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1. 发明申请

US20040197873A1 Use of novel cytokine receptors as biomarkers and therapeutic targets in human cancer 有权
标题翻译：使用新的细胞因子受体作为人类癌症的生物标志物和治疗靶点
公开(公告)号：US20040197873A1
公开(公告)日：2004-10-07
申请号：US10625137
申请日：2003-07-23
发明人： Murat O. Arcasoy , Zishan A. Haroon
IPC分类号： C07K014/505 , C07H021/04
CPC分类号： C12Q1/6886 , C07K14/71 , C07K14/72 , G01N33/6893
摘要： Nucleic acids encoding erythropoietin isoforms are described herein, as well as the encoded isoforms, methods of detecting the same, and methods of screening for and treating cancer.
摘要翻译：本文描述了编码红细胞生成素同种型的核酸，以及编码的同种型，检测其的方法，以及筛选和治疗癌症的方法。

2. 发明申请

US20040157293A1 Enhanced variants of erythropoietin and methods of use 审中-公开
标题翻译：红细胞生成素的增强变体和使用方法
公开(公告)号：US20040157293A1
公开(公告)日：2004-08-12
申请号：US10705217
申请日：2003-11-07
发明人： Glen A. Evans , Sally Jewell , Mark Ware
IPC分类号： C07K014/505
CPC分类号： C07K14/505
摘要： The invention provides a human erythropoietin polypeptide variant containing a human erythropoietin amino acid sequence having an amino acid difference in two or more different Epo-modification regions and an enhanced erythropoietin activity, or a functional fragment thereof. Also provided is a human erythropoietin polypeptide variant containing a human erythropoietin amino acid sequence having an amino acid difference in two or more different Epo-modification regions and a moderated erythropoietin activity, or a functional fragment thereof. The invention further provides a composition containing a human erythropoietin polypeptide variant having an amino acid sequence selected from SEQ ID NOS: 4, 6, 8, 14, 16, 18, 26, 28, 30, 34, 36, 38, 40, 42, 44, 48, 50, 54, 56, 60, 62, 66, 68, 70, 72, 74, 76, 82, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 112, 116, 118, 120, 122, 124, 132, 134, 138, 144, 148, 150, 152, 160, 162, 164, 166, 170, 172, 174, 184, 188, 192, 194, 196, 198, 200, 206, 210, 212, 218, 220, 222, 224, and a pharmaceutically acceptable medium.
摘要翻译：本发明提供含有人促红细胞生成素氨基酸序列的人促红细胞生成素多肽变体，其具有两个以上不同的Epo修饰区域和增强的红细胞生成素活性的氨基酸差异或其功能片段。还提供了含有人促红细胞生成素氨基酸序列的人促红细胞生成素多肽变体，其具有两个或更多个不同Epo修饰区域和中度促红细胞生成素活性的氨基酸差异或其功能片段。本发明还提供含有人促红细胞生成素多肽变体的组合物，所述变体具有选自SEQ ID NO：4,6,8,28,30,36,36,38,40,42的氨基酸序列，44,48,50,54,56,60,62,66,68,70,72,74,76,82,88,90,92,94,96,98,100,102,104,106,108,108 ，112,116,118,120,122,124,132,134,138,144,148,150,152,160,162,164,166,170,172,174,184,188,192,194,196 ，198,2200,206,210,212,218,220,222,224和药学上可接受的培养基。

3. 发明申请

US20040138430A1 Novel polypeptide compose substance for promoting blood and blood vessel cell growth 审中-公开
标题翻译：用于促进血液和血管细胞生长的新型多肽组成物质
公开(公告)号：US20040138430A1
公开(公告)日：2004-07-15
申请号：US10468910
申请日：2004-02-05
发明人： Han Zhongchao , Yongjun Liu , Yinglin Cai
IPC分类号： A61K038/18 , A61K038/19 , C12Q001/68 , C07H021/04 , C07K014/505
CPC分类号： C07K14/515
摘要： The present invention relates to a novel stimulating factor which can promote the growth of hematopoietic stem progenitor cells and vascular endothelial cells, i.e. hemangiopoietin (HAPO), characterized in that design a variety of primers based on known sequences, obtain a series of gene segments through PCR amplification, clone into prokaryotic expression vector using double-enzyme restrict sites, in which two fragments of 879 bp and 558 bp were expressed in engineered bacterium, HAPO of 31.8 KD and 20.1 KD (292 and 186 amino acids) were obtained through enzyme digestion, specific antibodies were obtained after purification and immunizing rabbit with it, the antibodies is a useful tool for clinical diagnosis and treatment of haemopoietic and vascular diseases.
摘要翻译：本发明涉及一种促进造血干细胞祖细胞和血管内皮细胞（即血管生成素（HAPO））生长的新型刺激因子，其特征在于设计基于已知序列的多种引物，获得一系列基因片段通过 PCR扩增，使用双酶限制位点克隆到原核表达载体中，其中在工程化细菌中表达879bp和558bp的两个片段，通过酶消化获得31.8KD和20.1KD（292和186个氨基酸）的HAPO ，纯化后获得特异性抗体，并用兔免疫，抗体是造血和血管疾病临床诊断和治疗的有用工具。

