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1. 发明申请

US20090029393A1 METHOD FOR PREPARING ANTIBODIES SELECTIVE FOR ACTIVATING FC RECEPTORS 审中-公开
标题翻译：制备选择性用于激活FC受体的抗体的方法
公开(公告)号：US20090029393A1
公开(公告)日：2009-01-29
申请号：US12097022
申请日：2006-12-15
申请人： Jean-Luc Teillaud , Sylvie Jorieux , Sophie Siberil , Renee Menez , Enrico Stura , Frederic Ducancel
发明人： Jean-Luc Teillaud , Sylvie Jorieux , Sophie Siberil , Renee Menez , Enrico Stura , Frederic Ducancel
IPC分类号： G01N33/566 , C07K16/18
CPC分类号： C07K16/00 , C07K16/34 , C07K2317/52 , C07K2317/71
摘要： The present invention relates to a method for preparing an antibody selective for activating antibody Fc region receptors (FcRs) comprising an ITAM motif or motifs (immunoreceptor tyrosine-based activation motif), comprising the steps of obtaining monoclonal antibodies from a hybridoma, from a heterohybridoma or from any animal, plant or human cell line, replacing each of the His 310 and His 435 residues (Cabat numbering) of the Fc region of said antibody with a residue chosen from lysine, alanine, glycine, valine, leucine, isoleucine, proline, methionine, tryptophan, phenylalanine, serine or threonine, and then selecting the antibodies for which the binding to inhibitory FcRs comprising ITIM motifs (immunoreceptor tyrosine-based inhibition motif) is decreased by at least 30%, preferably by at least 50%, 70%, 80% or else by at least 90% relative to the same antibody having a natural Fc region. The present invention also relates to the use of an antibody derived from the method of the invention in the production of a medicament for use in particular in the treatment of cancer and of infectious pathologies.
摘要翻译：本发明涉及一种制备用于激活包含ITAM基序或基序（基于免疫受体酪氨酸的激活基序）的抗体Fc区受体（FcR）的选择性抗体的方法，该方法包括以下步骤：从杂交瘤获得来自杂交瘤的单克隆抗体或来自任何动物，植物或人类细胞系，用选自赖氨酸，丙氨酸，甘氨酸，缬氨酸，亮氨酸，异亮氨酸，脯氨酸的残基替代所述抗体的Fc区的每个His 310和His 435残基（Cabat编号），甲硫氨酸，色氨酸，苯丙氨酸，丝氨酸或苏氨酸，然后选择与包含ITIM基序（基于免疫受体酪氨酸的抑制基序）的抑制性FcR结合的抗体降低至少30％，优选至少50％，70 ％，80％或者至少90％，相对于具有天然Fc区的相同抗体。本发明还涉及衍生自本发明方法的抗体在制备特别用于治疗癌症和感染性病理学的药物中的用途。

2. 发明授权

US5362644A Hybrid proteins between an extracytoplasmic enzyme and at least another protein, method for preparing them and also their applications 失效
标题翻译：胞质内蛋白质与至少另一种蛋白质之间的杂交蛋白质，其制备方法以及其应用
公开(公告)号：US5362644A
公开(公告)日：1994-11-08
申请号：US876910
申请日：1992-04-30
申请人： Paul Boquet , Jean-Claude Boulain , Frederic Ducancel , Daniel Gillet , Andre Menez
发明人： Paul Boquet , Jean-Claude Boulain , Frederic Ducancel , Daniel Gillet , Andre Menez
IPC分类号： C12N9/00 , C07H21/04 , C07K14/005 , C07K14/195 , C07K14/46 , C07K16/00 , C07K19/00 , C12N1/21 , C12N9/16 , C12N9/86 , C12N15/09 , C12N15/62 , C12P21/00 , C12R1/19 , G01N33/535 , C07K13/00
CPC分类号： C12N9/16 , C07K14/46 , C12N15/62 , C12N9/86 , G01N33/535 , C07K2319/00 , C07K2319/02 , C07K2319/55 , C07K2319/75 , Y10S435/975
摘要： The disclosed invention involves a DNA encoding a hybrid tripartite protein comprising an amino portion consisting of from 6 to 28 amino acid residues from the N-terminal of a mature E. coli alkaline phosphatase, a central portion corresponding to a heterologous polypeptide and a carboxyl portion which consists of the remainder of the mature E. coli alkaline phosphatase, a different alkaline phosphatase or an enzymatically active fragment of either. The tripartite proteins produced with this DNA can be used as a diagnostic reagent and in the screening of nucleic acid libraries or in the selection of recombinant clones.
摘要翻译：所公开的发明涉及编码混合三方蛋白的DNA，其包含由成熟大肠杆菌碱性磷酸酶的N末端起6至28个氨基酸残基的氨基部分，对应于异源多肽的中心部分和羧基部分其由剩余的成熟大肠杆菌碱性磷酸酶，不同的碱性磷酸酶或其中的酶促活性片段组成。用该DNA产生的三分体蛋白质可用作诊断试剂，并用于核酸文库筛选或重组克隆的筛选。

