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：US20120100166A1

公开(公告)日：2012-04-26

申请号：US13184485

申请日：2011-07-15

申请人： Viktor Roschke ,  David Lafleur ,  David M. Hilbert ,  Peter Kiener

发明人： Viktor Roschke ,  David Lafleur ,  David M. Hilbert ,  Peter Kiener

IPC分类号： A61K38/17 ,  C07K7/08 ,  C07K19/00 ,  C12N15/62 ,  A61P37/06 ,  C12P21/02 ,  C12N1/19 ,  A61P19/02 ,  A61P29/00 ,  A61P1/00 ,  C07K14/00 ,  C12N5/10

CPC分类号： C07K14/47 ,  A61K38/00 ,  A61K47/6811 ,  A61K47/6813 ,  A61K47/6843 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6879 ,  C07K16/22 ,  C07K16/24 ,  C07K16/241 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/3046 ,  C07K16/32 ,  C07K2317/73 ,  C07K2317/77 ,  C07K2319/01 ,  C07K2319/30 ,  C12N9/0002

摘要： Complexes containing one or more modular recognition domains (MRDs) and MRDs attached to scaffolds including antibodies are described. The manufacture of these complexes are the use of these complexes to treat and diagnose diseases and disorders are also described.

摘要翻译： 描述了包含一个或多个模块识别结构域（MRD）和连接到包括抗体的支架的MRD的复合物。 这些复合物的制备是也描述了这些复合物用于治疗和诊断疾病和病症的用途。

公开(公告)号：US20110287022A1

公开(公告)日：2011-11-24

申请号：US12999626

申请日：2009-06-19

申请人： Yihong Yao ,  Bahija Jallal ,  Ricardo Cibotti ,  Anthony Coyle ,  Peter Kiener ,  Barbara White

发明人： Yihong Yao ,  Bahija Jallal ,  Ricardo Cibotti ,  Anthony Coyle ,  Peter Kiener ,  Barbara White

IPC分类号： A61K39/395 ,  C40B30/04 ,  A61P29/00 ,  A61P17/06 ,  A61P19/02 ,  G01N33/53 ,  C12Q1/02

CPC分类号： C07K16/249 ,  A61K2039/505 ,  C07K2317/76 ,  G01N2800/205 ,  G01N2800/56 ,  G01N2800/60

摘要： The present invention encompasses type-I IFN and IFNα-induced PD marker expression profiles, kits, and methods for identifying such IFNα-induced PD marker expression profiles. The type-I IFN and IFNα-induced PD marker expression profiles may also be used in, for example, methods of treating patients having a type-I IFN or IFNα-mediated disorder, methods of monitoring disease progression of patients receiving treatment with a therapeutic agent that binds to and modulates IFNα activity, identifying patients as candidates to receive a therapeutic that binds to and neutralizes IFNα activity, and in diagnosing or providing a prognoses to patients having IFNα-induced disorders.

摘要翻译： 本发明包括I型IFN和IFNα诱导的PD标志物表达谱，试剂盒和用于鉴定这种IFNα诱导的PD标志物表达谱的方法。 I型IFN和IFNα诱导的PD标志物表达谱也可用于例如治疗患有I型IFN或IFNα介导的病症的患者的方法，监测接受治疗的患者的疾病进展的方法 结合并调节IFNα活性的试剂，鉴定患者作为接受结合并中和IFNα活性的治疗剂的候选物，以及诊断或提供具有IFNα诱导的病症的患者的预后。

公开(公告)号：US20110236406A1

公开(公告)日：2011-09-29

申请号：US13008354

申请日：2011-01-18

申请人： Davorka Messmer ,  Kevin Tracey ,  Peter Kiener ,  Scott Alban

发明人： Davorka Messmer ,  Kevin Tracey ,  Peter Kiener ,  Scott Alban

IPC分类号： A61K39/00 ,  A61K39/12 ,  A61K39/02 ,  A61P37/04 ,  A61P31/12 ,  A61P31/04 ,  A61P35/00 ,  C07K19/00 ,  C12N5/0784 ,  C07K7/08

CPC分类号： C07K14/47 ,  C07K14/52 ,  C07K2319/23

摘要： The present invention relates to novel immunogenic compositions (e.g., vaccines), the production of such immunogenic compositions and methods of using such compositions. More specifically, this invention provides unique immunogenic molecules comprising an HMGB1 polypeptide (e.g., an HMGB1 B-box polypeptide) and an antigen. Even more specifically, this invention provides novel fusion proteins comprising an isolated HMGB1 polypeptide and an antigen such that administration of these fusion proteins provides the two signals required for native T-cell activation.

