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公开(公告)号：US5510248A
公开(公告)日：1996-04-23
申请号：US82843
申请日：1993-06-22
CPC分类号： C12N9/6429 , C12Y304/21005 , A61K38/00
摘要： An isolated polynucleotide which encodes human prothrombin is modified to encode amino acid substitutions at positions 155, 271 and 284 of the prothrombin polypeptide. A second polynucleotide is further modified to encode an additional amino acid substitution at residue 320.The polypeptide encoded by the first polynucleotide is resistant to cleavage by thrombin and factor Xa, exhibits greatly reduced procoagulant activity towards fibrinogen and unchanged anticoagulant activity towards protein C. The polypeptide can be cleaved between amino acid positions 320 and 321 to produce an active serine protease which can activate protein C, thereby inhibiting coagulation and stimulating activated protein C fibrinolytic activity.The polypeptide encoded by the second polynucleotide cannot be cleaved, mimics inactive prothrombin and thereby acts as a reversible inhibitor of coagulation by competing with Factor Xa and Factor Va for interaction at the phospholipid surface.Methods of producing recombinant polypeptides using the two isolated, modified polynucleotides are described.
摘要翻译： 修饰编码人凝血酶原的分离的多核苷酸以在凝血酶原多肽的位置155,271和284处编码氨基酸取代。 进一步修饰第二个多核苷酸以在残基320处编码另外的氨基酸取代。由第一多核苷酸编码的多肽对凝血酶和因子Xa的切割具有抗性，显示出大大降低了对纤维蛋白原的促凝活性和对蛋白C的不变的抗凝血活性。 可以在氨基酸位置320和321之间切割多肽，以产生能活化蛋白C的活性丝氨酸蛋白酶，从而抑制凝血并刺激活化的蛋白C纤维蛋白溶解活性。 由第二多核苷酸编码的多肽不能被切割，模拟无活性凝血酶原，从而通过与因子Xa和因子Va竞争在磷脂表面上相互作用而作为可逆的凝血抑制剂。 描述了使用两个分离的修饰的多核苷酸产生重组多肽的方法。
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2.发明授权公开(公告)号：US08080640B2
公开(公告)日：2011-12-20
申请号：US10887711
申请日：2004-07-08
摘要： Recombinant transferrin, non-glycosylated recombinant transferrin, transferrin half-molecules and mutant transferrins having altered metal-binding or other properties are described. The recombinant transferrin molecules are expressed in functional form by stable eukaryotic cell lines such as baby hamster kidney cells transformed with an expression vector encoding the recombinant molecule. The recombinant transferrins can be used in metal chelation therapy to bind and clear excess toxic metals in patients suffering from metal overloads or as tissue culture medium supplements or replacements.
摘要翻译： 描述了具有改变的金属结合或其它性质的重组转铁蛋白，非糖基化重组转铁蛋白，转铁蛋白半分子和突变体转运蛋白。 重组转铁蛋白分子以稳定的真核细胞系如用编码重组分子的表达载体转化的幼仓鼠肾细胞以功能形式表达。 重组转移蛋白可用于金属螯合治疗，以结合和清除患有金属超负荷或组织培养基补充剂或替代物的患者中的过量有毒金属。
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3.发明授权
公开(公告)号：US5986067A
公开(公告)日：1999-11-16
申请号：US175158
申请日：1993-12-28
摘要： Recombinant transferrin, non-glycosylated recombinant transferrin, transferrin half-molecules and mutant transferrins having altered metal-binding or other properties are described. The recombinant transferrin molecules are expressed in functional form by stable eukaryotic cell lines such as baby hamster kidney cells transformed with an expression vector encoding the recombinant molecule. The recombinant transferrins can be used in metal chelation therapy to bind and clear excess toxic metals in patients suffering from metal overloads or as tissue culture medium supplements or replacements.
摘要翻译： 描述了具有改变的金属结合或其它性质的重组转铁蛋白，非糖基化重组转铁蛋白，转铁蛋白半分子和突变体转运蛋白。 重组转铁蛋白分子以稳定的真核细胞系如用编码重组分子的表达载体转化的幼仓鼠肾细胞以功能形式表达。 重组转移蛋白可用于金属螯合治疗，以结合和清除患有金属超负荷或组织培养基补充剂或替代物的患者中的过量有毒金属。
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