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    Stable and soluble antibodies inhibiting TNFα
    4.
    发明授权
    Stable and soluble antibodies inhibiting TNFα 有权
    稳定和可溶性抗体抑制TNFalpha

    公开(公告)号：US08673310B2

    公开(公告)日：2014-03-18

    申请号：US13000345

    申请日：2009-06-25

    申请人： Leonardo Borras ,  Tea Gunde ,  David Urech

    发明人： Leonardo Borras ,  Tea Gunde ,  David Urech

    IPC分类号： A61K39/395 ,  C07K16/24

    CPC分类号： C07K16/241 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/92

    摘要： The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

    摘要翻译： 本发明涉及特别稳定和可溶的scFv抗体和对TNF特异性的Fab片段，其包含针对TNF的稳定性，溶解性，体外和体内结合以及低免疫原性而优化的特异性轻链和重链序列。 所述抗体被设计用于诊断和/或治疗TNF介导的病症。 还公开了用于表达本发明的重组抗体的核酸，载体和宿主细胞，用于分离它们的方法和所述抗体在医学中的用途。

    METHODS OF MODIFYING ANTIBODIES, AND MODIFIED ANTIBODIES WITH IMPROVED FUNCTIONAL PROPERTIES
    8.
    发明申请
    METHODS OF MODIFYING ANTIBODIES, AND MODIFIED ANTIBODIES WITH IMPROVED FUNCTIONAL PROPERTIES 审中-公开
    抗体修饰方法及改良功能改良抗体

    公开(公告)号：US20090074780A1

    公开(公告)日：2009-03-19

    申请号：US12145600

    申请日：2008-06-25

    申请人： David Urech ,  Leonardo Borras

    发明人： David Urech ,  Leonardo Borras

    IPC分类号： A61K39/395 ,  C07K16/00

    CPC分类号： C07K16/241 ,  C07K2317/567 ,  C07K2317/622

    摘要： The invention provides methods of using sequence based analysis and rational strategies to modify and improve the structural and biophysical properties of immunobinders, and in particular of single chain antibodies (scFvs), including such properties as stability, solubility, and/or antigen binding affinity. The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions at amino acid positions identified by analysis of a database of selected, stable scFv sequences, wherein preferred amino acid residues for substitution have been identified. The invention also provides immunobinders prepared according to the engineering methods of the invention. The invention also provides preferred scFv framework scaffolds, into which CDR sequences can be inserted, as well as scFv antibodies made using these preferred framework scaffolds.

    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进免疫结合物，特别是单链抗体（scFv）的结构和生物物理性质的方法，包括稳定性，溶解性和/或抗原结合亲和力等性质。 本发明提供了通过在通过选择的稳定scFv序列的数据库的分析鉴定的氨基酸位置上进行一个或多个置换来确定免疫印迹物，特别是scFv的方法，其中已鉴定出优选的用于取代的氨基酸残基。 本发明还提供根据本发明的工程方法制备的免疫结合剂。 本发明还提供了可插入CDR序列的优选scFv框架支架，以及使用这些优选的框架支架制备的scFv抗体。

    SEQUENCE BASED ENGINEERING AND OPTIMIZATION OF SINGLE CHAIN ANTIBODIES
    9.
    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优化

    公开(公告)号：US20090028848A1

    公开(公告)日：2009-01-29

    申请号：US12145749

    申请日：2008-06-25

    申请人： David Urech ,  Leonardo Borras

    发明人： David Urech ,  Leonardo Borras

    IPC分类号： A61K39/395 ,  C07K16/18 ,  A61P43/00 ,  G06F7/06 ,  G06F17/30

    CPC分类号： C07K16/465 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/622 ,  G06F19/16

    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。