摘要翻译： 本发明涉及新的免疫原性组合物（例如疫苗），这种免疫原性组合物的生产和使用这些组合物的方法。 更具体地，本发明提供了包含HMGB1多肽（例如，HMGB1 B盒多肽）和抗原的独特的免疫原性分子。 更具体地，本发明提供了包含分离的HMGB1多肽和抗原的新型融合蛋白，使得这些融合蛋白的施用提供了天然T细胞活化所需的两种信号。

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：US20100278813A1

公开(公告)日：2010-11-04

申请号：US12001458

申请日：2007-12-11

申请人： James F. Young ,  Peter Kiener ,  Albertus Dominicus Erasmus Osterhaus ,  Ronaldus Adrianus Maria Fouchier

发明人： James F. Young ,  Peter Kiener ,  Albertus Dominicus Erasmus Osterhaus ,  Ronaldus Adrianus Maria Fouchier

IPC分类号： A61K39/42 ,  A61P31/12

CPC分类号： C07K16/1027 ,  A61K2039/505

摘要： The present invention relates to methods for broad spectrum prevention and treatment of viral respiratory infection. In particular, the present invention relates to methods for preventing, treating or ameliorating symptoms associated with respiratory syncytial virus (RSV), parainfluenza virus (PIV), and/or human metapneumovirus (hMPV) infection, the methods comprising administering to a subject an effective amount of one or more anti-RSV-antigen antibodies or antigen-binding fragments thereof, one or more anti-hMPV-antigen antibodies or antigen-binding fragments thereof, and/or one or more anti-PIV-antigen antibodies or antigen-binding fragments thereof. In certain embodiments, a certain serum titer of the anti-RSV-antigen antibodies, anti-PIV-antigen antibodies, and/or anti-hMPV-antigen antibodies or antigen-binding fragments thereof is achieved in said subject. In certain specific embodiments, the subject is human and, preferably, the anti-RSV-antigen antibody, anti-PIV-antigen antibody, and/or anti-hMPV-antigen antibodies are human or humanized. The present invention relates further to compositions comprising the anti-RSV-antigen is antibodies, anti-PIV-antigen antibodies, and/or anti-hMPV-antigen antibodies or antigen-binding fragments thereof. The present invention also relates to detectable or diagnostic compositions comprising the one or more anti-RSV-antigen antibodies, anti-PIV-antigen antibodies, and/or anti-hMPV-antigen antibodies or antigen-binding fragments thereof and methods for detecting or diagnosing RSV, PIV and/or hMPV infection utilizing the compositions.

摘要翻译： 本发明涉及广谱预防和治疗病毒性呼吸道感染的方法。 特别地，本发明涉及用于预防，治疗或改善与呼吸道合胞病毒（RSV），副流感病毒（PIV）和/或人类偏肺病毒（hMPV）感染相关的症状的方法，所述方法包括向受试者施用有效的 一种或多种抗RSV抗原抗体或其抗原结合片段，一种或多种抗hMPV抗原抗体或其抗原结合片段，和/或一种或多种抗PIV-抗原抗体或抗原结合 片段。 在某些实施方案中，在所述受试者中实现抗RSV抗原抗体，抗PIV抗原抗体和/或抗hMPV抗原抗体或其抗原结合片段的某一血清滴度。 在某些具体实施方案中，受试者是人，优选抗RSV抗原抗体，抗PIV抗原抗体和/或抗hMPV-抗原抗体是人或人源化的。 本发明进一步涉及包含抗RSV抗原的组合物是抗体，抗PIV抗原抗体和/或抗hMPV-抗原抗体或其抗原结合片段。 本发明还涉及包含一种或多种抗RSV抗原抗体，抗-PIV-抗原抗体和/或抗-hMPV-抗原抗体或其抗原结合片段的可检测或诊断组合物和用于检测或诊断的方法 使用组合物的RSV，PIV和/或hMPV感染。

