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1. 发明申请

WO9924075A3 AFFINITY MARKERS FOR HUMAN SERUM ALBUMIN 审中-公开
标题翻译：人类血清白蛋白的亲和标记
公开(公告)号：WO9924075A3
公开(公告)日：1999-09-02
申请号：PCT/US9823705
申请日：1998-11-06
申请人： CONJUCHEM INC , KRANTZ ALEXANDER , HUANG WOLIN , HANEL ARTHUR M , HOLMES DARREN L , BRIDON DOMINIQUE P
发明人： KRANTZ ALEXANDER , HUANG WOLIN , HANEL ARTHUR M , HOLMES DARREN L , BRIDON DOMINIQUE P
IPC分类号： A61K38/00 , A61K47/48 , A61K49/00 , C07K14/665 , G01N33/68
CPC分类号： A61K49/0021 , A61K38/00 , A61K47/62 , A61K47/6901 , A61K49/0043 , A61K49/0056 , C07K14/665
摘要： Methods and compositions are provided for identifying compounds having affinity or complementarity to a target molecule. Compounds according to the invention may be described by the formula E-Ca-R-Cb-A, wherein E is a therapeutic or diagnostic agent, R is a reactive group, Ca and Cb are connector groups between E and R and between R and A, respectively, and A is a group having an affinity for human serum albumin, wherein affinity group A comprises a sequence of amino acid residues -O1-O2-X1-X2-B in which the amino acid residues are independently selected from the group of all twenty naturally occurring amino acids. Compounds according to the invention may be used for labeling the target molecule, particularly where the target molecule is naturally found in a complex mixture, such as a physiological fluid, like blood. By affinity labeling in vivo, the lifetime of physiologically active entities can be greatly enhanced by becoming bound to long-lived blood components. The covalently bound entity may also serve as an antagonist or agonist of a particular binding protein or as an enzyme inhibitor.
摘要翻译：提供了用于鉴定具有与靶分子具有亲和力或互补性的化合物的方法和组合物。根据本发明的化合物可以由式E-Ca-R-Cb-A描述，其中E是治疗或诊断剂，R是反应性基团，Ca和Cb是E和R之间的连接基团，R和 A，A是对人血清白蛋白具有亲和性的基团，其中亲和基团A包含氨基酸残基-O1-O2-X1-X2-B的序列，其中氨基酸残基独立地选自的二十种天然存在的氨基酸。根据本发明的化合物可用于标记靶分子，特别是当目标分子天然存在于复杂混合物如生理液体如血液中时。通过在体内的亲和标记，生理活性物质的寿命可以通过与长寿命的血液成分结合而大大提高。共价结合的实体还可以用作特异性结合蛋白的拮抗剂或激动剂或作为酶抑制剂。

2. 发明申请

WO9924462A3 NOVEL CONJUGATES OF RGD-CONTAINING PEPTIDES AND ENDOGENOUS CARRIERS 审中-公开
标题翻译：含RGD的肽和内源性载体的新结合
公开(公告)号：WO9924462A3
公开(公告)日：1999-08-26
申请号：PCT/US9823702
申请日：1998-11-06
申请人： CONJUCHEM INC , BRIDON DOMINIQUE P , EZRIN ALAN M , HOLMES DARREN L , KRANTZ ALEXANDER , THIBAUDEAU KAREN , BLANCHARD DOMINIQUE
发明人： BRIDON DOMINIQUE P , EZRIN ALAN M , HOLMES DARREN L , KRANTZ ALEXANDER , THIBAUDEAU KAREN , BLANCHARD DOMINIQUE
IPC分类号： A61K35/16 , A61K38/00 , A61K47/48 , A61K49/00 , A61P7/02 , A61P25/04 , A61P43/00 , C07K7/08 , C07K14/665 , C07K14/75 , C07K14/78
CPC分类号： C07K14/665 , A61K38/00 , A61K47/64 , A61K47/6901
摘要： Conjugates are prepared from RGD containing peptides, by combining said peptides or analog with a material providing a functionally reactive group capable of reacting with a blood component (preferably a mobile blood cell or endogenous protein). The conjugates may be administered to patients to provide antiplatelet or antiadhesion properties through the inhibition of the binding of fibrinogen to the GPIIb/IIIa receptor, and may also be used as probes for receptor activity. The administration to the patient may be made either in vivo or ex vivo and may be performed by either introducing the RDG containing peptide including the reactive functional group into the patient's vascular system or preparing such a conjugate externally and introducing that conjugate to the patient's vascular system.
摘要翻译：通过将所述肽或类似物与提供能够与血液成分（优选移动血细胞或内源蛋白）反应的功能反应性基团的材料组合，由含RGD的肽制备缀合物。可以通过抑制纤维蛋白原与GPIIb / IIIa受体的结合来向患者施用缀合物以提供抗血小板或抗粘连性，并且也可以用作受体活性的探针。对患者的施用可以在体内或离体制备，并且可以通过将包含反应性官能团的含RDG的肽引入患者的血管系统或者将外部的这种缀合物引入到患者的血管系统中来进行。

