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1. 发明申请

WO0024770A9 DIMERIC THROMBOPOIETIN PEPTIDE MIMETICS BINDING TO MP1 RECEPTOR AND HAVING THROMBOPOIETIC ACTIVITY 审中-公开
标题翻译：二聚体血小板生成素肽模拟物与MP1受体结合并具有促血小板生成活性
公开(公告)号：WO0024770A9
公开(公告)日：2000-10-26
申请号：PCT/US9924834
申请日：1999-10-22
申请人： AMGEN INC
发明人： LIU CHUAN-FA , FEIGE ULRICH , CHEETHAM JANET
IPC分类号： C12N15/09 , A61K38/00 , A61P7/00 , C07K14/52 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12P21/02 , C12N15/19 , A61K38/19 , A61P7/06
CPC分类号： C07K14/524 , A61K38/00 , C07K7/06 , C07K7/08 , C07K2319/00 , C07K2319/30 , C07K2319/75
摘要： The invention relates to the field of compounds, especially peptides or polypeptides, that have thrombopoietic activity. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.
摘要翻译：本发明涉及具有血小板生成活性的化合物领域，特别是肽或多肽。本发明的肽和多肽可用于增加哺乳动物中的血小板或血小板前体（例如巨核细胞）。

2. 发明申请

WO0183525A3 MODIFIED PEPTIDES, COMPRISING AN FC DOMAIN, AS THERAPEUTIC AGENTS 审中-公开
标题翻译：修改的肽，包括FC域，作为治疗剂
公开(公告)号：WO0183525A3
公开(公告)日：2002-07-18
申请号：PCT/US0114310
申请日：2001-05-02
申请人： AMGEN INC
发明人： FEIGE ULRICH , LIU CHUAN-FA , CHEETHAM JANET C , BOONE THOMAS CHARLES , GUDAS JEAN MARIE
IPC分类号： C12N15/02 , A61K47/48 , A61P3/02 , A61P7/04 , A61P7/06 , A61P13/02 , A61P17/02 , A61P31/18 , A61P35/04 , A61P37/02 , A61P43/00 , C07K14/505 , C07K14/52 , C07K14/545 , C07K16/18 , C07K19/00 , C12N1/21 , C12P21/08 , C12R1/19 , C12N15/62 , C12N15/70
CPC分类号： A61K47/62 , C07K2319/00 , C07K2319/30
摘要： The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo . The preferred vehicle is an Fc domain. The peptide can be selected, for example, by phage display, E.coli display, ribosome display, RNA-peptide screening, yeast-based screening, chemical-peptide screening, rational design, or protein structural analysis.
摘要翻译：本发明涉及Fc结构域与生物活性肽的融合以及使用生物活性肽制备药物的方法。在本发明中，药理活性化合物通过以下方法制备，该方法包括：a）选择至少一种调节目的蛋白质活性的肽; 和b）制备包含与选定肽的至少一个氨基酸共价连接的Fc结构域的药理学试剂。与载体的连接增加了肽的半衰期，否则其将在体内迅速降解。优选的载体是Fc结构域。肽可以例如通过噬菌体展示，大肠杆菌展示，核糖体展示，RNA-肽筛选，酵母筛选，化学肽筛选，合理设计或蛋白质结构分析来选择。

