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公开(公告)号：US07553483B2
公开(公告)日：2009-06-30
申请号：US10499100
申请日：2002-12-16
CPC分类号： C07K14/523 , A61K38/00
摘要： Mutants of specific CC-chemokines containing a non-conservative substitution in a conserved consensus sequence act as CC-chemokine antagonists, and can be effectively used in the treatment of autoimmune and inflammatory diseases, cancers, and viral or bacterial infections. Particularly preferred are the RANTES/CCL5 mutants having the amino acid sequence of SEQ ID NO: 1, 2, 3, or 4.
摘要翻译： 在保守的共有序列中含有非保守取代的特异性CC-趋化因子的突变体作为CC-趋化因子拮抗剂，可以有效地用于治疗自身免疫性和炎性疾病，癌症和病毒或细菌感染。 特别优选的是具有SEQ ID NO：1,2,3或4的氨基酸序列的RANTES / CCL5突变体。
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公开(公告)号：US20050220757A1
公开(公告)日：2005-10-06
申请号：US10499100
申请日：2002-12-16
IPC分类号： C12N15/09 , A61K38/00 , A61K38/19 , A61K45/00 , A61P29/00 , A61P31/04 , A61P31/12 , A61P35/00 , A61P37/06 , C07K14/47 , C07K14/52 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/19 , C12P21/02
CPC分类号： C07K14/523 , A61K38/00
摘要： Mutants of specific CC-chemokines containing a non-conservative substitution in a conserved consensus sequence act as CC-chemokine antagonists, and can be effectively used in the treatment of autoimmune and inflammatory diseases, cancers, and viral or bacterial infections. Particularly preferred are the RANTES/CCL5 mutants having the amino acid sequence of SEQ ID NO: 1, 2, 3, or 4.
摘要翻译： 在保守的共有序列中含有非保守取代的特异性CC-趋化因子的突变体作为CC-趋化因子拮抗剂，可以有效地用于治疗自身免疫性和炎性疾病，癌症和病毒或细菌感染。 特别优选的是具有SEQ ID NO：1,2,3或4的氨基酸序列的RANTES / CCL5突变体。
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公开(公告)号：US20070004906A1
公开(公告)日：2007-01-04
申请号：US10510658
申请日：2003-04-09
CPC分类号： C07K14/523 , A61K38/00
摘要： Novel antagonists of MCP proteins, in particular of MCP-1 protein, can be obtained by generating MCP mutants whose GAG binding site, located at the N-terminal of MCP proteins, is eliminated following non-conservative substitutions. Compounds prepared in accordance with the present invention can be used in the treatment or prevention of diseases related to an undesirable activity of MCP proteins such, such as inflammatory disease, autoimmune diseases, vascular diseases, and cancer.
摘要翻译： MCP蛋白特别是MCP-1蛋白的新型拮抗剂可以通过产生MCP突变体获得，其MCP位点位于MCP蛋白的N-末端，其在非保守取代之后被消除。 根据本发明制备的化合物可用于治疗或预防与MCP蛋白质不期望的活性相关的疾病，例如炎性疾病，自身免疫性疾病，血管疾病和癌症。
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公开(公告)号：US07541435B2
公开(公告)日：2009-06-02
申请号：US10517726
申请日：2003-06-03
CPC分类号： C07K14/522 , A61K38/00
摘要： Novel antagonists of CXCR3-binding CXC chemokines, and in particular of human CXCL11, can be obtained by generating mutants of such chemokines in which the binding to glycosaminoglycans (GAGs) is impaired due to non-conservative substitutions of amino acids involved in this interaction. Compounds prepared in accordance with the present invention can be used to block the activity of CXCR3-binding CXC chemokines on CXCR3-expressing cells, thereby providing therapeutic compositions for use in the treatment or prevention of diseases related to excessive activated T cells migration, such as graft rejection and autoimmune diseases, and of diseases needing an increase of vascularization, such as ischemic heart disease.
摘要翻译： CXCR3结合CXC趋化因子，特别是人CXCL11的新型拮抗剂可以通过产生这样的趋化因子的突变体来获得，其中与糖胺聚糖（GAG）的结合由于涉及该相互作用的氨基酸的非保守取代而受损。 根据本发明制备的化合物可用于阻断CXCR3结合CXC趋化因子对CXCR3表达细胞的活性，从而提供用于治疗或预防与过度活化的T细胞迁移有关的疾病的治疗组合物，例如 移植排斥反应和自身免疫性疾病以及需要增加血管形成的疾病，如缺血性心脏病。
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公开(公告)号：US07402303B2
公开(公告)日：2008-07-22
申请号：US10398457
申请日：2001-10-03
CPC分类号： C07K14/523 , A61K38/00
摘要： Mutants of CC chemokines, which contain at least two mutations in the cationic site of the 40's loop and which, relative to the wild-type molecule, have a reduced GAG-binding activity. In particular it has been found that such mutated chemokines are effective in the treatment of multiple sclerosis and/or demyelinating diseases. A triple mutant of RANTES is the compound showing the best results.
