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    Serpentine transmembrane antigens expressed in human cancers and uses thereof
    3.
    发明授权
    Serpentine transmembrane antigens expressed in human cancers and uses thereof 有权
    在人类癌症中表达的蛇纹石跨膜抗原及其用途

    公开(公告)号：US07455991B2

    公开(公告)日：2008-11-25

    申请号：US10752421

    申请日：2004-01-05

    申请人： Daniel E. H. Afar ,  Rene S. Hubert ,  Arthur B. Raitano ,  Douglas Saffran ,  Steven Chappell Mitchell

    发明人： Daniel E. H. Afar ,  Rene S. Hubert ,  Arthur B. Raitano ,  Douglas Saffran ,  Steven Chappell Mitchell

    IPC分类号： C07H21/02 ,  C12N15/63

    CPC分类号： C07K16/30 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  C07K14/705 ,  C07K14/82 ,  C07K16/3038 ,  C07K16/3069 ,  C07K2317/34 ,  C07K2319/00 ,  C07K2319/30 ,  C12N2799/027 ,  G01N33/57434 ,  Y10S435/975

    摘要： Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed “STEAP” (Six Transmembrane Epithelial Antigen of the Prostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a “serpentine” manner into three extracellular and two intracellular loops. STEAP-1 protein expression is maintained at high levels across various stages of prostate cancer. Moreover, STEAP-1 is highly over-expressed in certain other human cancers.

    摘要翻译： 描述了一种新型的细胞表面蛇纹石跨膜抗原家族。 该家族中的两种蛋白质仅在或主要地在前列腺中表达，并且在前列腺癌中，因此该家族的成员被称为“STEAP”（ Six 上皮 Prostate的抗原。 本文描述和表征了四种特定的人STEAP。 人类STEAP在其中表现出高度的结构保守性，但与任何已知的人类蛋白质没有显着的结构同源性。 STEAP家族的原型成员STEAP-1似乎是主要在正常人体组织中的前列腺细胞中表达的IIIa型膜蛋白。 在结构上，STEAP-1是一种339个氨基酸的蛋白质，其特征在于六个跨膜结构域和细胞内N-和C-末端的分子拓扑结构，表明它以“蛇纹石”的方式折叠成三个胞外和两个细胞内环。 STEAP-1蛋白表达在前列腺癌的各个阶段保持在高水平。 此外，STEAP-1在某些其他人类癌症中高度过度表达。

    Tumor antigen useful in diagnosis and therapy of prostate and colon cancer
    8.
    发明授权
    Tumor antigen useful in diagnosis and therapy of prostate and colon cancer 失效
    肿瘤抗原可用于诊断和治疗前列腺和结肠癌

    公开(公告)号：US07037667B1

    公开(公告)日：2006-05-02

    申请号：US09615285

    申请日：2000-07-12

    申请人： Daniel E. H. Afar ,  Rene S. Hubert ,  Kahan Leong ,  Arthur B. Raitano ,  Douglas Saffran ,  Stephen C. Mitchell ,  Aya Jakobovits ,  Mary Faris ,  Igor Vivanco

    发明人： Daniel E. H. Afar ,  Rene S. Hubert ,  Kahan Leong ,  Arthur B. Raitano ,  Douglas Saffran ,  Stephen C. Mitchell ,  Aya Jakobovits ,  Mary Faris ,  Igor Vivanco

    IPC分类号： G01N33/574 ,  G01N33/48 ,  C12Q1/68

    CPC分类号： C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/154 ,  G01N33/57419 ,  G01N33/57434 ,  G01N33/57488 ,  G01N2333/95

    摘要： Compositions for the diagnosis and therapy of prostate and colon cancer, derived from or based on a novel prostate-specific, androgen-related, cell membrane associated and secreted serine protease termed 20P1F12/TMPRSS2 are described. A full length cDNA comprising the entire coding sequence of the 20P1F12/TMPRSS2 gene (also designated 20P1F12-GTC1 herein) is provided (FIG. 1). Among the compositions provided are antibodies that bind to 20P1F12/TMPRSS2 proteins and polypeptide fragments thereof, including antibodies labeled with a detectable marker or toxin or therapeutic composition. The invention also provides prognostic and diagnostic methods of examining a biological sample for evidence of disregulated cellular growth by comparing the status of 20P1F12/TMPRSS2 in the biological sample to the status of 20P1F12/TMPRSS2 in a corresponding normal sample, wherein alterations in the status of 20P1F12/TMPRSS2 in the biological sample are associated with disregulated cellular growth. The invention further provides various therapeutic compositions and strategies for treating prostate cancer, including particularly, 20P1F12/TMPRSS2 polypeptide and anti-20P1F12/TMPRSS2 antibody therapy methods and compositions, cancer vaccines, and small molecule therapy.

