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1. 发明公开

EP2275817A1 PROTEOLYTIC ENZYMES IN DIAGNOSIS OF KIDNEY DISORDERS 审中-公开
标题翻译：维他命C酶
公开(公告)号：EP2275817A1
公开(公告)日：2011-01-19
申请号：EP10180116.5
申请日：2001-05-17
申请人： Nederlandse Organisatie voor Toegepast -Natuurwetenschappelijk Onderzoek TNO , Leids Universitair Medisch Centrum
发明人： Verheijen, Johan Hendrikus , Hanemaaijer, Jan Roeland Occo , Diamant, Michaela
IPC分类号： G01N33/573 , C12Q1/37
CPC分类号： C12Q1/37 , G01N33/573 , G01N2333/96486 , Y10S436/811 , Y10S530/834
摘要： The present invention relates to a method for determining whether a urine sample has been obtained from a subject suffering from a kidney disorder involving kidney damage. The method is based on determining the level of a proteolytic enzyme in urine from the subject.sample and optionally comparing this level with a reference value. The proteolytic enzyme preferably is a matrix metalloproteases, in particular MMP-2 or MMP-9. The method is particularly suitable for subjects with a condition or disorder that is associated with an increased risk of kidney disorders, such as diabetes. The method may adavnatagcously be applied for early detection of kidney damage, in particular when the subject does not yet show any sign of microalbuminuria. The method may also be applied to a subject undergoing dialysis for determining whether the subject is suffering from remodelling of the peritoneal membrane. Thus, the method is particularly suited for patients undergoing continuous ambulatory peritoneal dialysis.
摘要翻译：本发明涉及一种用于确定是否从患有肾损害的肾脏疾病的受试者获得尿样的方法。该方法基于确定来自受试者样品的尿液中的蛋白水解酶的水平，并且可选地将该水平与参考值进行比较。蛋白水解酶优选是基质金属蛋白酶，特别是MMP-2或MMP-9。该方法特别适用于与肾脏疾病风险增加（如糖尿病）相关的疾病或病症的受试者。该方法可以广泛应用于早期检测肾损伤，特别是当受试者尚未显示微量白蛋白尿的任何迹象时。该方法还可以应用于经历透析的受试者以确定受试者是否患有腹膜的重塑。因此，该方法特别适用于进行连续不卧床腹膜透析的患者。

2. 发明授权

EP0094720B1 Process for assaying the activity of tissue plasminogen activator, and kit suitable for use in said process 有权
标题翻译：用于测定组织匀浆激活剂活性的方法和适用于合成方法的试剂盒
公开(公告)号：EP0094720B1
公开(公告)日：1986-10-15
申请号：EP83200670.4
申请日：1983-05-09
申请人： Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek TNO
发明人： Verheijen, Johan Hendrikus , Nieuwenhuizen, Willem
IPC分类号： C12Q1/56
CPC分类号： C12Q1/56 , C12Q2337/12 , G01N2333/75 , G01N2333/968 , G01N2333/9726

3. 发明授权

EP0691409B1 Modified proenzymes as substrates for proteolytic enzymes 失效
标题翻译：改性酶原作为用于蛋白质组的金属酶的底物
公开(公告)号：EP0691409B1
公开(公告)日：2002-10-23
申请号：EP95201859.6
申请日：1995-07-06
申请人： Nederlandse Organisatie voor toegepast-natuurwetenschappelijk Onderzoek TNO
发明人： Verheijen, Johan Hendrikus
IPC分类号： C12Q1/37 , C12N9/50 , C12N9/72
CPC分类号： C12N9/6462 , C12Q1/37 , C12Q2337/12 , C12Y304/21073 , G01N2333/78 , G01N2333/96486 , G01N2333/9723

4. 发明授权

EP0723782B1 Use of a preparation comprising a plasminogen activator to improve wound healing 失效
标题翻译：制剂的用途，其包括纤溶酶原激活剂，以改善伤口愈合
公开(公告)号：EP0723782B1
公开(公告)日：2002-10-16
申请号：EP95200208.7
申请日：1995-01-27
申请人： NEDERLANDSE ORGANISATIE VOOR TOEGEPAST-NATUURWETENSCHAPPELIJK ONDERZOEK TNO
发明人： Verheijen, Johan Hendrikus
IPC分类号： A61K38/49 , A61P17/02
CPC分类号： A61K38/49 , Y10S514/925 , Y10S514/928

