公开(公告)号：US20140072528A1

公开(公告)日：2014-03-13

申请号：US13961649

申请日：2013-08-07

申请人： Roche Glycart AG

发明人： Christian Gerdes ,  Christian Klein ,  Valeria G. Nicolini ,  Pablo Umana

IPC分类号： A61K47/48 ,  A61K39/395

CPC分类号： A61K47/48576 ,  A61K38/2013 ,  A61K45/06 ,  A61K47/642 ,  A61K47/6849 ,  A61K47/6853 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/2863 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/32 ,  C07K16/40 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/41 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732

摘要： The present invention provides combinations of (a) an immunoconjugate comprising a first antibody engineered to have reduced effector function and an effector moiety, and (b) a second antibody engineered to have increased effector function, for use in treating a disease in an individual in need thereof. Further provided are pharmaceutical compositions comprising the combinations, and methods of using them.

摘要翻译： 本发明提供了（a）包含工程改造为具有降低的效应子功能的第一抗体和效应子部分的免疫偶联物的组合，和（b）工程改造为具有增强的效应子功能的第二抗体，用于治疗个体中的疾病 需要。 还提供了包含组合的药物组合物和使用它们的方法。

公开(公告)号：US20140045242A1

公开(公告)日：2014-02-13

申请号：US14027770

申请日：2013-09-16

申请人： IBC PHARMACEUTICALS, INC.

发明人： Chien-Hsing Chang ,  David M. Goldenberg

IPC分类号： C07K16/46

CPC分类号： C07K16/46 ,  A61K39/0011 ,  A61K47/646 ,  A61K47/6897 ,  A61K2039/6056 ,  A61K2039/625 ,  B82Y5/00 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30

摘要： The present invention concerns methods and compositions for forming anti-cancer vaccine complexes. In preferred embodiments, the anti-cancer vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex. The anti-cancer vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

摘要翻译： 本发明涉及用于形成抗癌疫苗复合物的方法和组合物。 在优选的实施方案中，抗癌疫苗复合物包含与AD（锚定结构域）部分和异种抗原（例如CD20）连接的树突状细胞例如抗CD74抗体或其抗原结合片段的抗体部分 ，其连接到DDD（二聚化和对接结构域）部分，其中DDD部分的两个拷贝形成结合AD部分的二聚体，导致疫苗复合物的形成。 抗癌疫苗复合物能够诱导针对异种抗原表达癌细胞的免疫应答，例如CD138negCD20 + MM干细胞，并诱导凋亡并抑制癌细胞的生长或消除癌细胞。

公开(公告)号：US20140038261A1

公开(公告)日：2014-02-06

申请号：US14017885

申请日：2013-09-04

申请人： IBC PHARMACEUTICALS, INC. ,  IMMUNOMEDICS, INC.

发明人： Chien-Hsing Chang ,  David M. Goldenberg ,  Edmund A. Rossi

IPC分类号： C12N9/96

CPC分类号： A61K38/465 ,  A61K39/0011 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/62 ,  A61K47/646 ,  A61K47/6897 ,  A61K51/088 ,  A61K51/1027 ,  A61K2039/505 ,  A61K2039/6056 ,  A61K2039/625 ,  B82Y5/00 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2887 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  C12N9/96 ,  C12Y207/11011 ,  C12Y301/27

摘要： The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.

摘要翻译： 本发明涉及用于形成具有高效力和低全身毒性的免疫毒素复合物的方法和组合物。 在优选的实施方案中，毒素部分是兰普瑞酶（Rap），例如Rap（Q）。 在更优选的实施方案中，免疫毒素使用对接 - 锁（DNL）技术制备。 与单独的毒素，单独的抗体，未缀合的毒素加抗体或甚至其它类型的毒素 - 抗体构建体相比，免疫毒素表现出改进的药代动力学，具有较长的血清半衰期和显着更高的功效。 在最优选的实施方案中，构建体包含与Rap结合的抗Trop-2抗体，尽管抗体，抗体片段和毒素的其它组合可用于形成受试者免疫毒素。 免疫毒素可用于治疗各种疾病，例如癌症，自身免疫性疾病或免疫功能障碍。

公开(公告)号：US20130323204A1

公开(公告)日：2013-12-05

申请号：US13901737

申请日：2013-05-24

申请人： IBC Pharmaceuticals, Inc.

