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    BISPECIFIC ASYMMETRIC HETERODIMERS COMPRISING ANTI-CD3 CONSTRUCTS
    43.
    发明申请
    BISPECIFIC ASYMMETRIC HETERODIMERS COMPRISING ANTI-CD3 CONSTRUCTS 审中-公开
    包含抗CD3构建体的双向不对称穿孔剂

    公开(公告)号：WO2014012085A2

    公开(公告)日：2014-01-16

    申请号：PCT/US2013050411

    申请日：2013-07-13

    申请人： ZYMEWORKS INC

    发明人： DIXIT SURJIT BHIMARAO ,  SPRETER VON KREUDENSTEIN THOMAS ,  NG GORDON YIU KON

    IPC分类号： C07K14/76 ,  C07K16/00

    CPC分类号： C07K16/2809 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/32 ,  C07K2317/31 ,  C07K2317/35 ,  C07K2317/52 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/528 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/31

    摘要： Disclosed herein are isolated multispecific heteromultimer constructs comprising multispecific heteromultimer construct comprising: a first polypeptide construct comprising a first heavy chain polypeptide and a CD3 binding polypeptide construct that binds to a CD3 complex on at least one CD3 expressing cell; a second polypeptide construct comprising a second heavy chain polypeptide which is different from said first heavy chain polypeptide, and an antigen binding polypeptide construct that binds to a target antigen on at least one B cell; wherein: said multispecific heteromultimer construct simultaneously engages said at least one B cell and said at least one CD3 expressing cell such that the CD3 expressing cell is activated, thereby inducing killing of the B cell; and said first and second heavy chain polypeptides form a heterodimeric Fc region comprising a variant immunoglobulin CH3 region comprising at least one amino acid mutation that promotes the formation of said heterodimeric Fc with stability at least comparable to a native homodimeric Fc, and with high purity. Also provided are isolated multispecific heteromultimer construct comprising: a first polypeptide construct comprising a first transporter polypeptide fused to at least one CD3 binding polypeptide construct that binds to a CD3 complex on at least one CD3 expressing cell; a second polypeptide construct comprising a second transporter polypeptide which is different from said first transporter polypeptide, fused to at least one antigen binding polypeptide construct that binds to a target antigen on at least one B cell; wherein said first and second transporter polypeptides are derived from a protein by segmentation of said protein, each transporter polypeptide comprising an amino acid sequence with at least 90% identity to a segment of said protein, and wherein said transporter polypeptides self-assemble to form a quasi-native structure of said monomeric protein.

    摘要翻译： 本文公开了包含多特异性杂多聚体构建体的分离的多特异性异源多聚体构建体，其包含：包含结合至少一种CD3表达细胞上的CD3复合物的第一重链多肽和CD3结合多肽构建体的第一多肽构建体; 包含不同于所述第一重链多肽的第二重链多肽的第二多肽构建体和与至少一个B细胞上的靶抗原结合的抗原结合多肽构建体; 其中：所述多特异性异源多聚体构建体同时与所述至少一个B细胞和所述至少一个CD3表达细胞接合，使得CD3表达细胞被活化，从而诱导B细胞的杀伤; 并且所述第一和第二重链多肽形成包含变异免疫球蛋白CH3区的异二聚体Fc区，所述变体免疫球蛋白CH3区包含至少一个氨基酸突变，其促进所述异二聚体Fc的形成，其稳定性至少与天然同二聚体Fc相当，并具有高纯度。 还提供了分离的多特异性异源多聚体构建体，其包含：第一多肽构建体，其包含与至少一种CD3结合多肽构建体融合的第一转运蛋白多肽，其结合至少一种CD3表达细胞上的CD3复合物; 包含与所述第一转运蛋白多肽不同的第二转运蛋白多肽的第二多肽构建体，其与至少一种与至少一个B细胞上的靶抗原结合的抗原结合多肽构建体融合; 其中所述第一和第二转运蛋白多肽通过所述蛋白质的分割衍生自蛋白质，每个转运蛋白多肽包含与所述蛋白质片段至少90％同一性的氨基酸序列，并且其中所述转运蛋白多肽自组装形成 所述单体蛋白的准本机结构。

    ANTI-CD22 ANTI-IDIOTYPIC ANTIBODIES AND USES THEREOF
    44.
    发明申请
    ANTI-CD22 ANTI-IDIOTYPIC ANTIBODIES AND USES THEREOF 审中-公开
    抗CD22抗体抗体及其用途

