公开(公告)号：US08524460B2

公开(公告)日：2013-09-03

申请号：US13083205

申请日：2011-04-08

Applicant: Robert E. Reiter ,  Owen N. Witte

Inventor： Robert E. Reiter ,  Owen N. Witte

IPC: G01N33/53 ,  G01N33/574 ,  C07K16/00 ,  C07K17/00 ,  C12P21/08

CPC classification number: C07K16/3069 ,  A01K2217/05 ,  A61K31/704 ,  A61K38/00 ,  A61K39/395 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6869 ,  A61K51/106 ,  A61K51/1072 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K16/30 ,  C07K16/3038 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  G01N33/53 ,  G01N33/567 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57434 ,  G01N33/57438 ,  G01N33/577 ,  G01N2333/705 ,  A61K31/00 ,  A61K2300/00

Abstract: The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

公开(公告)号：US08404817B2

公开(公告)日：2013-03-26

申请号：US13308783

申请日：2011-12-01

Applicant: Mark A. Sherman ,  Anna M. Wu ,  Robert E. Reiter

Inventor： Mark A. Sherman ,  Anna M. Wu ,  Robert E. Reiter

IPC: C12P21/08

CPC classification number: C07K16/3069 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

Abstract: Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer patients, making it an ideal target for cancer immunotherapy. Murine monoclonal antibody 1G8 binds to PSCA with nanomolar affinity, but its efficacy as a therapeutic agent is limited by the generation of a HAMA response. The present invention discloses humanized 1G8 antibodies in which the majority of the mouse-derived epitopes have been removed. These humanized antibodies bind PSCA with high affinity and specificity, and have been shown to reduce human bladder tumor take in a nude mouse model. These characteristics make the humanized antibodies of the present invention attractive agents for the treatment and detection of tumors expressing PSCA.

Abstract translation: 前列腺干细胞抗原（PSCA）在大多数前列腺癌患者中表达，使其成为癌症免疫治疗的理想靶标。 鼠单克隆抗体1G8以纳摩尔亲和力结合PSCA，但其作为治疗剂的功效受到HAMA反应的产生的限制。 本发明公开了大部分小鼠来源的表位已被除去的人源化1G8抗体。 这些人源化抗体以高亲和力和特异性结合PSCA，并已显示可以减少人膀胱肿瘤的裸鼠模型。 这些特征使得本发明的人源化抗体用于治疗和检测表达PSCA的肿瘤的吸引剂。

公开(公告)号：US20120077962A1

公开(公告)日：2012-03-29

申请号：US13308783

申请日：2011-12-01

Applicant: Mark A. SHERMAN ,  Anna M. Wu ,  Robert E. Reiter

Inventor： Mark A. SHERMAN ,  Anna M. Wu ,  Robert E. Reiter

IPC: C07K16/18 ,  C07K17/00

CPC classification number: C07K16/3069 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

Abstract: Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer patients, making it an ideal target for cancer immunotherapy. Murine monoclonal antibody 1G8 binds to PSCA with nanomolar affinity, but its efficacy as a therapeutic agent is limited by the generation of a HAMA response. The present invention discloses humanized 1G8 antibodies in which the majority of the mouse-derived epitopes have been removed. These humanized antibodies bind PSCA with high affinity and specificity, and have been shown to reduce human bladder tumor take in a nude mouse model. These characteristics make the humanized antibodies of the present invention attractive agents for the treatment and detection of tumors expressing PSCA.

