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1. 发明申请

WO02066514A3 ARTIFICIAL FUSION PROTEINS WITH REDUCED IMMUNOGENICITY 审中-公开
标题翻译：具有降低免疫原性的人造融合蛋白
公开(公告)号：WO02066514A3
公开(公告)日：2003-02-13
申请号：PCT/EP0201690
申请日：2002-02-18
申请人： MERCK PATENT GMBH , GILLIES STEPHEN , CARR FRANCIS J , JONES TIM , CARTER GRAHAM , HAMILTON ANITA , WILLIAMS STEPHEN , HANLON MARIAN , WATKINS JOHN , BAKER MATTHEW , WAY JEFFREY C
发明人： GILLIES STEPHEN , CARR FRANCIS J , JONES TIM , CARTER GRAHAM , HAMILTON ANITA , WILLIAMS STEPHEN , HANLON MARIAN , WATKINS JOHN , BAKER MATTHEW , WAY JEFFREY C
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61P43/00 , C07K14/47 , C07K16/00 , C07K16/18 , C07K16/28 , C07K16/30 , C07K19/00 , C12P21/02 , C12N15/62
CPC分类号： C07K16/30 , C07K16/28 , C07K16/2863 , C07K2317/24 , C07K2317/34 , C07K2319/00 , C07K2319/30
摘要： The invention relates to artificial modified proteins, preferably fusion proteins, having a reduced immunogenicity compared to the parent non-modified molecule when exposed to a species in vivo. The invention relates, above all, to novel immunoglobulin fusion proteins which essentially consist of an immunoglobulin molecule or a fragment thereof covalently fused via its C-terminus to the N-terminus of a biologically active non-immunoglobulin molecule, preferably a polypeptide or protein or a biologically active fragment thereof. In a specific embodiment, the invention relates to fusion proteins consisting of an Fc portion of an antibody which is fused as mentioned to the non-immunological target molecule which elicits biological or pharmacological efficacy. The molecules of the invention have amino acid sequences which are altered in one or more amino acid residue positions but have in principal the same biological activity as compared with the non-altered molecules. The changes are made in regions of the molecules which are identified as T-cell epitopes, which contribute to an immune reaction in a living host. Thus, the invention also relates to a novel method of making such fusion proteins by identifying said epitopes comprising calculation of T-cell epitope values for MHC Class II molecule binding sites in a peptide by computer-aided methods.
摘要翻译：本发明涉及人体修饰蛋白，优选融合蛋白，当与体内物种暴露时，与亲本非修饰分子相比具有降低的免疫原性。本发明首先涉及新的免疫球蛋白融合蛋白，其基本上由免疫球蛋白分子或其通过C末端与生物活性非免疫球蛋白分子，优选多肽或蛋白质的N末端共价融合的片段组成，或其生物活性片段。在一个具体的实施方案中，本发明涉及由抗体的Fc部分组成的融合蛋白，所述Fc部分如提及的非免疫靶标分子融合而引起生物学或药理学功效。本发明的分子具有氨基酸序列，其在一个或多个氨基酸残基位置被改变，但与未改变的分子相比具有相同的生物学活性。在被鉴定为T细胞表位的分子的区域中进行改变，其有助于在宿主中的免疫反应。因此，本发明还涉及通过鉴定所述表位来制备此类融合蛋白的新方法，包括通过计算机辅助方法计算肽中MHC II类分子结合位点的T细胞表位值。

2. 发明申请

WO02069232A2 METHOD FOR IDENTIFICATION OF T-CELL EPITOPES AND USE FOR PREPARING MOLECULES WITH REEDUCED IMMUNOGENICITY 审中-公开
标题翻译：用于鉴定T细胞外膜的方法和用于制备具有免疫原性的分子的用途
公开(公告)号：WO02069232A2
公开(公告)日：2002-09-06
申请号：PCT/EP0201688
申请日：2002-02-18
申请人： MERCK PATENT GMBH , CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WILLIAMS STEPHEN , HAMILTON ANITA
发明人： CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WILLIAMS STEPHEN , HAMILTON ANITA
IPC分类号： G01N33/50 , A61K9/70 , A61K38/00 , A61K38/11 , A61K47/02 , A61K47/12 , C07K14/00 , C07K14/285 , C07K14/415 , C07K14/47 , C07K14/475 , C07K14/50 , C07K14/525 , C07K14/535 , C07K14/54 , C07K14/545 , C07K14/575 , C07K14/59 , C07K14/725 , C07K16/00 , C07K16/18 , C07K16/28 , C07K16/30 , C07K16/46 , C07K19/00 , C12N9/24 , C12N9/54 , C12N9/64 , C12N15/09 , G01N33/15 , G01N33/48 , G06F19/16 , G06F19/18 , G06F19/00
CPC分类号： G06F19/16 , A61K9/7015 , A61K38/00 , A61K47/02 , A61K47/12 , C07K14/54 , C07K16/18 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K16/3046 , C07K16/464 , C07K16/465 , C07K2319/00 , G06F19/18
摘要： This invention relates to a novel approach for identification of T-cell epitopes, that give rise to an immune reaction in a living host. By means of this novel method biological compounds can be generated which have a no or at least a reduced immunogenicity when exposed to the immune system of a given species and compared with the relevant non-modified entity. Thus the invention relates also to novel biological molecules, especially proteins and antibodies, obtained by the method according to the invention.
摘要翻译：本发明涉及用于鉴定在宿主中产生免疫反应的T细胞表位的新方法。通过这种新方法，可以产生当暴露于给定物种的免疫系统且与相关未修饰实体相比较时具有或至少具有降低的免疫原性的生物化合物。因此，本发明还涉及通过根据本发明的方法获得的新型生物分子，特别是蛋白质和抗体。