3. 发明申请

WO9924076A9 SALICYLATE DERIVATIZED THERAPEUTIC AND DIAGNOSTIC AGENTS 审中-公开
标题翻译：盐酸衍生的治疗和诊断试剂
公开(公告)号：WO9924076A9
公开(公告)日：2000-06-08
申请号：PCT/US9823706
申请日：1998-11-06
申请人： CONJUCHEM INC , KRANTZ ALEXANDER , SONG YONG HONG , BRIDON DOMINIQUE P , HARDY MARGARET , CHEN QI QI , SETTINERI TINA
发明人： KRANTZ ALEXANDER , SONG YONG HONG , BRIDON DOMINIQUE P , HARDY MARGARET , CHEN QI QI , SETTINERI TINA
IPC分类号： A61K35/16 , A61K38/00 , A61K47/48 , A61K49/00 , A61P7/02 , A61P25/04 , A61P43/00 , C07K7/08 , C07K14/665 , C07K14/75 , C07K14/78
CPC分类号： C07K14/665 , A61K38/00 , A61K47/64 , A61K47/6901
摘要： The present invention relates to novel salicylate compounds which comprise a salicylate moiety and a biologically active agent of interest, where the compound binds and bonds specifically through reaction of the salicylate ester to serum albumin at Lys 199. Albumin is a long-lived moiety present in the blood. Novel salicylate compounds of the present invention provide for long-lived maintenance of the biologically active entity in the host. These compounds find broad applications in prophylactic and therapeutic applications, production of antibodies, reduction of the biologically effective concentration or activity of an endogenous or exogenous blood component, and in other situations where long term administration of a physiologically active compound is of interest.
摘要翻译：本发明涉及包含水杨酸酯部分和感兴趣的生物活性剂的新型水杨酸酯化合物，其中该化合物通过水杨酸酯在Lys 199处与血清白蛋白的反应而特异性地结合和键合。白蛋白是存在于血液。本发明的新型水杨酸酯化合物提供宿主中生物活性实体的长期维持。这些化合物在预防和治疗应用中广泛应用，产生抗体，降低内源或外源性血液成分的生物学有效浓度或活性，以及其他感兴趣的生理活性化合物的长期给药的情况。

4. 发明申请

WO9924076A2 SALICYLATE DERIVATIZED THERAPEUTIC AND DIAGNOSTIC AGENTS 审中-公开
标题翻译： SALICYLATE DERIVATIZED THERAPATIZED THERAPEUTIC AND DIAGNOSTIC AGENTS
公开(公告)号：WO9924076A2
公开(公告)日：1999-05-20
申请号：PCT/US9823706
申请日：1998-11-06
申请人： CONJUCHEM INC , KRANTZ ALEXANDER , SONG YONG HONG , BRIDON DOMINIQUE P , HARDY MARGARET , CHEN QUI QUI , SETTINERI TINA
发明人： KRANTZ ALEXANDER , SONG YONG HONG , BRIDON DOMINIQUE P , HARDY MARGARET , CHEN QUI QUI , SETTINERI TINA
IPC分类号： A61K35/16 , A61K38/00 , A61K47/48 , A61K49/00 , A61P7/02 , A61P25/04 , A61P43/00 , C07K7/08 , C07K14/665 , C07K14/75 , C07K14/78 , G01N33/50
CPC分类号： C07K14/665 , A61K38/00 , A61K47/64 , A61K47/6901
摘要： The present invention relates to novel salicylate compounds which comprise a salicylate moiety and a biologically active agent of interest, where the compound binds and bonds specifically through reaction of the salicylate ester to serum albumin at Lys 199. Albumin is a long-lived moiety present in the blood. Novel salicylate compounds of the present invention provide for long-lived maintenance of the biologically active entity in the host. These compounds find broad applications in prophylactic and therapeutic applications, production of antibodies, reduction of the biologically effective concentration or activity of an endogenous or exogenous blood component, and in other situations where long term administration of a physiologically active compound is of interest.
摘要翻译：本发明涉及包含水杨酸酯部分和感兴趣的生物活性剂的新型水杨酸酯化合物，其中该化合物通过水杨酸酯与Lys 199的血清白蛋白反应而特异性地结合并键合。白蛋白是存在于血液。本发明的新型水杨酸酯化合物提供宿主中生物活性物质的长期维持。这些化合物在预防和治疗应用中广泛应用，产生抗体，降低内源性或外源性血液成分的生物学有效浓度或活性，以及其它感兴趣的生理活性化合物的长期给药的情况。