    公开(公告)号：WO2013188864A2

    公开(公告)日：2013-12-19

    申请号：PCT/US2013046053

    申请日：2013-06-16

    申请人： SINOMAB BIOSCIENCE LTD ,  LEUNG SHUI-ON

    发明人： LEUNG SHUI-ON

    IPC分类号： G01N33/554

    CPC分类号： G01N33/686 ,  A61K39/39566 ,  A61K39/44 ,  C07K16/2803 ,  C07K16/4258 ,  C07K2317/20 ,  C07K2317/33 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/76 ,  C07K2317/77 ,  G01N2333/705

    摘要： The present invention describes the generation of an anti-idiotype single-chain Fv (scFv) antibody specific for the murine (RFB4), chimeric (SM03) and humanized (SM06) versions of an anti-CD22 antibody (the anti-CD22 antibodies). The present invention further describes the construction of a murine IgG2a/kappa immunoglobulin carrying the variable region sequences of the anti-idiotype scFv sequences. Additionally, the present invention provides a cell line capable of producing an anti-idiotype murine antibody specific for the anti-CD22 antibodies. The present invention is directed against a method for identifying and evaluating the activities and concentration of the anti-CD22 antibodies. Additionally, the present invention provides a method for evaluating serum concentration of the anti-CD22 antibodies that are being used clinically. The present invention is also directed against a method to detect HAMA, HACA and HAHA responses in patients treated with the anti-CD22 antibodies. Specifically, the present invention is directed against the establishment of a cell line expressing surface concentration of the antibody of the invention; the said cell line expressing surface anti-idiotype antibodies or antibody fragments will be used as the target cell line for evaluating the functional activities of the anti-CD22 antibodies via complement dependent cytotoxicity (CDC) and/or antibody dependent cell cytotoxicity (ADCC) activities.

    摘要翻译： 本发明描述了抗CD22抗体（抗CD22抗体）的鼠（RFB4），嵌合（SM03）和人源化（SM06）型特异性的抗独特型单链Fv（scFv）抗体的产生， 。 本发明还描述了携带抗独特型scFv序列的可变区序列的鼠IgG2a /κ免疫球蛋白的构建。 另外，本发明提供能够产生抗CD22抗体特异性的抗独特型鼠抗体的细胞系。 本发明涉及用于鉴定和评估抗CD22抗体的活性和浓度的方法。 此外，本发明提供了用于临床使用的抗CD22抗体的血清浓度的评价方法。 本发明还针对在用抗CD22抗体治疗的患者中检测HAMA，HACA和HAHA应答的方法。 具体地，本发明涉及建立表达本发明抗体的表达浓度的细胞系; 所述表达表面抗独特型抗体或抗体片段的细胞系将用作用于通过补体依赖性细胞毒性（CDC）和/或抗体依赖性细胞毒性（ADCC）活性来评价抗CD22抗体的功能活性的靶细胞系 。

    NOVEL THERAPIES
    46.
    发明申请
    NOVEL THERAPIES 审中-公开
    新的疗法

    公开(公告)号：WO2013104901A3

    公开(公告)日：2013-12-05

    申请号：PCT/GB2013050032

    申请日：2013-01-09

    申请人： OHLIN PER MATS ,  LINDSTEDT MALIN MARIE ,  LEVIN KARL CHRISTIAN MATTIAS ,  SMITH STEPHEN E

    发明人： OHLIN PER MATS ,  LINDSTEDT MALIN MARIE ,  LEVIN KARL CHRISTIAN MATTIAS

    IPC分类号： C12N15/29 ,  A61K39/35 ,  C07K14/435 ,  C12N5/10

    CPC分类号： C07K16/16 ,  A61K39/35 ,  C07K14/415 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2317/64

    摘要： The present invention provides hypoallergenic polypeptides comprising or consisting of a variant of the amino acid sequence of SEQ ID NO: 1 wherein one or more amino acids of SEQ 1 within an IgE-binding epitope is mutated and wherein the polypeptide exhibits reduced IgE-reactivity compared to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 1. The invention further provides pharmaceutical compositions of such polypeptides, as well as methods for making and using said polypeptides, for example in the prevention of pollen grass allergies. Related aspects of the invention provide antibody polypeptides for passive immunisation against pollen grass allergies.

    摘要翻译： 本发明提供了包含或由SEQ ID NO：1的氨基酸序列变体组成的低变应原性多肽，其中IgE结合表位内的SEQ ID 1的一个或多个氨基酸发生突变，并且其中所述多肽表现出比较的IgE反应性降低 涉及由SEQ ID NO：1的氨基酸序列组成的多肽。本发明进一步提供了这些多肽的药物组合物，以及制备和使用所述多肽的方法，例如用于预防花粉草过敏。 本发明的相关方面提供了针对花粉草过敏的被动免疫的抗体多肽。

    SINGLE-ARM MONOVALENT ANTIBODY CONSTRUCTS AND USES THEREOF
    47.
    发明申请
    SINGLE-ARM MONOVALENT ANTIBODY CONSTRUCTS AND USES THEREOF 审中-公开
    单臂单体抗体构建体及其用途

    公开(公告)号：WO2013166604A1

    公开(公告)日：2013-11-14

    申请号：PCT/CA2013/050358

    申请日：2013-05-08

    申请人： ZYMEWORKS INC.

