公开(公告)号：US20120156217A1

公开(公告)日：2012-06-21

申请号：US13284398

申请日：2011-10-28

申请人： Julianto Setiady ,  Peter U. Park ,  Lingyun Rui ,  Thomas Chittenden

发明人： Julianto Setiady ,  Peter U. Park ,  Lingyun Rui ,  Thomas Chittenden

IPC分类号： A61K39/395 ,  C07K19/00 ,  A61P35/00 ,  C12N5/10 ,  C12P21/00 ,  C12N5/071 ,  C12N15/63 ,  C12N1/21 ,  C07K16/22 ,  C12N15/13

CPC分类号： C07K16/2863 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/6803 ,  A61K47/6849 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/92

摘要： Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to EGFR are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.

摘要翻译： 提供了与EGFR结合的新型抗癌剂，包括但不限于抗体和免疫偶联物。 进一步提供使用试剂，抗体或免疫缀合物的方法，例如抑制肿瘤生长的方法。

公开(公告)号：US20110195022A1

公开(公告)日：2011-08-11

申请号：US13024671

申请日：2011-02-10

申请人： Jutta DECKERT ,  Daniel J. TAVARES ,  Peter U. PARK

发明人： Jutta DECKERT ,  Daniel J. TAVARES ,  Peter U. PARK

IPC分类号： A61K51/00 ,  A61K49/00 ,  A61K39/395 ,  A61P11/00 ,  C12N5/02 ,  C12N15/63 ,  C07K14/435 ,  A61P31/12 ,  C07K17/02 ,  A61P3/10 ,  C07H21/04 ,  C12N5/10 ,  A61P35/00 ,  A61P1/00 ,  A61P17/02 ,  A61P11/06 ,  A61P29/00 ,  A61P37/00 ,  A61P19/02

CPC分类号： C07K16/2887 ,  A61K39/39541 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6849 ,  A61K51/1027 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C07K2319/55 ,  G01N33/57426

摘要： CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells and has been found on B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. Conversely, it is not found on hematopoietic stem cells, pro-B cells, differentiated plasma cells or non-lymphoid tissues. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). CD20 expressing cells are known to play a role in other diseases and disorders, including inflammation. The present invention includes anti-CD20 antibodies, forms and fragments, having superior physical and functional properties; immunoconjugates, compositions, diagnostic reagents, methods for inhibiting growth, therapeutic methods, improved antibodies and cell lines; and polynucleotides, vectors and genetic constructs encoding same.

公开(公告)号：US20110195021A1

公开(公告)日：2011-08-11

申请号：US13024556

申请日：2011-02-10

申请人： Jutta DECKERT ,  Lingyun Rui ,  Peter U. Park

发明人： Jutta DECKERT ,  Lingyun Rui ,  Peter U. Park

IPC分类号： A61K51/00 ,  C07K16/00 ,  A61K39/395 ,  A61P35/00 ,  C12N5/02 ,  A61K49/00 ,  C07H21/04 ,  C12N15/63 ,  C12N5/00

CPC分类号： C07K16/2887 ,  A61K39/39541 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6849 ,  A61K51/1027 ,  A61K2039/505 ,  C07K16/30 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/55 ,  C12N2501/48 ,  G01N33/57426

摘要： CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells and has been found on B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. Conversely, it is not found on hematopoietic stem cells, pro-B cells, differentiated plasma cells or non-lymphoid tissues. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). CD20 expressing cells are known to play a role in other diseases and disorders, including inflammation. The present invention includes anti-CD20 antibodies, forms and fragments, having superior physical and functional properties; immunoconjugates, compositions, diagnostic reagents, methods for inhibiting growth, therapeutic methods, improved antibodies and cell lines; and polynucleotides, vectors and genetic constructs encoding same.

摘要翻译： CD20是在B细胞表面表达的四跨连锁蛋白家族的跨膜蛋白，并且已经在外周血和淋巴组织的B细胞中发现。 CD20表达从早期B细胞前期持续到血浆细胞分化阶段。 相反，在造血干细胞，前B细胞，分化浆细胞或非淋巴组织中未发现。 除了在正常B细胞​​中表达外，CD20在B细胞衍生的恶性肿瘤如非霍奇金淋巴瘤（NHL）和B细胞慢性淋巴细胞白血病（CLL）中表达。 已知CD20表达细胞在其他疾病和病症中发挥作用，包括炎症。 本发明包括具有优异的物理和功能特性的抗CD20抗体，形式和片段; 免疫缀合物，组合物，诊断试剂，抑制生长的方法，治疗方法，改进的抗体和细胞系; 和编码相同的多核苷酸，载体和遗传构建体。

