Method of treating disturbances of iron distribution in inflammatory intestinal diseases
AssigneeHoffmann-La Roche Inc.
InventorsHorst Klima, Paul Lehmann, Ralf Roeddiger, Ruth Walter-Matsui
Life of this patent
Estimating the term…
Abstract
The present invention relates to the use of erythropoietin for the treatment of disturbances of iron distribution in chronic inflammatory intestinal diseases.
Claims14
A method of treating disturbances in iron distribution in a patient suffering from a chronic inflammatory intestinal disease comprising administering a;
- therapeutically effective amount of human erythropoietin protein having the amino acid sequence of SEQ ID NO:1, without administering iron.
A method of treating disturbances in iron distribution in a patient suffering from a chronic inflammatory intestinal 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:3);
- Ser87Asn88Thr90Thr92
- Ser87Asn88Thr90Ala162
- Asn69Thr71Ser87Asn88Thr90
- Asn30Thr32Val87Asn88Thr90;
- Asn89Ile90Thr91;
- Ser87Asn89Ile90Thr91;
- Asn136Thr138;
- Asn138Thr140;
- Thr125;
- and
- Pro124-Thr125:
- and wherein the position(s) of the corresponding unmodified erythropoietin protein indicated by the superscripted number(s) is changed to the amino acid(s) that immediately precede the respective superscripted number(s).
A method of treating disturbances in iron distribution in a patient suffering from a chronic inflammatory intestinal 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 lie Leu Pro Gln (SEQ ID NO:
- 4), extending from the carboxy terminus;
- (b) the analog in (a) further comprising Ser87 Asn88 Thr9° EPO;
- (c) the analog in (a) further comprising Asn3° Thr32 Va187 Asn88 Thr9° EPO;
- (d) the analog in (a) further comprising Gln24 Ser87 Asn88 Thr9° EPO;
- (e) the analog in (a) further comprising Gln38 Ser87 Asn88 Thr9° EPO;
- (f) the analog in (a) further comprising Gln83 Ser87 Asn 88 Thr9° EPO and (g) darbepoetin alfa.
A method of treating disturbances in iron distribution in a patient suffering from a chronic inflammatory intestinal disease comprising administering a conjugate of human erythropoietin protein of SEQ ID NO:1 without administering iron, wherein said conjugate comprises 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—(OCH2CH2)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 1to 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 iron distribution in a patient suffering from a chronic inflammatory intestinal disease comprising administering a conjugate of the erythropoietin protein of SEQ ID NO:1 without administering iron, wherein said conjugate comprises the erythropoietin protein of SEQ ID NO:1 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 —(CHz)k—or —CH2(O—CHz—CHz)k—, k is from 1 to 10, Y is
- wherein 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.