公开(公告)号：WO2007095748A1

公开(公告)日：2007-08-30

申请号：PCT/CA2007/000282

申请日：2007-02-23

Applicant: ARIUS RESEARCH, INC.

Inventor： YOUNG, David S.F. ,  FINDLAY, Helen, P. ,  HAHN, Susan, E. ,  DACRUZ, Luis, A., G. ,  FERRY, Alison, L.

IPC: C12N5/16 ,  A61K31/00 ,  A61K38/19 ,  A61K39/395 ,  A61K47/48 ,  A61K51/10 ,  A61P35/00 ,  C07K16/30 ,  C12P21/08 ,  G01N33/574 ,  G01N33/577

CPC classification number: C07K16/30 ,  A61K47/6851 ,  A61K51/1045 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565 ,  G01N33/57484

Abstract: The present invention relates to a method for producing cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells.

Abstract translation: 本发明涉及使用新颖的筛选范例来生产癌性疾病修饰抗体的方法。 通过使用癌细胞细胞毒性分离抗癌抗体作为终点，该方法使得可能产生用于治疗和诊断目的的抗癌抗体。 抗体可用于帮助分期和诊断癌症，并可用于治疗原发性肿瘤和肿瘤转移。 抗癌抗体可以与毒素，酶，放射性化合物，细胞因子，干扰素，靶或报告物部分和血细胞结合。

公开(公告)号：WO2008144891A1

公开(公告)日：2008-12-04

申请号：PCT/CA2008/000979

申请日：2008-05-23

Applicant: ARIUS RESEARCH INC.

Inventor： YOUNG, David, S., F. ,  FINDLAY, Helen P. ,  HAHN, Susan, E. ,  DA CRUZ, Luis, A., G. ,  FERRY, Alison, L.

IPC: C07K16/30 ,  A61K39/395 ,  A61K47/48 ,  A61K51/10 ,  A61P35/00 ,  A61P37/04 ,  C07K16/28 ,  C07K16/46 ,  C12P21/08 ,  G01N33/574 ,  G01N33/577

CPC classification number: G01N33/574 ,  A61K2039/505 ,  A61K2039/545 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/92

Abstract: Expression of TROP-2, an approximately 35 kDa transmembrane protein and a substrate of protein kinase C, has been linked to several cancers. TROP-2 is also known as GA733-1, epithelial glycoprotein 1 (EGP-I) and tumor-associated calcium signal transducer-2. A monoclonal antibody against TROP-2 from the hybridoma AR47A6.4.2, deposited with the International Depository Authority of Canada (IDAC) as accession number 141205-05, was previously shown to be a cancerous disease modifying antibody (CDMAB), preventing tumour growth and reducing tumour burden in several cancer models including prostate, pancreatic and breast cancer by cytotoxicity. The variable regions of this monoclonal antibody were also isolated, sequenced and complementarity determining regions (CDRs) determined. Now, a chimeric antibody and humanized antibodies are generated that have similar TROP-2 binding activity as the parent 141205-05 monoclonal antibody. The monoclonal, chimeric and humanized antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells to treat cancer. These antibodies are also used in binding assays to determine TROP-2 expression on cells.

Abstract translation: TROP-2（一种约35kDa的跨膜蛋白和蛋白激酶C的底物）的表达与几种癌症有关。 TROP-2也称为GA733-1，上皮糖蛋白1（EGP-1）和肿瘤相关钙信号转导-2。 保藏于加拿大国际保藏机构（IDAC）的保藏号为141205-05的来自杂交瘤AR47A6.4.2的TROP-2的单克隆抗体以前被证明是癌症疾病修饰抗体（CDMAB），预防肿瘤生长， 通过细胞毒性减少包括前列腺癌，胰腺癌和乳腺癌在内的几种癌症模型的肿瘤负荷。 该单克隆抗体的可变区也被分离，测序并确定互补决定区（CDR）。 现在，产生与母体141205-05单克隆抗体具有相似的TROP-2结合活性的嵌合抗体和人源化抗体。 单克隆，嵌合和人源化抗体可以与毒素，酶，放射性化合物，细胞因子，干扰素，靶或报告物部分和血源性细胞缀合以治疗癌症。 这些抗体也用于结合测定以确定细胞上的TROP-2表达。

公开(公告)号：WO2006032127A1

公开(公告)日：2006-03-30

申请号：PCT/CA2005/000450

申请日：2005-03-24

Applicant: ARIUS RESEARCH, INC.

Inventor： YOUNG, David, S., F. ,  HAHN, Susan, E. ,  FINDLAY, Helen, P. ,  FERRY, Alison, L.