3. 发明申请

WO02074783A3 MODIFIED INTERFERON BETA WITH REDUCED IMMUNOGENICITY 审中-公开
标题翻译：改良的干扰素与降低的免疫原性
公开(公告)号：WO02074783A3
公开(公告)日：2003-08-28
申请号：PCT/EP0202925
申请日：2002-03-15
申请人： MERCK PATENT GMBH , CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WATKINS JOHN , BAKER MATTHEW
发明人： CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WATKINS JOHN , BAKER MATTHEW
IPC分类号： C12N15/09 , A61K38/21 , A61K39/00 , A61P31/12 , A61P37/02 , C07K7/08 , C07K14/565 , C12N15/22 , C12P21/02
CPC分类号： C07K14/565
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 invention in particular relates to the modification of human interferon beta to result in 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。本发明特别涉及人类干扰素β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低免疫原性的蛋白质。

4. 发明申请

WO02062832A3 MODIFIED HUMAN BRAIN-DERIVED NEUTROPHIC FACTOR (BDNF) WITH REDUCED IMMUNOGENICITY 审中-公开
标题翻译：具有降低免疫原性的改良人脑中性粒细胞因子（BDNF）
公开(公告)号：WO02062832A3
公开(公告)日：2003-03-13
申请号：PCT/EP0201169
申请日：2002-02-05
申请人： MERCK PATENT GMBH , CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WILLIAMS STEPHEN
发明人： CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WILLIAMS STEPHEN
IPC分类号： C12N15/02 , A61K9/70 , A61K38/00 , A61K38/11 , A61K38/18 , A61K38/22 , A61K47/02 , A61K47/12 , A61P25/00 , A61P25/28 , C07K7/08 , C07K14/475 , C07K14/48 , C07K14/54 , C07K16/18 , C07K16/28 , C07K16/30 , C07K16/46 , C12N15/12 , G06F19/16 , G06F19/18 , C07K7/06
CPC分类号： G06F19/16 , A61K9/7015 , A61K38/00 , A61K38/185 , A61K47/02 , A61K47/12 , C07K14/475 , C07K14/54 , C07K16/18 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K16/3046 , C07K16/464 , C07K2319/00 , G06F19/18
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 invention in particular relates to the modification of human brain-derived neutrophic factor (BDNF) to result in BDNF 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。本发明特别涉及人类脑源性中性粒细胞因子（BDNF）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是非免疫原性或较少的免疫原性的BDNF蛋白质。

5. 发明申请

WO02062843A2 MODIFIED ERYTHROPOIETIN (EPO) WITH REDUCED IMMUNOGENICITY 审中-公开
标题翻译：具有降低免疫原性的改良型ERYTHROPOIETIN（EPO）
公开(公告)号：WO02062843A2
公开(公告)日：2002-08-15
申请号：PCT/EP0201174
申请日：2002-02-05
申请人： MERCK PATENT GMBH , CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WILLIAMS STEPHEN
发明人： CARR FRANCIS J , CARTER GRAHAM , JONES TIM , WILLIAMS STEPHEN
IPC分类号： C12N15/09 , A61K9/70 , A61K38/00 , A61K38/11 , A61K38/18 , A61K38/27 , A61K47/02 , A61K47/12 , A61P7/00 , A61P7/06 , C07K7/06 , C07K7/08 , C07K14/505 , C07K14/54 , C07K16/18 , C07K16/28 , C07K16/30 , C07K16/46 , C12N15/18 , C12P21/02 , G06F17/30 , G06F19/16 , G06F19/18 , C07K14/575
CPC分类号： G06F19/16 , A61K9/7015 , A61K38/00 , A61K47/02 , A61K47/12 , C07K14/505 , C07K14/54 , C07K16/18 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K16/3046 , C07K16/464 , C07K2319/00 , G06F19/18
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。

