CA2408685A1 - Liquid pharmaceutical composition containing an erythropoietin derivate - Google Patents

Liquid pharmaceutical composition containing an erythropoietin derivate Download PDF

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Publication number
CA2408685A1
CA2408685A1 CA002408685A CA2408685A CA2408685A1 CA 2408685 A1 CA2408685 A1 CA 2408685A1 CA 002408685 A CA002408685 A CA 002408685A CA 2408685 A CA2408685 A CA 2408685A CA 2408685 A1 CA2408685 A1 CA 2408685A1
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composition according
composition
erythropoietin
mmol
group
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CA2408685C (en
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Apollon Papadimitriou
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F Hoffmann La Roche AG
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A61K38/1816—Erythropoietin [EPO]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics

Abstract

The present invention relates to a liquid pharmaceutical composition comprising an erythropoietin protein, a multiple charged inorganic anion in a pharmaceutically acceptable buffer suitable to keep the solution pH in the range from about 5.5 to about 7.0, and optionally one or more pharmaceutical ly acceptable excipients. This composition is especially useful for the prophylaxis and treatment of diseases related to erythropoiesis.

Claims (60)

1. A liquid pharmaceutical composition comprising an erythropoietin protein, a multiple charged inorganic anion in a pharmaceutically acceptable buffer suitable to keep the solution pH in the range from about 5.5 to about 7.0, and optionally one or more pharmaceutically acceptable excipients.
2. The composition according to claim 1 which is an aqueous solution.
3. The composition according to claims 1 to 2 which is an isotonic solution.
4. The composition according to claims 1 to 3 wherein the anion is an anion of a multiple charged strong inorganic acid.
5. The composition according claims 1 to 4 wherein the anion is selected from the group consisting of sulfate, citrate or phosphate.
6. The composition according to claims 1 to 5 wherein the anion is a sulfate anion.
7. The composition according to claim 6 comprising 10 to 200 mmol/1 sulfate.
8. The composition according to claims 1 to 7 wherein the pH is 5.8 to 6.7
9. The composition according to claim 8 wherein the pH is 6.0 to 6.5
10. The composition according to claim 9 the pH is about 6.2.
11. The composition according to claims 1 to 10 wherein the buffer is selected form the group consisting of a phosphate or an arginine/H2SO4/Na2SO4 buffer.
12. The composition according to claim 11 wherein the buffer is a 10 to 50 mmol phosphate buffer.
13. The composition according claims 1 to 12 wherein the composition comprises one or more pharmaceutically acceptable excipients.
14. The composition according to claim 13 wherein one or more pharmaceutically acceptable excipients are selected form the group consisting of pharmaceutically acceptable salts, diluents, solvents and preservatives.
15. The composition according to claims 13 and 14 wherein the pharmaceutically acceptable excipients are selected from the group consisting of tonicity agents, polyols, anti-oxidants and non-ionic detergents.
16. The composition according to claims 13 to 15 wherein the pharmaceutically acceptable excipient a polyol.
17. The composition according to claim 16 wherein the polyol is selected from the group consisting of mannitol, sorbitol, glycerol, trehalose and saccharose.
18. The composition according to claim 17 wherein the polyol is mannitol.
19. The composition according to claims 13 to 18 comprising an anti-oxidant.
20. The composition according to claim 19 wherein the anti-oxidant is methionine.
21. The composition according to claims 13 to 20 comprising up to 1 mmol/1 CaCl2.
22. The composition according to claims 15 to 22 wherein the non-ionic detergent is polysorbate 80, polysorbate 20 or pluronic F68.
23. The composition according to claim 22 wherein the non-ionic detergent is pluronic F68.
24. The composition according to claims 22 or 23, wherein the composition comprises up to 1% (w/v) of the non-ionic detergent.
25. The composition according to any of claims 22 to 24, wherein the composition comprises up to 0.1% (w/v) of the non-ionic detergent.
26. The composition according to claims 1 to 25 wherein the erythropoietin protein is a human erythropoietin.
27. The composition according to claim 26 wherein the erythropoietin protein is expressed by endogenous gene activation.
28. The composition according to claims 26 to 27 wherein the erythropoietin protein has the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2.
29. The composition according to claims 26 to 28 wherein the protein has the sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites.
30. The composition according to claims 26 to 28 wherein the erythropoietin protein has the sequence of human erythropoietin modified by a modification selected from the group consisting of:
Asn30Thr32;
Asn51Thr53, Asn57Thr59;
Asn69;
Asn69Thr71;
Ser68Asn69Thr71;
Val87Asn88Thr90;
Ser87Asn88Thr90;
Ser87Asn88Gly89Thr90;
Ser87Asn88Thr90Thr92;
Ser87Asn88Thr90Ala162;
Asn69Thr71Ser87Asn88Thr90;
Asn30Thr32Val87Asn88Thr90;
Asn89Ile90Thr91;
Ser87Asn89Ile90Thr91;
Asn136Thr138;
Asn138Thr140;
Thr125; and Pro124Thr125.