IPC: C07K14/705

CPC classification number: G01N33/57492 ,  A61K47/6851 ,  A61K51/1045 ,  A61K51/1051 ,  A61K51/1096 ,  A61K2039/505 ,  C07K14/4748 ,  C07K16/00 ,  C07K16/30 ,  C07K16/3015 ,  C07K16/3023 ,  C07K16/3046 ,  C07K16/3053 ,  C07K16/3069 ,  C07K2317/34 ,  C12N9/1051 ,  G01N33/56966 ,  G01N33/5743 ,  G01N33/57484

Abstract: This invention relates to the diagnosis and treatment of cancerous diseases, particularly to the mediation of cytotoxicity of tumor cells; and most particularly to the use of cancerous disease modifying antibodies (CDMAB), optionally in combination with one or more chemotherapeutic agents, as a means for initiating the cytotoxic response. The invention further relates to binding assays which utilize the CDMABs of the instant invention.

Abstract translation: 本发明涉及癌症的诊断和治疗，特别涉及肿瘤细胞的细胞毒性的介导; 并且最特别地涉及使用任选与一种或多种化学治疗剂组合的癌性疾病修饰抗体（CDMAB）作为起始细胞毒性应答的手段。 本发明还涉及利用本发明的CDMABs的结合测定法。

公开(公告)号：WO2007095749A1

公开(公告)日：2007-08-30

申请号：PCT/CA2007/000283

申请日：2007-02-23

Applicant: ARIUS RESEARCH, INC.

Inventor： YOUNG, David, S. F. ,  FINDLAY, Helen, P. ,  HAHN, Susan, E. ,  DaCRUZ, Luis, A. G. ,  FERRY, Alison, L.

IPC: C12N5/16 ,  A61K39/00 ,  A61K39/395 ,  A61K47/48 ,  A61K51/10 ,  A61P35/00 ,  C07K16/18 ,  C07K16/30 ,  C12P21/08 ,  G01N33/574 ,  G01N33/577

CPC classification number: C07K16/30 ,  A61K47/6851 ,  A61K51/1045 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565 ,  G01N33/57484

Abstract: The present invention relates to a method for producing cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells.

Abstract translation: 本发明涉及使用新型筛选范例制备癌性疾病改良抗体的方法。 通过使用癌细胞细胞毒性将抗癌抗体分离为终点，该方法使得抗癌抗体的生产成为治疗和诊断目的的可能性。 抗体可用于帮助分期和诊断癌症，并可用于治疗原发性肿瘤和肿瘤转移。 抗癌抗体可以与毒素，酶，放射性化合物，细胞因子，干扰素，靶或报告物部分和血细胞结合。

公开(公告)号：WO2005092376A1

公开(公告)日：2005-10-06

申请号：PCT/CA2005/000442

申请日：2005-03-23

Applicant: ARIUS RESEARCH, INC.

Inventor： YOUNG, David, S., F. ,  HAHN, Susan, E. ,  FINDLAY, Helen, P. ,  FERRY, Alison, L.

IPC: A61K39/395

CPC classification number: C07K16/3053 ,  A61K47/6851 ,  A61K51/1045 ,  A61K51/1051 ,  A61K51/1096 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/30 ,  C07K16/3015 ,  C07K16/3023 ,  C07K16/3046 ,  C07K16/3069 ,  C07K16/3076 ,  G01N33/5002 ,  G01N33/5005 ,  G01N33/566 ,  G01N33/574 ,  G01N33/57484

Abstract: The use of a cancerous disease modifying antibody (CDMAB) 11 BD-2E11-2 for treating a tumor in humans and methods of isolating and identifying cancerous cells which express a melanoma-associated chondroitin sulfate proteoglycan (MCSP) antigenic moiety. The monoclonal antibody 11 BD-2E11-2 (ATCC accession number PTA-5643), which binds a MCSP antigenic moiety, is cytotoxic to cancer cells which express the antigenic moiety. The monoclonal antibody 11 BD-2E11-2 is useful for delaying the disease progression of a human tumor.

Abstract translation: 使用用于治疗人类肿瘤的癌性疾病修饰抗体（CDMAB）11BB-2E11-2以及分离和鉴定表达黑素瘤相关硫酸软骨素蛋白聚糖（MCSP）抗原部分的癌细胞的方法。 结合MCSP抗原部分的单克隆抗体11BB-2E11-2（ATCC登录号PTA-5643）对表达抗原部分的癌细胞具有细胞毒性。 单克隆抗体11BD-2E11-2可用于延缓人类肿瘤的疾病进展。