5. 发明公开

EP2850201A4 SITE-SPECIFIC LABELING AND TARGETED DELIVERY OF PROTEINS FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：点特异性标记及治疗癌症的蛋白靶向递送
公开(公告)号：EP2850201A4
公开(公告)日：2016-08-31
申请号：EP13787738
申请日：2013-05-13
申请人： KRANTZ ALEXANDER
发明人： KRANTZ ALEXANDER
IPC分类号： C07K2/00 , A61K38/17 , A61K38/38 , A61K38/40 , A61K47/48 , A61P35/00 , C07K1/10 , C07K14/435
CPC分类号： A61K47/48246 , A61K38/17 , A61K38/38 , A61K38/40 , A61K45/06 , A61K47/64 , C07K14/435
摘要： The present invention relates to the formation of protein conjugates from proteins chemically modified for linkage to (1) anticancer drug pharmacophores, (2) ligands to biomarkers on cancer cell surfaces, (3) and/or another protein molecule. It provides and specifies new compositions, methods and combinations for tumor, and tumor vasculature targeting and cancer treatment.

6. 发明申请

WO2013170272A3 SITE-SPECIFIC LABELING AND TARGETED DELIVERY OF PROTEINS FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：用于治疗癌症的特定标签和靶向递送蛋白质
公开(公告)号：WO2013170272A3
公开(公告)日：2014-02-27
申请号：PCT/US2013040823
申请日：2013-05-13
申请人： KRANTZ ALEXANDER
发明人： KRANTZ ALEXANDER
IPC分类号： C12P21/00 , C07K1/10 , C07K2/00
CPC分类号： A61K47/48246 , A61K38/17 , A61K38/38 , A61K38/40 , A61K45/06 , A61K47/64 , C07K14/435
摘要： The present invention relates to the formation of protein conjugates from proteins chemically modified for linkage to (1) anticancer drug pharmacophores, (2) ligands to biomarkers on cancer cell surfaces, (3) and/or another protein molecule. It provides and specifies new compositions, methods and combinations for tumor, and tumor vasculature targeting and cancer treatment.
摘要翻译：本发明涉及从化学修饰用于连接到（1）抗癌药物载体的蛋白质的蛋白质的形成，（2）癌细胞表面上生物标志物的配体，（3）和/或另一种蛋白质分子。它提供并指定肿瘤的新组合物，方法和组合以及肿瘤血管系统靶向和癌症治疗。

7. 发明申请

WO2010040147A3 SITE-SPECIFIC N-TERMINAL MODIFICATIONS OF PROTEINS AND CONJUGATE FORMATION 审中-公开
标题翻译：蛋白质和结合形成的特异性端点修饰
公开(公告)号：WO2010040147A3
公开(公告)日：2010-09-23
申请号：PCT/US2009059597
申请日：2009-10-05
申请人： ADVANCED PROTEOME THERAPEUTICS , YU PENG , KRANTZ ALEXANDER
发明人： YU PENG , KRANTZ ALEXANDER
IPC分类号： C07K1/107 , A61K38/00 , C07K14/00
CPC分类号： C07K1/006 , A61K38/00 , A61K49/0002 , C07K1/1077 , C07K14/465 , C07K14/4721 , C07K14/535 , C07K14/5759 , C07K14/765 , C07K14/805 , C07K2319/00 , C12N9/0089
摘要： Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.
摘要翻译：提供蛋白质在其N-末端的位点特异性修饰。特别地，提供了通过氨基反应在其N-末端进行蛋白质的化学修饰以形成均匀的加合物，例如相应的肟衍生物。还提供了在放射性标记，分子成像应用中制备和使用加合物的方法以及诸如癌症，克罗恩病，关节炎，动脉粥样硬化血栓形成和斑块破裂等疾病的治疗方法。

