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。

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。

公开(公告)号：US20090226921A1

公开(公告)日：2009-09-10

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： 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-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。

公开(公告)号：US08241626B2

公开(公告)日：2012-08-14

申请号：US11542758

申请日：2006-10-03

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

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

IPC分类号： A61K39/395 ,  A61K39/00 ,  C12P21/00

CPC分类号： C07K16/3069 ,  A61K38/00 ,  A61K39/00 ,  A61K51/1072 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K16/28 ,  C07K2317/34 ,  C07K2319/00 ,  C07K2319/30 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/57407 ,  G01N33/57419 ,  G01N33/57423 ,  G01N33/57434 ,  G01N33/57438 ,  G01N33/57449 ,  G01N33/57484 ,  G01N33/57492 ,  G01N2333/705

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.

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。 该家族中的两个蛋白质完全或主要地在前列腺中表达，也包括在前列腺癌中，因此该家族成员被称为“STEAP”（前列腺的六跨膜上皮抗原）。 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。

公开(公告)号：US07947459B2

公开(公告)日：2011-05-24

申请号：US10753195

申请日：2004-01-06

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

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

IPC分类号： G01N33/53 ,  G01N33/567 ,  C07K16/00 ,  C12P21/08 ,  G01N33/574

CPC分类号： C07K16/3069 ,  A61K38/00 ,  A61K39/00 ,  A61K51/1072 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K16/28 ,  C07K2317/34 ,  C07K2319/00 ,  C07K2319/30 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/57407 ,  G01N33/57419 ,  G01N33/57423 ,  G01N33/57434 ,  G01N33/57438 ,  G01N33/57449 ,  G01N33/57484 ,  G01N33/57492 ,  G01N2333/705

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. STEAP-2 is a 454 amino acid protein characterized by a predicted 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.

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。 该家族中的两个蛋白质完全或主要地在前列腺中表达，也包括在前列腺癌中，因此该家族成员被称为“STEAP”（前列腺的六跨膜上皮抗原）。 本文描述和表征了四种特定的人STEAP。 人类STEAPs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-2是一种454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-末端的预测分子拓扑结构，表明它以“蛇纹石”的方式折叠成三个细胞外和两个细胞内环。

公开(公告)号：US07351583B2

公开(公告)日：2008-04-01

申请号：US10991028

申请日：2004-11-16

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

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

IPC分类号： C12N15/85

CPC分类号： C07K16/28 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/00 ,  C07K14/705 ,  C07K16/3069 ,  C07K2317/34

摘要： A novel gene (designated PHOR-1) that is highly over-expressed in prostate and other cancers and its encoded protein are described. PHOR-1 is a G protein-coupled receptor with homology to receptors involved in olfaction. PHOR-1 in normal human tissues is restricted to prostate, and this gene is highly over-expressed in prostate cancer as well as in cancers of the kidney, uterus, cervix, stomach and rectum. Consequently, PHOR-1 provides a diagnostic and/or therapeutic target for prostate cancer.

摘要翻译： 描述了在前列腺和其他癌症及其编码的蛋白质中高度过表达的新基因（称为PHOR-1）。 PHOR-1是与涉及嗅觉的受体具有同源性的G蛋白偶联受体。 正常人组织中的PHOR-1仅限于前列腺，并且该基因在前列腺癌以及肾，子宫，宫颈，胃和直肠的癌症中高度过度表达。 因此，PHOR-1为前列腺癌提供了诊断和/或治疗靶点。

公开(公告)号：US07208280B2

公开(公告)日：2007-04-24

申请号：US10001469

申请日：2001-10-31

申请人： Aya Jakobovits ,  Arthur B. Raitano ,  Daniel E. H. Afar ,  Douglas Saffran ,  Rene S. Hubert ,  Mary Faris ,  Pia M. Challita-Eid

发明人： Aya Jakobovits ,  Arthur B. Raitano ,  Daniel E. H. Afar ,  Douglas Saffran ,  Rene S. Hubert ,  Mary Faris ,  Pia M. Challita-Eid

IPC分类号： G01M33/53

CPC分类号： C07K14/47 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  A61K2039/53 ,  C07K14/705 ,  C07K16/28 ,  C07K2317/34

摘要： A novel gene (designated 101P3A11 and also referred to as PHOR-1) and its encoded protein are described. While 101P3A11 exhibits tissue specific expression in normal adult tissue, it is aberrantly expressed in prostate, colon and kidney cancers. Thus, 101P3A11 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 101P3A11 gene or fragment thereof, or its encoded protein or a fragment thereof, can be used to elicit an immune response.

