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11. 发明公开

US20240158770A1 PDE5A DESTABILIZING DOMAINS 审中-公开
公开(公告)号：US20240158770A1
公开(公告)日：2024-05-16
申请号：US18391409
申请日：2023-12-20
申请人： The Board of Trustees of the Leland Stanford Junior University
发明人： Thomas J. Wandless , Ling-Chun CHEN , Yusaku MIYAMAE
IPC分类号： C12N9/16 , C07K14/435 , C12N15/10 , C12N15/62
CPC分类号： C12N9/16 , C07K14/435 , C12N15/1055 , C12N15/62 , C12Y301/04017 , C07K2319/70
摘要： Disclosed herein are systems, methods, and compositions for rapidly and reversibly destabilizing a target protein in vitro or in vivo, in the presence or absence of a cell-permeable, synthetic molecule or ligand.

12. 发明申请

US20150320761A1 NEURONAL PAIN PATHWAY 审中-公开
标题翻译：神经痛痛途径
公开(公告)号：US20150320761A1
公开(公告)日：2015-11-12
申请号：US14813990
申请日：2015-07-30
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
发明人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
IPC分类号： A61K31/55 , A61K9/00 , A61K47/48
CPC分类号： A61K38/06 , A61K9/0014 , A61K9/7023 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , A61K47/64 , C12N9/1205 , C12Y301/04017
摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.
摘要翻译：本发明涉及发现涉及感觉神经元的长期兴奋性的新型分子途径，其在高等动物中与持续性疼痛相关。基于这样的发现，在神经元轴突损伤之后，一氧化氮合酶活性的增加导致一氧化氮产生增加，这反过来激活鸟苷酸环化酶，从而增加cGMP的水平。增加的cGMP导致蛋白激酶G（“PKG”）的激活，其然后沿着轴突逆行转运到神经元细胞体，其中磷酸化MAPKerk。

13. 发明申请

US20100136010A1 Novel 27875, 22025, 27420, 17906, 16319, 55092 and 10218 molecules and uses therefor 审中-公开
标题翻译：小分子27875,22025,27420,17906,16319,55092和10218分子及其用途
公开(公告)号：US20100136010A1
公开(公告)日：2010-06-03
申请号：US12288465
申请日：2008-10-21
申请人： Rosana Kappeller-Libermann , David White , Keith E. Robison , Kyle J. MacBeth , Joseph M. Carroll , William James Cook , Rachel E. Meyers , Miyoung Chun , Mark J. Williamson
发明人： Rosana Kappeller-Libermann , David White , Keith E. Robison , Kyle J. MacBeth , Joseph M. Carroll , William James Cook , Rachel E. Meyers , Miyoung Chun , Mark J. Williamson
IPC分类号： A61K39/395 , A61K38/45 , A61K38/46 , A61K38/48 , C12Q1/68 , G01N33/53 , C12Q1/34 , C12P21/00 , C12N5/10 , C12N5/00 , A61K38/00 , A61K38/17 , A61K31/713 , A61K31/7088 , C07K14/435 , C07K16/40 , C07H21/04 , A61P31/12 , A61P9/00 , A61P35/00 , A61P19/08 , A61P7/00
CPC分类号： G01N33/5008 , A61K38/00 , C12N9/1007 , C12N9/16 , C12N9/6489 , C12Q1/37 , C12Q1/6883 , C12Q2600/158 , C12Y301/04017 , G01N33/5011 , G01N33/502 , G01N33/56983 , G01N33/56994 , G01N33/57426 , G01N33/5761 , G01N33/5767 , G01N33/68 , G01N2333/916 , G01N2333/96486 , G01N2500/04
摘要： The invention provides isolated nucleic acids molecules, designated 27875, 22025, 27420, 16319, 55092 and 10218 nucleic acid molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 27875, 22025, 27420, 16319, 55092 and 10218 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 27875, 22025, 27420, 16319, 55092 and 10218 gene has been introduced or disrupted. The invention still further provides isolated 27875, 22025, 27420, 17906, 16319, 55092 or 10218 proteins, fusion proteins, antigenic peptides and anti-27875, 22025, 27420, 17906, 16319, 55092 or 10218 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.
摘要翻译：本发明提供分离的核酸分子，命名为27875,22025,27420,16319,55092和10218核酸分子。本发明还提供反义核酸分子，含有27875,22025,27420,16319,55092和10218核酸分子的重组表达载体，已经引入表达载体的宿主细胞，以及非人类转基因动物，其中27875,22025， 27420,16319,55092和10218基因已被引入或破坏。本发明还进一步提供了分离的27875,22025,27420,17906,16319,55092或10218蛋白，融合蛋白，抗原肽和抗27875,22025,27420,17906,16319,55092或10218抗体。还提供了利用本发明组合物的诊断和治疗方法。

