Erythropoietin conjugates
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United States of America Patent
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Jun 24, 2003
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N/A
app pub date -
Jun 27, 2000
filing date -
Jul 2, 1999
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Abstract
Conjugates of erythropoietin with poly(ethylene glycol) comprise an erythropoietin glycoprotein having at least one free 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 sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; the glycoprotein being covalently linked to 'n' poly(ethylene glycol) groups of the formula --CO--(CH.sub.2).sub.x (OCH.sub.2 CH.sub.2).sub.m --OR with the carbonyl of each poly(ethylene glycol) group forming an amide bond with one of said amino groups; wherein R is lower alkyl; x is 2 or 3; m is about 450 to about 900; n is from 1 to 3; and n and m are chosen so that the molecular weight of the conjugate minus the erythropoietin glycoprotein is from 20 kilodaltons to 100 kilodaltons.
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