8. 发明申请

WO2011153250A3 CROSSLINKING OF PROTEINS AND OTHER ENTITIES VIA CONJUGATES OF ALPHA-HALOACETOPHENONES, BENZYL HALIDES, QUINONES, AND THEIR DERIVATIVES 审中-公开
标题翻译：蛋白质和其他实体的交联通过阿尔法 - 海洛因，苯甲酸，喹诺酮及其衍生物的结合
公开(公告)号：WO2011153250A3
公开(公告)日：2012-07-05
申请号：PCT/US2011038774
申请日：2011-06-01
申请人： ADVANCED PROTEOME THERAPEUTICS INC , KRANTZ ALEXANDER , YU PENG
发明人： KRANTZ ALEXANDER , YU PENG
IPC分类号： A61K51/00 , A61K39/00 , A61K39/38
CPC分类号： A61K47/6803 , A61K47/48215 , A61K47/54 , A61K47/542 , A61K47/60 , A61K47/642 , A61K47/6455 , A61K2039/60 , C07K1/1077
摘要： The present invention relates to the formation of conjugates (e.g., protein- protein dimers) using a-halo-acetophenones, benzylic halides, quinones, and related compounds as a conjugating system. The invention also features compositions that include the conjugates described herein, as well as uses of these conjugates in methods of medical treatment.
摘要翻译：本发明涉及使用α-卤代苯乙酮，苄基卤化物，醌类和相关化合物作为共轭体系形成缀合物（例如蛋白质 - 二聚体）。本发明还包括包含本文所述的缀合物的组合物，以及这些缀合物在医学治疗方法中的用途。

9. 发明申请

WO2007103540A3 COMBINATION THERAPY WITH NON-SELECTIVE COX INHIBITORS TO PREVENT COX-RELATED GASTRIC INJURIES 审中-公开
标题翻译：与非选择性COX抑制剂联合治疗以预防与相关的胃肠道损伤
公开(公告)号：WO2007103540A3
公开(公告)日：2008-12-18
申请号：PCT/US2007006004
申请日：2007-03-08
申请人： PHARMENA NORTH AMERICA INC , KRANTZ ALEXANDER
发明人： KRANTZ ALEXANDER
IPC分类号： A01N37/08 , A01N53/00 , A61K31/19
CPC分类号： A61K45/06 , A61K31/138 , A61K31/352 , A61K2300/00
摘要： The present invention is directed to nicotinamide, nicotinamide derivatives and prostaglandin mimetics, alone or in combination with an NSAID, and their use in treating pain, inflammation, and/or gastrointestinal toxicty.
摘要翻译：本发明涉及单独或与NSAID组合的烟酰胺，烟酰胺衍生物和前列腺素模拟物，以及它们在治疗疼痛，炎症和/或胃肠道毒性中的用途。

10. 发明申请

WO2004066917A3 TANDEM ANALYSES OF NONCOVALENTLY DRIVEN EFFECTORS FOR MODULATORY MAPPING OF ACTIVITIES OF PROTEIN SITES 审中-公开
标题翻译：用于调节蛋白质活性活性的非特异性驱动效应的分析仪
公开(公告)号：WO2004066917A3
公开(公告)日：2005-08-11
申请号：PCT/US2004001038
申请日：2004-01-16
申请人： ADVANCED PROTEOME THERAPEUTICS , KRANTZ ALEXANDER
发明人： KRANTZ ALEXANDER
IPC分类号： A61K20060101 , C07K14/52 , C07K14/575 , C07K14/705 , C07K16/00 , C07K16/46 , C12Q1/00 , G01N33/58 , G01N33/68
CPC分类号： G01N33/6845 , C07K14/52 , C07K16/00 , C12Q1/00 , G01N33/58 , G01N33/6842 , G01N2500/00
摘要： The present invention provides methods of discovering and mapping secondary binding sites on biological molecules (e.g., proteins), the effects, if any, of site occupancy on the primary function of the molecule, and the screening of small molecules against the secondary binding sites. The invention further provides novel complexes for modification of secondary binding sites and the resulting modified biological molecules.
摘要翻译：本发明提供发现和映射生物分子（例如蛋白质）上的二级结合位点，对分子的主要功能的位置占据的影响（如果有的话）以及针对二级结合位点筛选小分子的方法。本发明还提供用于修饰二级结合位点和所得修饰的生物分子的新型复合物。

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