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1. 发明授权

US06541494B1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 有权
公开(公告)号：US06541494B1
公开(公告)日：2003-04-01
申请号：US09479391
申请日：2000-01-06
申请人： K. George Chandy , Heike Wulff , Michael D. Cahalan , Stephan Grismer , Heiko J. Rauer , Mark J. Miller
发明人： K. George Chandy , Heike Wulff , Michael D. Cahalan , Stephan Grismer , Heiko J. Rauer , Mark J. Miller
IPC分类号： A61K31425
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.

2. 发明授权

US08026263B2 Methods for inhibiting neoproliferative changes in blood vessel walls 有权
标题翻译：抑制血管壁新生血管变化的方法
公开(公告)号：US08026263B2
公开(公告)日：2011-09-27
申请号：US10533060
申请日：2003-10-30
申请人： Ralf Koehler , Heike Wulff , Joachim Hoyer , K. George Chandy
发明人： Ralf Koehler , Heike Wulff , Joachim Hoyer , K. George Chandy
IPC分类号： A61K31/425
CPC分类号： A61K31/415
摘要： Methods, compositions and devices for inhibiting neoproliferative changes in blood vessel walls or other anatomical structures. One or more compounds of Formula I or I-A set forth herein are administered systemically and/or locally to human or veterinary patients to deter or prevent unwanted proliferative changes in blood vessels or other anatomical structures. The invention may be used to deter or prevent stenosis or restenosis of arteries following angioplasty and/or stent placement. In one embodiment, there is provided an implantable stent or stent graft from which one or more compounds of the present invention will elute or otherwise be delivered into an affected blood vessel wall.
摘要翻译：用于抑制血管壁或其他解剖结构中新生血管变化的方法，组合物和装置。本文所述的一种或多种式I或I-A化合物全身和/或局部施用于人或兽医患者以阻止或预防血管或其他解剖结构中不期望的增殖性变化。本发明可用于阻止或预防血管成形术和/或支架放置后的动脉狭窄或再狭窄。在一个实施方案中，提供了可植入支架或支架移植物，其中一种或多种本发明化合物将从其中洗脱或以其它方式递送到受影响的血管壁。

3. 发明申请

US20090048270A1 Compounds, Methods And Devices for Inhibiting Neoproliferative Changes in Blood Vessel Walls 有权
标题翻译：用于抑制血管壁新生血管变化的化合物，方法和装置
公开(公告)号：US20090048270A1
公开(公告)日：2009-02-19
申请号：US10533060
申请日：2003-10-30
申请人： Ralf Koehler , Heike Wulff , Joachim Hoyer , K. George Chandy
发明人： Ralf Koehler , Heike Wulff , Joachim Hoyer , K. George Chandy
IPC分类号： A61K31/505 , A61K31/136 , A61K31/165 , A61K31/426 , A61K31/4184 , A61P9/00 , A61K31/415 , A61K31/41 , A61K31/4035 , A61K31/44
CPC分类号： A61K31/415
摘要： Methods, compositions and devices for inhibiting neoproliferative changes in blood vessel walls or other anatomical structures. One or more compounds of Formula I or I-A set forth herein are administered systemically and/or locally to human or veterinary patients to deter or prevent unwanted proliferative changes in blood vessels or other anatomical structures. The invention may be used to deter or prevent stenosis or restenosis of arteries following angioplasty and/or stent placement. In one embodiment, there is provided an implantable stent or stent graft from which one or more compounds of the present invention will elute or otherwise be delivered into an affected blood vessel wall.
摘要翻译：用于抑制血管壁或其他解剖结构中新生血管变化的方法，组合物和装置。本文所述的一种或多种式I或I-A化合物全身和/或局部施用于人或兽医患者以阻止或预防血管或其他解剖结构中不期望的增殖性变化。本发明可用于阻止或预防血管成形术和/或支架放置后的动脉狭窄或再狭窄。在一个实施方案中，提供了可植入支架或支架移植物，其中一种或多种本发明化合物将从其中洗脱或以其它方式递送到受影响的血管壁。

4. 发明授权

US07235577B1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 有权
公开(公告)号：US07235577B1
公开(公告)日：2007-06-26
申请号：US10402532
申请日：2003-03-28
申请人： K. George Chandy , Heike Wulff
发明人： K. George Chandy , Heike Wulff
IPC分类号： A61K31/415
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.

