Claims for Patent: 7,459,429

Summary for Patent: 7,459,429

Title:	Method of treating disturbances of iron distribution in inflammatory intestinal diseases
Abstract:	The present invention relates to the use of erythropoietin for the treatment of disturbances of iron distribution in chronic inflammatory intestinal diseases.
Inventor(s):	Klima; Horst (Penzberg, DE), Lehmann; Paul (Worms, DE), Roeddiger; Ralf (Gorxheimertal, DE), Walter-Matsui; Ruth (Altenbuseck, DE)
Assignee:	Hoffmann-La Roche Inc. (Nutley, NJ)
Application Number:	11/013,560
Patent Claims:	1. 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. 2. The method of claim 1, wherein the patient is suffering from morbus crohn. 3. The method of claim 1, wherein the patient is suffering from colitis ulcerosa. 4. 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: TABLE-US-00002 Asn.sup.30Thr.sup.32; Asn.sup.51Thr.sup.53; Asn.sup.57Thr.sup.59; Asn.sup.69; Asn.sup.69Thr.sup.71; Ser.sup.68Asn.sup.69Thr.sup.71; Val.sup.87Asn.sup.88Thr.sup.90; Ser.sup.87Asn.sup.88Thr.sup.90 Ser.sup.87Asn.sup.88Gly.sup.89Thr.sup.90 (SEQ ID NO:3); Ser.sup.87Asn.sup.88Thr.sup.90Thr.sup.92 Ser.sup.87Asn.sup.88Thr.sup.90Ala.sup.162 Asn.sup.69Thr.sup.71Ser.sup.87Asn.sup.88Thr.sup.90 Asn.sup.30Thr.sup.32Val.sup.87Asn.sup.88Thr.sup.90; Asn.sup.89Ile.sup.90Thr.sup.91; Ser.sup.87Asn.sup.89Ile.sup.90Thr.sup.91; Asn.sup.136Thr.sup.138; Asn.sup.138Thr.sup.140; Thr.sup.125; and Pro.sup.124-Thr.sup.125: 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). 5. 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 Ser.sup.87 Asn.sup.88 Thr.sup.9.degree. EPO; (c) the analog in (a) further comprising Asn.sup.3.degree. Thr.sup.32 Va187 Asn.sup.88 Thr.sup.9.degree. EPO; (d) the analog in (a) further comprising Gln.sup.24 Ser.sup.87 Asn.sup.88 Thr.sup.9.degree. EPO; (e) the analog in (a) further comprising Gln.sup.38 Ser.sup.87 Asn.sup.88 Thr.sup.9.degree. EPO; (f) the analog in (a) further comprising Gln.sup.83 Ser.sup.87 Asn .sup.88 Thr.sup.9.degree. EPO and (g) darbepoetin alfa. 6. The method of claim 1, wherein the erythropoietin protein is pegylated. 7. 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--(CH.sub.2).sub.x--(OCH.sub.2CH.sub.2).sub.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. 8. The method of claim 7, wherein x is 2, m is from about 650 to about 750, n is 1 and R is methyl. 9. The method of claim 7 wherein the conjugate has the formula P-[NHCO--(CH.sub.2).sub.x--(OCH.sub.2CH.sub.2).sub.m--OR].sub.n wherein P is the residue of the erythropoietin without the free amino group that forms the amide linkage; R is lower alkyl; x is 2or 3; m is from about 450 to about 900; and n is 1; and wherein m and n are selected such that the molecular weight of the conjugate minus the erythropoietin protein is from about 20 kd to about 100 kd. 10. 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 ##STR00016## 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. 11. The method of claim 10, wherein the conjugate has the formula: ##STR00017## wherein n is 1; m is an integer from about 450 to about 900; R is lower-alkyl; X is --(CH.sub.2).sub.k-- or --CH.sub.2(O--CH.sub.2--CH.sub.2).sub.k--, k is 1 to 10 and P is the residue of the erythropoietin protein without the n amino groups which form an amide linkage with X. 12. The method of claim 1 wherein the amount of human erythropoietin protein administered to the patient is from about 100 U/kg to about 200 U/kg twice per week. 13. The method of claim 1 wherein the amount of human erythropoietin protein administered to the patient is about 200 U/kg once every three to four weeks. 14. The method of claim 7 wherein said conjugate comprises the erythropoietin protein of SEQ ID NO:1 having one free amino group covalently linked to n poly(ethylene glycol) groups of the formula --CO--(CH.sub.2).sub.x--(OCH.sub.2CH.sub.2).sub.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 1; 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.

Details for Patent 7,459,429

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	ARANESP	darbepoetin alpha	Injection	103951	09/17/2001		2023-12-19
Amgen, Inc.	ARANESP	darbepoetin alpha	Injection	103951	07/19/2002		2023-12-19
Amgen, Inc.	ARANESP	darbepoetin alpha	Injection	103951	12/17/2002		2023-12-19
Amgen, Inc.	ARANESP	darbepoetin alpha	Injection	103951	12/12/2003		2023-12-19