公开(公告)号：US20050175616A1

公开(公告)日：2005-08-11

申请号：US10854326

申请日：2004-05-26

申请人： Peter Kiener ,  Solomon Langermann ,  Michael Kinch ,  Elizabeth Bruckheimer

发明人： Peter Kiener ,  Solomon Langermann ,  Michael Kinch ,  Elizabeth Bruckheimer

IPC分类号： A61K20060101 ,  A61K39/395 ,  C07K16/28 ,  C07K16/30 ,  C12P21/04

CPC分类号： C07K16/2863

摘要： The present invention relates to the use of antitumor compositions capable of inhibiting PCDGF biological activity for the treatment of cancers. In particular the present invention relates to the use of PCDGF antagonist, e.g., antibodies that prevent PCDGF from binding its receptor, Rse (also referred to as “Sky” and “Tyro3”).

摘要翻译： 本发明涉及能够抑制PCDGF生物活性用于治疗癌症的抗肿瘤组合物的用途。 特别地，本发明涉及PCDGF拮抗剂的用途，例如防止PCDGF结合其受体Rse（也称为“Sky”和“Tyro3”）的抗体。

公开(公告)号：US20050059592A1

公开(公告)日：2005-03-17

申请号：US10823254

申请日：2004-04-12

申请人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann ,  Jennifer Reed

发明人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann ,  Jennifer Reed

IPC分类号： A61B20060101 ,  A61K39/00 ,  A61K39/395 ,  A61K49/00 ,  C07K16/28 ,  C07K16/32

CPC分类号： C07K16/28 ,  A61K2039/505 ,  C07K16/32

摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of a non-neoplastic hyperproliferative cell or excessive cell accumulation disorders, particularly those involving hyperproliferation of epithelial or endothelial cells. In one embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2 agonistic agents that bind to EphA2 and increase EphA2 cytoplasmic tail phosphorylation and/or increase EphA2 autophosphorylation in cells which EphA2 has been agonized. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2 agonistic agents that bind to EphA2 and reduce EphA2 activity (other than autophosphorylation). In another embodiment, the methods of the invention comprise administration of an effective amount of one or more EphA2 agonistic agents that bind to EphA2 and decrease a pathology-causing cell phenotype (e.g., a pathology-causing epithelial cell phenotype or a pathology-causing endothelial cell phenotype). In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more EphA2 agonistic agents that are EphA2 antibodies that bind to EphA2 with a very low Koff rate. In preferred embodiments, agents of the invention are monoclonal antibodies. The invention also provides pharmaceutical compositions comprising one or more EphA2 agonistic agents of the invention either alone or in combination with one or more other agents useful in therapy for non-neoplastic hyperproliferative cell or excessive cell accumulation disorders.

摘要翻译： 本发明涉及设计用于治疗，管理或预防非肿瘤性过度增殖性细胞或过度细胞累积障碍，特别是涉及上皮细胞或内皮细胞过度增殖的方法和组合物。 在一个实施方案中，本发明的方法包括施用有效量的一种或多种EphA2激动剂，其结合EphA2并增加EphA2细胞质尾磷酸化和/或增加EphA2已被激动的细胞中的EphA2自磷酸化。 在另一个实施方案中，本发明的方法包括施用有效量的一种或多种EphA2激动剂，其结合EphA2并降低EphA2活性（除了自磷酸化）。 在另一个实施方案中，本发明的方法包括施用有效量的一种或多种结合EphA2的EphA2激动剂并减少病理学引起的细胞表型（例如，导致病理的上皮细胞表型或致病性病因的内皮 细胞表型）。 在另一个实施方案中，本发明的方法包括施用有效量的一种或多种EphA2激动剂，其是以非常低的Koff率与EphA2结合的EphA2抗体。 在优选的实施方案中，本发明的试剂是单克隆抗体。 本发明还提供包含本发明的一种或多种EphA2激动剂的药物组合物，其单独或与一种或多种其它可用于治疗非肿瘤性过度增殖性细胞或过度细胞累积障碍的其它药物组合。