14. 发明申请

US20080113399A1 Novel 27875, 22025, 27420, 17906, 16319, 55092 and 10218 molecules and uses therefor 审中-公开
标题翻译：小分子27875,22025,27420,17906,16319,55092和10218分子及其用途
公开(公告)号：US20080113399A1
公开(公告)日：2008-05-15
申请号：US11981488
申请日：2007-10-31
申请人： Rosana Kapeller-Libermann , David White , Keith Robison , Kyle MacBeth , Joseph Carroll , William Cook , Rachel Meyers , Miyoung Chun , Mark Williamson
发明人： Rosana Kapeller-Libermann , David White , Keith Robison , Kyle MacBeth , Joseph Carroll , William Cook , Rachel Meyers , Miyoung Chun , Mark Williamson
IPC分类号： C12Q1/37
CPC分类号： G01N33/5008 , A61K38/00 , C12N9/1007 , C12N9/16 , C12N9/6489 , C12Q1/37 , C12Q1/6883 , C12Q2600/158 , C12Y301/04017 , G01N33/5011 , G01N33/502 , G01N33/56983 , G01N33/56994 , G01N33/57426 , G01N33/5761 , G01N33/5767 , G01N33/68 , G01N2333/916 , G01N2333/96486 , G01N2500/04
摘要： The invention provides isolated nucleic acids molecules, designated 27875, 22025, 27420, 16319, 55092 and 10218 nucleic acid molecules. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 27875, 22025, 27420, 16319, 55092 and 10218 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 27875, 22025, 27420, 16319, 55092 and 10218 gene has been introduced or disrupted. The invention still further provides isolated 27875, 22025, 27420, 17906, 16319, 55092 or 10218 proteins, fusion proteins, antigenic peptides and anti-27875, 22025, 27420, 17906, 16319, 55092 or 10218 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.
摘要翻译：本发明提供分离的核酸分子，命名为27875,22025,27420,16319,55092和10218核酸分子。本发明还提供反义核酸分子，含有27875,22025,27420,16319,55092和10218核酸分子的重组表达载体，已经引入表达载体的宿主细胞，以及非人类转基因动物，其中27875,22025， 27420,16319,55092和10218基因已被引入或破坏。本发明还进一步提供了分离的27875,22025,27420,17906,16319,55092或10218蛋白，融合蛋白，抗原肽和抗27875,22025,27420,17906,16319,55092或10218抗体。还提供了利用本发明组合物的诊断和治疗方法。

15. 发明申请

US20060216339A1 Neuronal pain pathway 有权
标题翻译：神经元疼痛途径
公开(公告)号：US20060216339A1
公开(公告)日：2006-09-28
申请号：US11385455
申请日：2006-03-21
申请人： Richard Ambron , Ying-Ju Sung , Donald Landry , Shi-Xian Deng
发明人： Richard Ambron , Ying-Ju Sung , Donald Landry , Shi-Xian Deng
IPC分类号： A61K38/10 , A61K38/08 , A61K38/05 , A61K9/70
CPC分类号： A61K38/06 , A61K9/0014 , A61K9/7023 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , A61K47/64 , C12N9/1205 , C12Y301/04017
摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.
摘要翻译：本发明涉及发现涉及感觉神经元的长期兴奋性的新型分子途径，其在高等动物中与持续性疼痛相关。它是基于这样的发现：在神经元轴突损伤之后，一氧化氮合酶活性的增加导致一氧化氮产生增加，这反过来激活鸟苷酸环化酶，从而增加cGMP的水平。增加的cGMP导致蛋白激酶G（“PKG”）的激活，其然后沿着轴突逆行转运到神经元细胞体，其中磷酸化MAPKerk。

