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    Methods of synthesizing heteromultimeric polypeptides in yeast using a haploid mating strategy
    1.
    发明申请
    Methods of synthesizing heteromultimeric polypeptides in yeast using a haploid mating strategy 有权
    使用单倍体交配策略在酵母中合成异源多聚体多肽的方法

    公开(公告)号：US20110183402A1

    公开(公告)日：2011-07-28

    申请号：US13070583

    申请日：2011-03-24

    申请人： JAMES M. CREGG ,  JOHN LATHAM ,  MARK LITTON ,  RANDALL SCHATZMAN ,  IIYA I. TOLSTORUKOV

    发明人： JAMES M. CREGG ,  JOHN LATHAM ,  MARK LITTON ,  RANDALL SCHATZMAN ,  IIYA I. TOLSTORUKOV

    IPC分类号： C12N1/19

    CPC分类号： C07K16/2896 ,  C07K16/00 ,  C07K16/18 ,  C07K16/2809 ,  C07K2317/24 ,  C12N15/81 ,  C12N15/815

    摘要： Methods are provided for the synthesis and secretion of recombinant proteins preferably large mammalian proteins or hetero-multimeric proteins at high levels and for prolonged time in polyploid, preferably diploid yeast. These methods use various mating competent yeast, including Pichia. In a preferred embodiment, a first expression vector is transformed into a first haploid cell; and a second expression vector is transformed into a second haploid cell. The transformed haploid cells, each individually synthesizing a non-identical polypeptide, are identified and then genetically crossed or fused. The resulting diploid strains are utilized to produce and secrete fully assembled and biologically functional hetero-multimeric protein.

    摘要翻译： 提供了用于在多倍体，优选二倍体酵母中以高水平合成和分泌重组蛋白，优选大量哺乳动物蛋白或杂多聚体蛋白并延长时间的方法。 这些方法使用各种交配的感受态酵母，包括毕赤酵母。 在优选的实施方案中，将第一表达载体转化为第一单倍体细胞; 并将第二表达载体转化成第二单倍体细胞。 鉴定转化的单倍体细胞，每个细胞各自合成不相同的多肽，然后遗传交叉或融合。 所得的二倍体菌株用于产生和分泌完全组装和生物功能的杂多聚体蛋白。

    ANTIBODIES TO IL-6 AND USE THEREOF
    3.
    发明申请
    ANTIBODIES TO IL-6 AND USE THEREOF 有权
    抗IL-6的抗体及其用途

    公开(公告)号：US20130034554A1

    公开(公告)日：2013-02-07

    申请号：US13511865

    申请日：2010-11-24

    申请人： Leon F. Garcia-Martinez ,  Anne Elisabeth Carvalho Jensen ,  Katie Olson ,  Benjamin H. Dutzar ,  John A. Latham ,  Brian Robert Kovacevich ,  Jeffrey T.L. Smith ,  Mark Litton ,  Randall Schatzman

    发明人： Leon F. Garcia-Martinez ,  Anne Elisabeth Carvalho Jensen ,  Katie Olson ,  Benjamin H. Dutzar ,  John A. Latham ,  Brian Robert Kovacevich ,  Jeffrey T.L. Smith ,  Mark Litton ,  Randall Schatzman

    IPC分类号： A61K39/395 ,  A61P37/06 ,  C12N5/071 ,  A61P35/00 ,  A61P1/04 ,  A61P35/04 ,  A61P29/00 ,  A61P35/02

    CPC分类号： A61K51/1033 ,  A61K49/0004 ,  A61K49/0058 ,  A61K2039/505 ,  C07K16/248 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/6863 ,  Y02A50/412 ,  Y02A50/58

    摘要： The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others. Additional preferred embodiments of the subject invention relate to therapeutic compositions and methods treating or preventing rheumatoid arthritis, especially subcutaneous and intravenous formulations and dosage regimens using IL-6 antagonists according to the invention, as well as methods for preventing or treating GVHD or leukemia relapse in subjects receiving transplanted cells, tissue or organs, use thereof in the treatment or prevention of mucositis, and use thereof to potentiate the cytotoxic, apoptotic, and anti-metastatic or anti-invasive effects of chemotherapeutics and radiation on cancers, especially cancers that have developed a resistance to radiation or chemotherapy, such as an EGFR inhibitor.

    摘要翻译： 本发明涉及使用IL-6拮抗剂例如Ab1抗体或对IL-6具有结合特异性的抗体片段来预防或治疗疾病或改善有需要的患者的生存能力或生活质量的治疗方法。 在优选实施方案中，这些患者将包括显示（或有发展风险）升高的血清C-反应蛋白水平，降低的血清白蛋白水平，升高的D-二聚体或其他凝血级联相关蛋白，恶病质，发热，虚弱和 /或治疗前的疲劳。 主题疗法还可以包括施用其它活性物质，例如化学治疗剂，抗凝血剂，他汀类药物等。 本发明的另外的优选实施方案涉及使用根据本发明的IL-6拮抗剂治疗或预防类风湿性关节炎，特别是皮下和静脉内制剂和剂量方案的治疗组合物和方法，以及用于预防或治疗GVHD或白血病复发的方法 接受移植细胞，组织或器官的受试者在治疗或预防粘膜炎中的用途及其用途来增强化学治疗剂和辐射对癌症尤其是已经发展的癌症的细胞毒性，凋亡和抗转移或抗侵袭作用 抗辐射或化学疗法，如EGFR抑制剂。

    Methods of synthesizing heteromultimeric polypeptides in yeast using a haploid mating strategy
    9.
    发明申请
    Methods of synthesizing heteromultimeric polypeptides in yeast using a haploid mating strategy 有权
    使用单倍体交配策略在酵母中合成异源多聚体多肽的方法

    公开(公告)号：US20060270045A1

    公开(公告)日：2006-11-30

    申请号：US11429053

    申请日：2006-05-08

    申请人： James Cregg ,  John Latham ,  Mark Litton ,  Randall Schatzman ,  Ilya Tolstorukov

    发明人： James Cregg ,  John Latham ,  Mark Litton ,  Randall Schatzman ,  Ilya Tolstorukov

    IPC分类号： C12N1/18 ,  C12N15/74

    CPC分类号： C07K16/2896 ,  C07K16/00 ,  C07K16/18 ,  C07K16/2809 ,  C07K2317/24 ,  C12N15/81 ,  C12N15/815

    摘要： Methods are provided for the synthesis and secretion of recombinant proteins preferably large mammalian proteins or hetero-multimeric proteins at high levels and for prolonged time in polyploid, preferably diploid yeast. These methods use various mating competent yeast, including Pichia. In a preferred embodiment, a first expression vector is transformed into a first haploid cell; and a second expression vector is transformed into a second haploid cell. The transformed haploid cells, each individually synthesizing a non-identical polypeptide, are identified and then genetically crossed or fused. The resulting diploid strains are utilized to produce and secrete fully assembled and biologically functional hetero-multimeric protein.

    摘要翻译： 提供了用于在多倍体，优选二倍体酵母中以高水平合成和分泌重组蛋白，优选大量哺乳动物蛋白或杂多聚体蛋白并延长时间的方法。 这些方法使用各种交配的感受态酵母，包括毕赤酵母。 在优选的实施方案中，将第一表达载体转化为第一单倍体细胞; 并将第二表达载体转化成第二单倍体细胞。 鉴定转化的单倍体细胞，每个细胞各自合成不相同的多肽，然后遗传交叉或融合。 所得的二倍体菌株用于产生和分泌完全组装和生物功能的杂多聚体蛋白。