31. The composition of according to claims 26 to 30, wherein the sequence of human erythropoietin is modified by a rearrangement of at least one glycosylation site.
32. The composition of claim 31, wherein the rearrangement comprises deletion of any of the N-linked glycosylation sites in human erythropoietin and addition of an N-linked glycosylation site at position 88 of the sequence of human erythropoietin.
33. The composition of claim 31, wherein the glycoprotein has the sequence of human erythropoietin modified by a modification selected from the group consisting of Gln24 Ser87 Asn88 Thr90;

Gln38 Ser87 Asn88 Thr90; and G1n83 Ser87 Asn88 Thr90.
34. The composition according to claims 26 to 33, wherein the erythropoietin protein as defined in any of claims is pegylated.
35. The composition according to claim 34, wherein the erythropoietin protein is a conjugate, said conjugate comprising 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; said glycoprotein being covalently linked to "n" polyethylene 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 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 glycoprotein is from 20 kilodaltons to 100 kilodaltons.
36. The composition according to claim 35 with an erythropoietin protein of the formula:
P-(NHCO-(CH2)x-(OCH2CH2)m-OR]n (I) wherein m, n, x and R are as above, and P is the residue of the glycoprotein without the n amino group(s) which form amide linkages) with the polyethylene glycol) group(s).
37. The composition according to claim 36, wherein in formula (I) x is 2, m is to 750, n is 1 and R is methyl.
38. The composition according to claim 34, wherein the erythropoietin protein is a conjugate, said conjugate comprising 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 the primary structure of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites; said glycoprotein being covalently linked to from one to three lower-alkoxy poly(ethylene glycol) groups, each poly(ethylene glycol) group being covalently linked to the glycoprotein 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-, 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.
39. The conjugate of claim 38, of the formula:
wherein n is an integer from 1 to 3; m is an integer from 450 to 900; R is lower alkyl; X is -(CH2)k- or -CH2(O-CH2-CH2)k-, and P is the residue of the erythropoietin glycoprotein without the amino group or groups which form an amide linkage with X.
40. The conjugate of claim 39, of the formula:
wherein n is an integer from 1 to 3; m is an integer from 450 to 900; R is lower alkyl; X is -(CH2)k- or -CH2(O-CH2-CH2)k-, and P is the residue of the erythropoietin glycoprotein without the amino group or groups which form an amide linkage with X.
41. The composition of claims 1 to 40 comprising 10 µg to..10000 µg erythropoietin protein per ml.
42. The composition of claims 1 to 41 comprising 10 µg to 10000 µg erythropoietin protein per ml, 10 - 200 mmol/l sulfate, and 10 to 50 mmol/l phosphate pH 6.0 to 6.5.
43. The composition of claim 42 comprising up to 20 mM methionine, 1- 5 % of a polyol (w/v), up to 0.1% pluronic F68 (w/v) and optionally up to 1 mM CaCl2 .
44. The composition according to claim 42 or 43 comprising 10 µg to 10000 µg erythropoietin protein per ml, 40 mmol/l sulfate, 10 mmol/l phosphate, 3%
mannitol (w/v), 10 mM methionine, 0.01% pluronic F68 (w/v), pH 6.2.
45. The composition claims 1 to 41 comprising 10 µg to 10000 µg erythropoietin protein per ml, 10 to 100 mmol/l NaCl, 10 to 50 mmol/l phosphate pH 6.0 to 7.0, optionally 1-5% of a polyol.
46. The composition of claim 45 up to 20 mM methionine, up to 0.1% pluronic and optionally 7.5 µmol/l CaCl2.
47. The composition of claim 45 or 46 comprising 10 µg to 10000 µg erythropoietin protein per ml, 100 mmol/l NaCl, 10 mM methionine, 0.01% pluronic F68, and 10 mmol/l phosphate, pH 7Ø
48. The composition of claims 1 to 41 comprising 10 µg to 10000 µg erythropoietin protein per ml, 10 to 50 mmol/l arginine, pH 6 to pH 6.5, 10 to 100 mmol/l sodium sulfate.
49. The composition of claim 48 comprising up to 20 mM methionine, up to 0.1%
pluronic F68, optionally up to 1 mmol/l CaCl2 and optionally 1- 5 % of a polyol.
50 50. The composition of claims 48 or 49, comprising 10 µg to 10000 µg erythropoietin protein per ml, 40 mmol/l arginine, pH 6.2, 30 mmol/l sodium sulfate, 3 % mannitol, 10 mM methionine, 0.01% pluronic F68 and optionally 1 mmol/l CaCl2.
51. The composition according to claims 1 to 41 comprising 25 to 2500 µg/ml erythropoietin and a) 10 mM sodium/potassium phosphate, 100 mM NaCl, pH 7.0 or b) 10 mM sodium phosphate, 120 mM sodium sulfate, pH 6.2 or c) 10 mM sodium phosphate, 40 mM sodium sulfate, 3% mannitol, pH 6.2 or d) 10 mM sodium phosphate, 40 mM sodium sulfate, 3% mannitol, 10 mM
methionine, 0.01% pluronic F68, pH 6.2 or e) 40 mM arginine, 30 mM sodium sulfate, 3% mannitol, pH 6.2 or f) 40 mM arginine, 30 mM sodium sulfate, 3% mannitol, 10 mM
methionine, 0.01% pluronic F68, pH 6.2.