4. 发明申请

US20040175800A1 Cysteine variants of granulocyte colony-stimulating factor 有权
标题翻译：粒细胞集落刺激因子的半胱氨酸变体
公开(公告)号：US20040175800A1
公开(公告)日：2004-09-09
申请号：US10774149
申请日：2004-02-05
申请人： Bolder Biotechnology, Inc.
发明人： George N. Cox III
IPC分类号： C12P021/02 , C07H021/04 , C07K014/54 , C07K014/53 , C07K014/61 , C07K014/505
CPC分类号： C07K14/5431 , A61K38/00 , A61K47/60 , C07K14/475 , C07K14/505 , C07K14/52 , C07K14/535 , C07K14/5403 , C07K14/5406 , C07K14/5409 , C07K14/5412 , C07K14/5418 , C07K14/5425 , C07K14/5428 , C07K14/5434 , C07K14/5437 , C07K14/5443 , C07K14/55 , C07K14/555 , C07K14/56 , C07K14/565 , C07K14/57 , C07K14/61
摘要： The growth hormone supergene family comprises greater than 20 structurally related cytokines and growth factors. A general method is provided for creating site-specific, biologically active conjugates of these proteins. The method involves adding cysteine residues to non-essential regions of the proteins or substituting cysteine residues for non-essential amino acids in the proteins using site-directed mutagenesis and then covalently coupling a cysteine-reactive polymer or other type of cysteine-reactive moiety to the proteins via the added cysteine residue. Disclosed herein are preferred sites for adding cysteine residues or introducing cysteine substitutions into the proteins, and the proteins and protein derivatives produced thereby.
摘要翻译：生长激素超基因家族包含大于20个结构相关的细胞因子和生长因子。提供了一种用于产生这些蛋白质的位点特异性，生物活性缀合物的通用方法。该方法包括将半胱氨酸残基添加到蛋白质的非必需区域中，或者使用定点突变将蛋白质中的非必需氨基酸取代半胱氨酸残基，然后将半胱氨酸反应性聚合物或其它类型的半胱氨酸反应性部分共价偶联到通过添加的半胱氨酸残基的蛋白质。本文公开了用于添加半胱氨酸残基或将半胱氨酸取代引入蛋白质的优选位点，以及由此产生的蛋白质和蛋白质衍生物。

5. 发明申请

US20040143857A1 Erythropoietin analog-human serum albumin fusion 审中-公开
标题翻译：红细胞生成素类似物 - 人血清白蛋白融合
公开(公告)号：US20040143857A1
公开(公告)日：2004-07-22
申请号：US10768873
申请日：2004-01-30
发明人： Michael Young , Harry Meade , Ian Krane
IPC分类号： A01K067/00 , C07K014/505
CPC分类号： C07K14/765 , A01K2217/05 , A61K38/00 , C07K14/505 , C07K2319/02
摘要： Erythropoietin analog-human serum albumin (EPOa-hSA) fusion protein and methods of making and using the fusion protein.
摘要翻译：红细胞生成素类似物 - 人血清白蛋白（EPOa-hSA）融合蛋白以及制备和使用融合蛋白的方法。

6. 发明申请

US20040091961A1 Enhanced variants of erythropoietin and methods of use 审中-公开
标题翻译：红细胞生成素的增强变体和使用方法
公开(公告)号：US20040091961A1
公开(公告)日：2004-05-13
申请号：US10291847
申请日：2002-11-08
发明人： Glen A. Evans , Sally Jewell , Mark Ware
IPC分类号： C07K014/505 , C07H021/04
CPC分类号： C07K14/505
摘要： The invention provides a human erythropoietin polypeptide variant containing a human erythropoietin amino acid sequence having an amino acid difference in two or more different Epo-modification regions and an enhanced erythropoietin activity, or a functional fragment thereof. Also provided is a human erythropoietin polypeptide variant containing a human erythropoietin amino acid sequence having an amino acid difference in two or more different Epo-modification regions and a moderated erythropoietin activity, or a functional fragment thereof. The invention further provides a composition containing a human erythropoietin polypeptide variant having an amino acid sequence selected from SEQ ID NOS: 4, 6, 8, 14, 16, 18, 26, 28, 30, 34, 36, 38, 40, 42, 44, 48, 50, 54, 56, 60, 62, 66, 68, 70, 72, 74, 76, 82, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 112, 116, 118, 120, 122, 124, 132, 134, 138, 144, 148, 150, 152, 160, 162, 164, 166, 170, 172, 174, 184, 188, 192, 194, 196, 198, 200, 206, 210, 212, and a pharmaceutically acceptable medium.
摘要翻译：本发明提供含有人促红细胞生成素氨基酸序列的人促红细胞生成素多肽变体，其具有两个以上不同的Epo修饰区域和增强的红细胞生成素活性的氨基酸差异或其功能片段。还提供了含有人促红细胞生成素氨基酸序列的人促红细胞生成素多肽变体，其具有两个或更多个不同Epo修饰区域和中度促红细胞生成素活性的氨基酸差异或其功能片段。本发明还提供含有人促红细胞生成素多肽变体的组合物，所述变体具有选自SEQ ID NO：4,6,8,28,30,36,36,38,40,42的氨基酸序列，44,48,50,54,56,60,62,66,68,70,72,74,76,82,88,90,92,94,96,98,100,102,104,106,108,108 ，112,116,118,120,122,124,132,134,138,144,148,150,152,160,162,164,166,170,172,174,184,188,192,194,196 ，198,200，206,210,212和药学上可接受的培养基。