公开(公告)号：US20100261172A1

公开(公告)日：2010-10-14

申请号：US12598526

申请日：2008-05-05

申请人： Yihong Yao ,  Bahija Jallal ,  Ricardo Cibotti ,  Anthony Coyle ,  Peter Kiener

发明人： Yihong Yao ,  Bahija Jallal ,  Ricardo Cibotti ,  Anthony Coyle ,  Peter Kiener

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6851 ,  C12Q2600/106

摘要： The present invention encompasses type-I IFN and IFNα-induced PD marker expression profiles, kits, and methods for identifying such IFNα-induced PD marker expression profiles. The type-I IFN and IFNα-induced PD marker expression profiles may also be used in, for example, methods of treating patients having a type-I IFN or IFNα-mediated disorder, methods of monitoring disease progression of patients receiving treatment with a therapeutic agent that binds to and modulates IFNα activity, identifying patients as candidates to receive a therapeutic that binds to and neutralizes IFNα activity, and in diagnosing or providing a prognosis to patients having IFNα-induced disorders.

摘要翻译： 本发明包括I型IFN和IFNα诱导的PD标志物表达谱，试剂盒和用于鉴定这种IFNα诱导的PD标志物表达谱的方法。 I型IFN和IFNα诱导的PD标志物表达谱也可用于例如治疗患有I型IFN或IFNα介导的病症的患者的方法，监测接受治疗的患者的疾病进展的方法 结合并调节IFNα活性的试剂，将患者鉴定为接受结合并中和IFNα活性的治疗剂的候选物，以及诊断或提供具有IFNα诱导的病症的患者的预后。

公开(公告)号：US20100143372A1

公开(公告)日：2010-06-10

申请号：US12517333

申请日：2007-12-06

申请人： Yihong Yao ,  Bahija Jallal ,  Ricardo Cibotti ,  Anthony Coyle ,  Peter Kiener

发明人： Yihong Yao ,  Bahija Jallal ,  Ricardo Cibotti ,  Anthony Coyle ,  Peter Kiener

IPC分类号： A61K39/395 ,  C12Q1/68

CPC分类号： C12Q1/6883 ,  A61K2039/505 ,  C07K16/249 ,  C07K2317/21 ,  C07K2317/565 ,  C07K2317/76 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/158 ,  Y02A90/22 ,  Y02A90/24 ,  Y02A90/26

摘要： The present invention encompasses type-1 IFN and IFNα-induced PD marker expression profiles, kits, and methods for identifying such IFNα-induced PD marker expression profiles. The type-I IFN and IFNα-induced PD marker expression profiles may also be used in, for example, methods of treating patients having a type-I IFN or IFNα-mediated disorder, methods of monitoring disease progression of patients receiving treatment with a therapeutic agent that binds to and modulates IFNα activity, identifying patients as candidates to receive a therapeutic that binds to and neutralizes IFNα activity, and in diagnosing or providing a prognosis to patients having IFNα-induced disorders.

摘要翻译： 本发明包括1型IFN和IFNα诱导的PD标志物表达谱，试剂盒和用于鉴定这种IFNα诱导的PD标志物表达谱的方法。 I型IFN和IFNα诱导的PD标志物表达谱也可用于例如治疗患有I型IFN或IFNα介导的病症的患者的方法，监测接受治疗的患者的疾病进展的方法 结合并调节IFNα活性的试剂，将患者鉴定为接受结合并中和IFNα活性的治疗剂的候选物，以及诊断或提供具有IFNα诱导的病症的患者的预后。

