Variants of humanized anti carcinoma monoclonal antibody cc49
    82.
    发明授权
    Variants of humanized anti carcinoma monoclonal antibody cc49 有权
    人源化抗癌单克隆抗体cc49的变体

    公开(公告)号:US06818749B1

    公开(公告)日:2004-11-16

    申请号:US09830748

    申请日:2001-04-30

    IPC分类号: C07K1600

    摘要: The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.

    摘要翻译: 本发明针对具有最小鼠含量的CC49单克隆抗体的小鼠 - 人嵌合变体。 本发明的第一方面提供了存在CC49的全部六(三个重链和三个轻链)互补决定区(CDR)的人源化单克隆抗体(HuCC49)的CDR变体。 本发明的第二方面提供了仅存在来自CC49的至少一个CDR的特异性确定区(SDR)的人源化单克隆抗体(HuCC49)的SDR变体。 本发明还涉及制备使用变体的变体和治疗方法的生物技术方法。

    Family of high affinity, modified antibodies for cancer treatment
    84.
    发明授权
    Family of high affinity, modified antibodies for cancer treatment 失效
    高亲和力家族,用于癌症治疗的修饰抗体

    公开(公告)号:US06207815B1

    公开(公告)日:2001-03-27

    申请号:US08479285

    申请日:1995-06-07

    IPC分类号: C12N1514

    摘要: This invention concerns a family of chimeric antibodies with high affinities to a high molecular weight, tumor-associated sialylated glycoprotein antigen (TAG-72) of human origin. These antibodies have (1) high affinity animal VH and VL sequences which mediate TAG-72 binding and (2) human CH and CL regions. They are thought to produce significantly fewer side-effects when administered to human patients by virtue of their human CH and CL antibody domains. The nucleotide and amino acid sequences of VH&agr;TAG VH, CC46 VH, CC49H, CC83 VH, and CC92 VH, and CC49L, CC83 VL, and CC92 VL idiotype sequences are disclosed, as well as in vivo methods of treatment and diagnostic assay using these chimeric antibodies.

    摘要翻译: 本发明涉及对人类高分子量肿瘤相关唾液酸化糖蛋白抗原(TAG-72)具有高亲和力的嵌合抗体家族。 这些抗体具有(1)介导TAG-72结合的高亲和力动物VH和VL序列,(2)人CH和CL区。 据认为,由于其人类CH和CL抗体结构域,当向人类患者施用时,它们会产生显着较少的副作用。 公开了VHαphaVV,CC46VH,CC49H,CC83VV和CC92VV,CC49L,CC83VL和CC92VV独立型序列的核苷酸和氨基酸序列,以及使用这些嵌合体的体内治疗和诊断测定方法 抗体。

    Production of a single-gene-encoded immunoglobulin
    87.
    发明授权
    Production of a single-gene-encoded immunoglobulin 失效
    生产单基因编码的免疫球蛋白

    公开(公告)号:US5892019A

    公开(公告)日:1999-04-06

    申请号:US299999

    申请日:1994-09-01

    摘要: Construction of a single gene encoding a signal-chain immunoglobulin-like molecule is described. This single-gene approach circumvents inefficiencies inherent in delivering two genes into a mammalian cell and in the assembly of a functional immunoglobulin molecule. It also facilitates ex vivo transfection of cells for gene-therapy protocols. The single-chain protein comprises the heavy- and light-chain variable (V.sub.H and V.sub.L) domains of a monoclonal antibody covalently joined through a short linker peptide, while the carboxyl end of a V domain is linked to the amino terminus of a human constant region such as .gamma.1 Fc, through the hinge region. The single-chain protein assembles into a dimeric molecule of .apprxeq.120 kDa and is secreted into the culture fluid. The single-chain immunoglobulin-like protein shows similar antigen binding affinity to that of chimeric or parental antibody and mediates ADCC. This single-gene construct approach provides a way of generating an immunoglobulin-like molecule which retains the specificity, binding properties, and cytolytic activity of a parental monoclonal antibody, and thus is a useful therapeutic and diagnostic reagent against a range of antigens, such as human carcinomas.

    摘要翻译: 描述编码信号链免疫球蛋白样分子的单个基因的构建。 这种单基因方法规避了将两个基因递送到哺乳动物细胞中以及在功能性免疫球蛋白分子的组装中固有的低效率。 它还有助于体外转染细胞用于基因治疗方案。 单链蛋白质包含通过短接头肽共价连接的单克隆抗体的重链和轻链可变(VH和VL)结构域,而V结构域的羧基末端连接到人类常数的氨基末端 区域,如γ1 Fc,通过铰链区。 单链蛋白质组装成约120kDa的二聚体分子,并分泌到培养液中。 单链免疫球蛋白样蛋白显示出与嵌合抗体或亲本抗体相似的抗原结合亲和力并介导ADCC。 该单基因构建方法提供了产生免疫球蛋白样分子的方法,其保留亲本单克隆抗体的特异性,结合特性和溶细胞活性,因此是针对一系列抗原的有用的治疗和诊断试剂,例如 人类癌。

    Monoclonal antibodies reactive with human breast cancer
    90.
    发明授权
    Monoclonal antibodies reactive with human breast cancer 失效
    与人乳腺癌反应的单克隆抗体

    公开(公告)号:US4612282A

    公开(公告)日:1986-09-16

    申请号:US707400

    申请日:1985-03-01

    摘要: Monoclonal antibodies demonstrating a reactivity with human breast cancer are produced. The hybridoma cultures secreting immunoglobins are produced by hydridoma technology. Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissue are fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. Screening of immunoglobulin reactivities and double cloning of cultures yielded 11 monoclonal antibodies that demonstrated activities with the surface of human mammary tumor cells and not with the surface of apparently normal human tissues. These monoclonal antibodies aid in the diagnosis, prognosis and treatment of human breast cancer.

    摘要翻译: 产生显示与人乳腺癌反应性的单克隆抗体。 分泌免疫球蛋白的杂交瘤培养物是通过胶体技术产生的。 用转移性人乳腺癌组织的膜富集部分免疫的小鼠的脾淋巴细胞与NS-1非免疫球蛋白分泌的小鼠骨髓瘤细胞系融合。 免疫球蛋白反应性的筛选和双克隆培养物产生了11种单克隆抗体,其表现出与人乳腺肿瘤细胞表面的活性,而不是表面上正常人组织的表面。 这些单克隆抗体有助于人乳腺癌的诊断,预后和治疗。