3. 发明授权

US5891699A Modified bacterial alkaline phosphatases and their applications 失效
标题翻译：改良细菌碱性磷酸酶及其应用
公开(公告)号：US5891699A
公开(公告)日：1999-04-06
申请号：US673312
申请日：1996-06-28
申请人： Jean-Claude Boulain , Laurence Cattolico , Frederic Ducancel , Andre Menez
发明人： Jean-Claude Boulain , Laurence Cattolico , Frederic Ducancel , Andre Menez
IPC分类号： C12N15/09 , C07K14/46 , C07K14/62 , C12N9/16 , C12N15/55 , C12R1/19 , C12N9/14 , C12N1/20 , C12N15/00 , C12P21/06
CPC分类号： C07K14/62 , C07K14/46 , C12N9/16 , C07K2319/00 , Y10S435/849
摘要： Modified alkaline phosphatases of bacterial origin (BAP or bacterial alkaline phosphatase) which consist of a bacterial alkaline phosphatase sequence in which at least one of the amino acid residues in position 329 or in position 330 is replaced by another amino acid residue, which modified bacterial alkaline phosphatases exhibit both significantly improved enzymic properties and an increased thermal stability, and their applications, in particular in immunoenzymic assays (reagents and diagnostic kits).Method for selecting mutants of alkaline phosphatases which possess significantly improved enzymic properties.
摘要翻译：由细菌碱性磷酸酶序列组成的细菌来源的碱性磷酸酶（BAP或细菌碱性磷酸酶），其中329位或330位的至少一个氨基酸残基被另一个氨基酸残基所取代磷酸酶表现出显着改善的酶特性和增加的热稳定性，以及它们的应用，特别是在免疫酶测定（试剂和诊断试剂盒）中。选择具有显着改善的酶性质的碱性磷酸酶突变体的方法。

4. 发明授权

US5534223A Hybrid proteins between an extracytoplasmic enzyme and at least another protein, method for preparing them and also their applications 失效
标题翻译：胞质内蛋白质与至少另一种蛋白质之间的杂交蛋白质，其制备方法以及其应用
公开(公告)号：US5534223A
公开(公告)日：1996-07-09
申请号：US269072
申请日：1994-06-30
申请人： Paul Boquet , Jean-Claude Boulain , Frederic Ducancel , Daniel Gillet , Andre Menez
发明人： Paul Boquet , Jean-Claude Boulain , Frederic Ducancel , Daniel Gillet , Andre Menez
IPC分类号： C12N9/00 , C07H21/04 , C07K14/005 , C07K14/195 , C07K14/46 , C07K16/00 , C07K19/00 , C12N1/21 , C12N9/16 , C12N9/86 , C12N15/09 , C12N15/62 , C12P21/00 , C12R1/19 , G01N33/535 , G01N33/531
CPC分类号： C12N9/16 , C07K14/46 , C12N15/62 , C12N9/86 , G01N33/535 , C07K2319/00 , C07K2319/02 , C07K2319/55 , C07K2319/75 , Y10S435/975
摘要： A kit for carrying out an immunoenzymological assay for protein, containing a diagnostic reagent consisting of a hybrid protein comprising, in order, a polypeptide P1 which is an N-terminal portion of mature alkaline phosphatase comprising from 6 to 28 of the N-terminal amino acids of said mature alkaline phosphatase, joined to a polypeptide P2, capable of interacting with an antibody or antigen joined to a polypeptide P3 which is selected from the group consisting of a) the C-terminal remaining amino acids of said mature alkaline phosphatase, b) the mature sequence of alkaline phosphatase, and c) enzymatically active fragments of b).
摘要翻译：一种用于进行蛋白质的免疫酶学测定的试剂盒，其含有由杂合蛋白组成的诊断试剂，所述试剂依次包含作为成熟碱性磷酸酶的N末端部分的多肽P1，所述成熟碱性磷酸酶包含6至28个N-末端氨基所述成熟碱性磷酸酶的酸与多肽P2连接，能够与连接到多肽P3的抗体或抗原相互作用，所述抗体或抗原选自a）所述成熟碱性磷酸酶的C末端剩余氨基酸，b ）碱性磷酸酶的成熟序列，和c）b）的酶促活性片段。

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