12P21/04

    CPC分类号： C07K14/47 ,  C12N9/6491 ,  C12N15/1034 ,  C12N15/63 ,  G01N33/6803

    摘要： The invention concerns a method for the generation of a polypeptide with specific binding properties to a predetermined target molecule which are not naturally inherent to that polypeptide. At the same time an optimization of the binding specifity and a process of production are described. The invention further concerns a method for the identification and modification of specific amino acid positions within a polypeptide scaffold.

    摘要翻译： 本发明涉及一种产生具有与该多肽天然不固有的预定靶分子特异性结合特性的多肽的方法。 同时描述了结合特异性和生产过程的优化。 本发明还涉及用于鉴定和修饰多肽支架内的特定氨基酸位置的方法。

    METHOD FOR SEQUENCE SPECIFIC BIOTINYLATION
    9.
    发明申请
    METHOD FOR SEQUENCE SPECIFIC BIOTINYLATION 审中-公开
    序列特异性生物化学方法

    公开(公告)号：US20080187957A1

    公开(公告)日：2008-08-07

    申请号：US11863733

    申请日：2007-09-28

    申请人： Dorothee Ambrosius ,  Martin Lanzendoerfer ,  Michael Schraeml ,  Manfred Watzele

    发明人： Dorothee Ambrosius ,  Martin Lanzendoerfer ,  Michael Schraeml ,  Manfred Watzele

    IPC分类号： C12P21/06

    CPC分类号： C07K1/1077 ,  C07K1/13

    摘要： A method of preparing a biotinylated polypeptide in a cell-free peptide synthesis reaction mixture by contacting, under suitable conditions, a polypeptide to be biotinylated, with a reaction mixture that includes ribosomes, tRNA, ATP, GTP, nucleotides, biotin and amino acids, and a polypeptide that includes an enzymatically active domain of a BirA enzyme. The polypeptide to be biotinylated includes a BirA substrate sequence tag, and the polypeptide to be biotinylated and the polypeptide comprising an enzymatically active domain of a BirA enzyme, are expressed in situ in the reaction mixture, by at least one nucleic acid molecule encoding the polypeptide to be biotinylated, and the enzymatically active domain of a BirA enzyme, respectively.

    摘要翻译： 在合适的条件下使待生物素化的多肽与包括核糖体，tRNA，ATP，GTP，核苷酸，生物素和氨基酸的反应混合物接触，在无细胞肽合成反应混合物中制备生物素化多肽的方法， 和包含BirA酶的酶活性结构域的多肽。 要生物素化的多肽包括BirA底物序列标签，并且待生物素化的多肽和包含BirA酶的酶活性结构域的多肽在反应混合物中原位表达，至少一个编码多肽的核酸分子 分别生物素化和BirA酶的酶活性结构域。

    Artificial binding proteins based on a modified alpha helical region of ubiquitin
    10.
    发明授权
    Artificial binding proteins based on a modified alpha helical region of ubiquitin 有权
    基于泛素修饰的α螺旋区的人工结合蛋白

    公开(公告)号：US08592179B2

    公开(公告)日：2013-11-26

    申请号：US12514550

    申请日：2007-11-15

    申请人： Michael Schraeml ,  Erik Fiedler

    发明人： Michael Schraeml ,  Erik Fiedler

    IPC分类号： C07K14/435

    CPC分类号： C07K14/00 ,  G01N33/6803

    摘要： The present invention is directed to a method for the generation of binding proteins derived from the protein super-family of ubiquitin like proteins with modifications in their alpha helical region as well as to a protein obtainable by said method. Furthermore, the invention provides the use of a protein for the specific recognition, binding and neutralization of a predescribed target molecule, for the detection, quantitative determination, separation and/or for the isolation of a corresponding binding partner and the use of a protein of the invention, for diagnosis, prophylaxis and treatment of diseases in which the corresponding binding partner is directly or indirectly involved.

    摘要翻译： 本发明涉及一种用于产生衍生自泛蛋白样蛋白质的蛋白质超家族的结合蛋白质的方法，其修饰在其α螺旋区域以及可通过所述方法获得的蛋白质。 此外，本发明提供蛋白质用于预测的靶分子的特异性识别，结合和中和用于检测，定量测定，分离和/或分离相应结合配偶体的用途以及使用蛋白质 本发明用于诊断，预防和治疗其中相应的结合伴侣直接或间接参与的疾病。