Selective removal of immune complexes
    1.
    发明授权
    Selective removal of immune complexes 失效
    选择性去除免疫复合物

    公开(公告)号:US5084398A

    公开(公告)日:1992-01-28

    申请号:US601029

    申请日:1990-10-23

    IPC分类号: A61M1/36 C07K14/31 C07K17/06

    摘要: Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and inidivdual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.

    摘要翻译: 公开了一种可用于将血液中的免疫复合物优先地去除可溶性抗体的方法和一系列材料。 该材料包含与免疫球蛋白Fc区结合的蛋白质的类似物。 类似物通过截短或以其它方式改变结合蛋白的氨基酸序列来降低它们对Fc的亲和力而产生。 在不溶性基质的表面附近设置的这种类似物的阵列具有在复合物中形成与多个Fc的多个连接点的能力,以便强烈地结合复合物,而仅在可溶性IgG的Fc区和 inidivdual类似物。 优选的类似物是与蛋白A或蛋白G的结合部分与Fc结合的截短的蛋白质。 可以使用材料和常规的血浆置换技术从全血或血清中除去复合物。

    DNA encoding a protein which enables selective removal of immune
complexes
    2.
    发明授权
    DNA encoding a protein which enables selective removal of immune complexes 失效
    编码能够选择性去除免疫复合物的蛋白质的DNA

    公开(公告)号:US5243040A

    公开(公告)日:1993-09-07

    申请号:US787669

    申请日:1991-11-04

    摘要: Disclosed is a method and a family of materials useful for removing immune complexes from blood preferentially to soluble antibodies. The material comprises analogs of proteins which bind to the Fc region of immunoglobulin. The analogs are produced by truncating or otherwise altering the amino acid sequence of the binding protein to reduce their affinity for Fc. An array of such analogs disposed about the surface of an insoluble matrix has the ability to form multiple points of attachment to the multiple Fc's in a complex so as to bind complex strongly, whereas only weak associations are developed between the Fc region of soluble IgG and individual analogs. The preferred analogs are truncated proteins homologous to a portion of the domains of Protein A or Protein G which bind with Fc. Complex may be removed from whole blood or serum using the material and conventional plasmapheresis techniques.

    摘要翻译: 公开了一种用于从血液中将免疫复合物优先地去除可溶性抗体的方法和一系列材料。 该材料包含与免疫球蛋白Fc区结合的蛋白质的类似物。 类似物通过截短或以其它方式改变结合蛋白的氨基酸序列来降低它们对Fc的亲和力而产生。 在不溶性基质的表面附近设置的这种类似物的阵列具有在复合物中形成与多个Fc的多个连接点的能力,以便强烈地结合复合物,而仅在可溶性IgG的Fc区和 个别类似物。 优选的类似物是与蛋白A或蛋白G的结合部分与Fc结合的截短的蛋白质。 可以使用材料和常规的血浆置换技术从全血或血清中除去复合物。

    Biosynthetic antibody binding sites
    5.
    发明授权
    Biosynthetic antibody binding sites 失效
    生物合成抗体结合位点

    公开(公告)号:US5091513A

    公开(公告)日:1992-02-25

    申请号:US636765

    申请日:1991-01-02

    IPC分类号: C07K16/00 C07K16/46 C12N15/62

    摘要: Disclosed are a family of synthetic proteins having affinity for a preselected antigen. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise 1) non-covalently associated or disulfide bonded synthetic V.sub.H and V.sub.L dimers, 2) V.sub.H -V.sub.L or V.sub.L -V.sub.H single chains wherein the V.sub.H and V.sub.L are attached by a polypeptide linker, or 3) individuals V.sub.H or V.sub.L domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function e.g., as an enzyme, toxin, binding site, or site of attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, and for producing analogs thereof.

    摘要翻译: 公开了对预选抗原具有亲和力的合成蛋白家族。 蛋白质的特征在于构成表现为生物合成抗体结合位点(BABS)的区域的一个或多个氨基酸序列。 所述位点包括1)非共价缔合或二硫键合的合成的VH和VL二聚体,2)VH-VL或VL-VH单链,其中VH和VL通过多肽接头连接,或3)个体VH或VL结构域。 结合域包含连接的CDR和FR区,其可以衍生自单独的免疫球蛋白。 蛋白质还可以包括其它多肽序列,其例如作为酶,毒素,结合位点或与固定化介质或放射性原子的连接位点起作用。 公开了用于生产蛋白质的方法,用于设计具有可通过体内产生抗体引发的任何特异性的BABS和用于制备其类似物的方法。