摘要翻译： 描述了一种新型基因（命名为101P3A11，也称为PHOR-1）及其编码的蛋白质。 虽然101P3A11在正常成人组织中表现出组织特异性表达，但在前列腺，结肠和肾癌中异常表达。 因此，101P3A11为癌症提供了诊断，预后，预防和/或治疗靶点。 101P3A11基因或其片段或其编码的蛋白质或其片段可用于引发免疫应答。

公开(公告)号：US07795391B2

公开(公告)日：2010-09-14

申请号：US11751621

申请日：2007-05-21

申请人： Aya Jakobovits ,  Arthur B. Raitano ,  Daniel E. H. Afar ,  Douglas Saffran ,  Rene S. Hubert ,  Mary Faris ,  Pia M. Challita-Eid

发明人： Aya Jakobovits ,  Arthur B. Raitano ,  Daniel E. H. Afar ,  Douglas Saffran ,  Rene S. Hubert ,  Mary Faris ,  Pia M. Challita-Eid

IPC分类号： C07K14/00

CPC分类号： G01N33/68 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  A61K2039/53 ,  C07K14/47 ,  C07K14/705 ,  C07K16/28 ,  C07K2317/34 ,  G01N33/5017 ,  G01N33/57434

摘要： A novel gene (designated 101P3A11 or PHOR-1) and its encoded protein, and variants thereof, are described wherein 101P3A11 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 101P3A11 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 101P3A11 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 101P3A11 can be used in active or passive immunization.

摘要翻译： 描述了一种新型基因（称为101P3A11或PHOR-1）及其编码蛋白及其变体，其中101P3A11在正常成人组织中表现出组织特异性表达，并且在表I中列出的癌症中异常表达。因此，101P3A11提供 诊断，预后，预防和/或治疗靶标。 101P3A11基因或其片段或其编码的蛋白质或其变体或其片段可用于引发体液或细胞免疫应答; 与101P3A11反应的抗体或T细胞可用于主动或被动免疫。

公开(公告)号：US08101372B2

公开(公告)日：2012-01-24

申请号：US12343170

申请日：2008-12-23

申请人： Rene S. Hubert ,  Arthur B. Raitano ,  Daniel E. H. Afar ,  Steve Chappell Mitchell ,  Mary Faris ,  Aya Jakobovits

发明人： Rene S. Hubert ,  Arthur B. Raitano ,  Daniel E. H. Afar ,  Steve Chappell Mitchell ,  Mary Faris ,  Aya Jakobovits

IPC分类号： G01N33/574

CPC分类号： G01N33/57434 ,  A01K2217/05 ,  A61K39/00 ,  C07K14/47 ,  C07K16/18 ,  C07K16/3069 ,  C07K2319/00 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/154 ,  C12Q2600/158

摘要： The present invention relates to methods and compositions for the diagnosis and therapy of prostate cancer which utilize isolated polynucleotides corresponding to the human SGP28 gene, proteins encoded by the SGP28 gene and fragments thereof, and antibodies capable of specifically recognizing and binding to SGP28 proteins.

摘要翻译： 本发明涉及用于诊断和治疗前列腺癌的方法和组合物，其利用对应于人SGP28基因的分离的多核苷酸，由SGP28基因及其片段编码的蛋白质，以及能够特异性识别和结合SGP28蛋白质的抗体。

公开(公告)号：US07928196B2

公开(公告)日：2011-04-19

申请号：US12820083

申请日：2010-06-21

申请人： Mary Faris ,  Pia M. Challita-Eid ,  Rene S. Hubert ,  Daniel E. H. Afar ,  Arthur B. Raitano ,  Wangmao Ge ,  Robert Kendall Morrison ,  Karen Jane Meyrick Morrison ,  Aya Jakobovits

发明人： Mary Faris ,  Pia M. Challita-Eid ,  Rene S. Hubert ,  Daniel E. H. Afar ,  Arthur B. Raitano ,  Wangmao Ge ,  Robert Kendall Morrison ,  Karen Jane Meyrick Morrison ,  Aya Jakobovits

IPC分类号： C07K14/00

CPC分类号： C07K14/47 ,  A61K38/00 ,  A61K39/00 ,  Y02A50/466

摘要： A novel gene (designated 125P5C8) and its encoded protein, and variants thereof, are described wherein 125P5C8 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 125P5C8 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 125P5C8 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 125P5C8 can be used in active or passive immunization.

摘要翻译： 描述了一种新型基因（称为125P5C8）及其编码的蛋白及其变体，其中125P5C8在正常成人组织中表现出组织特异性表达，并且在表I中列出的癌症中异常表达。因此，125P5C8提供诊断，预后， 癌症的预防和/或治疗靶标。 125P5C8基因或其片段或其编码的蛋白质或其变体或其片段可用于引发体液或细胞免疫应答; 与125P5C8反应的抗体或T细胞可用于主动或被动免疫。