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    Anti-CD38 antibodies for the treatment of cancer
    1.
    发明授权
    Anti-CD38 antibodies for the treatment of cancer 有权
    抗CD38抗体治疗癌症

    公开(公告)号：US08153765B2

    公开(公告)日：2012-04-10

    申请号：US12441466

    申请日：2007-10-16

    申请人： Peter U. Park ,  Laura M. Bartle ,  Anna Skaletskaya ,  Viktor Golmakher ,  Daniel Tavares ,  Jutta Deckert ,  Vincent Mikol ,  Veronique Blanc

    发明人： Peter U. Park ,  Laura M. Bartle ,  Anna Skaletskaya ,  Viktor Golmakher ,  Daniel Tavares ,  Jutta Deckert ,  Vincent Mikol ,  Veronique Blanc

    IPC分类号： C12P21/08

    CPC分类号： G01N33/57426 ,  A61K47/6803 ,  A61K47/6867 ,  A61K2039/505 ,  C07K16/2896 ,  C07K16/462 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  G01N33/57484 ,  G01N2333/924

    摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38+ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

    摘要翻译： 与CD38特异性结合的抗体，人源化抗体，表面抗体，抗体片段，衍生化抗体和与细胞毒性剂的缀合物能够通过细胞凋亡，抗体依赖性细胞介导的细胞毒性（ADCC）和/ 或补体依赖性细胞毒性（CDC）。 所述抗体及其片段可用于治疗表达CD38蛋白的肿瘤，例如多发性骨髓瘤，慢性淋巴细胞性白血病，慢性骨髓性白血病，急性骨髓性白血病或急性淋巴细胞白血病，或治疗自身免疫性和炎性疾病如 系统性红斑狼疮，类风湿关节炎，多发性硬化症，红斑狼疮和哮喘。 所述衍生化抗体可用于表达CD38水平升高的肿瘤的诊断和成像。 还提供了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含缀合物的治疗组合物，用于抑制细胞生长和治疗疾病的方法以及包含细胞毒性缀合物的试剂盒。 特别地，细胞结合剂是识别并结合CD38蛋白的单克隆抗体及其表位结合片段。

    NOVEL ANTI-CD38 ANTIBODIES FOR THE TREATMENT OF CANCER
    2.
    发明申请
    NOVEL ANTI-CD38 ANTIBODIES FOR THE TREATMENT OF CANCER 有权
    用于治疗癌症的新型抗CD38抗体

    公开(公告)号：US20090304710A1

    公开(公告)日：2009-12-10

    申请号：US12441466

    申请日：2007-10-16

    申请人： Peter U. Park ,  Laura M. Bartle ,  Anna Skaletskaya ,  Viktor Golmakher ,  Daniel Tavares ,  Jutta Deckert ,  Vincent Mikol ,  Veronique Blanc

    发明人： Peter U. Park ,  Laura M. Bartle ,  Anna Skaletskaya ,  Viktor Golmakher ,  Daniel Tavares ,  Jutta Deckert ,  Vincent Mikol ,  Veronique Blanc

    IPC分类号： A61K39/395 ,  C07K16/28 ,  A61P35/00 ,  G01N33/53 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10

    CPC分类号： G01N33/57426 ,  A61K47/6803 ,  A61K47/6867 ,  A61K2039/505 ,  C07K16/2896 ,  C07K16/462 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  G01N33/57484 ,  G01N2333/924

    摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38+ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

    摘要翻译： 与CD38特异性结合的抗体，人源化抗体，表面抗体，抗体片段，衍生化抗体和与细胞毒性剂的缀合物能够通过细胞凋亡，抗体依赖性细胞介导的细胞毒性（ADCC）和/ 或补体依赖性细胞毒性（CDC）。 所述抗体及其片段可用于治疗表达CD38蛋白的肿瘤，例如多发性骨髓瘤，慢性淋巴细胞性白血病，慢性骨髓性白血病，急性骨髓性白血病或急性淋巴细胞白血病，或治疗自身免疫性和炎性疾病如 系统性红斑狼疮，类风湿关节炎，多发性硬化症，红斑狼疮和哮喘。 所述衍生化抗体可用于表达CD38水平升高的肿瘤的诊断和成像。 还提供了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含缀合物的治疗组合物，用于抑制细胞生长和治疗疾病的方法以及包含细胞毒性缀合物的试剂盒。 特别地，细胞结合剂是识别并结合CD38蛋白的单克隆抗体及其表位结合片段。

    CD20 antibodies and uses thereof
    6.
    发明授权
    CD20 antibodies and uses thereof 有权
    CD20抗体及其用途

    公开(公告)号：US09173961B2

    公开(公告)日：2015-11-03

    申请号：US13024556

    申请日：2011-02-10

    申请人： Jutta Deckert ,  Lingyun Rui ,  Peter U. Park

    发明人： Jutta Deckert ,  Lingyun Rui ,  Peter U. Park

    IPC分类号： A61K39/395 ,  C07K16/28 ,  C07K16/30 ,  A61K47/48 ,  G01N33/574 ,  A61K51/10 ,  A61K39/00

    CPC分类号： C07K16/2887 ,  A61K39/39541 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6849 ,  A61K51/1027 ,  A61K2039/505 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/55 ,  C12N2501/48 ,  G01N33/57426

    摘要： CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). The present invention includes anti-CD20 antibodies and antigen-binding fragments thereof comprising a light chain variable region and a heavy chain variable region, wherein the CDR-L1, CDR-L2, and CDR-L3 of said light chain variable region comprise the amino acid sequences of SEQ ID NOs: 17-19, respectively, and wherein the CDR-H1, CDR-H2, and CDR-H3 of said heavy chain variable region comprise the amino acid sequences of SEQ ID NOs: 20-22, respectively.

