公开(公告)号：US6077680A

公开(公告)日：2000-06-20

申请号：US980858

申请日：1997-11-26

申请人： William R. Kem ,  Michael W. Pennington ,  Raymond S. Norton ,  K. George Chandy ,  Katalin Kalman

发明人： William R. Kem ,  Michael W. Pennington ,  Raymond S. Norton ,  K. George Chandy ,  Katalin Kalman

IPC分类号： A61K38/00 ,  C07K14/435 ,  C07K14/705 ,  G01N33/566 ,  A01N37/20 ,  A61K38/17

CPC分类号： C07K14/43595 ,  C07K14/705 ,  A61K38/00 ,  Y10S530/855

摘要： Disclosed are methods and compositions comprising DNA segments, and proteins derived from sea anemone species. More particularly, it concerns the novel ShK toxin, ShK toxin analogs, chemically-modified toxin analogs, and nucleic acid segments encoding the ShK toxin from Stichodactyla helianthus. Various methods for making and using these DNA segments, DNA segments encoding synthetically-modified ShK toxins, and native and synthetic ShK peptides are disclosed, such as, for example, the use of DNA segments as diagnostic probes and templates for protein production, and the use of proteins, fusion protein carriers and peptides in various immunological and diagnostic applications.

摘要翻译： 公开了包含DNA片段的方法和组合物，以及衍生自海葵种类的蛋白质。 更具体地说，它涉及新型的ShK毒素，ShK毒素类似物，化学修饰的毒素类似物，以及编码来自Stichodactyla helianthus的ShK毒素的核酸片段。 公开了制备和使用这些DNA片段的各种方法，编码合成修饰的ShK毒素的DNA片段和天然和合成的ShK肽，例如使用DNA片段作为蛋白质生产的诊断探针和模板，以及 在各种免疫学和诊断应用中使用蛋白质，融合蛋白载体和肽。

公开(公告)号：US07772408B1

公开(公告)日：2010-08-10

申请号：US10651618

申请日：2003-08-29

申请人： Julia Vennekamp ,  Heike Wulff ,  K. George Chandy ,  Stephan Grissmer ,  Wolfram Hansel

发明人： Julia Vennekamp ,  Heike Wulff ,  K. George Chandy ,  Stephan Grissmer ,  Wolfram Hansel

IPC分类号： C07D317/08 ,  C07D305/00 ,  C07D493/00

CPC分类号： C07D493/04

摘要： Compositions of matter comprising 5-phenylalkoxypsoralen compounds and their method of synthesis and use. The compounds are useable to treat diseases or disorders in human or veterinary patients, including autoimmune diseases such as multiple sclerosis. The compounds inhibit potassium channels, including the Kv1.3 channel and at least some of the therapeutic effects of such compounds may be due at least in part to potassium channel inhibition.

摘要翻译： 包含5-苯基烷氧基补骨脂素化合物的物质组合物及其合成和使用方法。 这些化合物可用于治疗人或兽医患者中的疾病或病症，包括自身免疫性疾病如多发性硬化症。 该化合物抑制钾通道，包括Kv1.3通道，并且这些化合物的至少一些治疗作用可能至少部分是由钾通道抑制引起的。

公开(公告)号：US07378496B2

公开(公告)日：2008-05-27

申请号：US10722189

申请日：2003-11-24

申请人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

发明人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

IPC分类号： C07K14/705

CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K48/00

摘要： The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

摘要翻译： 本发明是基于在神经细胞，骨骼肌，心脏和淋巴细胞中表达的人小电导钙激活钾通道3型（hKCa3 / KCNN3）基因的发现和克隆。 hKCa3 / KCNN3基因或其蛋白质产物的改变可能增加对精神分裂症和/或双相情感障碍的易感性。 hKCa3 / KCNN3可能参与神经精神，神经，神经肌肉和免疫疾病。 提供了大量纯化的hKCa3 / KCNN3多肽和多核苷酸。 还公开了与hKCa3 / KCNN3多肽结合的抗体。 提供了鉴定影响hKCa3 / KCNN3多核苷酸或多肽的化合物的方法。 还提供了用于诊断和确定具有hKCa3 / KCNN3相关病症或具有hKCa3 / KCNN3相关病症风险的受试者的预后和治疗方案的方法。 还提供了通过施用治疗有效量的编码SEQ ID NO：2的多核苷酸治疗患有或具有hKCa3 / KCNN3相关病症风险的受试者的方法。 提供了将hKCa3 / KCNN3给予治疗有效量的hKCa3 / KCNN3多肽的患者的制剂。 提供了可用于检测来自具有hKCa3 / KCNN3相关病症的受试者的样品中hKCa3 / KCNN3多肽或多核苷酸的存在的试剂盒。 还描述了具有编码hKCa3 / KCNN3的转基因的转基因非人动物。

