公开(公告)号：US20100286252A1

公开(公告)日：2010-11-11

申请号：US12776532

申请日：2010-05-10

申请人： Wu-Bo LI ,  Michael Kinch ,  Michael Goldblatt

发明人： Wu-Bo LI ,  Michael Kinch ,  Michael Goldblatt

IPC分类号： A61K31/7088 ,  C07H21/04 ,  C07K14/00 ,  C40B30/00 ,  C12N5/02 ,  A61K48/00

CPC分类号： C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158

摘要： A human gene, fg01, on chromosome 8, is identified, as well as a truncated form on chromosome 5. Upregulation appears to suppress the Alzheimer's phenotype, (AB plaques and hyperphosphorylated tau tangles) which may address the onset of symptoms or progression of symptoms associated with AD. Screening methods are also set forth.

摘要翻译： 鉴定出染色体8上的人基因fg01，以及染色体5上的截短形式。上调似乎抑制阿尔茨海默氏症表型（AB斑和超磷酸化tau缠结），其可以解决症状发作或症状发展 与AD相关。 还阐述了筛选方法。

公开(公告)号：US20080124341A1

公开(公告)日：2008-05-29

申请号：US11939122

申请日：2007-11-13

申请人： Roxanne Duan ,  Michael Kinch ,  Michael Goldblatt

发明人： Roxanne Duan ,  Michael Kinch ,  Michael Goldblatt

IPC分类号： A61K39/395 ,  A61K39/00 ,  A61P37/00

CPC分类号： C07K16/18

摘要： The invention provides for inhibition of viral disease by the provision to a mammalian host of antibodies directed against an escort protein likeTsg 101. These proteins appear on the surface of a cell, and thus can be bound by circulating antibodies thereto. By binding escort proteins on the cell surface, budding of viral particles is inhibited. The virus infects the initial cells, but cannot escape that cell to infect the body en masse.

摘要翻译： 本发明通过向哺乳动物宿主提供针对护送蛋白如T101的抗体来提供对病毒性疾病的抑制。这些蛋白质出现在细胞表面，因此可以通过循环其抗体而结合。 通过在细胞表面结合护送蛋白，病毒颗粒的出芽被抑制。 病毒感染初始细胞，但不能逃避该细胞大量感染身体。

公开(公告)号：US20080089931A1

公开(公告)日：2008-04-17

申请号：US11953653

申请日：2007-12-10

申请人： Michael Kinch

发明人： Michael Kinch

IPC分类号： A61K9/50 ,  A61K31/70 ,  A61P35/00 ,  A61K39/395

CPC分类号： A61K38/1709 ,  A61K9/127 ,  A61K48/00 ,  A61K2039/505 ,  C07K16/2866 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/622 ,  C12N9/12 ,  C12N9/16 ,  C12Y301/03048

摘要： The present invention relates to methods and compositions designed for treatment, management, or prevention of a hyperproliferative cell disease, particular cancer. The methods of the invention comprise the administration of an effective amount of a composition that targets cells expressing low molecular weight protein tyrosine kinase (“LMW-PTP”) in particular using moieties that bind an Eph family receptor tyrosine kinase, such as EphA2 or EphA4, and inhibits or reduces LMW-PTP expression and/or activity. In one embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety attached to a delivery vehicle, and one or more agents that inhibit LMW-PTP expression and/or activity operatively associated with the delivery vehicle. In another embodiment, the method of the invention comprises administering to a subject a composition comprising a nucleic acid comprising a nucleotide sequence encoding an EphA2 or EphA4 targeting moiety and an agent that inhibits or reduces LMW-PTP expression and/or activity. In yet another embodiment, the method of the invention comprises administering to a subject a composition comprising an EphA2 or EphA4 targeting moiety and a nucleic acid comprising a nucleotide sequence encoding an agent that inhibits or reduces LMW-PTP expression and/or activity, where the nucleic acid is operatively associated with the delivery vehicle. Pharmaceutical compositions are also provided by the present invention.