    Polypeptide linkers for production of biosynthetic proteins
    7.
    发明授权
    Polypeptide linkers for production of biosynthetic proteins 失效
    用于生物合成蛋白质的多肽接头

    公开(公告)号:US5482858A

    公开(公告)日:1996-01-09

    申请号:US139171

    申请日:1993-10-19

    摘要: Disclosed are a family of synthetic proteins having binding affinity for a preselected antigen, and multifunctional proteins having such affinity. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS). The sites comprise V.sub.H -V.sub.L or V.sub.L -V.sub.H -like single chains wherein the V.sub.H and V.sub.L -like sequences are attached by a polypeptide linker, or individual V.sub.H or V.sub.L -like domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site for attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody, for producing analogs thereof, and for producing multifunctional synthetic proteins which are self-targeted by virtue of their binding site region.

    摘要翻译: 公开了对预选抗原具有结合亲和力的合成蛋白质家族,以及具有这种亲和力的多功能蛋白质。 蛋白质的特征在于构成表现为生物合成抗体结合位点(BABS)的区域的一个或多个氨基酸序列。 所述位点包含VH-VL或VL-VH样单链,其中VH和VL样序列通过多肽接头或单独的VH或VL样结构域连接。 结合域包含连接的CDR和FR区,其可以衍生自单独的免疫球蛋白。 蛋白质还可以包括其它多肽序列,其功能例如作为酶,毒素,结合位点或用于附着到固定化介质或放射性原子的位点。 公开了用于制备蛋白质的方法,用于设计具有可通过体内产生抗体引起的任何特异性的BABS,用于产生其类似物,以及用于生产通过其结合位点区域自身靶向的多功能合成蛋白质。

    Serine-rich peptide linkers
    9.
    发明授权
    Serine-rich peptide linkers 失效
    富含丝氨酸的肽接头

    公开(公告)号:US5525491A

    公开(公告)日:1996-06-11

    申请号:US257341

    申请日:1994-06-09

    IPC分类号: C07K16/00 C12N15/62 C07K16/46

    摘要: Disclosed are serine-rich peptide linkers for linking two or more protein domains to form a fused protein. The peptide linkers contains at least 40% serine residues and preferably have the formula (Ser, Ser,Ser,Ser,Gly).sub.y where y is .gtoreq.1. The resulting fused domains are biologically active together or individually, have improved solubility in physiological media, and improved resistance to proteolysis.

    摘要翻译: 公开了用于连接两个或多个蛋白质结构域以形成融合蛋白的丝氨酸丰富的肽接头。 肽接头含有至少40%的丝氨酸残基,并且优选具有式(Ser,Ser,Ser,Ser,Gly)y,其中y为≥1。 所得的融合结构域在一起或单独地具有生物活性,在生理介质中具有改善的溶解性,并且改善了对蛋白水解的抵抗力。

    Polypeptide linkers for production of biosynthetic proteins
    10.
    发明授权
    Polypeptide linkers for production of biosynthetic proteins 失效
    用于生物合成蛋白质的多肽接头

    公开(公告)号:US5258498A

    公开(公告)日:1993-11-02

    申请号:US955399

    申请日:1992-10-01

    摘要: Disclosed are a family of synthetic proteins having binding affinity for a preselected antigen, and multifunctional proteins having such affinity. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS) The sites comprise V.sub.H -V.sub.L or V.sub.L -V.sub.H -like single chains wherein the V.sub.H and V.sub.L -like sequences are attached by a polypeptide linker, or individual V.sub.H or V.sub.L -like domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site for attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody for producing analogs thereof, and for producing multifunctional synthetic proteins which are self-targeted by virtue of their binding site region.

    摘要翻译: PCT No.PCT / US88 / 01737 Sec。 371日期1989年1月23日 102(e)日期1989年1月23日PCT提交1988年5月19日PCT公布。 出版物WO88 / 09344 日期为1988年12月1日。公开是对预选抗原具有结合亲和力的合成蛋白家族,以及具有这种亲和力的多功能蛋白质。 蛋白质的特征在于构成表现为生物合成抗体结合位点(BABS)的区域的一个或多个氨基酸序列。位点包含VH和VL-样的单链,其中VH和VL样序列被连接 通过多肽接头,或单独的VH或VL样结构域。 结合域包含连接的CDR和FR区,其可以衍生自单独的免疫球蛋白。 蛋白质还可以包括其它多肽序列,其功能例如作为酶,毒素,结合位点或用于附着到固定化介质或放射性原子的位点。 公开了用于制备蛋白质的方法,用于设计具有可通过体内产生抗体产生其类似物的任何特异性的BABS,以及用于生产通过其结合位点区域自身靶向的多功能合成蛋白质。