公开(公告)号：US06803375B1

公开(公告)日：2004-10-12

申请号：US09479391

申请日：2000-01-06

申请人： K. George Chandy ,  Heike Wulff

发明人： K. George Chandy ,  Heike Wulff

IPC分类号： A01K43495

CPC分类号： A61K31/415 ,  A61K31/065 ,  A61K31/16 ,  A61K31/277 ,  A61K31/40 ,  A61K31/41 ,  A61K31/425

摘要： Compounds, preparations and methods for immunosuppressive treatment of autoimmune disorders, graft rejection and/or graft/host disease. Therapeutically effective amounts of certain substituted triarylmethane compounds, such as 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole, are administered to mammalian patients to selectively inhibit the calcium-activated K+ channel (IKCa1) in lymphocytes, monocytes, macrophages, platelets or endothelial cells without concomitant inhibition of P450-dependent enzyme systems, resulting in reduction of antigen-, cytokine-, or mitogen-induced calcium entry through store operated calcium channels in these cells, suppression of cytokine production by these cells, and inhibition of activation of these cells. Such inhibition of the Ca++ activated K+ channel (IKCa1) prevents the pre-Ca++ stage of cell activation and thus causes immunosuppression and an anti-inflammatory response.

摘要翻译： 用于免疫抑制治疗自身免疫疾病，移植物排斥和/或移植物/宿主疾病的化合物，制剂和方法。 向哺乳动物患者施用治疗有效量的某些取代的三芳基甲烷化合物，例如1 - [（2-氯苯基）二苯基甲基] -1H-吡唑，以选择性抑制淋巴细胞，单核细胞中钙激活的K +通道（IKCa1） ，巨噬细胞，血小板或内皮细胞，而不伴随着P450依赖性酶系统的抑制，导致通过这些细胞中存储的钙通道降低抗原，细胞因子或丝裂原诱导的钙进入，抑制这些细胞的细胞因子产生， 并抑制这些细胞的活化。 Ca ++活化的K +通道（IKCa1）的这种抑制可预防细胞活化前的Ca ++阶段，从而引起免疫抑制和抗炎反应。

公开(公告)号：US06653100B1

公开(公告)日：2003-11-25

申请号：US09565590

申请日：2000-05-04

申请人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

发明人： K. George Chandy ,  J. Jay Gargus ,  George Gutman ,  Emmanuelle Fantino ,  Katarin Kalman

IPC分类号： C12N1512

CPC分类号： C07K14/705 ,  A61K38/00 ,  A61K48/00

摘要： The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.

摘要翻译： 本发明是基于在神经细胞，骨骼肌，心脏和淋巴细胞中表达的人小电导钙激活钾通道3型（hKCa3 / KCNN3）基因的发现和克隆。 hKCa3 / KCNN3基因或其蛋白质产物的改变可能增加对精神分裂症和/或双相情感障碍的易感性。 hKCa3 / KCNN3可能参与神经精神，神经，神经肌肉和免疫疾病。 提供了大量纯化的hKCa3 / KCNN3多肽和多核苷酸。 还公开了与hKCa3 / KCNN3多肽结合的抗体。 提供了鉴定影响hKCa3 / KCNN3多核苷酸或多肽的化合物的方法。 还提供了用于诊断和确定具有hKCa3 / KCNN3相关病症或具有hKCa3 / KCNN3相关病症风险的受试者的预后和治疗方案的方法。 还提供了通过施用治疗有效量的编码SEQ ID NO：2的多核苷酸治疗患有或具有hKCa3 / KCNN3相关病症风险的受试者的方法。 提供了将hKCa3 / KCNN3给予治疗有效量的hKCa3 / KCNN3多肽的患者的制剂。 提供了可用于检测来自具有hKCa3 / KCNN3相关病症的受试者的样品中hKCa3 / KCNN3多肽或多核苷酸的存在的试剂盒。 还描述了具有编码hKCa3 / KCNN3的转基因的转基因非人动物。