公开(公告)号：US20110177064A1

公开(公告)日：2011-07-21

申请号：US13011664

申请日：2011-01-21

申请人： Kathleen R. WHITEMAN ,  James J. O'Leary ,  Robert John Lutz

发明人： Kathleen R. WHITEMAN ,  James J. O'Leary ,  Robert John Lutz

IPC分类号： A61K39/395 ,  A61P35/00

CPC分类号： C07K16/2803 ,  A61K2039/505

摘要： The present invention relates to surprisingly effective anti-cancer drug combinations, pharmaceutical compositions comprising the same, and uses thereof in the treatment of ovarian cancer. In particular, the present invention is based on the discovery that the administration of a CD56 antibody linked to a cytotoxic compound (e.g.,, an immunoconjugate) in combination with at least two chemotherapeutic agents (in particular a taxane compound and a platinum compound), improves the therapeutic index in the treatment of ovarian cancer over and above the additive effects of the anticancer agents used alone. In one embodiment of the invention, combinations of the CD56 antibody, or fragment thereof, linked to a cytotoxic compound plus additional chemotherapeutic agents have a synergistic effect in the ovarian cancer therapeutic index. The present invention also provides methods of modulating the growth of selected cell populations, such as ovarian cancer cells, by administering a therapeutically effective amount of such combinations.

摘要翻译： 本发明涉及惊人的有效的抗癌药物组合，包含其的药物组合物及其在治疗卵巢癌中的用途。 特别地，本发明基于以下发现：与至少两种化学治疗剂（特别是紫杉烷化合物和铂化合物）组合施用与细胞毒性化合物（例如，免疫缀合物）连接的CD56抗体， 改善了治疗卵巢癌的治疗指标，超过了单独使用的抗癌剂的加和效应。 在本发明的一个实施方案中，与细胞毒性化合物加上其他化学治疗剂连接的CD56抗体或其片段的组合在卵巢癌治疗指数中具有协同作用。 本发明还提供了通过施用治疗有效量的这种组合来调节所选细胞群体如卵巢癌细胞的生长的方法。

公开(公告)号：US20110064733A1

公开(公告)日：2011-03-17

申请号：US12912107

申请日：2010-10-26

申请人： Gillian PAYNE ,  Philip Chun ,  Daniel J. Tavares

发明人： Gillian PAYNE ,  Philip Chun ,  Daniel J. Tavares

IPC分类号： A61K39/395 ,  C07K16/18 ,  C07H21/00 ,  C12N15/63 ,  C07K16/30 ,  C07K14/52 ,  C07K14/555 ,  C07K14/475 ,  C07K14/79 ,  C12N5/09 ,  A61P35/00

CPC分类号： C07K16/3092 ,  A61K31/537 ,  A61K39/39558 ,  A61K47/6803 ,  A61K47/6809 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6859 ,  A61K47/6869 ,  A61K47/6877 ,  A61K2039/505 ,  C07K14/4727 ,  C07K14/4748 ,  C07K16/3015 ,  C07K16/303 ,  C07K16/3069 ,  C07K16/464 ,  C07K2317/14 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/73 ,  C07K2317/92

摘要： Cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.

摘要翻译： 公开了包含细胞结合剂和细胞毒性剂的细胞毒性缀合物，包含缀合物的治疗组合物，用于抑制细胞生长和治疗疾病的方法，以及包含细胞毒性缀合物的试剂盒是本发明的所有实施方案 。 特别地，细胞结合剂是识别和结合CA6糖底骨的单克隆抗体及其表位结合片段。 本发明还涉及DS6，抗CA6鼠单克隆抗体及其表位结合片段的人源化或重新表达的形式。

公开(公告)号：US07851432B2

公开(公告)日：2010-12-14

申请号：US11778437

申请日：2007-07-16

申请人： Ravi V. J. Chari ,  Wayne C. Widdison

发明人： Ravi V. J. Chari ,  Wayne C. Widdison

IPC分类号： A01N61/00

CPC分类号： A61K39/39558 ,  A61K31/5365 ,  A61K47/6803 ,  A61K2039/505 ,  C07D498/16

摘要： New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

摘要翻译： 公开了在带有硫原子的α-碳原子上具有一或二烷基取代基的新的硫醇和二硫化物的美登木素生物碱。 还公开了合成这些新的美登木素生物碱的方法和将这些新的美登木素生物素连接到细胞结合剂的方法。 美登木素生物碱 - 细胞结合剂缀合物可用作治疗剂，其特异性递送至靶细胞并且是细胞毒性的。 与先前描述的试剂相比，这些缀合物在动物肿瘤模型中显示出显着改善的治疗功效。

公开(公告)号：US07811572B2

公开(公告)日：2010-10-12

申请号：US11503781

申请日：2006-08-14

申请人： Yong Dai ,  Yong Wang ,  Shengjin Jin ,  Deborah H. Meshulam ,  Godfrey W. Amphlett

发明人： Yong Dai ,  Yong Wang ,  Shengjin Jin ,  Deborah H. Meshulam ,  Godfrey W. Amphlett

IPC分类号： A61K39/395 ,  G01N33/53 ,  C07K16/28

CPC分类号： A61K47/6803 ,  A61K47/6809 ,  A61K47/6867 ,  C07K16/2839 ,  C07K16/2884 ,  C07K16/2896 ,  C07K2317/24 ,  C07K2317/40

摘要： The invention provides a process for preparing a cell-binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent and a subsequent purification step.