5. 发明公开

EP0691409A1 Modified proenzymes as substrates for proteolytic enzymes 失效
标题翻译： Modifizierte Proenzyme als Substratefürproteolische Enzyme
公开(公告)号：EP0691409A1
公开(公告)日：1996-01-10
申请号：EP95201859.6
申请日：1995-07-06
申请人： NEDERLANDSE ORGANISATIE VOOR TOEGEPAST-NATUURWETENSCHAPPELIJK ONDERZOEK TNO
发明人： Verheijen, Johan Hendrikus
IPC分类号： C12Q1/37 , C12N9/50 , C12N9/72
CPC分类号： C12N9/6462 , C12Q1/37 , C12Q2337/12 , C12Y304/21073 , G01N2333/78 , G01N2333/96486 , G01N2333/9723
摘要： Detection or determination of a protease in a sample by incubating the sample with a substrate of the protease and observing proteolytic cleavage of said substrate. The substrate is a modified proenzyme containing a recognition site, e.g., an activation site, cleavable by said protease. Proteolytic cleavage of the modified proenzyme is detected by observing the resulting activity using a suitable substrate of the activated proenzyme. The protease may be e.g. an aspartic protease or a metalloprotease, and the modified proenzyme e.g. pro-urokinase having a mutant activation site which is cleavable by the protease to be determined.
摘要翻译：通过将样品与蛋白酶的底物孵育并观察所述底物的蛋白水解切割来检测或测定样品中的蛋白酶。底物是含有可被所述蛋白酶切割的识别位点，例如活化位点的修饰的酶。通过使用活化的酶原的合适底物观察所得的活性来检测修饰的酶的蛋白水解切割。蛋白酶可以是例如。天冬氨酸蛋白酶或金属蛋白酶，以及修饰的酶原。具有突变活化位点的尿激酶，其可被被测定的蛋白酶切割。

6. 发明公开

EP0094720A1 Process for assaying the activity of tissue plasminogen activator, and kit suitable for use in said process 有权
标题翻译：一种用于确定组织的纤溶酶原激活剂的效力的方法，以及用于本方法的合适的试剂盒的用途。
公开(公告)号：EP0094720A1
公开(公告)日：1983-11-23
申请号：EP83200670.4
申请日：1983-05-09
申请人： Nederlandse Organisatie voor toegepast-natuurwetenschappelijk onderzoek TNO
发明人： Verheijen, Johan Hendrikus , Nieuwenhuizen, Willem
IPC分类号： C12Q1/56
CPC分类号： C12Q1/56 , C12Q2337/12 , G01N2333/75 , G01N2333/968 , G01N2333/9726
摘要： The invention relates to a process for assaying the activity of tissue plasminogen activator (TA), in which a sample is incubated with plasminogen, a substrate for plasmin giving a detectable reaction product on reaction with plasmin, preferably H-D-Val-Leu-Lys-pNA, and, as a stimulator for the conversion of plasminogen to plasmin by TA. water-soluble fibrinogen or fibrin fragments comprising at least partially the D-domains of the fibrinogen or fibrin molecule. The amount of the detectable reaction product of the plasmin substrate is measured. Preferably, said fibrinogen or fibrin fragments have been obtained by reacting fibrinogen or fibrin with CNBr and removing lower molecular components from the reaction product.
The invention also relates to kits for performing the assay and comprising the reagents to be used.