公开(公告)号：US20080305120A1

公开(公告)日：2008-12-11

申请号：US11570695

申请日：2005-06-16

申请人： Davorka Messmer ,  Kevin Tracey ,  Peter Kiener ,  Scott Alban

发明人： Davorka Messmer ,  Kevin Tracey ,  Peter Kiener ,  Scott Alban

IPC分类号： A61K39/00 ,  C07H21/04 ,  C12N1/20 ,  A61P35/04

CPC分类号： C07K14/47 ,  C07K14/52 ,  C07K2319/23

摘要： The present invention relates to novel immunogenic compositions (e.g., vaccines), the production of such immunogenic compositions and methods of using such compositions. More specially, this invention provides unique immunogenic molecules comprising an HMGB1 polypeptide (e.g., an HMGB1 B-box polypeptide) and an antigen. Even more specifically, this invention provides novel fusion proteins comprising an isolated HMGB1 polypeptide and an antigen such that administration of these fusion proteins provides the two signals required for native T-cell activation.

摘要翻译： 本发明涉及新的免疫原性组合物（例如疫苗），这种免疫原性组合物的生产和使用这些组合物的方法。 更具体地，本发明提供了包含HMGB1多肽（例如，HMGB1B盒多肽）和抗原的独特的免疫原性分子。 更具体地，本发明提供了包含分离的HMGB1多肽和抗原的新型融合蛋白，使得这些融合蛋白的施用提供了天然T细胞活化所需的两种信号。

公开(公告)号：US20080044413A1

公开(公告)日：2008-02-21

申请号：US11645290

申请日：2006-12-21

申请人： Scott Hammond ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Michael Kinch ,  Shannon Roff ,  Ralf Lutterbuese ,  Petra Lutterbuese ,  Bernd Schlereth ,  Patrick Baeuerle ,  Peter Kufer

发明人： Scott Hammond ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Michael Kinch ,  Shannon Roff ,  Ralf Lutterbuese ,  Petra Lutterbuese ,  Bernd Schlereth ,  Patrick Baeuerle ,  Peter Kufer

IPC分类号： A61K39/395 ,  A61P31/00 ,  A61P35/00 ,  A61P43/00 ,  C07K16/28

CPC分类号： C07K16/2866 ,  C07K16/2809 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/92 ,  C07K2319/30

摘要： The present invention relates to bispecific single chain antibodies comprising a first binding domain that immunospecifically binds to the T-cell antigen CD3 and a second binding domain that immunospecifically binds to the EphA2 receptor. Such bispecific single chain antibodies are encompassed by the term “EphA2-BiTEs.” The present invention further relates to methods and compositions designed for the treatment, prevention and/or management of disorders associated with aberrant expression and/or activity of EphA2. Such disorders include, but are not limited to, cancer, non-cancer hyperproliferative cell disorders, and infections. The invention further relates to vectors comprising polynucleotides encoding the EphA2-BiTEs of the invention, host cells transformed therewith, and their use in the production of said EphA2-BiTEs. The invention also provides compositions, including pharmaceutical compositions, comprising any of the aforementioned EphA2-BiTEs, polynucleotides or vectors either alone or in combination with one or more prophylactic or therapeutic agents. Also disclosed are methods of screening for said EphA2-BiTEs and kits comprising any of the aforementioned compositions and diagnostic reagents.

摘要翻译： 本发明涉及双特异性单链抗体，其包含免疫特异性结合T细胞抗原CD3的第一结合结构域和免疫特异性结合EphA2受体的第二结合结构域。 这种双特异性单链抗体包括在术语“EphA2-BiTEs”中。 本发明还涉及设计用于治疗，预防和/或控制与EphA2的异常表达和/或活性相关的病症的方法和组合物。 这些疾病包括但不限于癌症，非癌症过度增殖性细胞病症和感染。 本发明还涉及包含编码本发明的EphA2-BiTE的多核苷酸，转化的宿主细胞的载体及其在所述EphA2-BiTE的生产中的用途。 本发明还提供包含单独或与一种或多种预防或治疗剂组合的任何上述EphA2-BiTE，多核苷酸或载体的组合物，包括药物组合物。 还公开了筛选所述EphA2-BiTE和包含任何上述组合物和诊断试剂的试剂盒的方法。