52. The composition of claims 1 to 51 wherein the amount of erythropoietin is 50, 100, 400, 800 or 2500 µg/ml.
53. The composition of claim 52 comprising 10 mM sodium phosphate, 40 mM
sodium sulfate, 3% mannitol, 10 mM methionine, 0.01% pluronic F68, pH 6.2.
54. The composition of claim 52 comprising 40 mM arginine, 30 mM sodium sulfate, 3% mannitol, 10 mM methionine, 0.01% pluronic F68, pH 6.2.
55. The composition of claims 1 to 54 which is a lyophilisate or a spray-dried powder.
56. A process for preparing a composition according to any of claims 1 - 54, comprising mixing a erythropoietin protein with a solution comprising a multiple, negatively charged anion and optionally one or more pharmaceutically acceptable excipients.
57. Use of a composition according to any of claims 1 - 54 for the preparation of medicaments useful for the treatment and prevention of diseases correlated with anemia in chronic renal failure patients (CRF), AIDS and/or for the treatment of cancer patients undergoing chemotherapy.
58. Method for the treatment and prevention of diseases involving anemia in chronic renal failure patients (CRF), AIDS and cancer patients undergoing chemotherapy comprising the step of administering to a patient a composition as claimed in any one of claims 1 to 54.
59. Device for local and systemic sustained release comprising a composition according to any of claims 1 - 54.
60. The invention as hereinbefore described.
CA2408685A 2000-05-15 2001-05-08 Liquid pharmaceutical composition containing an erythropoietin derivate Expired - Lifetime CA2408685C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP00110355.5 2000-05-15
EP00110355 2000-05-15
PCT/EP2001/005187 WO2001087329A1 (en) 2000-05-15 2001-05-08 Liquid pharmaceutical composition containing an erythropoietin derivate

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CA2408685A1 true CA2408685A1 (en) 2001-11-22
CA2408685C CA2408685C (en) 2011-02-01

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US (2) US7169754B2 (en)
EP (2) EP1525889A1 (en)
JP (1) JP3967594B2 (en)
KR (3) KR20070032815A (en)
CN (1) CN1309416C (en)
AR (2) AR035034A1 (en)
AT (1) ATE291436T2 (en)
AU (1) AU784091B2 (en)
BR (1) BRPI0110914B8 (en)
CA (1) CA2408685C (en)
CZ (1) CZ304855B6 (en)
DE (1) DE60109625T3 (en)
DK (1) DK1311285T4 (en)
EC (2) ECSP024352A (en)
ES (1) ES2237574T5 (en)
HK (1) HK1056683A1 (en)
HR (1) HRP20020880B1 (en)
HU (1) HU230874B1 (en)
IL (2) IL152659A0 (en)
JO (1) JO3404B1 (en)
MA (1) MA26901A1 (en)
ME (1) ME00673B (en)
MX (1) MXPA02011303A (en)
MY (1) MY128654A (en)
NO (1) NO330934B1 (en)
NZ (1) NZ522030A (en)
PE (1) PE20020050A1 (en)
PL (1) PL219131B1 (en)
PT (1) PT1311285E (en)
RS (1) RS51292B (en)
RU (1) RU2281116C2 (en)
SI (1) SI1311285T1 (en)
TW (2) TWI288644B (en)
UY (1) UY26704A1 (en)
WO (1) WO2001087329A1 (en)
ZA (1) ZA200208500B (en)

Families Citing this family (130)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2686899B1 (en) * 1992-01-31 1995-09-01 Rhone Poulenc Rorer Sa NOVEL BIOLOGICALLY ACTIVE POLYPEPTIDES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM.