Abstract translation: 前列腺干细胞抗原（PSCA）在大多数前列腺癌患者中表达，使其成为癌症免疫治疗的理想靶标。 鼠单克隆抗体1G8以纳摩尔亲和力结合PSCA，但其作为治疗剂的功效受到HAMA反应的产生的限制。 本发明公开了大部分小鼠来源的表位已被除去的人源化1G8抗体。 这些人源化抗体以高亲和力和特异性结合PSCA，并已显示可以减少人膀胱肿瘤的裸鼠模型。 这些特征使得本发明的人源化抗体用于治疗和检测表达PSCA的肿瘤的吸引剂。

公开(公告)号：US20100278821A1

公开(公告)日：2010-11-04

申请号：US12730862

申请日：2010-03-24

Applicant: Robert E. Reiter

Inventor： Robert E. Reiter

IPC: A61K39/395 ,  C07K16/00 ,  G01N33/53 ,  G01N33/566 ,  C07K14/00 ,  A61K39/00 ,  C07H21/04 ,  C12N15/63 ,  A61P35/00

CPC classification number: C07K16/2896 ,  A61K2039/505 ,  C07K2317/34 ,  C07K2317/73 ,  G01N33/57492 ,  G01N2333/705

Abstract: The present invention provides methods of diagnosis, providing a prognosis and a therapeutic target for the treatment of cancers according to their expression of N-cadherin, including prostrate and bladder cancers.

Abstract translation: 本发明提供诊断方法，根据N钙粘蛋白（包括前列腺癌和膀胱癌）的表达，提供癌症治疗的预后和治疗靶标。

公开(公告)号：US07462691B2

公开(公告)日：2008-12-09

申请号：US10997735

申请日：2004-11-23

Applicant: Robert E. Reiter ,  Owen N. Witte

Inventor： Robert E. Reiter ,  Owen N. Witte

IPC: C07K14/00 ,  C07K16/00

CPC classification number: C07K16/3069 ,  A01K2217/05 ,  A61K31/704 ,  A61K38/00 ,  A61K39/395 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6869 ,  A61K51/106 ,  A61K51/1072 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K16/30 ,  C07K16/3038 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  G01N33/53 ,  G01N33/567 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57434 ,  G01N33/57438 ,  G01N33/577 ,  G01N2333/705 ,  A61K31/00 ,  A61K2300/00

Abstract: The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

Abstract translation: 本发明提供了一种新的前列腺细胞表面抗原，其命名为前列腺干细胞抗原（PSCA），其在前列腺癌的所有阶段中广泛过表达，包括高级前列腺上皮内瘤变（PIN），雄激素依赖性和雄激素依赖性 前列腺肿瘤。

公开(公告)号：US06960443B2

公开(公告)日：2005-11-01

申请号：US10224720

申请日：2002-08-20

Applicant: Robert E. Reiter ,  Owen N. Witte

Inventor： Robert E. Reiter ,  Owen N. Witte

IPC: A61K38/00 ,  A61K39/395 ,  A61K47/48 ,  C07K14/47 ,  C07K14/705 ,  C07K16/30 ,  G01N33/574 ,  G01N33/53

CPC classification number: G01N33/57434 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/395 ,  A61K47/6869 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K16/30 ,  C07K16/3069 ,  C07K2317/73 ,  A61K2300/00

Abstract: The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

Abstract translation: 本发明提供了一种新的前列腺细胞表面抗原，其命名为前列腺干细胞抗原（PSCA），其在前列腺癌的所有阶段中广泛过表达，包括高级前列腺上皮内瘤变（PIN），雄激素依赖性和雄激素依赖性 前列腺肿瘤。

公开(公告)号：US06815574B2

公开(公告)日：2004-11-09

申请号：US10062684

申请日：2002-01-30

Applicant: Charles L. Sawyers ,  Karen A. Klein ,  Owen N. Witte ,  Robert E. Reiter

Inventor： Charles L. Sawyers ,  Karen A. Klein ,  Owen N. Witte ,  Robert E. Reiter

IPC: A01K6700

CPC classification number: A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  A61K49/0008

Abstract: The present invention provides an immune deficient mouse having a human prostate xenograft of locally advanced or metastatic prostate cancer and uses thereof.

