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1. 发明授权

US5039791A Peptide fragments of tissue plasminogen activator 失效
标题翻译：组织纤溶酶原激活物的肽片段
公开(公告)号：US5039791A
公开(公告)日：1991-08-13
申请号：US432256
申请日：1989-11-06
申请人： Arthur J. Wittwer , Michael A. Sanzo
发明人： Arthur J. Wittwer , Michael A. Sanzo
IPC分类号： A61K38/00 , C12N9/72
CPC分类号： C12N9/6459 , C12Y304/21069 , A61K38/00
摘要： Novel peptide fragments of tissue plasminogen activator are described which have activity for inhibiting (a) the binding of tPA to human endothelial cells, and (b) the inactivation of tPA by plasminogen activator inhibitor-1 (PAI-1). Six peptides or peptide amides with these activities have the sequences, numbered according to the native protein:tPA (31-55),tPA (81-105),tPA (181-205),tPA (301-325),tPA (451-475, andtPA (531-555).It is hoped that small, synthesizeable molecules which prevent the inactivation of tPA by PAI-1 may provide a means for improving the efficacy of therapeutically administered tPA or for reducing the tendency of patients with elevated plasma PAI-1 concentrations to form fibrin clots.
摘要翻译：描述了组织纤溶酶原激活物的新型肽片段，其具有抑制（a）tPA与人内皮细胞结合的活性，和（b）通过纤溶酶原激活物抑制剂-1（PAI-1）灭活tPA。具有这些活性的六种肽或肽酰胺具有根据天然蛋白质编号的序列：tPA（31-55），tPA（81-105），tPA（181-205），tPA（301-325），tPA（451 -475和tPA（531-555），希望通过PAI-1阻止tPA失活的小的合成分子可以提供治疗性给药tPA或降低患者倾向的方法血浆PAI-1浓度形成纤维蛋白凝块。

2. 发明授权

US4927630A Tissue plasminogen activator from normal human colon cells 失效
标题翻译：来自正常人结肠细胞的组织纤溶酶原激活物
公开(公告)号：US4927630A
公开(公告)日：1990-05-22
申请号：US167946
申请日：1988-03-11
申请人： Joseph Feder , Susan C. Howard , Arthur J. Wittwer , Thomas W. Rademacher , Raj B. Parekh , Raymond A. Dwek
发明人： Joseph Feder , Susan C. Howard , Arthur J. Wittwer , Thomas W. Rademacher , Raj B. Parekh , Raymond A. Dwek
IPC分类号： A61K38/00 , C08B37/00 , C12N9/72 , C12N9/48 , A61K37/547 , C12N9/50
CPC分类号： C12N9/6459 , C08B37/00 , C12Y304/21069 , A61K38/00 , Y10S514/822
摘要： Normal human colon fibroblast tissue plasminogen activator is separated by lysine-Sepharose affinity chromatography into Types I and II glycoforms and characterized with respect to the relative incidence of each type of oligosaccharide comprising the respective Types I and II glycoforms.
摘要翻译：正常人结肠成纤维细胞组织纤溶酶原激活物通过赖氨酸琼脂糖亲和层析分离成I型和II型糖型，并且针对包含各自I型和II型糖型的各种类型寡糖的相对发生率进行表征。

3. 发明授权

US4857320A Method of enhancing the solubility of tissue plasminogen activator 失效
标题翻译：提高组织纤溶酶原激活物溶解度的方法
公开(公告)号：US4857320A
公开(公告)日：1989-08-15
申请号：US16295
申请日：1987-02-19
申请人： Arthur J. Wittwer
发明人： Arthur J. Wittwer
IPC分类号： A61K38/49 , A61K47/18 , A61K47/26
CPC分类号： A61K47/26 , A61K38/49 , A61K47/183
摘要： The solubility of tissue plasminogen activator in aqueous solution is enhanced by incorporating therein arginine or a non-toxic salt of arginine in an amount effective to increase the solubility of the t-PA without substantially inhibiting its potential biological activity upon administration.
摘要翻译：通过在其中加入精氨酸或无毒的精氨酸盐来提高组织纤溶酶原激活剂在水溶液中的溶解度，其量可以有效地增加t-PA的溶解度，而基本上不抑制其施用时的潜在的生物学活性。

