MODIFIED ERYTHROPOIETIN TO WHICH WATER-SOLUBLE LONG-CHAIN MOLECULE IS ADDED
An object of the invention is to provide a pharmaceutical composition that contains erythropoietin as the active ingredient and has, when administered in humans and/or animals, a hematopoietic effect that lasts for not less than seven days. The invention provides a pharmaceutical composition containing, in an amount equal to not less than 50% of the total erythropoietin, erythropoietin to which two or more water-soluble long-chain molecules are added. The invention also provides a pharmaceutical composition containing erythropoietin to which a water-soluble long-chain molecule is added, wherein the water-soluble long-chain molecule has a molecular weight of not less than 30 kDa. The invention further provides a pharmaceutical composition containing erythropoietin to which a water-soluble long-chain molecule is added, wherein the water-soluble long-chain molecule has a branched chain.
1 . A pharmaceutical composition comprising an erythropoietin to which two or more straight-chain polyethylene glycols are added, wherein an amount of said erythropoietin is not less than 50% of total erythropoietin, and
wherein the erythropoietin is the following (a) to (c):
(a) a polypeptide having an amino acid sequence set forth in SEQ ID NO:1;
(b) a polypeptide that has an amino acid sequence of not less than 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:1, and has an erythropoietin activity in a cell proliferation assay using BaF/EPOR cells; or
(c) a polypeptide that has one or a plurality of amino acid substitutions, deletions, insertions and/or additions with respect to the amino acid sequence set forth in SEQ ID NO:1, and has an erythropoietin activity in a cell proliferation assay using BaF/EPOR cells.
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15 . The pharmaceutical composition according to claim 1 , wherein the subject of administration is an animal of the family Felidae and/or the family Canidae.
16 . The pharmaceutical composition according to claim 1 , which has a hematopoietic effect in an animal of the family Felidae and/or the family Canidae which lasts for not less than seven days.
17 . The pharmaceutical composition according claim 1 , which is a solution or gel having a pH of not less than 4 but not more than 8.
18 . The pharmaceutical composition according to claim 1 , wherein not less than one polyethylene glycol addition site is a lysine-78 residue.
19 . The pharmaceutical composition according to claim 1 , wherein even when repeatedly administered, the pharmaceutical composition does not trigger the production of an antibody to erythropoietin.
20 . A drug for treating anemia, comprising the pharmaceutical composition according to claim 1 .
21 . A hematopoietic drug, comprising the pharmaceutical composition according to claim 1 .
22 . The pharmaceutical composition according to claim 15 , which has a hematopoietic effect in an animal of the family Felidae and/or the family Canidae which lasts for not less than seven days.
23 . The pharmaceutical composition according claim 15 , which is a solution or gel having a pH of not less than 4 but not more than 8.
24 . The pharmaceutical composition according claim 16 , which is a solution or gel having a pH of not less than 4 but not more than 8.
25 . The pharmaceutical composition according to claim 15 , wherein not less than one polyethylene glycol addition site is a lysine-78 residue.
26 . The pharmaceutical composition according to claim 16 , wherein not less than one polyethylene glycol addition site is a lysine-78 residue.
27 . The pharmaceutical composition according to claim 17 , wherein not less than one polyethylene glycol addition site is a lysine-78 residue.
28 . The pharmaceutical composition according to claim 15 , wherein even when repeatedly administered, the pharmaceutical composition does not trigger the production of an antibody to erythropoietin.
29 . The pharmaceutical composition according to claim 16 , wherein even when repeatedly administered, the pharmaceutical composition does not trigger the production of an antibody to erythropoietin.
30 . The pharmaceutical composition according to claim 17 , wherein even when repeatedly administered, the pharmaceutical composition does not trigger the production of an antibody to erythropoietin.
31 . The pharmaceutical composition according to claim 18 , wherein even when repeatedly administered, the pharmaceutical composition does not trigger the production of an antibody to erythropoietin.
32 . A drug for treating anemia, comprising the pharmaceutical composition according to claim 15 .
33 . A drug for treating anemia, comprising the pharmaceutical composition according to claim 16 .