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1. 发明授权

US08278262B2 Use of microproteins as tryptase inhibitors 失效
标题翻译：使用微蛋白作为类胰蛋白酶抑制剂
公开(公告)号：US08278262B2
公开(公告)日：2012-10-02
申请号：US11663435
申请日：2005-09-19
申请人： Harald Kolmar , Christian Sommerhoff , Alexander Wentzel
发明人： Harald Kolmar , Christian Sommerhoff , Alexander Wentzel
IPC分类号： A61K38/00 , G01N33/567
CPC分类号： A61K38/56 , C07K14/47 , C07K2319/00 , C30B7/00 , C30B29/58
摘要： Disclosed are uses of microproteins preferably microproteins forming a cystine knot (i.e. belonging to the family of inhibitor cystine knot (ICK) polypeptides) or polynucleotides encoding said microproteins for the preparation of a pharmaceutical composition for treating or preventing a disease that can be treated or prevented by inhibiting the activity of tryptase as well as corresponding methods of treatment. Also disclosed are uses of the microproteins for inhibiting tryptase activity, for purifying tryptase, as a carrier molecule for tryptase and for deleting or quantifying tryptase in a sample, including corresponding diagnostic applications. Furthermore disclosed are fusion proteins comprising an inactive barnase as well as fusion proteins comprising barnase and a microprotein. Also encompassed are nucleic acid molecules encoding such a fusion protein, as well as corresponding vectors, host cells, preparation methods and uses of the fusion protein. Moreover, the present application discloses a crystal of a microprotein fused with barnase, preferably inactive barnase. The disclosure also refers to corresponding preparation methods for the crystal, structure analysis methods using the crystal data storage media comprising the structure data obtained, as well as to in silico methods using the structure data for characterizing the binding of microproteins to target molecules. Furthermore, disclosed are pharmaceutical compositions comprising the crystal and corresponding medical uses.
摘要翻译：公开了微型蛋白质的使用，优选微型蛋白质形成胱氨酸结（即属于抑制剂胱氨酸结（ICK）多肽家族）或编码所述微蛋白的多核苷酸用于制备用于治疗或预防可被治疗或预防的疾病的药物组合物通过抑制类胰蛋白酶的活性以及相应的治疗方法。还公开了微蛋白用于抑制类胰蛋白酶活性，纯化类胰蛋白酶的作用，作为类胰蛋白酶的载体分子以及删除或定量样品中的类胰蛋白酶的用途，包括相应的诊断应用。此外，还公开了包含非活性芽孢杆菌RNA酶的融合蛋白以及包含芽孢杆菌RNA酶和微蛋白的融合蛋白。还包括编码这种融合蛋白的核酸分子，以及相应的载体，宿主细胞，制备方法和融合蛋白的用途。此外，本申请公开了一种与芽孢杆菌酶融合的微蛋白的晶体，优选不活泼的芽孢杆菌RNA酶。本公开还涉及晶体的相应制备方法，使用包含所获得的结构数据的晶体数据存储介质的结构分析方法，以及使用结构数据表征微结构蛋白与靶分子的结合的计算机方法。此外，公开了包含晶体和相应医疗用途的药物组合物。