7. 发明申请

US20040229318A1 Erythropoietin conjugate compounds with extended half-lives 失效
标题翻译：具有延长半衰期的红细胞生成素缀合物
公开(公告)号：US20040229318A1
公开(公告)日：2004-11-18
申请号：US10439870
申请日：2003-05-17
发明人： George Heavner
IPC分类号： C07K014/505 , C07H021/04 , A61K038/18
CPC分类号： C07K14/505 , A61K38/00 , C07H21/04
摘要： The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein EPO is covalently conjugated to a non-antigenic hydrophilic polymer covalently linked to an organic molecule that increases the circulating serum half-life of the composition. The invention thus relates to EPO derivatives described by the formula EPOnull(XnullY)N where EPO is erythropoietin or its pharmaceutical acceptable derivatives having biological properties of causing bone marrow cells to increase production of reticulocytes and red blood cells, X is PEG or other water soluble polymers, Y is an organic molecule that increases the circulating half-life of the construct more than the PEG alone and N is an integer from 1 to 15. Other molecules may be included between EPO and X and between X and Y to provide the proper functionality for coupling or valency.
摘要翻译：本发明提供生物活性促红细胞生成素（EPO）缀合物组合物，其中EPO与共价连接到增加组合物的循环血清半衰期的有机分子的非抗原性亲水性聚合物共价缀合。因此，本发明涉及由EPO-（XY）N表示的EPO衍生物，其中EPO是红细胞生成素或其具有引起骨髓细胞增加网织红细胞和红细胞生成的生物学特性的药物可接受的衍生物，X是PEG或其它水可溶性聚合物，Y是一种有机分子，其比单独的PEG增加了构建体的循环半衰期，N是1至15的整数。在EPO和X之间以及X和Y之间可以包括其它分子，以提供适当的偶联或价态功能。

8. 发明申请

US20040063917A1 Modified erythropoietin (epo) with reduced immunogenicity 审中-公开
标题翻译：改良的红细胞生成素（epo）具有降低的免疫原性
公开(公告)号：US20040063917A1
公开(公告)日：2004-04-01
申请号：US10467115
申请日：2003-08-05
发明人： Francis J. Carr , Carter Graham , Tim Jones , Stephen Williams
IPC分类号： C07K014/505
CPC分类号： C07K16/464 , A61K9/7015 , A61K38/00 , A61K47/02 , A61K47/12 , C07K14/505 , C07K14/54 , C07K16/18 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K16/3046 , C07K2319/00 , G16B15/00 , G16B20/00
摘要： The present invention relates to polypeptides to be administered especially to humans and in particular for therapeutic use. The polypeptides are modified polypeptides whereby the modification results in a reduced propensity for the polypeptide to elicit an immune response upon administration to the human subject. The inention in particular relates to the modification of erythropoietin (EPO) to result in erythropoietin proteins that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.
摘要翻译：本发明涉及特别用于人，特别是用于治疗用途的多肽。所述多肽是修饰的多肽，其中所述修饰导致多肽在施用于人受试者时引起免疫应答的倾向降低。本发明特别涉及红细胞生成素（EPO）的修饰，以产生当在体内使用时与任何未修饰的对应物基本上不具有免疫原性或较少免疫原性的促红细胞生成素蛋白。

9. 发明申请

US20030211579A1 Methods for increasing polypeptide production 有权
标题翻译：增加多肽生产的方法
公开(公告)号：US20030211579A1
公开(公告)日：2003-11-13
申请号：US10400334
申请日：2003-03-27
发明人： Kirk P. Van Ness , Michael T. Trentalange , Bradley D. Dell , Jeffrey T. McGrew
IPC分类号： C12P021/02 , C12N005/06 , C07K014/715 , C07K016/18 , C07K014/505
CPC分类号： C12P21/02 , C07K2319/00 , C12N5/0018 , C12N15/67 , C12N2500/36 , C12N2501/01 , C12N2510/02
摘要： The invention provides methods of increasing the production of polypeptides, optionally recombinant polypeptides, from mammalian cells using xanthine derivatives or hybrid polar compounds and cultures containing the same. Combinations of inducers including a hybrid polar compound and/or a xanthine derivative and/or an alkanoic acid can also be used, optionally at temperatures less than 37null C.
摘要翻译：本发明提供了使用黄嘌呤衍生物或杂交极性化合物和含有它们的培养物从哺乳动物细胞增加多肽，任选重组多肽的产生的方法。包括杂化极性化合物和/或黄嘌呤衍生物和/或链烷酸的诱导剂的组合也可以任选地在低于37℃的温度下使用

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