5. 发明授权

US07772408B1 Substituted 5-alkoxypsoralens as inhibitors of potassium channel activity in lymphocytes and other cells 有权
标题翻译：取代的5-烷氧基补骨脂素作为淋巴细胞和其他细胞中钾通道活性的抑制剂
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。

6. 发明授权

US06803375B1 Non-peptide inhibition of T-lymphocyte activation and therapies related thereto 失效
标题翻译：非肽抑制T淋巴细胞活化和与之相关的疗法
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。

7. 发明授权

US07022480B1 Exons of the hSKCa3/KCNN3 gene 失效
标题翻译： hSKCa3 / KCNN3基因的外显子
公开(公告)号：US07022480B1
公开(公告)日：2006-04-04
申请号：US10269503
申请日：2002-10-11
申请人： J. Jay Gargus , K. George Chandy , Vikram Shakkottai , Hiroaki Tomita
发明人： J. Jay Gargus , K. George Chandy , Vikram Shakkottai , Hiroaki Tomita
IPC分类号： C12Q1/68 , C12N15/867 , C12N5/02
CPC分类号： C07K14/705
摘要： The present invention is based on the discovery and cloning of two variants of the small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene. The isoform variants are identical to the structure of the SKCa3-1a transcript with regard to exons 2–8, but differ in that one variant, SKCa3-1b, contains exon 1b in place of exon 1a and in that the other variant, SKCa3-1c, contains exon 1c in place of exon 1a. When expressed simultaneously with SKCa3-1a, the variants will independently dominantly negatively suppress SKCa3-1a and other functional members of the SKCa channel family. Accordingly, the present invention provides the novel gene variants, methods for the detection of the variants and treatment of disorders related to the activity of these variants. Kits employing the methods of the invention are also described.
摘要翻译：本发明基于小电导钙激活钾通道3型（hKCa3 / KCNN3）基因的两个变体的发现和克隆。异构体变体与外显子2-8的SKCa3-1a转录物的结构相同，但不同之处在于，一个变体SKCa3-1b含有外显子1b代替外显子1a，而另一个变体SKCa3- 1c，含有外显子1c代替外显子1a。当与SKCa3-1a同时表达时，变体将独立地主要负面地抑制SKCa3-1a和SKCa3通道家族的其它功能成员。因此，本发明提供了新的基因变体，检测变体的方法和治疗与这些变体的活性有关的紊乱。还描述了采用本发明方法的试剂盒。

8. 发明授权

US6077680A ShK toxin compositions and methods of use 失效
标题翻译： ShK毒素组成及使用方法
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。

9. 发明授权

US6165719A hKCa3/KCNN3 small conductance calcium activated potassium channel: a diagnostic marker and therapeutic target 失效
标题翻译： hKCa3 / KCNN3小电导钙激活钾通道：诊断标记和治疗靶点
公开(公告)号：US6165719A
公开(公告)日：2000-12-26
申请号：US115446
申请日：1998-07-14
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： A61K38/00 , A61K48/00 , C07K14/705 , C12N1/19 , C12N15/12 , C12Q1/68 , C07H21/02 , C07H21/04 , C12P21/00
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/KNN3 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 / KNN3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。

10. 发明授权

US07378496B2 hKCa3/KCNN3 small conductance calcium activated potassium channel: a diagnostic marker and therapeutic target 有权
标题翻译： hKCa3 / KCNN3小电导钙激活钾通道：诊断标记和治疗靶点
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。

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