    摘要翻译： 描述了源自或基于名为20P1F12 / TMPRSS2的新型前列腺特异性雄激素相关的细胞膜相关和分泌的丝氨酸蛋白酶的前列腺和结肠癌的诊断和治疗的组合物。 提供了包含20P1F12 / TMPRSS2基因（本文中也称为20P1F12-GTC1）的整个编码序列的全长cDNA（图1）。 所提供的组合物是结合20P1F12 / TMPRSS2蛋白和其多肽片段的抗体，包括用可检测标记或毒素或治疗组合物标记的抗体。 本发明还提供了通过将生物样品中20P1F12 / TMPRSS2的状态与对应的正常样品中的20P1F12 / TMPRSS2的状态进行比较来检查生物样品以检测细胞生长失调的证据的预后和诊断方法，其中， 生物样品中的20P1F12 / TMPRSS2与细胞生长失调有关。 本发明还提供了治疗前列腺癌的各种治疗组合物和策略，特别包括20P1F12 / TMPRSS2多肽和抗-20P1F12 / TMPRSS2抗体治疗方法和组合物，癌症疫苗和小分子治疗。

    Methods to detect tumors using 20P1F12/TMPRSS2 expression
    9.
    发明授权
    Methods to detect tumors using 20P1F12/TMPRSS2 expression 有权
    使用20P1F12 / TMPRSS2表达检测肿瘤的方法

    公开(公告)号：US07981624B2

    公开(公告)日：2011-07-19

    申请号：US12389293

    申请日：2009-02-19

    申请人： Daniel E. H. Afar ,  Rene S. Hubert ,  Kahan Leong ,  Arthur B. Raitano ,  Douglas Saffran ,  Stephen C. Mitchell ,  Aya Jakobovits ,  Mary Faris ,  Igor Vivanco

    发明人： Daniel E. H. Afar ,  Rene S. Hubert ,  Kahan Leong ,  Arthur B. Raitano ,  Douglas Saffran ,  Stephen C. Mitchell ,  Aya Jakobovits ,  Mary Faris ,  Igor Vivanco

    IPC分类号： G01N33/53

    CPC分类号： C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/154 ,  G01N33/57419 ,  G01N33/57434 ,  G01N33/57488 ,  G01N2333/95

    摘要： Compositions for the diagnosis and therapy of prostate and colon cancer, derived from or based on a novel prostate-specific, androgen-regulated, cell membrane associated and secreted serine protease termed 20P1F12/TMPRSS2 are described. A full length cDNA comprising the entire coding sequence of the 20P1F12/TMPRSS2 gene (also designated 20P1F12-GTC1 herein) is provided (FIG. 1). Among the compositions provided are antibodies that bind to 20P1F12/TMPRSS2 proteins and polypeptide fragments thereof, including antibodies labeled with a detectable marker or toxin or therapeutic composition. The invention also provides prognostic and diagnostic methods of examining a biological sample for evidence of disregulated cellular growth by comparing the status of 20P1F12/TMPRSS2 in the biological sample to the status of 20P1F12/TMPRSS2 in a corresponding normal sample, wherein alterations in the status of 20P1F12/TMPRSS2 in the biological sample are associated with disregulated cellular growth. The invention further provides various therapeutic compositions and strategies for treating prostate cancer, including particularly, 20P1F12/TMPRSS2 polypeptide and anti-20P1F12/TMPRSS2 antibody therapy methods and compositions, cancer vaccines, and small molecule therapy.

    摘要翻译： 描述了衍生自或基于称为20P1F12 / TMPRSS2的新型前列腺特异性，雄激素调节的细胞膜相关和分泌的丝氨酸蛋白酶的前列腺和结肠癌的诊断和治疗的组合物。 提供了包含20P1F12 / TMPRSS2基因（本文中也称为20P1F12-GTC1）的整个编码序列的全长cDNA（图1）。 所提供的组合物是结合20P1F12 / TMPRSS2蛋白和其多肽片段的抗体，包括用可检测标记或毒素或治疗组合物标记的抗体。 本发明还提供了通过将生物样品中20P1F12 / TMPRSS2的状态与对应的正常样品中的20P1F12 / TMPRSS2的状态进行比较来检查生物样品以检测细胞生长失调的证据的预后和诊断方法，其中， 生物样品中的20P1F12 / TMPRSS2与细胞生长失调有关。 本发明还提供了治疗前列腺癌的各种治疗组合物和策略，特别包括20P1F12 / TMPRSS2多肽和抗-20P1F12 / TMPRSS2抗体治疗方法和组合物，癌症疫苗和小分子治疗。