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    ROR1-BINDING MOLECULES, AND METHODS OF USE THEREOF
    1.
    发明申请
    ROR1-BINDING MOLECULES, AND METHODS OF USE THEREOF 审中-公开
    ROR1结合分子及其使用方法

    公开(公告)号：WO2017142928A1

    公开(公告)日：2017-08-24

    申请号：PCT/US2017/017939

    申请日：2017-02-15

    申请人： MACROGENICS, INC.

    发明人： BARAT, Bhaswati ,  JOHNSON, Leslie, S. ,  MOORE, Paul, A. ,  ALDERSON, Ralph, Froman ,  BONVINI, Ezio

    IPC分类号： C07K16/28

    CPC分类号： C07K16/28 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/2815 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/92

    摘要： The present invention is directed to optimized ROR1-binding molecules having enhanced affinity and superior ability to mediate redirected cytotoxicity of tumor cells relative to prior ROR1-binding molecules. More specifically, the invention relates to optimized ROR1-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been optimized for binding to an epitope present on the human ROR1 polypeptide so as to exhibit enhanced binding affinity for human ROR1 and/or a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific ROR1-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such optimized ROR1-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such ROR1-binding molecules, and to methods involving the use of any of such ROR1-binding molecules in the treatment of cancer and other diseases and conditions.

    摘要翻译： 本发明涉及与先前的ROR1结合分子相比具有增强的亲和力和优异的介导肿瘤细胞的重定向细胞毒性的能力的优化的ROR1结合分子。 更具体地说，本发明涉及包含可变轻链和/或可变重链（VH）结构域的优化的ROR1结合分子，所述可变轻链和/或可变重链（VH）结构域已经被优化用于结合存在于人ROR1多肽上的表位， 人类ROR1和/或在给予受体对象时降低的免疫原性。 本发明尤其涉及双特异性，三特异性或多特异性ROR1结合分子，包括双特异性双抗体，BiTE，双特异性抗体，三价结合分子等，其包含：（i）此类优化的ROR1结合可变结构域和（ii） 与存在于效应细胞表面上的分子的表位结合。 本发明还涉及含有任何此类ROR1结合分子的药物组合物，并且涉及涉及使用任何此类ROR1结合分子治疗癌症和其他疾病和病症的方法。

    VARIANT CD3-BINDING DOMAINS AND THEIR USE IN COMBINATION THERAPIES FOR THE TREATMENT OF DISEASE
    3.
    发明申请
    VARIANT CD3-BINDING DOMAINS AND THEIR USE IN COMBINATION THERAPIES FOR THE TREATMENT OF DISEASE 审中-公开

    公开(公告)号：WO2019160904A1

    公开(公告)日：2019-08-22

    申请号：PCT/US2019/017772

    申请日：2019-02-13

    申请人： MACROGENICS, INC.

    发明人： BONVINI, Ezio ,  HUANG, Ling ,  LAM, Chia-Ying, Kao ,  CHICHILI, Gurunadh, Reddy ,  ALDERSON, Ralph, Froman ,  MOORE, Paul, A. ,  JOHNSON, Leslie, S.

    IPC分类号： A61K39/395 ,  C07K16/28 ,  C07K16/30 ,  C07K16/32 ,  C07K16/44

    摘要： The present invention is directed to DA x CD3 Binding Molecules comprising a vCD3- Binding Domain, which comprises a CDRHI Domain, a CDRH2 Domain, a CDRH3 Domain, a CDRL I Domain, a CDRL2 Domain, and a CDRL3 Domain, at least one of which differs in amino acid sequence from the amino acid sequence of the corresponding CDR of a rCD3- Binding Domain, wherein the DA x CD3 Binding Molecule comprising such vCD3-Binding Domain exhibits an altered affinity for CD3, relative to a DA x CD3 Binding Molecule comprising such rCD3-Binding Domain. The invention particularly concerns to such DA x CD3 Binding Molecules comprising a vCD3-Binding Domain which exhibit reduced affinity for CD3 and are capable of mediating redirected killing of target cells expressing a DA and exhibit lower levels of cytokine release relative to a DA x CD3 Binding Molecule comprising a rCD3-Binding Domain. The invention particularly concerns the use of DA x CD3 Binding Molecules comprising a vCD3 -Binding Domain in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).