US5545553A (en) * 1994-09-26 1996-08-13 The Rockefeller University Glycosyltransferases for biosynthesis of oligosaccharides, and genes encoding them
US7304150B1 (en) * 1998-10-23 2007-12-04 Amgen Inc. Methods and compositions for the prevention and treatment of anemia
CZ299516B6 (en) * 1999-07-02 2008-08-20 F. Hoffmann-La Roche Ag Erythropoietin glycoprotein conjugate, process for its preparation and use and pharmaceutical composition containing thereof
JP2004506407A (en) * 2000-04-12 2004-03-04 ヒューマン　ゲノム　サイエンシズ　インコーポレイテッド Albumin fusion protein
HU230874B1 (en) 2000-05-15 2018-11-29 F. Hoffmann-La Roche Ag Liquid pharmaceutical compositions stable at room temperature which comprising a pegylated human erythropoietin protein
JP4656814B2 (en) 2000-12-20 2011-03-23 エフ．ホフマン−ラ ロシュ アーゲー Erythropoietin conjugate
WO2002049673A2 (en) * 2000-12-20 2002-06-27 F. Hoffmann-La Roche Ag Conjugates of erythropoietin (pep) with polyethylene glycol (peg)
FR2823220B1 (en) * 2001-04-04 2003-12-12 Genodyssee NOVEL ERYTHROPOIETIN (EPO) POLYNUCLEOTIDES AND POLYPEPTIDES
US20030143191A1 (en) * 2001-05-25 2003-07-31 Adam Bell Chemokine beta-1 fusion proteins
US20030104996A1 (en) * 2001-08-30 2003-06-05 Tiansheng Li L-methionine as a stabilizer for NESP/EPO in HSA-free formulations
JP2003152145A (en) * 2001-08-31 2003-05-23 Sumitomo Electric Ind Ltd Semiconductor heat dissipating substrate, method for its manufacture, and package
US7179617B2 (en) * 2001-10-10 2007-02-20 Neose Technologies, Inc. Factor IX: remolding and glycoconjugation of Factor IX
US7173003B2 (en) 2001-10-10 2007-02-06 Neose Technologies, Inc. Granulocyte colony stimulating factor: remodeling and glycoconjugation of G-CSF
US7696163B2 (en) 2001-10-10 2010-04-13 Novo Nordisk A/S Erythropoietin: remodeling and glycoconjugation of erythropoietin
US7795210B2 (en) * 2001-10-10 2010-09-14 Novo Nordisk A/S Protein remodeling methods and proteins/peptides produced by the methods
US8008252B2 (en) 2001-10-10 2011-08-30 Novo Nordisk A/S Factor VII: remodeling and glycoconjugation of Factor VII
US7157277B2 (en) 2001-11-28 2007-01-02 Neose Technologies, Inc. Factor VIII remodeling and glycoconjugation of Factor VIII
US7399613B2 (en) * 2001-10-10 2008-07-15 Neose Technologies, Inc. Sialic acid nucleotide sugars
US7214660B2 (en) 2001-10-10 2007-05-08 Neose Technologies, Inc. Erythropoietin: remodeling and glycoconjugation of erythropoietin
US7473680B2 (en) 2001-11-28 2009-01-06 Neose Technologies, Inc. Remodeling and glycoconjugation of peptides
WO2003059934A2 (en) * 2001-12-21 2003-07-24 Human Genome Sciences, Inc. Albumin fusion proteins
AU2002364586A1 (en) 2001-12-21 2003-07-30 Delta Biotechnology Limited Albumin fusion proteins
MXPA04012496A (en) * 2002-06-21 2005-09-12 Novo Nordisk Healthcare Ag Pegylated factor vii glycoforms.
SI21258A (en) * 2002-07-17 2004-02-29 LEK farmacevtska dru�ba d.d. Stable pharmaceutical preparation containing erythropoietin and poloxamer polyol
US7459435B2 (en) * 2002-08-29 2008-12-02 Hoffmann-La Roche Inc. Treatment of disturbances of iron distribution
JP2006511468A (en) * 2002-09-09 2006-04-06 ウォーレン ファーマシューティカルズ，インコーポレーテッド Long-acting erythropoietin maintains the tissue protective activity of endogenous erythropoietin
US7470779B2 (en) * 2002-09-20 2008-12-30 Pfizer Inc. Process for decreasing aggregate levels of pegylated protein
US7459436B2 (en) 2002-11-22 2008-12-02 Hoffmann-La Roche Inc. Treatment of disturbances of iron distribution
AU2004221824B2 (en) * 2003-03-14 2009-08-27 Ratiopharm Gmbh Branched water-soluble polymers and their conjugates
WO2004091499A2 (en) * 2003-04-09 2004-10-28 Neose Technologies, Inc. Intracellular formation of peptide conjugates
CA2522345A1 (en) 2003-04-09 2004-11-18 Neose Technologies, Inc. Glycopegylation methods and proteins/peptides produced by the methods
US8791070B2 (en) 2003-04-09 2014-07-29 Novo Nordisk A/S Glycopegylated factor IX
EP1624847B1 (en) * 2003-05-09 2012-01-04 BioGeneriX AG Compositions and methods for the preparation of human growth hormone glycosylation mutants
EA010099B1 (en) * 2003-05-12 2008-06-30 Афимакс, Инк. Novel peptides that bind to the erythropoietin receptor and methods for use thereof
US7919118B2 (en) 2003-05-12 2011-04-05 Affymax, Inc. Spacer moiety for poly (ethylene glycol) modified peptide based compounds
RS51130B (en) * 2003-05-12 2010-10-31 Affymax Inc. Novel peptides that bind to the erythropoietin receptor
MXPA05012315A (en) * 2003-05-12 2006-04-18 Affymax Inc Novel poly(ethylene glycol) modified compounds and uses thereof.