    摘要翻译： CD20是来自外周血和淋巴组织的B细胞表面上表达的四跨连锁蛋白家族的跨膜蛋白。 CD20表达从早期B细胞前期持续到血浆细胞分化阶段。 除了在正常B细胞​​中表达外，CD20在B细胞衍生的恶性肿瘤如非霍奇金淋巴瘤（NHL）和B细胞慢性淋巴细胞白血病（CLL）中表达。 本发明包括抗CD20抗体及其包含轻链可变区和重链可变区的抗原结合片段，其中所述轻链可变区的CDR-L1，CDR-L2和CDR-L3包含氨基 分别为SEQ ID NO：17-19的酸序列，并且其中所述重链可变区的CDR-H1，CDR-H2和CDR-H3分别包含SEQ ID NO：20-22的氨基酸序列。

    CD20 antibodies and uses thereof
    7.
    发明授权
    CD20 antibodies and uses thereof 有权
    CD20抗体及其用途

    公开(公告)号：US09175086B2

    公开(公告)日：2015-11-03

    申请号：US13024671

    申请日：2011-02-10

    申请人： Jutta Deckert ,  Daniel J. Tavares ,  Peter U. Park

    发明人： Jutta Deckert ,  Daniel J. Tavares ,  Peter U. Park

    IPC分类号： A61K39/395 ,  C07K16/28 ,  C07K16/30 ,  A61K47/48 ,  A61K51/10 ,  G01N33/574 ,  A61K39/00

    CPC分类号： C07K16/2887 ,  A61K39/39541 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6849 ,  A61K51/1027 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C07K2319/55 ,  G01N33/57426

    摘要： CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). The present invention includes anti-CD20 antibodies and antigen-binding fragments thereof comprising a light chain variable region and a heavy chain variable region, wherein the CDR-L1, CDR-L2, and CDR-L3 of said light chain variable region comprise the amino acid sequences of SEQ ID NOs: 23-25, respectively, and wherein the CDR-H1, CDR-H2, and CDR-H3 of said heavy chain variable region comprise the amino acid sequences of SEQ ID NOs: 26-28, respectively.

    摘要翻译： CD20是来自外周血和淋巴组织的B细胞表面上表达的四跨连锁蛋白家族的跨膜蛋白。 CD20表达从早期B细胞前期持续到血浆细胞分化阶段。 除了在正常B细胞​​中表达外，CD20在B细胞衍生的恶性肿瘤如非霍奇金淋巴瘤（NHL）和B细胞慢性淋巴细胞白血病（CLL）中表达。 本发明包括抗CD20抗体及其包含轻链可变区和重链可变区的抗原结合片段，其中所述轻链可变区的CDR-L1，CDR-L2和CDR-L3包含氨基 分别为SEQ ID NO：23-25的酸序列，并且其中所述重链可变区的CDR-H1，CDR-H2和CDR-H3分别包含SEQ ID NO：26-28的氨基酸序列。

    CD20 ANTIBODIES AND USES THEREOF
    9.
    发明申请
    CD20 ANTIBODIES AND USES THEREOF 有权
    CD20抗体及其用途

    公开(公告)号：US20110195021A1

    公开(公告)日：2011-08-11

    申请号：US13024556

    申请日：2011-02-10

    申请人： Jutta DECKERT ,  Lingyun Rui ,  Peter U. Park

    发明人： Jutta DECKERT ,  Lingyun Rui ,  Peter U. Park

    IPC分类号： A61K51/00 ,  C07K16/00 ,  A61K39/395 ,  A61P35/00 ,  C12N5/02 ,  A61K49/00 ,  C07H21/04 ,  C12N15/63 ,  C12N5/00

    CPC分类号： C07K16/2887 ,  A61K39/39541 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6849 ,  A61K51/1027 ,  A61K2039/505 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/55 ,  C12N2501/48 ,  G01N33/57426

    摘要： CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells and has been found on B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. Conversely, it is not found on hematopoietic stem cells, pro-B cells, differentiated plasma cells or non-lymphoid tissues. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). CD20 expressing cells are known to play a role in other diseases and disorders, including inflammation. The present invention includes anti-CD20 antibodies, forms and fragments, having superior physical and functional properties; immunoconjugates, compositions, diagnostic reagents, methods for inhibiting growth, therapeutic methods, improved antibodies and cell lines; and polynucleotides, vectors and genetic constructs encoding same.

    摘要翻译： CD20是在B细胞表面表达的四跨连锁蛋白家族的跨膜蛋白，并且已经在外周血和淋巴组织的B细胞中发现。 CD20表达从早期B细胞前期持续到血浆细胞分化阶段。 相反，在造血干细胞，前B细胞，分化浆细胞或非淋巴组织中未发现。 除了在正常B细胞​​中表达外，CD20在B细胞衍生的恶性肿瘤如非霍奇金淋巴瘤（NHL）和B细胞慢性淋巴细胞白血病（CLL）中表达。 已知CD20表达细胞在其他疾病和病症中发挥作用，包括炎症。 本发明包括具有优异的物理和功能特性的抗CD20抗体，形式和片段; 免疫缀合物，组合物，诊断试剂，抑制生长的方法，治疗方法，改进的抗体和细胞系; 和编码相同的多核苷酸，载体和遗传构建体。