16. 发明授权

US6146876A 22025, a novel human cyclic nucleotide phosphodiesterase 失效
标题翻译： 22025，一种新的人类环状核苷酸磷酸二酯酶
公开(公告)号：US6146876A
公开(公告)日：2000-11-14
申请号：US330970
申请日：1999-06-11
申请人： Keith E. Robision , Rosana Kapeller-Libermann , David White
发明人： Keith E. Robision , Rosana Kapeller-Libermann , David White
IPC分类号： G01N33/53 , A61K38/00 , A61P7/02 , A61P9/10 , A61P9/12 , A61P11/06 , A61P13/12 , A61P15/08 , A61P19/00 , A61P19/10 , A61P25/24 , A61P25/28 , A61P29/00 , A61P37/06 , A61P37/08 , A61P43/00 , C07K16/40 , C12N5/10 , C12N9/16 , C12N15/09 , C12N15/55 , C12Q1/02 , C12Q1/44 , C12Q1/68 , G01N33/566 , C12N1/20 , C07H21/04 , C12N15/00
CPC分类号： C12Y301/04017 , C12N9/16 , A61K38/00
摘要： The present invention relates to a newly identified human cyclic nucleotide phosphodiesterase belonging to the superfamily of mammalian phosphodiesterases. The invention also relates to polynucleotides encoding the phosphodiesterase. The invention further relates to methods using the phosphodiesterase polypeptides and polynucleotides as a target for diagnosis and treatment in phosphodiesterase-mediated or -related disorders. The invention further relates to drug-screening methods using the phosphodiesterase polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the phosphodiesterase polypeptides and polynucleotides. The invention further relates to procedures for producing the phosphodiesterase polypeptides and polynucleotides.
摘要翻译：本发明涉及属于哺乳动物磷酸二酯酶超家族的新鉴定的人环核苷酸磷酸二酯酶。本发明还涉及编码磷酸二酯酶的多核苷酸。本发明还涉及使用磷酸二酯酶多肽和多核苷酸作为磷酸二酯酶介导的或相关病症中的诊断和治疗的靶标的方法。本发明还涉及使用磷酸二酯酶多肽和多核苷酸鉴定用于诊断和治疗的激动剂和拮抗剂的药物筛选方法。本发明还包括基于磷酸二酯酶多肽和多核苷酸的激动剂和拮抗剂。本发明还涉及产生磷酸二酯酶多肽和多核苷酸的方法。

17. 发明授权

US10485845B2 Neuronal pain pathway 有权
公开(公告)号：US10485845B2
公开(公告)日：2019-11-26
申请号：US14813990
申请日：2015-07-30
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK
发明人： Richard Ambron , Ying-Ju Sung , Donald W. Landry , Shi-Xian Deng
IPC分类号： A61K47/64 , A61K38/06 , A61K38/02 , A61K9/00 , A61K38/07 , A61K38/46 , A61K31/352 , A61K31/4422 , A61K31/55 , C12N9/12 , A61K9/70
CPC分类号： A61K38/06 , A61K9/0014 , A61K31/352 , A61K31/4422 , A61K31/55 , A61K38/02 , A61K38/07 , A61K38/465 , A61K47/64 , C12N9/1205 , C12Y301/04017 , A61K9/7023
摘要： The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

18. 发明授权

US09994830B2 Methods for modulating cyclic nucleotide-mediated signaling in cardiac myocytes and compositions 有权
公开(公告)号：US09994830B2
公开(公告)日：2018-06-12
申请号：US14800657
申请日：2015-07-15
申请人： Matthew Movsesian , Manuela Zaccolo
发明人： Matthew Movsesian , Manuela Zaccolo
IPC分类号： C12N9/16 , C12Q1/44 , A61K38/00
CPC分类号： C12N9/16 , A61K38/00 , C12Q1/44 , C12Y301/04017 , G01N2333/916 , G01N2500/04 , G01N2500/20
摘要： The invention provides a polypeptide possessing anti-hypertrophic activity in a cardiac myocyte, wherein the polypeptide is a mutant variant derived from wild-type PDE3A1 protein and wherein the wild-type PDE3A1 protein has the amino acid sequence given in SEQ ID NO:1 at amino acid position 146 to 1141.