NZ543859A (en) 2003-06-10 2008-01-31 Lg Life Sciences Ltd Aqueous formulation that has storage stability over a long period without serum albumin comprising human erythropoietin; non-ionic surfactant, polyhydric alcohol, neutral amino acid and sugar alcohol as stabilizers
US9005625B2 (en) 2003-07-25 2015-04-14 Novo Nordisk A/S Antibody toxin conjugates
US8633157B2 (en) * 2003-11-24 2014-01-21 Novo Nordisk A/S Glycopegylated erythropoietin
US7405198B2 (en) * 2003-11-24 2008-07-29 Neose Technologies, Inc. Glycopegylated erythropoietin
US20080305992A1 (en) * 2003-11-24 2008-12-11 Neose Technologies, Inc. Glycopegylated erythropoietin
US20080318850A1 (en) * 2003-12-03 2008-12-25 Neose Technologies, Inc. Glycopegylated Factor Ix
US7956032B2 (en) 2003-12-03 2011-06-07 Novo Nordisk A/S Glycopegylated granulocyte colony stimulating factor
US20060040856A1 (en) 2003-12-03 2006-02-23 Neose Technologies, Inc. Glycopegylated factor IX
MXPA06006029A (en) * 2003-12-03 2006-08-23 Neose Technologies Inc Glycopegylated granulocyte colony stimulating factor.
PL1696947T3 (en) 2003-12-19 2014-08-29 Hoffmann La Roche Use of erythropoietin in the treatment of disturbances of iron distribution in chronic inflammatory intestinal diseases
JP5743368B2 (en) * 2004-01-08 2015-07-01 ラショファーム ゲーエムベーハー O-linked glycosylation of peptides
GB2429207A (en) * 2004-02-02 2007-02-21 Ambrx Inc Modified human interferon polypeptides and their uses
DE102004011663B4 (en) * 2004-03-10 2006-04-27 Bioceuticals Arzneimittel Ag Erythropoietin liquid formulation
JPWO2005089743A1 (en) * 2004-03-19 2008-01-31 味の素株式会社 Treatment for renal anemia
US20050282751A1 (en) * 2004-03-19 2005-12-22 Ajinomoto Co., Inc. Therapeutic agent for renal anemia
CN1960745A (en) * 2004-03-26 2007-05-09 詹森药业有限公司 Combination dosing regimen for erythropoietin
AR049580A1 (en) * 2004-07-07 2006-08-16 Lundbeck & Co As H CARBAMILATED EPO AND METHOD FOR YOUR PRODUCTION
WO2006010143A2 (en) 2004-07-13 2006-01-26 Neose Technologies, Inc. Branched peg remodeling and glycosylation of glucagon-like peptide-1 [glp-1]
US20090292110A1 (en) * 2004-07-23 2009-11-26 Defrees Shawn Enzymatic modification of glycopeptides
US20060029551A1 (en) * 2004-08-05 2006-02-09 Kui Liu Stable particle formulations of erythropoietin receptor agonists
US7772182B2 (en) * 2004-08-05 2010-08-10 Alza Corporation Stable suspension formulations of erythropoietin receptor agonists
US8268967B2 (en) * 2004-09-10 2012-09-18 Novo Nordisk A/S Glycopegylated interferon α
SI2586456T1 (en) * 2004-10-29 2016-05-31 Ratiopharm Gmbh Remodeling and glycopegylation of fibroblast growth factor (FGF)
JP2006137678A (en) * 2004-11-10 2006-06-01 Shionogi & Co Ltd Interleukin-2 composition
WO2006062685A2 (en) * 2004-11-11 2006-06-15 Affymax, Inc. Novel peptides that bind to the erythropoietin receptor
EA200700990A1 (en) * 2004-11-11 2008-04-28 Афимакс, Инк. NEW PEPTIDES THAT BIND THE ERYTHROPOIETIN RECEPTOR
WO2006074279A1 (en) * 2005-01-06 2006-07-13 Neose Technologies, Inc. Glycoconjugation using saccharyl fragments
AU2006203792B2 (en) 2005-01-10 2011-11-03 Ratiopharm Gmbh Glycopegylated Granulocyte Colony Stimulating Factor
WO2006079155A1 (en) * 2005-01-25 2006-08-03 Apollo Life Sciences Limited Molecules and chimeric molecules thereof
WO2006105426A2 (en) * 2005-03-30 2006-10-05 Neose Technologies, Inc. Manufacturing process for the production of peptides grown in insect cell lines
US20070154992A1 (en) * 2005-04-08 2007-07-05 Neose Technologies, Inc. Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants
US20070037886A1 (en) * 2005-04-26 2007-02-15 Ajinomoto Co., Inc. Bone marrow erythroid progenitor cell(s) differentiation inducer
EP1891231A4 (en) 2005-05-25 2011-06-22 Novo Nordisk As Glycopegylated factor ix
EP1888098A2 (en) * 2005-05-25 2008-02-20 Neose Technologies, Inc. Glycopegylated erythropoietin formulations
