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Conjugates comprising human erythropoietin glycoprotein linked to poly(ethylene glycol) groups and pharmaceutical use
Conjugates comprising human erythropoietin glycoprotein linked to poly(ethylene glycol) groups and pharmaceutical use
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机译:包含与聚乙二醇连接的人促红细胞生成素糖蛋白的结合物和药物用途
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摘要
Conjugates are provided comprising a modified human erythropoietin glycoprotein covalently linked to "n" poly(ethylene glycol) groups of the formula: -CO-(CH2)x-(OCH2CH2)m-OR- The erythropoietin glycoprotein has at least one free amino group and the in vivo biological activity causing bone marrow cells to increase production of reticulocytes and red blood cells. The erythropoietin glycoprotein is modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site. The -CO of each poly(ethylene glycol) group forms an amide bond with one of the amino groups of the glycoprotein. R is lower alkyl, x is 2 or 3, m is 450 to 900, n is 1 to 3 and n and m are chosen so that the molecular weight of the conjugate minus the erythropoietin is from 20 kDa to 100 kDa. The conjugates can be used in medicaments to treat or prevent diseases correlated with anemia in chronic renal failure patients, AIDS and cancer patients undergoing chemotherapy.
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