    发明人： NG, Gordon Yiu Kon ,  DIXIT, Surjit Bhimarao ,  SPRETER VON KREUDENSTEIN, Thomas

    IPC分类号： C07K16/28 ,  A61K39/395 ,  A61K47/48 ,  A61P35/00 ,  C07K16/00 ,  C07K16/30 ,  C12N15/13 ,  C12N15/85 ,  C12N5/10 ,  C12P21/08 ,  G01N30/72

    CPC分类号： C07K16/32 ,  A61K39/39558 ,  A61K47/6803 ,  A61K47/6855 ,  A61K2039/505 ,  C07K16/3015 ,  C07K2317/35 ,  C07K2317/41 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94 ,  C12P21/02

    摘要： Provided herein are monovalent antibody constructs. In specific embodiments is a monovalent antibody construct comprising: an antigen-binding polypeptide construct which monovalently binds an antigen; and a dimeric Fc polypeptide construct comprising a CH3 domain, said construct comprising two monomeric Fc polypeptides, wherein one said monomeric Fc polypeptide is fused to at least one polypeptide from the antigen-binding polypeptide construct. These therapeutically novel molecules encompass monovalent constructs that display an increase in binding density and Bmax (maximum binding at a target to antibody ratio of 1:1) to a target cell displaying said antigen as compared to a corresponding monospecific bivalent antibody construct with two antigen binding regions. Provided herein are methods for creation of monovalent antibody constructs that shows superior effector efficacy as compared to the corresponding bivalent antibody construct at equimolar concentrations. Provided herein are methods for creation of monovalent antibody constructs that unexpectedly inhibit tumor cell growth and can be internalized and show greater efficacy compared to a bivalent antibody construct at equimolar saturating concentrations. Provided are monovalent antibody constructs for the treatment of HER2 expressing diseases.

    摘要翻译： 本文提供单价抗体构建体。 在具体实施方案中是单价抗体构建体，其包含：单价结合抗原的抗原结合多肽构建体; 和包含CH3结构域的二聚Fc多肽构建体，所述构建体包含两个单体Fc多肽，其中一个所述单体Fc多肽与来自抗原结合多肽构建体的至少一种多肽融合。 与具有两个抗原结合的相应的单特异性二价抗体构建体相比，这些治疗性新颖的分子包括显示结合密度和Bmax（目标与抗体比1:1的最大结合）与显示所述抗原的靶细胞的增加的单价构建体 区域。 本文提供了用于产生与等摩尔浓度相对于相应的二价抗体构建体相比优异的效应子功效的单价抗体构建体的方法。 本文提供用于产生意想不到地抑制肿瘤细胞生长并且可以内化的单价抗体构建体的方法，并且在等摩尔饱和浓度下与二价抗体构建体相比显示更大的功效。 提供用于治疗HER2表达疾病的单价抗体构建体。

    IMMUNOTHERAPEUTIC MOLECULES AND USES
    48.
    发明申请
    IMMUNOTHERAPEUTIC MOLECULES AND USES 审中-公开
    免疫分子和用途

    公开(公告)号：WO2013128194A1

    公开(公告)日：2013-09-06

    申请号：PCT/GB2013/050499

    申请日：2013-02-28

    申请人： THE UNIVERSITY OF BIRMINGHAM

    发明人： COBBOLD, Mark ,  MILLAR, David

    IPC分类号： A61K47/48 ,  C07K16/28 ,  C07K16/26 ,  C07K16/30

    CPC分类号： C07K16/2896 ,  A61K39/3955 ,  A61K45/06 ,  C07K16/2803 ,  C07K16/2809 ,  C07K2317/30 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/622 ,  C07K2317/64

    摘要： The invention provides molecule comprising: (i) a targeting moiety capable of directly or indirectly targeting to unwanted cells, and (ii) a further moiety that has a masked immune cell binding region so as to prevent binding of the further moiety to an immune cell, wherein the masked immune cell binding region is capable of being selectively unmasked when the molecule is in the vicinity of the unwanted cells so as to allow binding of the further moiety to an immune cell.

    摘要翻译： 本发明提供分子，其包含：（i）能够直接或间接靶向不想要的细胞的靶向部分，和（ii）具有掩蔽的免疫细胞结合区域的另外的部分，以防止另外部分与免疫细胞的结合 其中当所述分子在所述不需要的细胞附近时，所述被掩蔽的免疫细胞结合区域能够选择性地被掩蔽，以便允许另外的部分与免疫细胞的结合。