US20110003744A1 (en) * 2005-05-25 2011-01-06 Novo Nordisk A/S Glycopegylated Erythropoietin Formulations
US7550433B2 (en) 2005-06-03 2009-06-23 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
US7919461B2 (en) 2005-06-03 2011-04-05 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
US8324159B2 (en) * 2005-06-03 2012-12-04 Affymax, Inc. Erythropoietin receptor peptide formulations and uses
EP1916997B1 (en) 2005-08-05 2018-04-18 Amgen Inc. Stable aqueous protein pharmaceutical formulations and their preparation
US20070105755A1 (en) 2005-10-26 2007-05-10 Neose Technologies, Inc. One pot desialylation and glycopegylation of therapeutic peptides
JP2009515508A (en) * 2005-08-19 2009-04-16 ネオス テクノロジーズ インコーポレイテッド GlycoPEGylated Factor VII and Factor VIIA
US20070072795A1 (en) * 2005-09-28 2007-03-29 Anton Haselbeck Treatment of neurodegenerative disorders
US20090048440A1 (en) 2005-11-03 2009-02-19 Neose Technologies, Inc. Nucleotide Sugar Purification Using Membranes
KR20190097310A (en) 2005-11-23 2019-08-20 악셀레론 파마 인코포레이티드 Activin-actrπa antagonists and uses for promoting bone growth
US8128933B2 (en) 2005-11-23 2012-03-06 Acceleron Pharma, Inc. Method of promoting bone growth by an anti-activin B antibody
CN101015684B (en) * 2006-02-10 2011-08-24 华北制药集团新药研究开发有限责任公司 Recombinant erythropoietin liquor preparation
WO2007108505A1 (en) * 2006-03-22 2007-09-27 Chugai Seiyaku Kabushiki Kaisha Erythropoietin solution preparation
US20080280818A1 (en) * 2006-07-21 2008-11-13 Neose Technologies, Inc. Glycosylation of peptides via o-linked glycosylation sequences
EP2054074B8 (en) * 2006-08-04 2014-11-12 Prolong Pharmaceuticals, LLC Modified erythropoietin
WO2008057683A2 (en) 2006-10-03 2008-05-15 Novo Nordisk A/S Methods for the purification of polypeptide conjugates
CN101600448B (en) * 2006-10-04 2015-11-25 诺和诺德公司 The sugar of the PEGization that glycerol connects and glycopeptide
WO2008073620A2 (en) * 2006-11-02 2008-06-19 Neose Technologies, Inc. Manufacturing process for the production of polypeptides expressed in insect cell-lines
US8895016B2 (en) 2006-12-18 2014-11-25 Acceleron Pharma, Inc. Antagonists of activin-actriia and uses for increasing red blood cell levels
TWI782836B (en) 2007-02-02 2022-11-01 美商艾瑟勒朗法瑪公司 Variants derived from actriib and uses therefor
US9050304B2 (en) 2007-04-03 2015-06-09 Ratiopharm Gmbh Methods of treatment using glycopegylated G-CSF
US20090053167A1 (en) * 2007-05-14 2009-02-26 Neose Technologies, Inc. C-, S- and N-glycosylation of peptides
US20080286341A1 (en) * 2007-05-16 2008-11-20 Sven-Borje Andersson Buffered coated nicotine containing products
CN101778937A (en) * 2007-06-04 2010-07-14 诺和诺德公司 o-linked glycosylation using n-acetylglucosaminyl transferases
MX2009013259A (en) 2007-06-12 2010-01-25 Novo Nordisk As Improved process for the production of nucleotide sugars.
JP5513380B2 (en) * 2007-06-25 2014-06-04 アムジエン・インコーポレーテツド Composition of specific binding agents for hepatocyte growth factor
US7968811B2 (en) * 2007-06-29 2011-06-28 Harley-Davidson Motor Company Group, Inc. Integrated ignition and key switch
CL2008002054A1 (en) * 2007-07-17 2009-05-29 Hoffmann La Roche Method for the regeneration of a cation exchange chromatography column after elusion of monopeglated erythropoietin and method to obtain a monopeglated erythropoietin, incorporating the regeneration method of the cation exchange column.
CL2008002053A1 (en) 2007-07-17 2009-05-22 Hoffmann La Roche Method for the purification of a monopeglated erythropoietin (epompeg) which consists of providing a solution containing mono, poly and non-peglated erythropoietin and passing it through two steps of cation exchange chromatography and a method to produce epo mpeg that includes a purification method.