摘要翻译： 本发明提供了一种制备与药物化学偶联的细胞结合剂的方法。 该方法包括将接头共价连接到细胞结合剂，纯化步骤，将药物与细胞结合剂缀合，随后的纯化步骤。

公开(公告)号：US20100028346A1

公开(公告)日：2010-02-04

申请号：US12485446

申请日：2009-06-16

申请人： Robert J. Lutz ,  Kathleen R. Whiteman

发明人： Robert J. Lutz ,  Kathleen R. Whiteman

IPC分类号： A61K39/395 ,  A61K31/436 ,  A61K31/664 ,  A61P35/00 ,  A61P37/06 ,  A61P31/12 ,  A61P33/00 ,  A61K31/713 ,  A61K31/56

CPC分类号： C07K16/2803 ,  A61K31/198 ,  A61K31/436 ,  A61K31/454 ,  A61K31/57 ,  A61K31/675 ,  A61K31/69 ,  A61K39/3955 ,  A61K45/06 ,  A61K47/6803 ,  A61K47/6849 ,  A61K2039/505 ,  C07K2317/24 ,  A61K2300/00

摘要： The present invention encompasses a combination of at least one conjugate and one or more chemotherapeutic agent(s) which when administered exerts an unexpectedly enhanced therapeutic effect. The therapeutic effectiveness of the combination is greater than that of the conjugate alone or the administration of one or more of the drug(s) without the conjugate. The present invention is also directed to compositions comprising at least one conjugate and at one or more of chemotherapeutic agent and to methods of treating cancer using at least one conjugate and at least one or more of chemotherapeutic agent (s). The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of one or more chemotherapeutic agent(s) and at least one conjugate. In each case, such combination has therapeutic synergy or improves the therapeutic index in the treatment of cancer over the anticancer agent(s) alone.

摘要翻译： 本发明包括至少一种缀合物和一种或多种化学治疗剂的组合，其当施用时施加意想不到的增强的治疗效果。 组合的治疗效果大于单独的缀合物或施用一种或多种没有缀合物的药物。 本发明还涉及包含至少一种缀合物和一种或多种化学治疗剂的组合物和使用至少一种缀合物和至少一种或多种化学治疗剂治疗癌症的方法。 本发明还提供了通过施用治疗有效量的一种或多种化学治疗剂和至少一种缀合物来调节所选细胞群体如癌细胞的生长的方法。 在每种情况下，这种组合具有治疗性协同作用或改善治疗癌症的治疗指数超过单独的抗癌剂。

公开(公告)号：US07655661B2

公开(公告)日：2010-02-02

申请号：US12144612

申请日：2008-06-23

申请人： Robert Yongxin Zhao ,  Ravi V. J. Chari

发明人： Robert Yongxin Zhao ,  Ravi V. J. Chari

IPC分类号： A61K31/497 ,  C07D209/56

CPC分类号： C07D307/85 ,  A61K31/407 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/496 ,  A61K31/675 ,  A61K47/545 ,  A61K47/548 ,  A61K47/60 ,  C07D209/42 ,  C07D209/60 ,  C07D403/14 ,  C07D405/12 ,  C07F9/5728 ,  C07F9/65583 ,  Y02A50/423 ,  Y02A50/491 ,  Y02P20/55

摘要： Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytotoxic drugs in a targeted fashion.

摘要翻译： 具有可切割保护基的抗肿瘤抗生素CC-1065类似物的前药，例如哌嗪基氨基甲酸酯，4-哌啶子基 - 哌啶子基氨基甲酸酯或磷酸酯，其中保护基团赋予增强的水溶性和在前药上的稳定性， 其中前药还具有可与细胞结合试剂例如抗体缀合的部分，例如二硫化物。 还描述了这种前药缀合物的治疗用途; 这种细胞毒性药物的前药具有治疗用途，因为它们可以将细胞毒性前药递送至特定的细胞群，以靶向方式酶促转化成细胞毒性药物。

公开(公告)号：US20090162284A1

公开(公告)日：2009-06-25

申请号：US12251884

申请日：2008-10-15

申请人： Rajeeva SINGH ,  Daniel J. Tavares ,  Nancy E. Dagdigian

发明人： Rajeeva SINGH ,  Daniel J. Tavares ,  Nancy E. Dagdigian

IPC分类号： A61K49/00 ,  C07K16/18 ,  A61K39/395 ,  C12N15/11 ,  C12N15/00

CPC分类号： A61K39/39558 ,  A61K31/337 ,  A61K31/4745 ,  A61K39/39541 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/2863 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92 ,  A61K2300/00

摘要： Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of these molecules with cytotoxic agents, which specifically bind to and inhibit insulin-like growth factor-I receptor, antagonize the effects of IGF-I and are substantially devoid of agonist activity toward the insulin-like growth factor-I receptor. These molecules can be conjugated to cytotoxic agents for use in the treatment of tumors that express elevated levels of IGF-I receptor, such as breast cancer, colon cancer, lung cancer, ovarian carcinoma, synovial sarcoma and pancreatic cancer. These molecules can also be labeled for in vitro and in vivo diagnostic uses, such as in the diagnosis and imaging of tumors that express elevated levels of IGF-I receptor.