Abstract translation: 本发明提供了具有局部晚期或转移性前列腺癌的人前列腺异种移植物的免疫缺陷小鼠及其用途。

公开(公告)号：US06261789B1

公开(公告)日：2001-07-17

申请号：US09251835

申请日：1999-02-17

Applicant: Robert E. Reiter ,  Owen N. Witte

Inventor： Robert E. Reiter ,  Owen N. Witte

IPC: G01N3353

CPC classification number: C07K14/4748 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/705 ,  C07K16/3069 ,  G01N33/57434

Abstract: The invention provides methods for detecting the presence of a PSCA protein comprising contacting the sample with PSCA antibodies designated 1G8 (ATCC No. HB-12612), 2A2 (ATCC No. HB-12613), 2H9 (ATCC No. HB-12614), 3C5 (ATCC No. HB-12616), 3E6 (ATCC No. HB12618), 3G3 (ATCC No. HB-12615), or 4A10 (ATCC No. HB-12617).

Abstract translation: 本发明提供了检测PSCA蛋白质存在的方法，包括使样品与称为1G8（ATCC No.HB-12612），2A2（ATCC No.HB-12613），2H9（ATCC No.HB-12614）， 3C5（ATCC No.HB-12616），3E6（ATCC No.HB12618），3G3（ATCC No.HB-12615）或4A10（ATCC No.BB-12617）。

公开(公告)号：US08759006B2

公开(公告)日：2014-06-24

申请号：US12169561

申请日：2008-07-08

Applicant: Robert E. Reiter ,  Owen N. Witte

Inventor： Robert E. Reiter ,  Owen N. Witte

IPC: G01N33/53 ,  G01N33/567 ,  G01N33/574

CPC classification number: C07K16/3069 ,  A01K2217/05 ,  A61K31/704 ,  A61K38/00 ,  A61K39/395 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6869 ,  A61K51/106 ,  A61K51/1072 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K16/30 ,  C07K16/3038 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  G01N33/53 ,  G01N33/567 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57434 ,  G01N33/57438 ,  G01N33/577 ,  G01N2333/705 ,  A61K31/00 ,  A61K2300/00

Abstract: The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

Abstract translation: 本发明提供了一种新的前列腺细胞表面抗原，其命名为前列腺干细胞抗原（PSCA），其在前列腺癌的所有阶段中广泛过度表达，包括高级前列腺上皮内瘤变（PIN），雄激素依赖性和雄激素依赖性 前列腺肿瘤。

公开(公告)号：US08088908B2

公开(公告)日：2012-01-03

申请号：US11432304

申请日：2006-05-10

Applicant: Mark A. Sherman ,  Anna M. Wu ,  Robert E. Reiter

Inventor： Mark A. Sherman ,  Anna M. Wu ,  Robert E. Reiter

IPC: C07H21/04

CPC classification number: C07K16/3069 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565

Abstract: Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer patients, making it an ideal target for cancer immunotherapy. Murine monoclonal antibody 1G8 binds to PSCA with nanomolar affinity, but its efficacy as a therapeutic agent is limited by the generation of a HAMA response. The present invention discloses humanized 1G8 antibodies in which the majority of the mouse-derived epitopes have been removed. These humanized antibodies bind PSCA with high affinity and specificity, and have been shown to reduce human bladder tumor take in a nude mouse model. These characteristics make the humanized antibodies of the present invention attractive agents for the treatment and detection of tumors expressing PSCA.

Abstract translation: 前列腺干细胞抗原（PSCA）在大多数前列腺癌患者中表达，使其成为癌症免疫治疗的理想靶标。 鼠单克隆抗体1G8以纳摩尔亲和力结合PSCA，但其作为治疗剂的功效受到HAMA反应的产生的限制。 本发明公开了大部分小鼠来源的表位已被除去的人源化1G8抗体。 这些人源化抗体以高亲和力和特异性结合PSCA，并已显示可以减少人膀胱肿瘤的裸鼠模型。 这些特征使得本发明的人源化抗体用于治疗和检测表达PSCA的肿瘤的吸引剂。