摘要翻译： 本发明涉及用于治疗，治疗或预防过度增殖性细胞疾病，特定癌症的方法和组合物。 本发明的方法包括施用有效量的靶向表达低分子量蛋白酪氨酸激酶（“LMW-PTP”）的细胞的组合物，特别是使用结合Eph家族受体酪氨酸激酶（例如EphA2或EphA4）的部分 ，并且抑制或降低LMW-PTP表达和/或活性。 在一个实施方案中，本发明的方法包括向受试者施用包含与递送载体​​连接的EphA2或EphA4靶向部分的组合物，以及一种或多种抑制LMW-PTP表达和/或与递送载体​​可操作地相关的活性的试剂 。 在另一个实施方案中，本发明的方法包括向受试者施用包含核酸的组合物，所述核酸包含编码EphA2或EphA4靶向部分的核苷酸序列和抑制或降低LMW-PTP表达和/或活性的试剂。 在另一个实施方案中，本发明的方法包括向受试者施用包含EphA2或EphA4靶向部分的组合物和包含编码抑制或降低LMW-PTP表达和/或活性的试剂的核苷酸序列的核酸，其中 核酸与递送载体​​可操作地相关联。 药物组合物也由本发明提供。

公开(公告)号：US20060121042A1

公开(公告)日：2006-06-08

申请号：US11259133

申请日：2005-10-27

申请人： William Dall'Acqua ,  Melissa Damschroder ,  Michael Kinch ,  Kelly Carles-Kinch

发明人： William Dall'Acqua ,  Melissa Damschroder ,  Michael Kinch ,  Kelly Carles-Kinch

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

CPC分类号： C07K16/2866 ,  C07K16/005 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/92

摘要： The present invention relates to methods and compositions designed for the treatment, management, prevention and/or amelioration of various disorders associated with aberrant expression and/or activity of one or more Eph receptor tyrosine kinase family members and/or one or more Eph receptor ligands, particularly the Ephrins. In particular, the invention provides methods for the treatment, management, prevention and/or amelioration of a disorder associated with aberrant expression and/or activity(ies) of one or more Eph receptors and/or one or more Ephrins, the method comprising administering to a subject in need thereof an effective amount of one or more Eph/Ephrin Modulators. The present invention further relates to methods of modulating antibody specificity by tailoring the affinity to cognate antigens.

摘要翻译： 本发明涉及设计用于治疗，管理，预防和/或改善与一种或多种Eph受体酪氨酸激酶家族成员和/或一种或多种Eph受体配体的异常表达和/或活性相关的各种疾病的方法和组合物 ，特别是Ephrins。 特别地，本发明提供了治疗，管理，预防和/或改善与一种或多种Eph受体和/或一种或多种Ephrins的异常表达和/或活性相关的病症的方法，所述方法包括施用 对有需要的受试者有效量的一种或多种Eph / Ephrin调节剂。 本发明还涉及通过调整对同源抗原的亲和力来调节抗体特异性的方法。

公开(公告)号：US20060088541A1

公开(公告)日：2006-04-27

申请号：US11297548

申请日：2005-12-08

申请人： Michael Kinch ,  Nicole Zantek ,  Patrick Hein

发明人： Michael Kinch ,  Nicole Zantek ,  Patrick Hein

IPC分类号： A61K39/395 ,  A61K38/17

CPC分类号： C07K16/2866 ,  A61K38/19 ,  A61K2039/505 ,  C07K16/3069

摘要： The present invention is directed to compounds and methods for the treatment of cancer. The compounds of this invention have specificity for EphA2, an epithelial cell tyrosine kinase that is overexpressed in metastatic tumor cells. The compounds used in accordance with this invention may be provided in a pharmaceutical composition for treatment of metastatic cancer.

摘要翻译： 本发明涉及治疗癌症的化合物和方法。 本发明的化合物对于转移性肿瘤细胞中过表达的上皮细胞酪氨酸激酶EphA2具有特异性。 根据本发明使用的化合物可以提供在用于治疗转移性癌症的药物组合物中。

公开(公告)号：US20050152899A1

公开(公告)日：2005-07-14

申请号：US10994129

申请日：2004-11-19

申请人： Michael Kinch ,  Kelly Carles-Kinch ,  Jane Stewart

发明人： Michael Kinch ,  Kelly Carles-Kinch ,  Jane Stewart

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

CPC分类号： C07K16/30 ,  A61K2039/505 ,  C07K16/24 ,  C07K16/2866 ,  C07K16/3015 ,  C07K16/3069 ,  C07K16/3076 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/75

摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. The methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to and agonize EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels in cells which EphA2 has been agonized. The invention also encompasses antibodies that preferentially bind an EphA2 epitope exposed on cancer cells but not non-cancer cells. 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。 本发明的方法包括施用有效量的一种或多种与EphA2结合并激动EphA2的抗体，从而增加EphA2被激动的细胞中的EphA2磷酸化和降低EphA2水平。 本发明还包括优先结合暴露于癌细胞但不是非癌细胞的EphA2表位的抗体。 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：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：US08207209B2

公开(公告)日：2012-06-26

申请号：US12256571

申请日：2008-10-23

申请人： Michael Kinch ,  Michael Goldblatt

发明人： Michael Kinch ,  Michael Goldblatt

IPC分类号： A61K31/4184

CPC分类号： A61K31/4745 ,  A61K31/131 ,  A61K31/155 ,  A61K31/4184

摘要： A method of inhibiting viral respiratory infection in a mammal in need of same, includes administering an effective amount of 2-[2-(5-carbamimidoyl-benzofuran-2-yl)-vinyl]-H-benzoimidazole-5-carboxamidine or the Bis-N-hydroxyamidine prodrug thereof, prior to viral infection, or therapeutically following viral infection, to inhibit that viral infection. The compound selectively inhibits Caspase 2 and/or 8 as to prevent infective viral particle release. It is optionally administered IV, IP, orally or via other conventional administration routes in a dosage range of 1 ng/kg-200 mg/kg of body weight.

摘要翻译： 在需要相同的哺乳动物中抑制病毒呼吸道感染的方法包括给予有效量的2- [2-（5-甲脒基 - 苯并呋喃-2-基） - 乙烯基] -H-苯并咪唑-5-甲脒或 双-N-羟基脒前药，在病毒感染之前，或治疗性地在病毒感染之后，以抑制该病毒感染。 该化合物选择性地抑制胱天蛋白酶2和/或8以防止感染性病毒颗粒释放。 任选地以1ng / kg-200mg / kg体重的剂量范围以IV，IP口服或经由其它常规给药途径施用。

公开(公告)号：US20090220527A1

公开(公告)日：2009-09-03

申请号：US12158651

申请日：2006-12-20

申请人： Melissa Damschroder ,  William Dall'Acqua ,  Herren Wu ,  Michael Kinch

发明人： Melissa Damschroder ,  William Dall'Acqua ,  Herren Wu ,  Michael Kinch

IPC分类号： A61K39/395 ,  C07K16/00 ,  C07H21/00 ,  C12N15/63 ,  C12N5/00 ,  A61P35/00

CPC分类号： C07K16/2866 ,  C07K2317/24 ,  C07K2317/622 ,  C07K2317/92

摘要： The present invention relates to antibodies with increased affinities that preferentially bind an EphA2 epitope exposed on cancer cells but not non-cancer cells. The present invention further relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. 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： 本发明涉及具有较高亲和力的抗体，其优先结合暴露于癌细胞而非非癌细胞的EphA2表位。 本发明还涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。 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：US20090170890A1

公开(公告)日：2009-07-02

申请号：US12256571

申请日：2008-10-23

申请人： Michael Kinch ,  Michael Goldblatt

发明人： Michael Kinch ,  Michael Goldblatt

IPC分类号： A61K31/4745 ,  A61P31/12

CPC分类号： A61K31/4745 ,  A61K31/131 ,  A61K31/155 ,  A61K31/4184

摘要： A method of inhibiting viral infection in a mammal in need of same, includes administering an effective amount of at least one of the compounds of FGI-103 which are represented by 273, 365 and 510 either prophylactically to prevent viral infection, or therapeutically following viral infection. These compounds appear to selectively inhibit Caspase 8 as a method of preventing infective viral particle release. They can be administered IV, IP, orally or via other conventional administration routes. The compounds are highly effective, requiring relatively low dosages on the order of 1 ng/kg-200 mg/kg of body weight.

摘要翻译： 在需要相同的哺乳动物中抑制病毒感染的方法包括以预防方式施用有效量的至少一种由273,355和510表示的FGI-103化合物，以预防病毒感染或治疗性病毒感染 感染。 这些化合物似乎选择性地抑制胱天蛋白酶8作为预防感染性病毒颗粒释放的方法。 它们可以IV，IP，口服或其他常规给药途径给药。 这些化合物是非常有效的，需要相当低的剂量约1ng / kg-200mg / kg体重。