2. 发明申请

US20090130692A1 Use of microproteins as tryptase 失效
标题翻译：使用微蛋白作为类胰蛋白酶
公开(公告)号：US20090130692A1
公开(公告)日：2009-05-21
申请号：US11663435
申请日：2005-09-19
申请人： Harald Kolmar , Christian Sommerhoff , Alexander Wentzel
发明人： Harald Kolmar , Christian Sommerhoff , Alexander Wentzel
IPC分类号： G01N33/567 , C07K14/00 , C07H21/00 , C12N9/24 , C07H21/04 , C12N5/10 , C12Q1/34 , A61K38/47 , C12P21/02 , C12N15/63 , A61K35/12 , A61K31/7088 , A61K38/16
CPC分类号： A61K38/56 , C07K14/47 , C07K2319/00 , C30B7/00 , C30B29/58
摘要： Disclosed are uses of microproteins preferably microproteins forming a cystine knot (i.e. belonging to the family of inhibitor cystine knot (ICK) polypeptides) or polynucleotides encoding said microproteins for the preparation of a pharmaceutical composition for treating or preventing a disease that can be treated or prevented by inhibiting the activity of tryptase as well as corresponding methods of treatment. Also disclosed are uses of the microproteins for inhibiting tryptase activity, for purifying tryptase, as a carrier molecule for tryptase and for deleting or quantifying tryptase in a sample, including corresponding diagnostic applications. Furthermore disclosed are fusion proteins comprising an inactive barnase as well as fusion proteins comprising barnase and a microprotein. Also encompassed are nucleic acid molecules encoding such a fusion protein, as well as corresponding vectors, host cells, preparation methods and uses of the fusion protein. Moreover, the present application discloses a crystal of a microprotein fused with barnase, preferably inactive barnase. The disclosure also refers to corresponding preparation methods for the crystal, structure analysis methods using the crystal data storage media comprising the structure data obtained, as well as to in silico methods using the structure data for characterizing the binding of microproteins to target molecules. Furthermore, disclosed are pharmaceutical compositions comprising the crystal and corresponding medical uses.
摘要翻译：公开了微型蛋白质的使用，优选微型蛋白质形成胱氨酸结（即属于抑制剂胱氨酸结（ICK）多肽家族）或编码所述微蛋白的多核苷酸用于制备用于治疗或预防可被治疗或预防的疾病的药物组合物通过抑制类胰蛋白酶的活性以及相应的治疗方法。还公开了微蛋白用于抑制类胰蛋白酶活性，纯化类胰蛋白酶的作用，作为类胰蛋白酶的载体分子以及删除或定量样品中的类胰蛋白酶的用途，包括相应的诊断应用。此外，还公开了包含非活性芽孢杆菌RNA酶的融合蛋白以及包含芽孢杆菌RNA酶和微蛋白的融合蛋白。还包括编码这种融合蛋白的核酸分子，以及相应的载体，宿主细胞，制备方法和融合蛋白的用途。此外，本申请公开了一种与芽孢杆菌酶融合的微蛋白的晶体，优选不活泼的芽孢杆菌RNA酶。本公开还涉及晶体的相应制备方法，使用包含所获得的结构数据的晶体数据存储介质的结构分析方法，以及使用结构数据表征微结构蛋白与靶分子的结合的计算机方法。此外，公开了包含晶体和相应医疗用途的药物组合物。

3. 发明授权

US06489327B1 Tryptase inhibitors 失效
标题翻译：胰蛋白酶抑制剂
公开(公告)号：US06489327B1
公开(公告)日：2002-12-03
申请号：US09601317
申请日：2000-10-20
申请人： Thomas Bär , Thomas Martin , Josef Stadlwieser , Wolf-Rüdiger Ulrich , Andreas Dominik , Ulrich Thibaut , Daniela Bundschuh , Rolf Beume , Karl-Josef Goebel , Wolfram Bode , Luis Moroder , Pedro Jose Barbosa Pereira , Andreas Bergner , Robert Huber , Christian Sommerhoff , Norbert Schaschke
发明人： Thomas Bär , Thomas Martin , Josef Stadlwieser , Wolf-Rüdiger Ulrich , Andreas Dominik , Ulrich Thibaut , Daniela Bundschuh , Rolf Beume , Karl-Josef Goebel , Wolfram Bode , Luis Moroder , Pedro Jose Barbosa Pereira , Andreas Bergner , Robert Huber , Christian Sommerhoff , Norbert Schaschke
IPC分类号： A61K31495
CPC分类号： C07D213/81 , C07C279/16 , C07D211/58 , C07D213/82 , C07D295/185 , C07D295/215 , C07D401/14
摘要： The invention relates to novel inhibitors of human tryptase which are used in the pharmaceutical industry for the production of medicaments.
摘要翻译：本发明涉及用于药物工业用于生产药物的人类类胰蛋白酶的新型抑制剂。

4. 发明授权

US5861377A Antistasin type serine protease inhibitors 失效
标题翻译：抗丝氨酸型丝氨酸蛋白酶抑制剂
公开(公告)号：US5861377A
公开(公告)日：1999-01-19
申请号：US369829
申请日：1995-01-06
申请人： Hans Fritz , Christian Sommerhoff , Jutta Heim
发明人： Hans Fritz , Christian Sommerhoff , Jutta Heim
IPC分类号： C12N15/09 , A61K38/55 , A61P7/02 , A61P35/00 , A61P43/00 , C07H21/04 , C07K1/16 , C07K14/81 , C07K14/815 , C12N1/19 , C12N1/21 , C12P21/02 , C12R1/19 , C12R1/865 , A61K38/57
CPC分类号： C07K14/815 , C07K2319/02
摘要： The present invention relates to novel inhibitors belonging to the family of antistasin-type serine proteinase inhibitors, to their isolation from the medical leech Hirudo medicinalis, to DNA sequences encoding the novel inhibitors, to variants obtained by recombinant DNA technology or peptide synthesis, pharmaceutical compositions containing the inhibitors, and to their use in diagnosis and therapy.
摘要翻译：本发明涉及属于抗静脉蛋白型丝氨酸蛋白酶抑制剂家族的新型抑制剂，其分离自医药水蛭水蛭素，编码新型抑制剂的DNA序列，通过重组DNA技术或肽合成获得的变体，药物组合物含有抑制剂，并用于诊断和治疗。