公开(公告)号：US20070166314A1

公开(公告)日：2007-07-19

申请号：US11717799

申请日：2007-03-12

申请人： Michael Kinch ,  Kelly Carles-Kinch ,  Peter Kiener ,  Solomon Langermann

发明人： Michael Kinch ,  Kelly Carles-Kinch ,  Peter Kiener ,  Solomon Langermann

IPC分类号： A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C12N5/06 ,  C07K16/30

CPC分类号： C07K16/2866 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/73 ,  C07K2317/75 ,  C07K2317/92

摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and agonizes EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels. In other embodiments, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and inhibits cancer cell colony formation in soft agar, inhibits tubular network formation in three-dimensional basement membrane or extracellular matrix preparation, preferentially binds to an EphA2 epitope that is exposed on cancer cells but not non-cancer cells, and/or has a low Koff, thereby, inhibiting tumor cell growth and/or metastasis. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.

摘要翻译： 本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。 在一个实施方案中，本发明的方法包括施用有效量的结合EphA2并激动EphA2的抗体，从而增加EphA2磷酸化并降低EphA2水平。 在其它实施方案中，本发明的方法包括施用有效量的结合EphA2的抗体并抑制软琼脂中的癌细胞集落形成，抑制三维基底膜或细胞外基质制剂中的管状网络形成，优先结合 涉及暴露于癌细胞但不暴露于非癌细胞的EphA2表位，和/或具有低K off，从而抑制肿瘤细胞生长和/或转移。 本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

公开(公告)号：US20050049176A1

公开(公告)日：2005-03-03

申请号：US10823259

申请日：2004-04-12

申请人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann

发明人： Peter Kiener ,  Michael Kinch ,  Solomon Langermann

IPC分类号： A61K38/00 ,  A61K38/19 ,  A61K39/395 ,  A61K48/00 ,  C07K14/715 ,  C07K16/28 ,  C12N20060101

CPC分类号： C07K16/2866 ,  A61K38/19 ,  C07K14/715

摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of a hypoproliferative cell disorder, especially those disorders relating to the destruction, shedding, or inadequate proliferation of epithelial and/or endothelial cells, particularly interstitial cystitis (IC) and lesions associated with inflammatory bowel disease (IBD). The methods of the invention comprise the administration of an effective amount of one or more agents that are antagonists of EphA2. In certain embodiments, the EphA2 antagonistic agent of the invention decreases EphA2-endogenous ligand binding, upregulates EphA2 gene expression and/or translation, increases EphA2 protein stability or protein accumulation, decreases EphA2 cytoplasmic tail phosphorylation, promotes EphA2 kinase activity (other than autophosphorylation or ligand-mediated EphA2 signaling), increases proliferation of EphA2 expressing cells, increases survival of EphA2 expressing cells, and/or maintains/reconstitutes epithelial and/or endothelial cell layer integrity. The invention also provides pharmaceutical compositions comprising one or more EphA2 antagonistic agents of the invention either alone or in combination with one or more other agents useful for therapy for a hypoproliferative cell disorder. Diagnostic methods and methods for screening for therapeutically useful agents are also provided.

摘要翻译： 本发明涉及设计用于治疗，治疗或预防低增殖性细胞病症的方法和组合物，特别是与上皮和/或内皮细胞，特别是间质性膀胱炎（IC）的破坏，脱落或不充分增殖有关的那些疾病， 和与炎症性肠病（IBD）相关的损伤。 本发明的方法包括施用有效量的一种或多种作为EphA2拮抗剂的试剂。 在某些实施方案中，本发明的EphA2拮抗剂降低EphA2-内源性配体结合，上调EphA2基因表达和/或翻译，增加EphA2蛋白稳定性或蛋白质积累，降低EphA2胞质尾磷酸化，促进EphA2激酶活性（除了自磷酸化或 配体介导的EphA2信号传导）增加EphA2表达细胞的增殖，增加EphA2表达细胞的存活，和/或保持/重建上皮和/或内皮细胞层完整性。 本发明还提供包含本发明的一种或多种EphA2拮抗剂的药物组合物，其单独或与一种或多种其它用于治疗低增殖性细胞病症的其它药剂组合。 还提供了用于筛选治疗有用的试剂的诊断方法和方法。

公开(公告)号：US20100278838A1

公开(公告)日：2010-11-04

申请号：US12755468

申请日：2010-04-07

申请人： Michael S. Kinch ,  Kelly Carles-Kinch ,  Peter Kiener ,  Solomon Langermann