7. 发明公开

EP1557474A1 Method for determination of protein modifying or demodifying activity and suitable materials therefor 审中-公开
标题翻译：用于确定蛋白质修饰或-demodifizierenden活性和开发适合材料的方法
公开(公告)号：EP1557474A1
公开(公告)日：2005-07-27
申请号：EP04075185.1
申请日：2004-01-21
申请人： Nederlandse Organisatie voor Toegepast-Natuurwetenschappelijk Onderzoek TNO
发明人： Verheijen, Johan Hendrikus , Hanemaaijer, Jan Roeland Occo
IPC分类号： C12Q1/37 , G01N33/573 , G01N33/58 , G01N33/68
CPC分类号： G01N33/58 , C12Q1/37 , G01N33/573 , G01N33/581 , G01N33/68
摘要： Method for determining protein modifying activity or protein demodifying activity in a sample by providing a detection enzyme construct comprising at least one site of modification and at least one site of activation or inactivation, wherein activation or inactivation of the detection enzyme construct results from cleavage of the site of activation or inactivation by a protease, wherein the site of modification of the detection enzyme construct is capable of being modified by the protein modifying activity to be determined or demodified by the protein demodifying activity to be determined, and wherein modification or demodification of the site of modification affects cleavage of the site of activation or inactivation by the protease, contacting the sample with the detection enzyme construct under suitable conditions for the protein modifying or demodifying activity to be determined, contacting the detection enzyme construct with the protease under suitable conditions for activity of the protease, and determining the occurrence or level of detection enzyme activity. Active detection enzyme may be detectable by its conversion of a substrate of the detection enzyme to a reaction product. The detection enzyme construct may be derived from a protease (pro-)enzyme, like pro-urokinase or pro-caspase, and may comprise artificial modification site, activation cleavage site, and/or inactivation cleavage site.
摘要翻译：对于方法确定性采矿蛋白质修饰通过从裂解提供检测酶构建体包含修饰中的至少一个位点和活化或失活中的至少一个位点，worin检测酶的活化或失活构建体的结果的样品中的酶活性或蛋白质demodifying活性通过蛋白酶，worin检测酶构建体的修饰位点能够通过将蛋白质修饰活性的被修改为可确定性开采或通过蛋白质demodifying活性demodified是确定性的开采激活或失活的位点，和worin修改或的demodification 修饰的位点被蛋白酶影响激活或失活的部位的裂解，接触与检测酶样品对蛋白质修饰或demodifying活性合适的条件下构造为确定性的开采，接触检测酶与合适的条件下蛋白酶构建日活动 È蛋白酶和确定性采矿的发生或检测酶活性的水平。活性检测的酶可以是通过其转化的酶检测反应产物的底物的可检测的。检测酶构建体可以选自蛋白酶（PRO）酶衍生，像前尿激酶或促胱天蛋白酶，并且可以包括人工修饰位点，激活切割位点，和/或失活的切割位点。

8. 发明公开

EP1443116A1 Improved method for the detection of proteolytic enzymes 审中-公开
标题翻译： Verbessertes Verfahren zum Nachweis von proteolytischen Enzymen
公开(公告)号：EP1443116A1
公开(公告)日：2004-08-04
申请号：EP03075319.8
申请日：2003-01-31
申请人： Nederlandse Organisatie voor Toegepast-Natuurwetenschappelijk Onderzoek TNO
发明人： Verheijen, Johan Hendrikus , Hanemaaijer, Jan Roeland Occo
IPC分类号： C12Q1/37
CPC分类号： C12N9/6475 , C12Q1/37
摘要： The present invention provides an improved protease assay in which the proteases are detected on basis of their capability to cleave a modified pro-caspase which will yield an activated caspase which can then further be detected. Also part of the invention are the modified pro-caspases and kits comprising said modified pro-caspases.
摘要翻译：本发明提供了一种改进的蛋白酶测定法，其中基于其裂解修饰的前半胱天冬酶的能力来检测蛋白酶，其将产生活化的半胱天冬酶，其可以进一步被检测。本发明的一部分还包括修饰的前胱天蛋白酶和包含所述修饰的前半胱天冬酶的试剂盒。

9. 发明公开

EP0723782A1 Use of a preparation comprising a plasminogen activator to improve wound healing 失效
标题翻译： Verwendung einer Zubereitungsenthaltend ein纤溶酶原激活剂
公开(公告)号：EP0723782A1
公开(公告)日：1996-07-31
申请号：EP95200208.7
申请日：1995-01-27
申请人： NEDERLANDSE ORGANISATIE VOOR TOEGEPAST-NATUURWETENSCHAPPELIJK ONDERZOEK TNO
发明人： Verheijen, Johan Hendrikus
IPC分类号： A61K38/49
CPC分类号： A61K38/49 , Y10S514/925 , Y10S514/928
摘要： The present invention relates to the use of non-bacterial plasminogen activators in the manufacture of a topical medical preparation for the treatment of slow- or non-healing wounds. In addition, the present invention relates to a composition comprising a physiologically acceptable carrier and an effective amount of a non-bacterial plasminogen activator, with the exclusion of t-PA. Finally, the present invention is directed to a method of treatment of slow- or non-healing wounds comprising the topical application of a non-bacterial plasminogen activator to the site of a wound.
摘要翻译：本发明涉及非细菌性纤溶酶原激活剂在制备用于治疗慢性或非愈合伤口的局部医疗制剂中的用途。此外，本发明涉及不包括t-PA的包含生理上可接受的载体和有效量的非细菌纤溶酶原激活剂的组合物。最后，本发明涉及一种治疗慢性或非愈合伤口的方法，其包括将非细菌纤溶酶原激活剂局部施用于伤口部位。

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