3. 发明申请

WO0181415A9 MODULATORS OF RECEPTORS FOR PARATHYROID HORMONE AND PARATHYROID HORMONE-RELATED PROTEIN 审中-公开
标题翻译： PARATHYROID HORMONE和PARATHYROID HORMONE相关蛋白的受体调节剂
公开(公告)号：WO0181415A9
公开(公告)日：2002-02-14
申请号：PCT/US0113528
申请日：2001-04-27
申请人： AMGEN INC
发明人： KOSTENUIK PAUL , LIU CHUAN-FA , LACEY DAVID LEE
IPC分类号： C12N15/09 , A61K31/663 , A61K38/00 , A61K38/22 , A61K38/23 , A61K39/395 , A61K45/00 , A61K47/48 , A61P1/02 , A61P1/16 , A61P3/10 , A61P3/14 , A61P5/06 , A61P5/14 , A61P5/16 , A61P5/22 , A61P5/46 , A61P7/06 , A61P9/00 , A61P11/00 , A61P11/06 , A61P13/12 , A61P17/14 , A61P19/00 , A61P19/02 , A61P19/08 , A61P19/10 , A61P21/00 , A61P29/00 , A61P35/00 , A61P35/02 , A61P35/04 , A61P37/06 , C07K14/635 , C07K16/18 , C07K19/00 , C12N1/21 , C07K14/705
CPC分类号： C07K14/635 , A61K38/00 , A61K47/60 , A61K47/61 , A61K47/6425 , C07K2319/00
摘要： The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP. In accordance with the present invention, modulators of PTH and PTHrP comprise: (a) a PTH/PTHrP modulating domain; and (b) a vehicle, such as a polymer (e.g. PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the C-terminus of the PTH/PTHrP modulating domain. The vehicle and the PTH/PTHrP modulating domain may be linked through the N- or C-terminus of the PTH/PTHrP modulating domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred PTH/PTHrP modulating domains comprise the PTH and PTHrP-derived amino acid sequences described hereinafter. Other PTH/PTHrP modulating domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein. Such peptides typically will be modulators of both PTH activity and PTHrP activity, although such techniques can be used to generate peptide sequences that serve as selective modulators (e.g., agonists of PTH activity but not PTHrP activity).
摘要翻译：本发明涉及调节PTH和PTHrP活性的治疗剂。根据本发明，PTH和PTHrP的调节剂包括：（a）PTH / PTHrP调节结构域; 和（b）优选的载体，例如聚合物（例如PEG或葡聚糖）或Fc结构域; 其中载体共价连接到PTH / PTHrP调节结构域的C末端。载体和PTH / PTHrP调节结构域可以通过PTH / PTHrP调节结构域的N末端或C末端连接，如下文进一步描述的。优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。优选的PTH / PTHrP调节结构域包含下文描述的PTH和PTHrP衍生的氨基酸序列。其他PTH / PTHrP调节结构域可以通过噬菌体展示，RNA-肽筛选和本文提及的其他技术产生。尽管这样的技术可用于产生用作选择性调节剂的肽序列（例如，PTH活性的激动剂但不是PTHrP活性），但是这些肽通常将是PTH活性和PTHrP活性的调节剂。