6. 发明申请

WO2004074486A2 FUSION PROTEINS OF INTERFERON ALPHA MUTEINS WITH IMPROVED PROPERTIES 审中-公开
标题翻译：具有改善性质的干扰素ALPHA MUTEIN的融合蛋白
公开(公告)号：WO2004074486A2
公开(公告)日：2004-09-02
申请号：PCT/EP2004001524
申请日：2004-02-18
申请人： MERCK PATENT GMBH , JONES TIM , BAKER MATTHEW , HANLON MARIAN , CARR FRANCIS JOSEPH
发明人： JONES TIM , BAKER MATTHEW , HANLON MARIAN , CARR FRANCIS JOSEPH
IPC分类号： A61K38/21 , C07K14/56 , C12N15/21
CPC分类号： A61K38/212 , C07K14/56 , C07K2319/30
摘要： The invention concerns human interferon alpha and in particular modified forms of interferon alpha 2 with improved properties. The improved proteins contain amino acid substitutions at specific positions that confer increased relative activity in biological assays. The invention provides also modified interferon alpha with improved biological activity concomitant with reduced immunogenic potential in the protein. The improved proteins are intended for therapeutic use in the treatment of diseases in humans.
摘要翻译：本发明涉及人类干扰素α，特别涉及具有改进性质的干扰素α2的修饰形式。改进的蛋白质在特定位置含有氨基酸取代，其在生物测定中赋予增加的相对活性。本发明还提供修饰的干扰素α，其具有改善的生物活性，伴随蛋白质中的免疫原性潜力降低。改进的蛋白质用于治疗人类疾病的治疗用途。

7. 发明申请

WO2007002147A2 SYSTEM FOR REINFORCING TOWERS AND THE LIKE 审中-公开
标题翻译：用于增强塔和类似的系统
公开(公告)号：WO2007002147A2
公开(公告)日：2007-01-04
申请号：PCT/US2006024073
申请日：2006-06-21
申请人： JONES TIM
发明人： JONES TIM
IPC分类号： E04C3/30
CPC分类号： E04C3/30 , E04H12/085 , H01Q1/1242
摘要： A system for reinforcing a tower is disclosed. The system includes a number of vertically elongated primary support risers. Each riser is attached to the tower at a series of spaced apart locations.
摘要翻译：公开了一种用于加强塔的系统。该系统包括许多垂直拉长的主支撑立管。每个立管在一系列间隔开的位置处连接到塔架。

8. 发明申请

WO2009133375A3 DOWNHOLE TOOL FOR DETERMINING THE TUINNEL DEPTH OF PERFORATION TUNNELS 审中-公开
标题翻译：用于确定管道隧道深度的井下工具
公开(公告)号：WO2009133375A3
公开(公告)日：2011-08-18
申请号：PCT/GB2009001108
申请日：2009-05-01
申请人： ADVANCED PERFORATING TECHNOLOGIES LTD , ATHERTON ERIC , JONES TIM
发明人： ATHERTON ERIC , JONES TIM
IPC分类号： E21B43/119 , E21B47/08 , E21B47/09 , G01B21/18
CPC分类号： E21B43/11 , E21B43/119 , E21B47/08 , E21B47/09 , E21B49/00 , G01B5/18
摘要： A means of investigating the quality and/or nature of perforations in a downhole environment is disclosed. A "pecking1 finger (4) and depth measuring probe (40A) that can be axially and radially displaced enables the perforation to be located and its depth determined, through sequentially pecking around the wall lining in patterns such as radial, axial, and spiral sequences. By swinging a pecking finger that supports a depth measuring probe or cable with a bullet or conically shaped tip and measuring the displacement of the finger, the edge and centre of the hole can be determined with the largest displacement being when the tip is fully in the hole. When this position has been determined, the depth measuring cable is deployed and the depth of the perforation can be established by both an increase in the force required to push the cable and by the displacement of the pecking finger as it is pushed back by the reaction forces on the cable. Thus, a downhole tool comprises a elongate housing for insertion into a downhole environment, from which a probe extends radially by a variable amount, means for driving the probe in a radial direction, and means for sensing resistance to outward radial movement of the probe.
摘要翻译：公开了一种调查井下环境中穿孔质量和/或性质的方法。可以轴向和径向移位的“啄食1手指（4）和深度测量探针（40A）使得能够定位穿孔并且通过依次以诸如径向，轴向和螺旋序列的图案啄围壁衬垫来确定其深度通过摆动支撑深度测量探针或电缆的啄食手指，其具有子弹或圆锥形尖端并测量手指的位移，可以确定孔的边缘和中心，当尖端完全处于最大位移时当确定该位置时，展开深度测量电缆，并且可以通过推动电缆所需的力的增加和被推回的啄食手指的位移两者来建立穿孔的深度因此，井下工具包括用于插入井下环境的细长壳体，探头从该井下径向径向延伸可变量，我用于沿径向方向驱动探头，以及用于感测对探针向外径向运动的阻力的装置。

