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    scFv antibodies which pass epithelial and/or endothelial layers
    3.
    发明授权
    scFv antibodies which pass epithelial and/or endothelial layers 有权
    通过上皮和/或内皮层的scFv抗体

    公开(公告)号：US08936785B2

    公开(公告)日：2015-01-20

    申请号：US12307875

    申请日：2007-07-10

    申请人： Adrian Auf Der Maur ,  Alcide Barberis ,  David M. Urech ,  Peter Lichtlen

    发明人： Adrian Auf Der Maur ,  Alcide Barberis ,  David M. Urech ,  Peter Lichtlen

    IPC分类号： A61K39/395 ,  C07K16/18 ,  C07K16/22 ,  C07K16/24 ,  A61K39/00

    CPC分类号： C07K16/18 ,  A61K39/39591 ,  A61K2039/505 ,  A61K2039/54 ,  C07K16/22 ,  C07K16/241 ,  C07K2317/24 ,  C07K2317/622

    摘要： scFv antibodies which specifically bind selected antigens and are obtainable by a method comprising (i) selecting from a pool of soluble and stable antibody frameworks a soluble and stable framework matching best the framework of a non-human antibody against the antigen with a certain binding specificity, (ii) either providing said soluble and stable framework with CDRs that bind specifically to said antigen, or mutating the framework of said non-human antibody towards the sequence of said soluble and stable framework, to generate scFv antibodies, (iii) testing the generated antibody for solubility and stability, and testing the generated antibody for antigen binding, and (iv) selecting an scFV that is soluble, stable and binds to the antigen specifically. Also provided are pharmaceutical compositions comprising said scFv antibody, methods of treatment and diagnosis for diseases related to over expression of antigens that are specifically bound by said antibody.

    摘要翻译： scFv抗体，其特异性结合所选择的抗原，并且可通过以下方法获得：（i）从可溶性和稳定的抗体框架库中选择可溶性和稳定的框架，以最佳匹配抗人抗体的框架与一定的结合特异性 提供与所述抗原特异性结合的CDR提供所述可溶性和稳定的框架，或者将所述非人抗体的框架朝向所述可溶性和稳定框架的序列突变以产生scFv抗体，（iii）测试 产生抗体的溶解度和稳定性，并测试所产生的抗体的抗原结合，和（iv）选择可溶性，稳定并特异性结合抗原的scFV。 还提供了包含所述scFv抗体的药物组合物，与由所述抗体特异性结合的抗原过度表达相关疾病的治疗和诊断方法。

    Sequence based engineering and optimization of single chain antibodies
    4.
    发明授权
    Sequence based engineering and optimization of single chain antibodies 有权
    基于序列的单链抗体工程和优化

    公开(公告)号：US08280711B2

    公开(公告)日：2012-10-02

    申请号：US12530756

    申请日：2008-03-12

    申请人： David M. Urech ,  Leonardo Borras

    发明人： David M. Urech ,  Leonardo Borras

    IPC分类号： G06F7/60 ,  G06F19/00 ,  G06F17/30

    CPC分类号： C07K16/00 ,  C07K16/241 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/94 ,  G06F19/18

    摘要： The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of single chain antibodies (scFvs), including stability, solubility, and antigen binding affinity. These methods and strategies can be used individually or in combination. The methods of the present invention also include the use of a database comprising scFv sequences from an experimentally screened scFv library of antibodies that have been selected to have superior solubility and stability. The invention also provides methods of using the properties found for these selected antibodies in a general approach for reshaping scFv antibodies to improve stability and solubility properties of a single chain antibody fragment.

    摘要翻译： 本发明提供了使用基于序列的分析和合理策略来修饰和改善单链抗体（scFv）的结构和生物物理性质（包括稳定性，溶解度和抗原结合亲和力）的方法。 这些方法和策略可以单独使用或组合使用。 本发明的方法还包括使用包含已被选择具有优异溶解度和稳定性的抗体的实验筛选的scFv文库的scFv序列的数据库。 本发明还提供了在通用方法中使用针对这些所选抗体发现的性质的方法，用于重塑scFv抗体以改善单链抗体片段的稳定性和溶解性质。

    Sequence Based Engineering and Optimization of Single Chain Antibodies
    5.
    发明申请
    Sequence Based Engineering and Optimization of Single Chain Antibodies 有权
    基于序列的工程和单链抗体的优化

    公开(公告)号：US20100137150A1

    公开(公告)日：2010-06-03

    申请号：US12530756

    申请日：2008-03-12

    申请人： David M. Urech ,  Leonardo Borras

    发明人： David M. Urech ,  Leonardo Borras

    IPC分类号： C40B30/02

    CPC分类号： C07K16/00 ,  C07K16/241 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/94 ,  G06F19/18

    摘要： The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of single chain antibodies (scFvs), including stability, solubility, and antigen binding affinity. These methods and strategies can be used individually or in combination. The methods of the present invention also include the use of a database comprising scFv sequences from an experimentally screened scFv library of antibodies that have been selected to have superior solubility and stability. The invention also provides methods of using the properties found for these selected antibodies in a general approach for reshaping scFv antibodies to improve stability and solubility properties of a single chain antibody fragment.