4. 发明授权

US5506115A Reagent and method for determining activity of herpes protease 失效
标题翻译：用于测定疱疹蛋白酶活性的试剂和方法
公开(公告)号：US5506115A
公开(公告)日：1996-04-09
申请号：US235412
申请日：1994-04-29
申请人： Mihaly V. Toth , Arthur J. Wittwer , Barry C. Holwerda
发明人： Mihaly V. Toth , Arthur J. Wittwer , Barry C. Holwerda
IPC分类号： C07K14/03 , C12Q1/37 , C07K5/00 , C07K7/00 , C07K17/00
CPC分类号： C12Q1/37 , G01N2333/03 , G01N2333/045
摘要： A class of compounds is described for use as fluorogenic substrates for herpesvirus proteases and for use in an assay to identify inhibitors of herpesvirus proteases. Compounds of particular interest are defined by Formula II ##STR1## wherein W is selected from glycine, 4-aminobutyric acid, 5-aminopentanoic acid, 6-aminocaproic acid and 7-aminoheptanoic acid; wherein Y is selected from EDANS, Abz, DANSYL, nicotinic acid, 4-guanidino-benzoic acid, N-methyl-Abz, 4-chloro-Abz, 5-chloro-Abz, 6-chloro-Abz, 3,5-dibromo-Abz, 6-amino-nicotinic acid, 2-aminonicotinic acid, 2-chloronicotinic acid, niflumic acid and fluorogenic derivatives thereof; and wherein Z is selected from tryptophan, tyrosine, phenylalanine, p-nitrophenylalanine, m-nitrophenylalanine, DABSYL, DABCYL and halogenated derivatives thereof.
摘要翻译：描述了一类化合物用作疱疹病毒蛋白酶的荧光底物，并用于鉴定疱疹病毒蛋白酶抑制剂的测定中。特别感兴趣的化合物由式II的化合物定义，其中W选自甘氨酸，4-氨基丁酸，5-氨基戊酸，6-氨基己酸和7-氨基庚酸; 其中Y选自EDANS，Abz，DANSYL，烟酸，4-胍基 - 苯甲酸，N-甲基 - Abz，4-氯 - Abz，5-氯 - Abz，6-氯 - Abz，3,5-二溴 -Abz，6-氨基烟酸，2-氨基烟酸，2-氯烟酸，尼氟酸及其荧光衍生物; 并且其中Z选自色氨酸，酪氨酸，苯丙氨酸，对硝基苯丙氨酸，间硝基苯丙氨酸，DABSYL，DABCYL及其卤化衍生物。

5. 发明授权

US5134065A Tissue plasminogen activator inhibitor and method of purification 失效
标题翻译：组织纤溶酶原激活物抑制剂和纯化方法
公开(公告)号：US5134065A
公开(公告)日：1992-07-28
申请号：US864070
申请日：1986-05-16
申请人： Michael A. Sanzo , Arthur J. Wittwer , Jayne C. Marasa , Joseph Feder
发明人： Michael A. Sanzo , Arthur J. Wittwer , Jayne C. Marasa , Joseph Feder
IPC分类号： C07K14/81
CPC分类号： C07K14/8132
摘要： A novel and unique plasminogen activator inhibitor fragment is obtained from human umbilical vein endothelial cells which has the following characteristics:A. it is derived from a native t-PA inhibitor that binds to and inhibits the activity of t-PA,B. it is dissociated from a complex formed between said native t-PA inhibitor and t-PA, said complex existing in two distinct interconvertible conformations with molecular weight of about 88 KDa and 105 KDa, respectively, and being partially reversible in the presence of fibrin,C. it has a molecular weight of about 40 KDa when dissociated from the complex, andD. it has a novel partial N-terminal amino acid sequence when dissociated from the complex.
摘要翻译：从人脐静脉内皮细胞获得一种新颖独特的纤溶酶原激活物抑制剂片段，其具有以下特征：A.它衍生自结合并抑制t-PA，B的活性的天然t-PA抑制剂。它是从所述天然t-PA抑制剂和t-PA之间形成的复合物解离，所述复合物分别存在于分子量约88KDa和105KDa的两种不同的可互变构象中，并且在纤维蛋白C存在下部分可逆。当从络合物中解离时，其具有约40KDa的分子量，以及D.当从络合物解离时，其具有新的部分N-末端氨基酸序列。