19. 发明授权

US09951335B2 Compositions and methods for treating otitis media and other conditions with inhibitors of CYLD 有权
公开(公告)号：US09951335B2
公开(公告)日：2018-04-24
申请号：US14391890
申请日：2013-04-09
申请人： Georgia State University Research Foundation, Inc.
发明人： Jian-Dong Li
IPC分类号： A61K31/277 , A61K31/4015 , A61K31/44 , A61K31/4174 , A61K31/685 , A61K31/7064 , C12N15/113 , C12Q1/68 , A61K31/713
CPC分类号： C12N15/1137 , A61K31/277 , A61K31/4015 , A61K31/4174 , A61K31/44 , A61K31/685 , A61K31/7064 , A61K31/713 , C12N2310/11 , C12N2310/14 , C12N2310/141 , C12Q1/68 , C12Y301/04017 , C12Y304/19012
摘要： The present invention is based, in part, on our studies of molecular pathways that include the deubiquitinase CYLD. Accordingly, the present invention features, inter alia, nucleic acid constructs that express CYLD or a biologically active variant thereof (e.g., a variant including the catalytic domain), nucleic acids that inhibit the expression of a negative regulator of CYLD (e.g., PDE4B or LNK2), nucleic acids that modulate the expression of downstream CYLD targets (e.g., Akt, by inhibiting or promoting the expression of the downstream target), compositions including one or more of these types of constructs (e.g., pharmaceutical compositions), kits including one or more of the compositions described herein and instructions for use, screening methods to identify therapeutic agents {e.g., anti-inflammatory agents) that upregulate CYLD, downregulate a negative regulatory of CYLD, or modulate (e.g., inhibit) a downstream CYLD target (e.g., Akt), and various methods of treatment including the administration of the nucleic acids described above, protein biotherapeutics, and/or small molecules, alone or in combination, to address cancer, inflammation, and fibrosis. The compositions described herein can be used in the preparation of a medicament (e.g., used in the preparation of a medicament to treat cancer, inflammation, fibrosis, or one or more of the more specific conditions described herein).

20. 发明授权

US08778621B2 Phosphodiesterase 4D7 as marker for malignant, hormone-sensitive prostate cancer 有权
标题翻译：磷酸二酯酶4D7作为恶性，激素敏感性前列腺癌的标志物
公开(公告)号：US08778621B2
公开(公告)日：2014-07-15
申请号：US13320050
申请日：2010-05-11
申请人： Ralf Hoffmann , Miles Douglas Houslay , David James Peter Henderson
发明人： Ralf Hoffmann , Miles Douglas Houslay , David James Peter Henderson
IPC分类号： G01N33/574
CPC分类号： C12Q1/6886 , C12N9/16 , C12N15/1137 , C12N15/115 , C12N2310/11 , C12N2310/14 , C12N2310/16 , C12Q1/44 , C12Q2600/106 , C12Q2600/112 , C12Q2600/158 , C12Y301/04017 , G01N33/57434 , G01N2800/52
摘要： The present invention relates to phosphodiesterase 4D7 (PDE4D7) for use as a marker for malignant, hormone-sensitive prostate cancer, wherein the expression of the marker is increased when comparing the expression in malignant, hormone-sensitive prostate cancer tissue, to the expression in normal tissue or benign prostate tumor tissue, and the use of PDE4D7 as a diagnostic marker for malignant, hormone-sensitive prostate cancer. The present invention also relates to a composition for diagnosing, detecting, monitoring or prognosticating malignant, hormone-sensitive prostate cancer, a corresponding detection method, a method allowing to discriminate between a benign and malignant hormone-sensitive prostate cancer and a method of data acquisition, as well as corresponding immunoassays. The present invention also relates to a method of identifying an individual for eligibility for malignant, hormone-sensitive prostate cancer as well as an immunoassay for stratifying an individual with such prostate cancer. The present invention further envisages pharmaceutical compositions and their use for the treatment of malignant, hormone-sensitive prostate cancer.
摘要翻译：本发明涉及用作恶性，激素敏感性前列腺癌的标记物的磷酸二酯酶4D7（PDE4D7），其中当将恶性，激素敏感性前列腺癌组织中的表达与恶性，激素敏感性前列腺癌组织中的表达比较时，标志物的表达增加正常组织或良性前列腺肿瘤组织，并使用PDE4D7作为恶性，激素敏感性前列腺癌的诊断标记。本发明还涉及用于诊断，检测，监测或预测恶性，激素敏感性前列腺癌的组合物，相应的检测方法，允许区分良性和恶性激素敏感性前列腺癌的方法和数据采集方法，以及相应的免疫测定。本发明还涉及鉴定个体对恶性，激素敏感性前列腺癌的资格的方法以及用这种前列腺癌分层个体的免疫测定法。本发明进一步设想药物组合物及其用于治疗恶性，激素敏感性前列腺癌的用途。

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