发明人： Michael S. Kinch ,  Kelly Carles-Kinch ,  Peter Kiener ,  Solomon Langermann

IPC分类号： A61K39/395 ,  C07K16/00 ,  C12N15/13 ,  C12N15/63 ,  C12N5/00 ,  G01N33/567 ,  A61P35/00

CPC分类号： C07K16/2866 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/73 ,  C07K2317/75 ,  C07K2317/92

摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and agonizes EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels. In other embodiments, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and inhibits cancer cell colony formation in soft agar, inhibits tubular network formation in three-dimensional basement membrane or extracellular matrix preparation, preferentially binds to an EphA2 epitope that is exposed on cancer cells but not non-cancer cells, and/or has a low Koff, thereby, inhibiting tumor cell growth and/or metastasis. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.

摘要翻译： 本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。 在一个实施方案中，本发明的方法包括施用有效量的结合EphA2并激动EphA2的抗体，从而增加EphA2磷酸化并降低EphA2水平。 在其它实施方案中，本发明的方法包括施用有效量的结合EphA2的抗体并抑制软琼脂中的癌细胞集落形成，抑制三维基底膜或细胞外基质制剂中的管状网络形成，优先结合 涉及暴露于癌细胞但不暴露于非癌细胞的EphA2表位，和/或具有低Koff，从而抑制肿瘤细胞生长和/或转移。 本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

公开(公告)号：US09011853B2

公开(公告)日：2015-04-21

申请号：US13392811

申请日：2010-08-31

申请人： Solomon Langermann ,  Linda Liu ,  Joseph R. Podojil ,  Stephen D. Miller ,  Shannon Marshall

发明人： Solomon Langermann ,  Linda Liu ,  Joseph R. Podojil ,  Stephen D. Miller ,  Shannon Marshall

IPC分类号： A61K38/16 ,  C07K14/705 ,  C07K16/46 ,  G01N33/68 ,  A61K38/17 ,  C07K16/28

CPC分类号： C07K14/70532 ,  A61K9/0019 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/44 ,  C07K16/2827 ,  C07K2317/50 ,  C07K2317/56 ,  C07K2317/72 ,  C07K2319/30 ,  C07K2319/32 ,  G01N33/6863 ,  G01N33/6866 ,  G01N33/6869 ,  G01N2800/52

摘要： Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1β, TNF-α, TGF-beta, IFN-γ, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.

摘要翻译： 公开了含有B7-H4多肽的融合蛋白。 B7-H4融合蛋白可以包括全长B7-H4多肽，或可以含有全长B7-H4多肽的片段，包括B7-H4多肽的一些或全部细胞外结构域。 还公开了使用融合蛋白来下调T细胞活化和治疗炎性和自身免疫性疾病和病症的方法。 B7-H4融合蛋白可用于通过抑制或减少Th1，Th17，Th22和/或分泌或引起其他细胞的其他细胞的分化，增殖，活性和/或细胞因子产生和/或分泌来治疗炎症 包括但不限于IL-1和bgr; TNF-α，TGF-β，IFN-γ，IL-17，IL-6，IL-23，IL-22，IL-21， 和MMPs; 或增强Treg的IL-10分泌，增加Treg的分化，增加Treg的数量或其组合。

公开(公告)号：US20140044738A1

公开(公告)日：2014-02-13

申请号：US14111402

申请日：2012-04-19

申请人： Solomon Langermann ,  Linda Liu ,  Shannon Marshall ,  Sheng Yao

发明人： Solomon Langermann ,  Linda Liu ,  Shannon Marshall ,  Sheng Yao

IPC分类号： C07K16/28 ,  G01N33/68 ,  A61K39/395

CPC分类号： C07K16/2827 ,  A61K39/3955 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2818 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/75 ,  C07K2317/76 ,  G01N33/6854

摘要： The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to B7-H1 or PD-1. In some embodiments such molecules are additionally capable of modulating the ability of B7-H1 or B7-DC to bind to PD-1 or are capable of affecting the signaling activity of the B7-H1 or PD-1. The invention additionally concerns the uses of such molecules in the diagnosis and treatment of cancer and other diseases.