DE202008017456U1 (en) 2007-08-27 2009-08-27 Biogenerix Ag Liquid formulation of G-CSF conjugates
US8207112B2 (en) * 2007-08-29 2012-06-26 Biogenerix Ag Liquid formulation of G-CSF conjugate
CN101456911A (en) * 2007-12-12 2009-06-17 江苏豪森药业股份有限公司 Erythrocyte-stimulating factor mimic peptide derivative, medical salts thereof, preparation method and use thereof
WO2009089396A2 (en) * 2008-01-08 2009-07-16 Neose Technologies, Inc. Glycoconjugation of polypeptides using oligosaccharyltransferases
EP2626080A3 (en) 2008-02-27 2014-03-05 Novo Nordisk A/S Conjugated factor VIII molecules
US8216997B2 (en) 2008-08-14 2012-07-10 Acceleron Pharma, Inc. Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators
DK3494986T3 (en) 2008-08-14 2020-08-03 Acceleron Pharma Inc GDF catches
CN102164954B (en) * 2008-09-23 2018-04-06 弗·哈夫曼-拉罗切有限公司 The purifying of hematopoietin
AU2010258931B2 (en) 2009-06-08 2015-04-23 Acceleron Pharma Inc. Methods for increasing thermogenic adipocytes
KR20120028358A (en) 2009-06-12 2012-03-22 악셀레론 파마 인코포레이티드 Truncated actriib-fc fusion proteins
ES2535268T3 (en) 2009-06-24 2015-05-07 F. Hoffmann-La Roche Ag Characterization of reusable chromatography equipment
BRPI0902481B8 (en) * 2009-07-31 2021-05-25 Soc Beneficente De Senhoras Hospital Sirio Libanes pharmaceutical composition comprising hemopressin and its use.
KR20200124322A (en) * 2009-08-13 2020-11-02 악셀레론 파마 인코포레이티드 Combined use of gdf traps and erythropoietin receptor activators to increase red blood cell levels
CA2775012A1 (en) * 2009-09-23 2011-03-31 Biogenerix Ag Process for the purification of recombinant human erythropoietin (epo), epo thus purified and pharmaceutical compositions comprising same
JP6267425B2 (en) 2009-11-17 2018-01-24 アクセルロン ファーマ， インコーポレイテッド ACTRIIB protein and its variants and uses thereof for utrophin induction for the treatment of muscular dystrophy
ES2524897T3 (en) 2010-12-21 2014-12-15 F. Hoffmann-La Roche Ag Chromatography equipment characterization
AR094821A1 (en) 2012-07-25 2015-09-02 Hanmi Pharm Ind Co Ltd LIQUID FORMULATION OF AN INSULINOTROPIC PEPTIDE CONJUGATE OF PROLONGED ACTION
CN102816227A (en) * 2012-08-30 2012-12-12 深圳赛保尔生物药业有限公司 Erythropoietin recovery method
KR20210091358A (en) 2012-11-02 2021-07-21 셀진 코포레이션 Activin-actrii antagonists and uses for treating bone and other disorders
CU20140003A7 (en) 2014-01-08 2015-08-27 Ct De Inmunología Molecular Biofarmacuba CONJUGATE UNDERSTANDING ERYTHROPOYETIN AND A RAMIFIED POLYMER STRUCTURE
CA2943906A1 (en) 2014-03-29 2015-10-08 Intas Pharmaceuticals Ltd. Liquid pharmaceutical composition of conjugated erythropoietin
MX2016016531A (en) 2014-06-13 2017-04-25 Acceleron Pharma Inc Methods and compositions for treating ulcers.
US11608357B2 (en) 2018-08-28 2023-03-21 Arecor Limited Stabilized antibody protein solutions
EP3372241A1 (en) 2017-03-06 2018-09-12 Ares Trading S.A. Liquid pharmaceutical composition
EP3372242A1 (en) 2017-03-06 2018-09-12 Ares Trading S.A. Liquid pharmaceutical composition
WO2018184692A1 (en) * 2017-04-07 2018-10-11 Ares Trading S.A. Liquid pharmaceutical composition
SI3731873T1 (en) * 2017-12-29 2022-05-31 F. Hoffmann-La Roche Ag Process for providing pegylated protein composition
CN111558046A (en) * 2020-05-27 2020-08-21 华润昂德生物药业有限公司 Application of trehalose in preparation of recombinant human erythropoietin liquid preparation, preparation method and application
TWI740635B (en) * 2020-09-09 2021-09-21 財團法人工業技術研究院 Polyvinylidene fluoride film composition, and polyvinylidene fluoride isolation film

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US147431A (en) * 1874-02-10 Improvement in game boards
US115833A (en) * 1871-06-13 Improvement in grain-driers
JPS6197229A (en) * 1984-10-18 1986-05-15 Chugai Pharmaceut Co Ltd Stable erythropoietin preparation
US4732889A (en) 1985-02-06 1988-03-22 Chugai Seiyaku Kabushiki Kaisha Pharmaceutical composition for the treatment of the anemia of rheumatoid arthritis
DE3729863A1 (en) * 1987-09-05 1989-03-16 Boehringer Mannheim Gmbh STABILIZED ERYTHROPOIETIN LYOPHILISATES
DE3734923C1 (en) 1987-10-15 1989-01-26 Biotest Pharma Gmbh Process for the preparation of a sterile plasma protein solution containing fibrinogen and coagulation factor XIII
