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314 条记录 (耗时 0.047 秒)

    Structural variants of antibodies for improved therapeutic characteristics
    61.
    发明授权
    Structural variants of antibodies for improved therapeutic characteristics 有权
    用于改善治疗特征的抗体的结构变体

    公开(公告)号：US07919273B2

    公开(公告)日：2011-04-05

    申请号：US12506992

    申请日：2009-07-21

    申请人： David M. Goldenberg ,  Chien-Hsing Chang ,  Hans J. Hansen

    发明人： David M. Goldenberg ,  Chien-Hsing Chang ,  Hans J. Hansen

    IPC分类号： C12P21/04 ,  C12N7/00 ,  A61K39/395 ,  C12P21/08 ,  C07K16/00

    CPC分类号： C07K16/2887 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/732 ,  C07K2317/734

    摘要： The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, more preferably 50 mg or less, most preferably 30 mg or less of naked antibody when administered i.v. or s.c.

    摘要翻译： 本发明提供取代的人源化，嵌合或人抗CD20抗体或其抗原结合片段和包含取代的抗体或其抗原结合片段的双特异性抗体或融合蛋白。 抗体，融合蛋白或片段可用于治疗B细胞病变，如B细胞恶性肿瘤和自身免疫性疾病，以及GVHD，器官移植排斥，溶血性贫血和冷球蛋白血症。 氨基酸取代，特别是取代CDR3 VH（CDRH3）Kabat 101位天冬氨酸残基导致改善的治疗性质，例如降低的解离速率，改善的CDC活性，改善的细胞凋亡，改善的B细胞消耗和改善的治疗功效 非常低的剂量 Veltuzumab是与不同CDRH3序列的相似抗体相比具有改善的治疗效果的，具有这种序列变异性的人源化抗-CD20抗体，其能够以低至200mg或更低，更优选为100mg或更少，更优选为80mg mg或更少，更优选50mg或更少，最优选30mg或更少的裸抗体 或s.c.

    Anti-CD74 immunoconjugates and methods of use
    67.
    发明授权
    Anti-CD74 immunoconjugates and methods of use 有权
    抗CD74免疫缀合物及其使用方法

    公开(公告)号：US08367037B2

    公开(公告)日：2013-02-05

    申请号：US13347934

    申请日：2012-01-11

    申请人： John C. Byrd ,  David M. Goldenberg ,  Hans J. Hansen

    发明人： John C. Byrd ,  David M. Goldenberg ,  Hans J. Hansen

    IPC分类号： A61K51/00 ,  C07K16/00

    CPC分类号： A61K47/48823 ,  A61K39/395 ,  A61K47/6907 ,  A61K47/6913 ,  A61K51/1234 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2896 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/73 ,  G01N33/574 ,  G01N2333/70596 ,  G01N2800/245 ,  A61K2300/00

    摘要： Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

    摘要翻译： 公开了包含抗CD74免疫偶联物和任选的治疗和/或诊断剂的组合物。 在优选的实施方案中，免疫偶联物包含缀合至脂质体或胶束的一种或多种抗CD74抗体或其抗原结合片段。 还公开了在诊断和治疗过程中制备免疫缀合物和使用免疫缀合物的方法。 在某些优选实施方案中，治疗方法包括向具有表达CD74的疾病的受试者施用抗CD74免疫偶联物，从而诱导表达CD74的细胞的凋亡。 在更优选的实施方案中，CD74免疫缀合物能够在不存在任何其它治疗剂的情况下诱导细胞死亡，尽管可以任选地在施用抗CD74免疫缀合物之前，之后或之后施用这些试剂。 组合物可以是用于施用抗CD74免疫缀合物或组合物的试剂盒的一部分。