发明人： Edmund A. Rossi ,  Chien-Hsing Chang ,  David M. Goldenberg

IPC分类号： A61K39/395 ,  A61K45/06 ,  C07K16/30

CPC分类号： C07K16/3092 ,  A61K45/06 ,  A61K47/6813 ,  A61K47/6815 ,  A61K47/6817 ,  A61K47/6829 ,  A61K47/6849 ,  A61K2039/505 ,  C07K14/56 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2863 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/44 ,  C07K2317/24 ,  C07K2317/30 ,  C07K2317/32 ,  C07K2317/526 ,  C07K2317/55 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/94 ,  C07K2319/00 ,  C12N9/12 ,  C12N9/22 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/00 ,  C12N2320/32 ,  C12Y207/11011 ,  C12Y301/27

摘要： The present invention concerns multimeric complexes based on antibody fusion proteins comprising an AD moiety attached to the C-terminal end of each antibody light chain. The complexes further comprise effector moities attached to DDD moieties. Two copies of the DDD moiety form a dimer that binds to the AD moiety. The complexes may be trimers, pentamers, hexamers or other multimers. The effector moieties may be selected from a second antibody or antigen-binding fragment thereof, a cytokine, an interferon, a toxin, an antigen, a xenoantigen, a hapten, a protamine, a hormone, an enzyme, a ligand-binding protein, a pro-apoptotic agent and an anti-angiogenic agent. Surprisingly, attachment of the AD moiety to the C-terminal end of the antibody light chain results in improved pharmacokinetics and in vivo stability and efficacy, compared to homologous complexes wherein the AD moiety is attached to the antibody heavy chain.

摘要翻译： 本发明涉及基于抗体融合蛋白的多聚体复合物，其包含连接于每个抗体轻链的C末端的AD部分。 复合物还包含与DDD部分连接的效应物。 DDD部分的两个拷贝形成与AD部分结合的二聚体。 络合物可以是三聚体，五聚体，六聚体或其它多聚体。 效应部分可以选自第二抗体或其抗原结合片段，细胞因子，干扰素，毒素，抗原，异种抗原，半抗原，鱼精蛋白，激素，酶，配体结合蛋白， 促凋亡剂和抗血管生成剂。 令人惊讶的是，与其中AD部分连接到抗体重链的同源复合物相比，AD部分与抗体轻链的C-末端的连接导致改善的药代动力学和体内稳定性和功效。

公开(公告)号：US08569054B2

公开(公告)日：2013-10-29

申请号：US13735244

申请日：2013-01-07

申请人： Immunomedics, Inc.

发明人： David M. Goldenberg ,  Zhengxing Qu ,  Chien-Hsing Chang ,  Edmund A. Rossi ,  Jeng-Dar Yang ,  Diane Nordstrom

IPC分类号： C12N5/00 ,  C12N15/00

CPC分类号： C07K16/2896 ,  A61K2039/505 ,  C07K14/005 ,  C07K14/4747 ,  C07K16/00 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/3007 ,  C07K2317/24 ,  C07K2317/31 ,  C12N5/0694 ,  C12N15/85 ,  C12N15/86 ,  C12N2500/90 ,  C12N2501/48 ,  C12N2510/02 ,  C12N2710/20022 ,  C12N2740/10043 ,  C12P21/02

摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.

公开(公告)号：US20130273050A1

公开(公告)日：2013-10-17

申请号：US13740358

申请日：2013-01-14

申请人： Micromet AG

发明人： Ralf LUTTERBÜSE ,  Petra Mayer ,  Evelyne Schaller ,  Doris Rau ,  Susanne Mangold ,  Peter Kufer ,  Alexander Murr ,  Tobias Raum ,  Monkia Wissinger

IPC分类号： C07K16/46 ,  A61K45/06 ,  A61K39/395

CPC分类号： C07K16/468 ,  A61K39/39558 ,  A61K45/06 ,  C07K16/2809 ,  C07K16/3007 ,  C07K16/46 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/565 ,  C07K2319/00

摘要： The present disclosure relates to a bispecific single chain antibody which has a first binding domain specifically binding to human CD3, and a second binding domain specifically binding to human CEA, where the second binding domain comprises at least a part of the CDR-H3 or the complete CDR-H3 of murine monoclonal antibody A5B7, a pharmaceutical composition comprising the bispecific single chain antibody, and methods for the treatment of an epithelial tumor in a human with the pharmaceutical compositions containing the bispecific single chain antibody. Furthermore, processes for the production of the pharmaceutical compositions as well as medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CEA antigen are disclosed.

摘要翻译： 本公开内容涉及具有特异性结合人CD3的第一结合结构域和特异性结合人CEA的第二结合结构域的双特异性单链抗体，其中第二结合结构域包含至少一部分CDR-H3或 含有双特异性单链抗体的单克隆抗体A5B7的完整CDR-H3，包含双特异性单链抗体的药物组合物，以及用含有双特异性单链抗体的药物组合物治疗人的上皮肿瘤的方法。 此外，公开了用于生产药物组合物的方法以及具有对人CD3抗原和人CEA抗原具有特异性的特异性双特异性单链抗体分子的医学/药物用途。

公开(公告)号：US08491914B2

公开(公告)日：2013-07-23

申请号：US12964021

申请日：2010-12-09

申请人： Chien-Hsing Chang ,  David M. Goldenberg

发明人： Chien-Hsing Chang ,  David M. Goldenberg

IPC分类号： A61K39/44 ,  C07K16/28 ,  C07K16/46 ,  C07K14/00 ,  C07H21/02

CPC分类号： A61K47/484 ,  A61K47/48561 ,  A61K47/48576 ,  A61K47/48723 ,  A61K47/6849 ,  A61K47/6853 ,  A61K47/6891 ,  B82Y5/00 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2318/10 ,  C07K2319/00 ,  C07K2319/30

