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1. 发明授权

US5242810A Bifunctional inhibitors of thrombin and platelet activation 失效
标题翻译：双功能抑制剂和血小板激活
公开(公告)号：US5242810A
公开(公告)日：1993-09-07
申请号：US623611
申请日：1990-12-07
申请人： John M. Maraganore , Betty H. Chao , Kathryn L. Strauch , Jeffrey S. Thompson
发明人： John M. Maraganore , Betty H. Chao , Kathryn L. Strauch , Jeffrey S. Thompson
IPC分类号： A61K38/55 , A61K38/00 , A61K38/58 , A61P7/02 , A61P9/00 , A61P35/00 , C07K14/245 , C07K14/46 , C07K14/815 , C12N1/21 , C12N15/09 , C12N15/62 , C12P21/02
CPC分类号： C12N15/62 , A61K38/58 , C07K14/245 , C07K14/46 , C07K14/815 , C07K2319/00 , C07K2319/02 , C07K2319/24 , C07K2319/50 , Y10S530/856
摘要： The present invention relates to novel, bifunctional inhibitors of both platelet activation and thrombin. These bifunctional inhibitors are characterized by two domains -- a glycoprotein IIb/IIIa inhibitory domain and a thrombin inhibitory domain. The invention also relates to DNA sequences which encode the bifunctional inhibitors of this invention, recombinant DNA molecules which contain these DNA sequences and host transformed with these DNA molecules. The invention further relates to he recombinant expression of the bifunctional inhibitors of this invention by transformed hosts as well as to methods for purifying such recombinant bifunctional inhibitors. This invention also provides compositions and methods employing the novel bifunctional inhibitors alone or together with a fibrinolytic agent. Such compositions may be useful in patients for treating thrombotic disease, increasing reocclusion time, decreasing reperfusion time, simultaneously inhibiting thrombin- and platelet-mediated functions and inhibiting malignant cell growth.
摘要翻译：本发明涉及血小板活化和凝血酶两种新型双功能抑制剂。这些双功能抑制剂的特征在于两个结构域 - 糖蛋白IIb / IIIa抑制结构域和凝血酶抑制结构域。本发明还涉及编码本发明的双功能抑制剂的DNA序列，含有这些DNA序列的重组DNA分子和用这些DNA分子转化的宿主。本发明还涉及其通过转化的宿主重组表达本发明的双功能抑制剂以及纯化这些重组双功能抑制剂的方法。本发明还提供单独或与纤维蛋白溶解剂一起使用新型双功能抑制剂的组合物和方法。这样的组合物可用于治疗血栓形成疾病，增加再闭塞时间，减少再灌注时间，同时抑制凝血酶和血小板介导的功能并抑制恶性细胞生长的患者。

2. 发明授权

US4946783A Periplasmic protease mutants of Escherichia coli 失效
标题翻译：大肠杆菌的周质蛋白酶突变体
公开(公告)号：US4946783A
公开(公告)日：1990-08-07
申请号：US85402
申请日：1987-08-14
申请人： Jonathan R. Beckwith , Kathryn L. Strauch
发明人： Jonathan R. Beckwith , Kathryn L. Strauch
IPC分类号： C12N1/21 , C12N9/16 , C12N9/52 , C12N15/57 , C12N15/70
CPC分类号： C12R1/19 , C12N15/70 , C12N9/16 , C12N9/52 , C07K2319/00 , C07K2319/034 , C07K2319/036 , C07K2319/61 , Y10S435/849
摘要： This invention features a method of isolating a mutant strain of Escherichia coli, having a defective periplasmic protease, the method comprising the steps of: mutagenizing an E. coli cell, wherein the cell comprises: (a) an inner and an outer membrane, (b) a periplasmic space between the membranes, (c) a protein which in a first state is mobile, being able to move through the outer membrane and enter medium surrounding the cells, the protein in the first state being detectable in the medium, and in a second state is not mobile, remaining inside the cell, and (d) a periplasmic protease which converts the protein from the second state to the first state in the cell, and selecting a mutant cell which produces a reduced level of the detectable protein in the medium compared to the E. coli cell, wherein the mutant cell comprises the defective periplasmic protease.This invention also features mutant strains of E. coli having a defective periplasmic protease.
摘要翻译：本发明的特征在于分离具有缺陷周质蛋白酶的大肠杆菌突变菌株的方法，所述方法包括以下步骤：诱变大肠杆菌细胞，其中所述细胞包含：（a）内膜和外膜， b）膜之间的周质空间，（c）蛋白质，其在第一状态下是可移动的，能够移动通过外膜并进入细胞周围的介质，第一状态中的蛋白质可在培养基中检测，以及在第二状态下不能移动，保留在细胞内，和（d）将蛋白质从细胞中的第二种状态转化为第一状态的周质蛋白酶，并且选择产生可检测蛋白质水平降低的突变细胞在所述培养基中与大肠杆菌细胞相比，其中所述突变细胞包含有缺陷的周质蛋白酶。本发明还涉及具有缺陷周质蛋白酶的大肠杆菌突变菌株。

3. 发明授权

US06897297B1 Hydrophobically-modified protein compositions and methods 有权
标题翻译：疏水改性蛋白质组合物和方法
公开(公告)号：US06897297B1
公开(公告)日：2005-05-24
申请号：US09579680
申请日：2000-05-26
申请人： R. Blake Pepinsky , Chenhui Zeng , Darren P. Baker , Dingyi Wen , Kevin P. Williams , Ellen A. Garber , Kathryn L. Strauch , Frederick R. Taylor , Paul H. Weinreb , Russell C. Petter , Alphonse Galdes , Jeffrey Porter
发明人： R. Blake Pepinsky , Chenhui Zeng , Darren P. Baker , Dingyi Wen , Kevin P. Williams , Ellen A. Garber , Kathryn L. Strauch , Frederick R. Taylor , Paul H. Weinreb , Russell C. Petter , Alphonse Galdes , Jeffrey Porter
IPC分类号： A61K38/00 , A61K38/17 , C07K14/46 , C07K14/435 , C07K1/107
CPC分类号： C07K14/46 , A61K38/1709 , C07K2319/00
摘要： Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.
摘要翻译：描述了疏水性修饰的蛋白质及其制备方法。疏水部分连接到蛋白质的表面氨基酸残基。疏水部分可以是脂质或肽。或者，蛋白质可以通过向蛋白质附加疏水结构的各种化学反应衍生化。优选的蛋白质是哺乳动物来源的，并且选自Sonic，Indian和Desert hedgehog。疏水部分用作方便的系链，其可以连接囊泡，例如细胞膜，脂质体或胶束。

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