DE4014654A1 (en) 1990-05-08 1991-11-14 Behringwerke Ag GALENIC AQUEOUS FORMULATIONS OF ERYTHROPOIETIN AND THEIR USE
CA2069746A1 (en) * 1990-09-28 1992-03-29 Jonathan I. Rosen Hybrid growth factors
US5272135A (en) 1991-03-01 1993-12-21 Chiron Ophthalmics, Inc. Method for the stabilization of methionine-containing polypeptides
US6565841B1 (en) 1991-03-15 2003-05-20 Amgen, Inc. Pulmonary administration of granulocyte colony stimulating factor
NZ244778A (en) 1991-10-21 1994-03-25 Ortho Pharma Corp Peg imidates and protein derivatives thereof
DE4135542A1 (en) 1991-10-28 1993-04-29 Boehringer Mannheim Gmbh STORAGE PROTEIN SOLUTIONS
US5460944A (en) 1991-10-28 1995-10-24 Boehringer Mannheim Gmbh Storable protein solution
US5716644A (en) * 1992-06-11 1998-02-10 Alkermes, Inc. Composition for sustained release of non-aggregated erythropoietin
US5661125A (en) * 1992-08-06 1997-08-26 Amgen, Inc. Stable and preserved erythropoietin compositions
US5354934A (en) † 1993-02-04 1994-10-11 Amgen Inc. Pulmonary administration of erythropoietin
WO1994028024A1 (en) 1993-06-01 1994-12-08 Enzon, Inc. Carbohydrate-modified polymer conjugates with erythropoietic activity
CN1057534C (en) * 1993-08-17 2000-10-18 柯瑞英-艾格公司 Erythropoietin analogs
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
TWI240627B (en) 1996-04-26 2005-10-01 Chugai Pharmaceutical Co Ltd Erythropoietin solution preparation
AU3908597A (en) * 1996-08-02 1998-02-25 Ortho-Mcneil Pharmaceutical, Inc. Polypeptides having a single covalently bound n-terminal water-soluble polymer
US5919656A (en) 1996-11-15 1999-07-06 Amgen Canada Inc. Genes encoding telomerase protein 1
EP0885613A1 (en) 1997-06-21 1998-12-23 Roche Diagnostics GmbH Use of modified hemoglobins for treatment of anemias and erythropoietin and modified hemoglobin containing combined preparations
DE19734293A1 (en) 1997-08-08 1999-02-11 Boehringer Mannheim Gmbh Use of pharmaceutical combination preparations containing erythropoietin and iron preparations for the treatment of rheumatic diseases
PT1813624E (en) 1998-10-23 2010-10-27 Amgen Inc Methods and compositions for the prevention and treatment of anemia
UY25790A1 (en) 1998-11-06 2000-08-21 Bio Sidus S A PHARMACEUTICAL FORMS OF RECOMBINANT HUMAN ERYTHROPOYETIN STABLE AT ROOM TEMPERATURE AND SUITABLE FOR USE IN HUMANS, FORMULATIONS AND FREEZE PROCEDURES FOR THEIR OBTAINING.
JP2000247903A (en) * 1999-03-01 2000-09-12 Chugai Pharmaceut Co Ltd Long-term stabilized pharmaceutical preparation
ES2308978T3 (en) 1999-04-09 2008-12-16 Ortho-Mcneil Pharmaceutical, Inc. PHARMACEUTICAL COMPOSITION OF ERYTHROPOYETINE.
US6309663B1 (en) 1999-08-17 2001-10-30 Lipocine Inc. Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents
JO2291B1 (en) * 1999-07-02 2005-09-12 اف . هوفمان لاروش ايه جي Erythopintin derivatives
CZ299516B6 (en) † 1999-07-02 2008-08-20 F. Hoffmann-La Roche Ag Erythropoietin glycoprotein conjugate, process for its preparation and use and pharmaceutical composition containing thereof
EP1200115B9 (en) 1999-07-22 2006-01-18 Aventis Pharmaceuticals Inc. Multi-dose erythropoietin formulations
AU6875900A (en) † 1999-09-08 2001-04-10 Chugai Seiyaku Kabushiki Kaisha Protein solution preparation and method of stabilizing the same
US7163671B2 (en) 2000-02-29 2007-01-16 Chugai Seiyaku Kabushiki Kaisha Long-term stabilized formulations
US6586398B1 (en) 2000-04-07 2003-07-01 Amgen, Inc. Chemically modified novel erythropoietin stimulating protein compositions and methods
HU230874B1 (en) * 2000-05-15 2018-11-29 F. Hoffmann-La Roche Ag Liquid pharmaceutical compositions stable at room temperature which comprising a pegylated human erythropoietin protein
EP1336410A4 (en) † 2000-08-04 2005-10-12 Chugai Pharmaceutical Co Ltd Protein injection preparations
JP4656814B2 (en) * 2000-12-20 2011-03-23 エフ．ホフマン−ラ ロシュ アーゲー Erythropoietin conjugate
US20030104996A1 (en) 2001-08-30 2003-06-05 Tiansheng Li L-methionine as a stabilizer for NESP/EPO in HSA-free formulations
US6818613B2 (en) 2001-11-07 2004-11-16 Ortho-Mcneil Pharmaceutical, Inc. Aqueous sustained-release formulations of proteins

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