9. 发明申请

WO0127282A8 PLANT VIRUS PARTICLES WITH EXOGENOUS INTERNAL EITOPES 审中-公开
标题翻译：植物病毒颗粒与外部内部的EITOPES
公开(公告)号：WO0127282A8
公开(公告)日：2001-08-16
申请号：PCT/US0028430
申请日：2000-10-13
申请人： DOW CHEMICAL CO , HELLENDOORN KOEN , JONES TIM
发明人： HELLENDOORN KOEN , JONES TIM
IPC分类号： C12N15/09 , A61K39/12 , A61P31/12 , C07K14/02 , C07K14/08 , C07K14/12 , C07K14/145 , C12N7/00 , C12N7/01 , C12N15/40 , C12N15/82 , A61K39/00 , C12N15/62
CPC分类号： C07K14/005 , A61K2039/57 , C07K2319/00 , C12N15/8203 , C12N15/8257 , C12N2730/10122 , C12N2760/18722 , C12N2760/20122
摘要： The present invention relates to the expression of peptides on viral particles, and more particularly to the expression of peptides on the interior of the viral capsid. Methods are described for modifying viruses so that exogenous epitopes are expressed on the interior of the viral capsid. Viruses that can be modified include (+) stranded RNA viruses, especially plant (+) stranded RNA viruses such as the cowpea mosaic virus. Internal expression is especially useful for the expression of hydrophobic epitopes. The modified viral particles also find use as vaccines and as such are capable of eliciting an immune response.
摘要翻译：本发明涉及肽在病毒颗粒上的表达，并且更具体地涉及肽在病毒衣壳内部上的表达。描述了修饰病毒的方法，以使外源表位在病毒衣壳内部表达。可以修饰的病毒包括（+）链RNA病毒，特别是植物（+）链RNA病毒，如豇豆花叶病毒。内部表达对疏水性表位的表达特别有用。修饰的病毒颗粒也可用作疫苗，并因此能够引发免疫应答。

10. 发明申请

WO2009051936A4 METHODS AND APPARATUS TO CHANGE THE MOBILITY OF FORMATION FLUIDS USING THERMAL AND NON-THERMAL STIMULATION 审中-公开
标题翻译：用热和非热刺激改变成形流体流动性的方法和装置
公开(公告)号：WO2009051936A4
公开(公告)日：2009-07-23
申请号：PCT/US2008077219
申请日：2008-09-22
申请人： SCHLUMBERGER CA LTD , SCHLUMBERGER TECHNOLOGY BV , PRAD RES & DEV LTD , SCHLUMBERGER SERVICES PETROL , SCHLUMBERGER HOLDINGS , GOODWIN ANTHONY , JONES TIM , MASSIE KEITH JAMES , NIGHSWANDER JOHN , TUSTIN GARY
发明人： GOODWIN ANTHONY , JONES TIM , MASSIE KEITH JAMES , NIGHSWANDER JOHN , TUSTIN GARY
IPC分类号： E21B43/24 , E21B43/25
CPC分类号： E21B43/255 , E21B43/24
摘要： Methods and apparatus to change the mobility of formation fluids using thermal and non- thermal stimulation are described. An example apparatus (300) to simultaneously provide thermal and non-thermal stimulation to change a mobility of a fluid in a subsurface formation includes one or more containers (310,311) to hold one or more reactants. Additionally, the example apparatus includes a reactor (312) to initiate a chemical reaction with at least one of the reactants. Further, the example apparatus includes an injector (514) to inject a product of the chemical reaction into a formation. The product of the chemical reaction includes heat and a gaseous diluent to change a mobility of a fluid in a subsurface formation.
摘要翻译：描述了使用热和非热刺激改变地层流体流动性的方法和装置。一种用于同时提供热和非热刺激以改变地下地层中的流体的移动性的示例设备（300）包括一个或多个容器（310,311）以容纳一种或多种反应物。另外，该示例性装置包括反应器（312）以引发与至少一种反应物的化学反应。此外，示例装置包括用于将化学反应的产物注入地层的注入器（514）。化学反应的产物包括热量和气体稀释剂以改变地下地层中流体的流动性。

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