摘要： Described herein are compositions and methods of use of targeted delivery complexes for delivery of siRNA to a disease-associated cell, tissue or pathogen. The targeted delivery complex comprises a targeting molecule, such as an antibody or fragment thereof, conjugated to one or more siRNA carriers. In preferred embodiments the siRNA carrier is a dendrimer or protamine and the targeting molecule is an anti-cancer antibody, such as hRS7. More preferably, the antibody or fragment is rapidly internalized into the target cell to facilitate uptake of the siRNA. Most preferably, the targeted delivery complex is made by the DNL technique. The compositions and methods are of use to treat a variety of disease states, such as cancer, autoimmune disease, immune dysfunction, cardiac disease, neurologic disease, inflammatory disease or infectious disease.

摘要翻译： 本文描述了使用靶向递送复合物以将siRNA递送至疾病相关细胞，组织或病原体的组合物和方法。 靶向递送复合物包含与一种或多种siRNA载体缀合的靶向分子，例如抗体或其片段。 在优选的实施方案中，siRNA载体是树状聚合物或鱼精蛋白，靶向分子是抗癌抗体，例如hRS7。 更优选地，抗体或片段快速内化到靶细胞中以促进siRNA的摄取。 最优选地，靶向递送复合物通过DNL技术制备。 组合物和方法可用于治疗各种疾病状态，例如癌症，自身免疫疾病，免疫功能障碍，心脏病，神经系统疾病，炎性疾病或感染性疾病。

公开(公告)号：US20130164816A1

公开(公告)日：2013-06-27

申请号：US13549906

申请日：2012-07-16

申请人： Chien-Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

发明人： Chien-Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

IPC分类号： C12N9/96

CPC分类号： A61K47/48438 ,  A61K31/00 ,  A61K38/00 ,  A61K47/48415 ,  A61K47/48484 ,  A61K47/485 ,  A61K47/48538 ,  A61K47/48546 ,  A61K47/48561 ,  A61K47/48569 ,  A61K47/6811 ,  A61K47/6817 ,  A61K47/6829 ,  A61K47/6833 ,  A61K47/6843 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y15/00 ,  C07K14/475 ,  C07K16/18 ,  C07K16/22 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2863 ,  C07K16/2881 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/3007 ,  C07K16/3092 ,  C07K16/32 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2319/30 ,  C07K2319/35 ,  C07K2319/70 ,  C07K2319/74 ,  C12N9/12 ,  C12N9/22 ,  C12N9/96 ,  C12Y207/11001 ,  G01N33/54353 ,  G01N33/588 ,  Y02A50/491

摘要： The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

公开(公告)号：US20130095033A1

公开(公告)日：2013-04-18

申请号：US13688812

申请日：2012-11-29

申请人： IBC Pharmaceuticals, Inc.

发明人： Chien-Hsing Chang ,  David M. Goldenberg

IPC分类号： A61K39/395

CPC分类号： A61K39/39558 ,  A61K47/48746 ,  A61K47/6897 ,  A61K51/088 ,  B82Y5/00 ,  B82Y10/00 ,  C07K16/2863 ,  C07K16/30 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/35 ,  C07K2317/522 ,  C07K2317/526 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/64 ,  C07K2317/73 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/70 ,  A61K2300/00

摘要： The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-α2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

摘要翻译： 本发明涉及包含用于治疗癌症或自身免疫性疾病的抗IGF-1R抗体或其片段的方法和组合物。 优选地，癌症是肾细胞癌，乳腺癌或胰腺癌。 抗IGF-1R抗体或片段可以是复合物的一部分，例如DOCK-AND-LOCK TM（DNL TM）（DNL TM）复合物。 优选地，DNL TM复合物还包含第二抗体，第二抗体片段，亲和体或细胞因子。 更优选地，细胞因子是干扰素-α2b。 最优选地，第二抗体，第二片段或亲和体结合IGF-1R，TROP2或CEACAM6。 抗IGF-1R抗体或复合物可以单独施用或与治疗剂如mTOR抑制剂组合施用。

公开(公告)号：US20130078249A1

公开(公告)日：2013-03-28

申请号：US13590886

申请日：2012-08-21

申请人： Oliver Ast ,  Peter Bruenker ,  Tanja Fauti ,  Anne Freimoser-Grundschober ,  Christiane Jaeger ,  Christian Klein ,  Ekkehard Moessner ,  Pablo Umana

发明人： Oliver Ast ,  Peter Bruenker ,  Tanja Fauti ,  Anne Freimoser-Grundschober ,  Christiane Jaeger ,  Christian Klein ,  Ekkehard Moessner ,  Pablo Umana

IPC分类号： C07K16/46

CPC分类号： C07K16/468 ,  C07K16/2809 ,  C07K16/2863 ,  C07K16/3007 ,  C07K16/3053 ,  C07K16/40 ,  C07K2317/31 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/626 ,  C07K2317/64 ,  C07K2317/66 ,  C07K2317/73 ,  C07K2317/92 ,  C07K2317/94 ,  C07K2319/00

摘要： The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.