    摘要翻译： 本发明提供了使用基于序列的分析和合理策略来修饰和改善单链抗体（scFv）的结构和生物物理性质（包括稳定性，溶解度和抗原结合亲和力）的方法。 这些方法和策略可以单独使用或组合使用。 本发明的方法还包括使用包含已被选择具有优异溶解度和稳定性的抗体的实验筛选的scFv文库的scFv序列的数据库。 本发明还提供了在通用方法中使用针对这些所选抗体发现的性质的方法，用于重塑scFv抗体以改善单链抗体片段的稳定性和溶解性质。

    SEQUENCE BASED ENGINEERING AND OPTIMIZATION OF SINGLE CHAIN ANTIBODIES
    8.
    发明申请
    SEQUENCE BASED ENGINEERING AND OPTIMIZATION OF SINGLE CHAIN ANTIBODIES 审中-公开

    公开(公告)号：US20130053259A1

    公开(公告)日：2013-02-28

    申请号：US13592885

    申请日：2012-08-23

    申请人： David M. Urech ,  Leonardo Borras

    发明人： David M. Urech ,  Leonardo Borras

    IPC分类号： C40B30/02

    CPC分类号： C07K16/00 ,  C07K16/241 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/94 ,  G06F19/18

    摘要： The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of single chain antibodies (scFvs), including stability, solubility, and antigen binding affinity. These methods and strategies can be used individually or in combination. The methods of the present invention also include the use of a database comprising scFv sequences from an experimentally screened scFv library of antibodies that have been selected to have superior solubility and stability. The invention also provides methods of using the properties found for these selected antibodies in a general approach for reshaping scFv antibodies to improve stability and solubility properties of a single chain antibody fragment.

    SCFV ANTIBODIES WHICH PASS EPITHELIAL AND/OR ENDOTHELIAL LAYERS
    9.
    发明申请
    SCFV ANTIBODIES WHICH PASS EPITHELIAL AND/OR ENDOTHELIAL LAYERS 有权
    通过上皮和/或内皮层的SCFV抗体

    公开(公告)号：US20090311251A1

    公开(公告)日：2009-12-17

    申请号：US12307875

    申请日：2007-07-10

    申请人： Adrian Auf Der Maur ,  Alcide Barberis ,  David M. Urech ,  Peter Lichtlen

    发明人： Adrian Auf Der Maur ,  Alcide Barberis ,  David M. Urech ,  Peter Lichtlen

    IPC分类号： A61K39/395 ,  G01N33/53 ,  C07K16/00

    CPC分类号： C07K16/18 ,  A61K39/39591 ,  A61K2039/505 ,  A61K2039/54 ,  C07K16/22 ,  C07K16/241 ,  C07K2317/24 ,  C07K2317/622

    摘要： scFv antibodies which specifically bind selected antigens and are obtainable by a method comprising (i) selecting from a pool of soluble and stable antibody frameworks a soluble and stable framework matching best the framework of a non-human antibody against the antigen with a certain binding specificity, (ii) either providing said soluble and stable framework with CDRs that bind specifically to said antigen, or mutating the framework of said non-human antibody towards the sequence of said soluble and stable framework, to generate scFv antibodies, (iii) testing the generated antibody for solubility and stability, and testing the generated antibody for antigen binding, and (iv) selecting an scFV that is soluble, stable and binds to the antigen specifically. Also provided are pharmaceutical compositions comprising said scFv antibody, methods of treatment and diagnosis for diseases related to over expression of antigens that are specifically bound by said antibody.

    摘要翻译： scFv抗体，其特异性结合所选择的抗原，并且可通过以下方法获得：（i）从可溶性和稳定的抗体框架库中选择可溶性和稳定的框架，以最佳匹配抗人抗体的框架与一定的结合特异性 提供与所述抗原特异性结合的CDR提供所述可溶性和稳定的框架，或者将所述非人抗体的框架朝向所述可溶性和稳定框架的序列突变以产生scFv抗体，（iii）测试 产生抗体的溶解度和稳定性，并测试所产生的抗体的抗原结合，和（iv）选择可溶性，稳定并特异性结合抗原的scFV。 还提供了包含所述scFv抗体的药物组合物，与由所述抗体特异性结合的抗原过度表达相关疾病的治疗和诊断方法。