6. 发明授权

US5132214A Large scale production of plasminogen activator from normal human colon cells 失效
标题翻译：来自正常人类细胞的大规模生产PLASMINOGEN激活剂
公开(公告)号：US5132214A
公开(公告)日：1992-07-21
申请号：US849933
申请日：1986-04-09
申请人： Joseph Feder , Nicholaos K. Harakas , Jon P. Schaumann , Daniel T. Connolly , Arthur J. Wittwer
发明人： Joseph Feder , Nicholaos K. Harakas , Jon P. Schaumann , Daniel T. Connolly , Arthur J. Wittwer
IPC分类号： C12N9/64 , A61K38/00 , C07K1/14 , C08B37/00 , C12N5/00 , C12N9/72 , C12R1/91
CPC分类号： C12N9/6459 , C08B37/00 , C12Y304/21069 , A61K38/00
摘要： Plasminogen activators (PA) are obtained from cultured normal human colon cells which are adaptable to large scale production. A purified tissue PA (t-PA) is obtained from CCD-18Co normal human colon fibroblast cells which shows chemical differences from Bowes melanoma t-PA.
摘要翻译：纤维蛋白溶酶原激活物（PA）是从适合大规模生产的培养的正常人结肠细胞获得的。从CT-18Co正常人结肠成纤维细胞获得纯化的组织PA（t-PA），其显示与Bowes黑素瘤t-PA的化学差异。

7. 发明授权

US5708137A Reagent and method for determining activity of herpes protease 失效
标题翻译：用于测定疱疹蛋白酶活性的试剂和方法
公开(公告)号：US5708137A
公开(公告)日：1998-01-13
申请号：US544519
申请日：1995-10-18
申请人： Mihaly V. Toth , Arthur J. Wittwer , Barry C. Holwerda
发明人： Mihaly V. Toth , Arthur J. Wittwer , Barry C. Holwerda
IPC分类号： C07K14/03 , C12Q1/37 , A61K38/02 , C07K5/00 , C07K7/00 , C07K17/00
CPC分类号： C12Q1/37 , G01N2333/03 , G01N2333/045
摘要： A class of compounds is described for use as fluorogenic substrates for herpesvirus proteases and for use in an assay to identify inhibitors of herpesvirus proteases. ##STR1## wherein W is selected from glycine, 4-aminobutyric acid, 5-aminopentanoic acid, 6-aminocaproic acid and 7-aminoheptanoic acid; wherein Y is selected from EDANS, Abz, DANSYL, nicotinic acid, 4-guanidino-benzoic acid, N-methyl-Abz, 4-chloro-Abz, 5-chloro-Abz, 6-chloro-Abz, 3,5-dibromo-Abz, 6-amino-nicotinic acid, 2-amino-nicotinic acid, 2-chloronicotinic acid, niflumic acid and fluorogenic derivatives thereof; and wherein Z is selected from tryptophan, tyrosine, phenylalanine, p-nitrophenylalanine, m-nitrophenylalanine, DABSYL, DABCYL and halogenated derivatives thereof.
摘要翻译：描述了一类化合物用作疱疹病毒蛋白酶的荧光底物，并用于鉴定疱疹病毒蛋白酶抑制剂的测定中。（II）其中W选自甘氨酸，4-氨基丁酸，5-氨基戊酸，6-氨基己酸和7-氨基庚酸; 其中Y选自EDANS，Abz，DANSYL，烟酸，4-胍基 - 苯甲酸，N-甲基 - Abz，4-氯 - Abz，5-氯 - Abz，6-氯 - Abz，3,5-二溴 -Abz，6-氨基烟酸，2-氨基烟酸，2-氯烟酸，尼氟酸及其荧光衍生物; 并且其中Z选自色氨酸，酪氨酸，苯丙氨酸，对硝基苯丙氨酸，间硝基苯丙氨酸，DABSYL，DABCYL及其卤化衍生物。

8. 发明授权

US5089409A Method of increasing specific activity of t-PA 失效
标题翻译：增加T-PA特异性活性的方法
公开(公告)号：US5089409A
公开(公告)日：1992-02-18
申请号：US413806
申请日：1989-09-28
申请人： Susan C. Howard , Joseph K. Welply , Arthur J. Wittwer
发明人： Susan C. Howard , Joseph K. Welply , Arthur J. Wittwer
IPC分类号： C12N9/64 , A61K38/46 , A61P7/02 , C12N5/08 , C12N9/72
CPC分类号： C12N9/6459 , C12Y304/21069
摘要： A method of increasing the specific activity of tissue plasminogen activator is disclosed which comprises increasing the proportion of neutral oligosaccharides in the tissue plasminogen activator glycoprotein.

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