4. 发明申请

WO0183526A3 CALCITONIN-RELATED MOLECULES 审中-公开
标题翻译：钙激素相关分子
公开(公告)号：WO0183526A3
公开(公告)日：2002-08-15
申请号：PCT/US0114320
申请日：2001-05-03
申请人： AMGEN INC
发明人： LIU CHUAN-FA , MARSHALL WILLIAM S , REYNOLDS ANGELA
IPC分类号： A61K38/00 , C07K14/585 , C12N15/62 , A61K47/48 , C07K14/575 , C07K19/00 , C12N1/21 , C12N15/70
CPC分类号： C07K14/585 , A61K38/00
摘要： The present invention concerns therapeutic agents that modulate the activity of CT receptor. In accordance with the present invention, modulators of CT receptor comprise: a. a CT receptor modulating domain, preferably the amino acid sequence of SEQ ID NO:7, or sequences derived therefrom by phage display, RNA-peptide screening, or the other techniques; and b. a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the CT receptor modulating domain. The vehicle and the CT receptor modulating domain may be linked through the N- or C-terminus of the CT receptor modulating domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred CT receptor modulating domains comprise the amino acid sequences described in Table 1. Other CT receptor modulating domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein. Further in accordance with the present invention is a process for making CT receptor modulators, which comprises: a. selecting at least one peptide that binds to the CT receptor; and b. covalently linking said peptide to a vehicle. The preferred vehicle is an Fc domain. Step (a) is preferably carried out by selection from the peptide sequences in Table 1 hereinafter or from phage display, RNA-peptide screening, or the other techniques mentioned herein.
摘要翻译：本发明涉及调节CT受体活性的治疗剂。根据本发明，CT受体的调节剂包括：a。 CT受体调节结构域，优选SEQ ID NO：7的氨基酸序列，或通过噬菌体展示，RNA-肽筛选或其它技术从其衍生的序列; 和b。诸如聚合物（例如PEG或葡聚糖）或Fc结构域的载体，其是优选的; 其中载体共价连接到CT受体调节结构域。载体和CT受体调节结构域可以通过CT受体调节结构域的N-或C-末端连接，如下文进一步描述的。优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。优选的CT受体调节结构域包含表1中所述的氨基酸序列。可以通过噬菌体展示，RNA-肽筛选和本文提及的其它技术产生其他CT受体调节结构域。另外根据本发明是制造CT受体调节剂的方法，其包括：a。选择至少一种结合CT受体的肽; 和b。将所述肽共价连接至载体。优选的载体是Fc结构域。步骤（a）优选通过从下文表1中的肽序列或从噬菌体展示，RNA-肽筛选或本文提及的其它技术中选择进行。

5. 发明申请

WO0024782A3 MODIFIED PEPTIDES, COMPRISING AN FC DOMAIN, AS THERAPEUTIC AGENTS 审中-公开
标题翻译：修改的肽，包括FC域，作为治疗剂
公开(公告)号：WO0024782A3
公开(公告)日：2002-06-06
申请号：PCT/US9925044
申请日：1999-10-25
申请人： AMGEN INC
发明人： FEIGE ULRICH , LIU CHUAN-FA , CHEETHAM JANET , BOONE THOMAS CHARLES
IPC分类号： G01N33/50 , A61K38/00 , A61P3/04 , A61P19/02 , A61P29/00 , A61P31/04 , A61P31/12 , A61P31/18 , A61P35/00 , A61P35/02 , A61P37/02 , A61P43/00 , C07K20060101 , C07K14/47 , C07K14/505 , C07K14/52 , C07K14/525 , C07K14/545 , C07K16/18 , C07K19/00 , C12N20060101 , C12N1/21 , C12N9/64 , C12N15/09 , C12N15/62 , C12N15/70 , C12P21/02 , C12R1/19 , G01N33/15 , G01N33/566
CPC分类号： C12N9/6491 , A61K38/00 , C07K14/505 , C07K14/52 , C07K14/524 , C07K14/525 , C07K14/545 , C07K14/8146 , C07K2319/00 , C07K2319/30
摘要： The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.
摘要翻译：本发明涉及Fc结构域与生物活性肽的融合以及使用生物活性肽制备药物的方法。在本发明中，药理活性化合物通过以下方法制备，该方法包括：a）选择至少一种调节目的蛋白质活性的肽; 和b）制备包含与选定肽的至少一个氨基酸共价连接的Fc结构域的药理学试剂。与载体的连接增加了肽的半衰期，否则其将在体内迅速降解。优选的载体是Fc结构域。优选通过噬菌体展示，大肠杆菌展示，核糖体展示，RNA-肽筛选或化学 - 肽筛选来选择肽。