摘要翻译： CC趋化因子的突变体，其在40个环的阳离子位点含有至少两个突变，相对于野生型分子具有降低的GAG结合活性。 特别地已经发现，这种突变趋化因子在多发性硬化症和/或脱髓鞘疾病的治疗中是有效的。 RANTES的三重突变体是显示最好结果的化合物。
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公开(公告)号：US07335350B2
公开(公告)日：2008-02-26
申请号：US10510014
申请日：2003-03-31
CPC分类号： A61K38/195
摘要： The oral efficacy of C—C chemokines containing a dibasic site in the 40's conserved cationic sequence, such as RANTES and MIP-1β, is improved by substituting at least one of the residues in the dibasic site in a non-conservative manner.
摘要翻译： 通过以非保守的方式代替二元位点中的至少一个残基，改善了含有二十一位点在40位保守阳离子序列（如RANTES和MIP-1beta）中的C-C趋化因子的口服功效。
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公开(公告)号：US20060204498A1
公开(公告)日：2006-09-14
申请号：US10517726
申请日：2003-06-03
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C07K16/24
CPC分类号： C07K14/522 , A61K38/00
摘要： Novel antagonists of CXCR3-binding CXC chemokines, and in particular of human CXCL11, can be obtained by generating mutants of such chemokines in which the binding to glycosaminoglycans (GAGs) is impaired due to non-conservative substitutions of amino acids involved in this interaction. Compounds prepared in accordance with the present invention can be used to block the activity of CXCR3-binding CXC chemokines on CXCR3-expressing cells, thereby providing therapeutic compositions for use in the treatment or prevention of diseases related to excessive activated T cells migration, such as graft rejection and autoimmune diseases, and of diseases needing an increase of vascularization, such as ischemic heart disease.
摘要翻译： CXCR3结合CXC趋化因子，特别是人CXCL11的新型拮抗剂可以通过产生这样的趋化因子的突变体来获得，其中与糖胺聚糖（GAG）的结合由于涉及该相互作用的氨基酸的非保守取代而受损。 根据本发明制备的化合物可用于阻断CXCR3结合CXC趋化因子对CXCR3表达细胞的活性，从而提供用于治疗或预防与过度活化的T细胞迁移有关的疾病的治疗组合物，例如 移植排斥反应和自身免疫性疾病以及需要增加血管形成的疾病，如缺血性心脏病。
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公开(公告)号：US07425324B2
公开(公告)日：2008-09-16
申请号：US10510658
申请日：2003-04-09
CPC分类号： C07K14/523 , A61K38/00
摘要： Novel antagonists of MCP proteins, in particular of MCP-1 protein, can be obtained by generating MCP mutants whose GAG binding site, located at the N-terminal of MCP proteins, is eliminated following non-conservative substitutions. Compounds prepared in accordance with the present invention can be used in the treatment or prevention of diseases related to an undesirable activity of MCP proteins such, such as inflammatory disease, autoimmune diseases, vascular diseases, and cancer.
摘要翻译： MCP蛋白特别是MCP-1蛋白的新型拮抗剂可以通过产生MCP突变体获得，其MCP位点位于MCP蛋白的N-末端，其在非保守取代之后被消除。 根据本发明制备的化合物可用于治疗或预防与MCP蛋白质不期望的活性相关的疾病，例如炎性疾病，自身免疫性疾病，血管疾病和癌症。
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公开(公告)号：US20050220759A1
公开(公告)日：2005-10-06
申请号：US10510014
申请日：2003-03-31
IPC分类号： A61K38/00 , A61K38/19 , A61P25/00 , A61P29/00 , A61P31/00 , A61P31/04 , A61P31/12 , A61P37/00 , A61P37/02 , C07K14/47
CPC分类号： A61K38/195
摘要： The oral efficacy of C—C chemokines containing a dibasic site in the 40's conserved cationic sequence, such as RANTES and MIP-1β, is improved by substituting at least one of the residues in the dibasic site in a non-conservative manner.
摘要翻译： 通过以非保守的方式代替二元位点中的至少一个残基，改善了含有二十一位点在40位保守阳离子序列（如RANTES和MIP-1beta）中的C-C趋化因子的口服功效。
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公开(公告)号：US20100183554A1
公开(公告)日：2010-07-22
申请号：US12750385
申请日：2010-03-30
申请人： Bernard Mach , Yann Dean , Marie Kosco-Vilbois , Greg Elson , Nicolas Fischer , Olivier Leger
发明人： Bernard Mach , Yann Dean , Marie Kosco-Vilbois , Greg Elson , Nicolas Fischer , Olivier Leger
IPC分类号： A61K39/395 , A61K38/21 , C07K16/28
CPC分类号： C07K16/2809 , A61K39/3955 , A61K45/06 , C07K2317/21 , C07K2317/34 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/74
摘要： The present invention is related to antibodies directed to the antigen CD3 and uses of such antibodies. In particular, the present invention provides fully human monoclonal antibodies directed to CD3. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.
摘要翻译： 本发明涉及针对抗原CD3的抗体和这种抗体的用途。 特别地，本发明提供了完全针对CD3的人单克隆抗体。 编码的核苷酸序列和包含重链和轻链免疫球蛋白分子的氨基酸序列，特别是对应于跨越框架区和/或互补决定区（CDR）的连续重链和轻链序列的序列，特别是从FR1至FR4或CDR1至CDR3 ，被提供。 还提供了表达这种免疫球蛋白分子和单克隆抗体的杂交瘤或其它细胞系。
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