Treatment of disturbances of iron distribution
AssigneeHoffmann-La Roche Inc.
InventorsPaul Lehmann, Ralf Roeddiger, Ruth Walter-Matsui
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Abstract
The present invention relates to the use of erythropoietin for the treatment of disturbances of iron distribution in heart diseases.
Claims12
A method of treating disturbances in iron distribution in a patient suffering from heart disease comprising administering to a patient suffering from heart disease and disturbances in iron distribution, an amount of human erythropoietin protein having the amino acid sequence of SEQ ID NO:1 sufficient to treat said disturbances in iron distribution without administering iron.
A method of treating disturbances in iron distribution in a patient suffering from heart disease comprising administering a therapeutically effective amount of human erythropoietin protein having the amino acid sequence of SEQ ID NO:
- 1 modified by the addition of up to three glycosylation sites, without administering iron, wherein the modification is selected from the group consisting of:
- Asn30Thr32;
- Asn51Thr53;
- Asn57Thr59;
- Asn69;
- Asn69Thr71;
- Ser68Asn69Thr71;
- Val87Asn88Thr90;
- Ser87Asn88Thr90;
- Ser87Asn88Gly89Thr90;
- (SEQ ID NO:
- 2);
- Ser87Asn88Thr90Thr92;
- Ser87Asn88Thr90Ala162;
- Asn69Thr71Ser87Asn88Thr90;
- Asn30Thr32Val87Asn88Thr90;
- Asn89Ile90Thr91;
- Ser87Asn89Ile90Thr91;
- Asn136Thr138;
- Asn138Thr140;
- Thr125;
- and
- Pro124Thr125.
A method of treating disturbances in iron distribution in a patient suffering from heart disease comprising administering a therapeutically effective amount of human erythropoietin protein, without administering iron, wherein the protein (EPO) is an analog of SEQ ID NO:
- 1, said analog is selected from the group consisting of:
- (a) human erythropoietin protein having the amino acid sequence, Ser Ser Ser Ser Lys Ala Pro Pro Pro Ser Leu Pro Ser Pro Ser Arg Leu Pro Gly Pro Ser Asp Thr Pro Ile Leu Pro Gln (SEQ ID NO:
- 3), extending from the carboxy terminus;
- (b) the analog Tin (a) further comprising Ser87 Asn88 Thr90 EPO;
- (c) the analog in (a) further comprising Asn30 Thr32 Val87 Asn88 Thr90 EPO;
- (d)the analog in (a) further comprising Gln38 Ser87 Asn88 Thr90 EPO;
- (e) the analog in (a) further comprising Gln38 Ser87 Asn88 Thr90 EPO;
- (f) the analog in (a) further comprising Gln83 Ser87 Asn88 Thr90 EPO and (g) darbepoetin alfa.
A method of treating disturbances in iron distribution in a patient suffering from heart disease comprising administering a conjugate of human erythropoietin protein of SEQ ID NO:
- 1 without administering iron, wherein said conjugate comprising the erythropoietin protein of SEQ ID NO:1 having one to three free amino groups covalently linked to n poly(ethylene glycol) groups of The formula —CO—(CH2)x—(OCH2CO2)m—OR with the —CO of each poly(ethylene glycol) group forming an amide bond with one of said amino groups;
- wherein R is a lower-alkyl;
- x is 2 or 3;
- m is from 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 protein is from 20 kilodaltons to 100 kilodaltons.
A method of treating disturbances in a patient suffering from heart disease comprising administering a conjugate of human erythropoietin protein of SEQ ID NO:
- 1, without administering iron, wherein said conjugate comprises the erythropoietin protein having one to three free amino groups covalently linked to from one to three lower-alkoxy poly(ethylene glycol) groups, each poly(ethylene glycol) group being covalently linked to the erythropoietin protein via a linker of the formula —C(O)—X—S—Y— with the C(O) of the linker forming an amide bond with one of said amino groups, X is —(CH2)k— or —CH2(O—CH2—CH2)k—2 k is from 1 to 10, Y is
- the average molecular weight of each poly(ethylene glycol) moiety is from about 20 kilodaltons to about 40 kilodaltons, and the molecular weight of the conjugate is from about 51 kilodaltons to about 175 kilodaltons.
Dependencies are inferred from the claim text.