5. 发明授权

US06613769B1 Tryptase inhibitors 失效
标题翻译：胰蛋白酶抑制剂
公开(公告)号：US06613769B1
公开(公告)日：2003-09-02
申请号：US09601318
申请日：2001-01-22
申请人： Wolfram Bode , Luis Moroder , Pedro Jose Barbosa Pereira , Andreas Bergner , Robert Huber , Christian Sommerhoff , Norbert Schaschke , Thomas Bär , Thomas Martin , Josef Stadlwieser , Wolf-Rüdiger Ulrich , Andreas Dominik , Ulrich Thibaut , Daniela Bundschuh , Rolf Beume , Karl-Josef Goebel
发明人： Wolfram Bode , Luis Moroder , Pedro Jose Barbosa Pereira , Andreas Bergner , Robert Huber , Christian Sommerhoff , Norbert Schaschke , Thomas Bär , Thomas Martin , Josef Stadlwieser , Wolf-Rüdiger Ulrich , Andreas Dominik , Ulrich Thibaut , Daniela Bundschuh , Rolf Beume , Karl-Josef Goebel
IPC分类号： A61K31495
CPC分类号： C07D213/81 , C07C237/22 , C07C279/16 , C07D211/58 , C07D213/82 , C07D295/185 , C07D295/215 , C07D401/14
摘要： The invention relates to bifunctional tryptase inhibitors of formula (I) wherein H1 and H2 comprise a Q group and L is a linker of formula and the conformation of the H1, H2 and L groups is such that the groups are separated by a distance of from 20 to 45 Å. Pharmaceutical compositions and crystal forms of the compounds are described in addition to methods for producing and identifying such compounds, as well as the use of such compounds in methods of treating allergic and inflammatory diseases.
摘要翻译：本发明涉及式（I）的双功能类胰蛋白酶抑制剂，其中H1和H2包含Q基团，L是式的连接体，并且H1，H2和L基团的构象使得基团被隔开距离为20 至45Å。除了制备和鉴定这些化合物的方法之外，还描述了化合物的药物组合物和晶体形式，以及这些化合物在治疗过敏性和炎性疾病的方法中的用途。

6. 发明授权

US5972698A Tryptase inhibitor 失效
标题翻译：胰蛋白酶抑制剂
公开(公告)号：US5972698A
公开(公告)日：1999-10-26
申请号：US586676
申请日：1996-01-25
申请人： Hans Fritz , Christian Sommerhoff
发明人： Hans Fritz , Christian Sommerhoff
IPC分类号： C12N15/09 , A61K38/00 , A61K38/55 , A61P1/02 , A61P7/02 , A61P11/00 , A61P29/00 , A61P43/00 , C07H21/04 , C07K14/81 , C07K14/815 , C12N9/99 , C12N15/81 , C12P21/02 , C12R1/865 , A61K38/58 , C12N15/11
CPC分类号： C07K14/811 , C12N15/81 , A61K38/00
摘要： The present invention relates to novel inhibitors of human tryptase, to their isolation from leeches, to nucleotide sequences encoding the novel inhibtor molecules or fragments thereof, to vectors containing the coding sequence thereof, to host cells transformed with such vectors, to the recombinant production of the inibitors, to pharmaceutical compositions containing the novel inhibitor molecules, and to their use in diagnosis and therapy.
摘要翻译： PCT No.PCT / EP94 / 02445 Sec。 371日期：1996年1月25日 102（e）日期1996年1月25日PCT 1994年7月25日PCT公布。公开号WO95 / 03333 日期1995年2月2日本发明涉及新型的类胰蛋白酶抑制剂，其从水蛭分离到编码新型抑制剂分子或其片段的核苷酸序列，涉及含有其编码序列的载体，宿主用这些载体转化的细胞，涉及重组生产的内含子，含有新型抑制剂分子的药物组合物及其在诊断和治疗中的应用。

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