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公开(公告)号：US20050281783A1
公开(公告)日：2005-12-22
申请号：US10966483
申请日：2004-10-15
IPC分类号： A61K20060101 , A61K39/00 , A61K48/00 , C12N1/21
CPC分类号： A61K39/0011 , A61K2039/522 , A61K2039/523
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly metastatic cancer and cancers of T cell origin, and hyperproliferative diseases involving EphA2-expressing cells. The methods of the invention entail the use of a Listeria-based EphA2 vaccine. The invention also provides pharmaceutical compositions comprising one or more Listeria-based vaccines of the invention either alone or in combination with one or more other agents useful for cancer therapy. In certain aspects of the invention, the methods entail eliciting both CD4+ and CD8+ T-cell responses against EphA2 and/or EphA2-expressing cells.
摘要翻译： 本发明涉及设计用于治疗，治疗或预防癌症，特别是转移性癌症和T细胞来源的癌症以及涉及EphA2表达细胞的过度增殖性疾病的方法和组合物。 本发明的方法需要使用基于李斯特菌的EphA2疫苗。 本发明还提供包含本发明的一种或多种基于李斯特菌的疫苗的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。 在本发明的某些方面，所述方法需要引起针对EphA2和/或EphA2表达细胞的CD4 +和/或CD8 + T细胞应答。
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公开(公告)号：US20050175616A1
公开(公告)日：2005-08-11
申请号：US10854326
申请日：2004-05-26
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。
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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。
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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。
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公开(公告)号：US20070166314A1
公开(公告)日：2007-07-19
申请号：US11717799
申请日：2007-03-12
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。
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6.发明申请EphA2, hypoproliferative cell disorders and epithelial and endothelial reconstitution 审中-公开EphA2，低增殖细胞疾病和上皮和内皮重建公开(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。
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公开(公告)号：US07585504B2
公开(公告)日：2009-09-08
申请号：US11254679
申请日：2005-10-21
申请人： Herren Wu , Christian B. Allan , Changshou Gao , Ling-Ling An , Peter Kiener , Su-Yau Mao , Anthony Coyle
发明人： Herren Wu , Christian B. Allan , Changshou Gao , Ling-Ling An , Peter Kiener , Su-Yau Mao , Anthony Coyle
IPC分类号： A61K39/395
CPC分类号： C07K16/24 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/565 , C07K2317/76 , C07K2317/92 , C07K2319/30 , Y02A50/412
摘要： Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.
摘要翻译： 公开了用于抑制促炎细胞因子从脊椎动物细胞中释放并抑制患者炎性细胞因子级联的组合物和方法。 组合物包含例如特异性结合HMG1的高亲和力抗体及其抗原性片段。 本发明的高亲和力抗体和包含其的药物组合物可用于许多目的，例如作为针对广泛范围的炎性疾病和病症的治疗剂，例如败血症，类风湿性关节炎，腹膜炎，克罗恩病，再灌注损伤，败血症 内毒素性休克，囊性纤维化，心内膜炎，牛皮癣，牛皮癣关节炎，关节炎，过敏性休克，器官缺血，再灌注损伤和同种异体移植排斥。 此外，本发明的高亲和力抗体可用作诊断抗体。
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8.发明申请Method of Identifying Membrane Ig Specific Antibodies and Use Thereof for Targeting Immunoglobulin-Producing Precursor Cells 有权鉴定膜Ig特异性抗体的方法及其用途靶向免疫球蛋白产生前体细胞公开(公告)号：US20090130111A1
公开(公告)日：2009-05-21
申请号：US12067396
申请日：2006-09-28
申请人： Herren Wu , Peter Kiener , Partha S. Chowdhury , James F. Young
发明人： Herren Wu , Peter Kiener , Partha S. Chowdhury , James F. Young
IPC分类号： A61K39/395 , C07K16/18 , C12N15/11 , C40B30/04 , C12N5/06
CPC分类号： G01N33/56972 , A61K2039/505 , C07K16/4291 , C07K2317/52 , C07K2317/55 , Y10S424/805 , Y10S530/862 , Y10S530/868
摘要： The present invention relates to the discovery of antibodies that bind to novel epitopes present on membrane-anchored immunoglobulins and which bind to these novel epitopes on the surface of B cells and plasma cells. In addition, the antibodies of the present invention can mediate ADCC and can be useful to deplete those B cells and plasma cells expressing the novel epitopes of the invention. The antibodies of the present invention can be useful for the treatment of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells. Accordingly the present invention also provides compositions and methods for the prevention, management, treatment or amelioration of B cell-mediated diseases and diseases caused by monoclonal expansion of B cells.
摘要翻译： 本发明涉及结合存在于膜锚定的免疫球蛋白上并与B细胞和浆细胞表面上的这些新表位结合的抗体的发现。 此外，本发明的抗体可以介导ADCC，并且可用于消耗表达本发明的新表位的那些B细胞和浆细胞。 本发明的抗体可用于治疗由B细胞的单克隆扩增引起的B细胞介导的疾病和疾病。 因此，本发明还提供了用于预防，治疗或改善由B细胞的单克隆扩增引起的B细胞介导的疾病和疾病的组合物和方法。
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公开(公告)号：US07964706B2
公开(公告)日：2011-06-21
申请号：US12094447
申请日：2006-11-27
申请人： Herren Wu , Changshou Gao , Ling-Ling An , Peter Kiener , Su-Yau Mao , Anthony Coyle , Jane Tian
发明人： Herren Wu , Changshou Gao , Ling-Ling An , Peter Kiener , Su-Yau Mao , Anthony Coyle , Jane Tian
IPC分类号： C07K16/00
CPC分类号： C07K16/24 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C07K2319/32
摘要： Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn s disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.
摘要翻译： 公开了用于抑制促炎细胞因子从脊椎动物细胞中释放并抑制患者炎性细胞因子级联的组合物和方法。 组合物包含例如特异性结合HMG1的高亲和力抗体及其抗原性片段。 本发明的高亲和力抗体和包含其的药物组合物可用于许多目的，例如作为针对广泛范围的炎性疾病和病症的治疗剂，例如败血症，类风湿性关节炎，腹膜炎，克罗恩病，再灌注损伤， 败血症，内毒素性休克，囊性纤维化，心内膜炎，牛皮癣，牛皮癣关节炎，关节炎，过敏性休克，器官缺血，再灌注损伤和同种异体移植排斥。 此外，本发明的高亲和力抗体可用作诊断抗体。
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公开(公告)号：US20100278838A1
公开(公告)日：2010-11-04
申请号：US12755468
申请日：2010-04-07
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。
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