6. 发明申请

WO0181415A3 PARATHYROID HORMONE AND PARATHYROID HORMONE-RELATED PROTEIN ANTAGONISTS 审中-公开
标题翻译： PARATHYROID HORMONE和PARATHYROID HORMONE相关蛋白质拮抗剂
公开(公告)号：WO0181415A3
公开(公告)日：2002-11-28
申请号：PCT/US0113528
申请日：2001-04-27
申请人： AMGEN INC
发明人： KOSTENUIK PAUL , LIU CHUAN-FA , LACEY DAVID LEE
IPC分类号： C12N15/09 , A61K31/663 , A61K38/00 , A61K38/22 , A61K38/23 , A61K39/395 , A61K45/00 , A61K47/48 , A61P1/02 , A61P1/16 , A61P3/10 , A61P3/14 , A61P5/06 , A61P5/14 , A61P5/16 , A61P5/22 , A61P5/46 , A61P7/06 , A61P9/00 , A61P11/00 , A61P11/06 , A61P13/12 , A61P17/14 , A61P19/00 , A61P19/02 , A61P19/08 , A61P19/10 , A61P21/00 , A61P29/00 , A61P35/00 , A61P35/02 , A61P35/04 , A61P37/06 , C07K14/635 , C07K16/18 , C07K19/00 , C12N1/21 , A61K38/29 , C07K16/46 , C12N15/62 , C12N15/70
CPC分类号： C07K14/635 , A61K38/00 , A61K47/60 , A61K47/61 , A61K47/6425 , C07K2319/00
摘要： The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP. In accordance with the present invention, modulators of PTH and PTHrP comprise: (a) a PTH/PTHrP modulating domain; and (b) a vehicle, such as a polymer (e.g. PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the C-terminus of the PTH/PTHrP modulating domain. The vehicle and the PTH/PTHrP modulating domain may be linked through the N- or C-terminus of the PTH/PTHrP modulating domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred PTH/PTHrP modulating domains comprise the PTH and PTHrP-derived amino acid sequences described hereinafter. Other PTH/PTHrP modulating domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein. Such peptides typically will be modulators of both PTH activity and PTHrP activity, although such techniques can be used to generate peptide sequences that serve as selective modulators (e.g., agonists of PTH activity but not PTHrP activity).
摘要翻译：本发明涉及调节PTH和PTHrP活性的治疗剂。根据本发明，PTH和PTHrP的调节剂包括：（a）PTH / PTHrP调节结构域; 和（b）优选的载体，例如聚合物（例如PEG或葡聚糖）或Fc结构域; 其中载体共价连接到PTH / PTHrP调节结构域的C末端。载体和PTH / PTHrP调节结构域可以通过PTH / PTHrP调节结构域的N末端或C末端连接，如下文进一步描述的。优选的载体是Fc结构域，优选的Fc结构域是IgG Fc结构域。优选的PTH / PTHrP调节结构域包含下文描述的PTH和PTHrP衍生的氨基酸序列。其他PTH / PTHrP调节结构域可以通过噬菌体展示，RNA-肽筛选和本文提及的其他技术产生。尽管这样的技术可用于产生用作选择性调节剂的肽序列（例如，PTH活性的激动剂但不是PTHrP活性），但是这些肽通常将是PTH活性和PTHrP活性的调节剂。

7. 发明申请

WO0024770A2 THROMBOPOIETIC COMPOUNDS 审中-公开
标题翻译：微波化合物
公开(公告)号：WO0024770A2
公开(公告)日：2000-05-04
申请号：PCT/US9924834
申请日：1999-10-22
申请人： AMGEN INC
发明人： LIU CHUAN-FA , FEIGE ULRICH , CHEETHAM JANET
IPC分类号： C12N15/09 , A61K38/00 , A61P7/00 , C07K14/52 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12P21/02 , C07K14/00
CPC分类号： C07K14/524 , A61K38/00 , C07K7/06 , C07K7/08 , C07K2319/00 , C07K2319/30 , C07K2319/75
摘要： The invention relates to the field of compounds, especially peptides or polypeptides, that have thrombopoietic activity. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.
摘要翻译：本发明涉及具有血小板生成活性的化合物，特别是肽或多肽的领域。本发明的肽和多肽可用于增加哺乳动物中的血小板或血小板前体（例如巨核细胞）。

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