公开(公告)号：US07128913B2

公开(公告)日：2006-10-31

申请号：US10014363

申请日：2001-12-11

申请人： Josef Burg ,  Alfred Engel ,  Reinhard Franze ,  Bernd Hilger ,  Hartmut Ernst Schurig ,  Wilhelm Tischer ,  Manfred Wozny

发明人： Josef Burg ,  Alfred Engel ,  Reinhard Franze ,  Bernd Hilger ,  Hartmut Ernst Schurig ,  Wilhelm Tischer ,  Manfred Wozny

IPC分类号： A61K39/385 ,  C07K1/00 ,  A61K35/14

CPC分类号： A61K47/62 ,  A61K47/60

摘要： The present invention refers to conjugates of erythropoietin with poly(ethylene glycol) comprising an erythropoietin glycoprotein having an N-terminal α-amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have the sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to one poly(ethylene glycol) group of the formula —CO—(CH2)x—(OCH2CH2)m—OR wherein the —CO of the poly(ethylene glycol) group forms an amide bond with said N-terminal α-amino group; and wherein R is lower alkyl; x is 2 or 3; and m is from about 450 to about 1350.

摘要翻译： 本发明涉及红细胞生成素与聚（乙二醇）的缀合物，其包含具有N-末端α-氨基的促红细胞生成素糖蛋白，并且具有引起骨髓细胞增加网织红细胞和红细胞产生的体内生物学活性并选择 由人红细胞生成素及其类似物组成，其具有通过加入1至6个糖基化位点或至少一个糖基化位点的重排而修饰的促红细胞生成素序列; 所述糖蛋白共价连接到一个式（Ⅳ）的聚（乙二醇）基团，其中：-in-line-formula description =“In-line Formulas”end =“lead”→CO-（CH 2 >） - （OCH 2 CH 2）m -OR <βin-line-formula description = “直链式”末端=“尾”→其中聚（乙二醇）基团的-CO与所述N-末端α-氨基形成酰胺键; 并且其中R是低级烷基; x为2或3; m为约450至约1350。