摘要翻译： 本发明涉及抗体及其抗原结合片段和能够免疫特异性结合B7-H1或PD-1的其它分子。 在一些实施方案中，此类分子另外能够调节B7-H1或B7-DC结合PD-1或能够影响B7-H1或PD-1的信号传导活性的能力。 本发明还涉及这些分子在诊断和治疗癌症和其它疾病中的用途。

公开(公告)号：US08609089B2

公开(公告)日：2013-12-17

申请号：US13332154

申请日：2011-12-20

申请人： Solomon Langermann ,  Linda Liu

发明人： Solomon Langermann ,  Linda Liu

IPC分类号： A61K39/395

CPC分类号： A61K38/177 ,  A61K31/675 ,  A61K45/06 ,  C07K14/70532 ,  C07K2319/33 ,  Y02A50/402 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/423 ,  Y02A50/475 ,  Y02A50/478 ,  Y02A50/48 ,  A61K2300/00

摘要： Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.

摘要翻译： 描述了使用治疗方案治疗癌症和感染性疾病的方法，其包括与增强剂（例如环磷酰胺）联合降低T细胞中的抑制性信号转导的化合物以产生有效的T细胞介导的应答。 还公开了包含可用于本发明方法的PD-1拮抗剂和增效剂的组合物。

公开(公告)号：US20120177645A1

公开(公告)日：2012-07-12

申请号：US13392399

申请日：2010-08-31

申请人： Solomon Langermann ,  Linda Liu

发明人： Solomon Langermann ,  Linda Liu

IPC分类号： A61K39/395 ,  A61P41/00 ,  C07K16/00

CPC分类号： C07K14/70532 ,  A61K9/0019 ,  A61K38/00 ,  A61K38/1709 ,  A61K39/44 ,  C07K16/2827 ,  C07K2317/50 ,  C07K2317/56 ,  C07K2317/72 ,  C07K2319/30 ,  C07K2319/32 ,  G01N33/6863 ,  G01N33/6866 ,  G01N33/6869 ,  G01N2800/52

摘要： Methods for modulating immune responses in a subject are provided. A preferred embodiment provides methods and compositions for reducing or inhibiting transplant rejection in a subject, preferably a human subject. Transplant rejection can be inhibited or reduced in a subject by administering an effective amount of B7-H4 polypeptide, fragments or fusions thereof to inhibit or reduce the biological activity of an immune cell or to reduce the amounts of proinflammatory molecules at a site of transplant. Th1, Th17 and Th22 cells are exemplary T cells that can be targeted for inhibition by B7-H4 polypeptides, fusion proteins or fragments thereof to inhibit or reduce inflammation.

摘要翻译： 提供了调节受试者中免疫应答的方法。 优选的实施方案提供用于减少或抑制受试者，优选人受试者的移植排斥的方法和组合物。 通过施用有效量的B7-H4多肽，其片段或融合物来抑制或降低免疫细胞的生物活性或减少移植部位的促炎症分子的量，可以抑制或减少受试者的移植排斥反应。 Th1，Th17和Th22细胞是可被B7-H4多肽，融合蛋白或其片段抑制或减少炎症的靶向的示例性T细胞。

公开(公告)号：US06500434B1

公开(公告)日：2002-12-31

申请号：US09298494

申请日：1999-04-23

申请人： Solomon Langermann ,  Scott J. Hultgren ,  Jerome S. Pinkner ,  Christine Gale Auguste

发明人： Solomon Langermann ,  Scott J. Hultgren ,  Jerome S. Pinkner ,  Christine Gale Auguste

IPC分类号： A61K39385

CPC分类号： A61K39/0258 ,  Y02A50/474

摘要： The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.

摘要翻译： 本发明提供用于给予人和非人动物以刺激免疫应答的细菌免疫原性试剂。 它特别涉及用异源蛋白复合物对哺乳动物物种进行疫苗接种，作为刺激保护疫苗接受者免受病原菌种感染的抗体产生的机制。 在另一方面，本发明提供了抗这种蛋白质和蛋白质复合物的抗体，其可以用作诊断和/或作为病原菌种的保护/治疗剂。 还公开了用于以最佳水平表达FimC-H复合物的新载体。