CN104689333B - G-csf 缀合物的液体制剂 - Google Patents
G-csf 缀合物的液体制剂 Download PDFInfo
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- CN104689333B CN104689333B CN201510065114.9A CN201510065114A CN104689333B CN 104689333 B CN104689333 B CN 104689333B CN 201510065114 A CN201510065114 A CN 201510065114A CN 104689333 B CN104689333 B CN 104689333B
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- SLBXZQMMERXQAL-UHFFFAOYSA-M sodium;1-dodecoxy-4-hydroxy-1,4-dioxobutane-2-sulfonate Chemical compound [Na+].CCCCCCCCCCCCOC(=O)C(S(O)(=O)=O)CC([O-])=O SLBXZQMMERXQAL-UHFFFAOYSA-M 0.000 description 1
- GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 description 1
- NWZBFJYXRGSRGD-UHFFFAOYSA-M sodium;octadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOS([O-])(=O)=O NWZBFJYXRGSRGD-UHFFFAOYSA-M 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
- C07K17/02—Peptides being immobilised on, or in, an organic carrier
- C07K17/08—Peptides being immobilised on, or in, an organic carrier the carrier being a synthetic polymer
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Neurology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurosurgery (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07115047.8 | 2007-08-27 | ||
| EP07115047 | 2007-08-27 | ||
| CN200880104971A CN101827864A (zh) | 2007-08-27 | 2008-08-27 | G-csf缀合物的液体制剂 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880104971A Division CN101827864A (zh) | 2007-08-27 | 2008-08-27 | G-csf缀合物的液体制剂 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104689333A CN104689333A (zh) | 2015-06-10 |
| CN104689333B true CN104689333B (zh) | 2018-05-29 |
Family
ID=39862881
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510065114.9A Expired - Fee Related CN104689333B (zh) | 2007-08-27 | 2008-08-27 | G-csf 缀合物的液体制剂 |
| CN200880104971A Pending CN101827864A (zh) | 2007-08-27 | 2008-08-27 | G-csf缀合物的液体制剂 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880104971A Pending CN101827864A (zh) | 2007-08-27 | 2008-08-27 | G-csf缀合物的液体制剂 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US8546328B2 (enExample) |
| EP (2) | EP2197919B1 (enExample) |
| JP (2) | JP5570988B2 (enExample) |
| KR (1) | KR20100052501A (enExample) |
| CN (2) | CN104689333B (enExample) |
| AU (1) | AU2008292186B9 (enExample) |
| BR (1) | BRPI0815975B8 (enExample) |
| CA (1) | CA2696594C (enExample) |
| CY (1) | CY1115908T1 (enExample) |
| DE (1) | DE202008017456U1 (enExample) |
| DK (1) | DK2197919T3 (enExample) |
| EA (1) | EA020069B1 (enExample) |
| ES (1) | ES2476915T3 (enExample) |
| HR (1) | HRP20140590T1 (enExample) |
| IL (1) | IL204190A (enExample) |
| MX (1) | MX2010002448A (enExample) |
| NZ (1) | NZ583276A (enExample) |
| PL (1) | PL2197919T3 (enExample) |
| PT (1) | PT2197919E (enExample) |
| RS (1) | RS53404B (enExample) |
| SI (1) | SI2197919T1 (enExample) |
| UA (1) | UA98001C2 (enExample) |
| WO (1) | WO2009027437A1 (enExample) |
| ZA (1) | ZA201000798B (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT2525787T (pt) * | 2010-01-19 | 2017-12-18 | Hanmi Science Co Ltd | Formulações líquidas para conjugado de g-csf de longa ação |
| US8703123B2 (en) | 2010-03-17 | 2014-04-22 | Biogenerix Gmbh | Method for obtaining biologically active recombinant human G-CSF |
| EP2384759A1 (en) | 2010-05-06 | 2011-11-09 | Suomen Punainen Risti Veripalvelu | Sulphated hyaluronic acid in combination with G-CSF for use in mobilising blood stem cells |
| WO2017181920A1 (zh) * | 2016-04-18 | 2017-10-26 | 江苏恒瑞医药股份有限公司 | 一种重组人粒细胞集落刺激因子的制备方法 |
| IT201700108526A1 (it) * | 2017-09-28 | 2019-03-28 | Alfasigma Spa | Composizioni orali per il trattamento del refluso gastroesofageo. |
| EP3773468A2 (en) * | 2018-05-04 | 2021-02-17 | Ilkogen Ilaç Sanayi ve Ticaret A.S. | Stable hybrid fc fusion g-csf formulation |
| KR102375269B1 (ko) * | 2021-01-27 | 2022-03-17 | 한미약품 주식회사 | 단백질 액상 제제 및 이의 제조방법 |
| CN114224853B (zh) * | 2022-01-04 | 2022-09-23 | 山东新时代药业有限公司 | 聚乙二醇化重组人粒细胞刺激因子注射用冻干制剂 |
| JP2025526877A (ja) * | 2022-08-19 | 2025-08-15 | エバイブ バイオテクノロジー （シャンハイ） リミテッド | Ｇ－ｃｓｆを含む製剤及びその使用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006074467A2 (en) * | 2005-01-10 | 2006-07-13 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
Family Cites Families (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1479268A (en) | 1973-07-05 | 1977-07-13 | Beecham Group Ltd | Pharmaceutical compositions |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| CH596313A5 (enExample) | 1975-05-30 | 1978-03-15 | Battelle Memorial Institute | |
| US4414147A (en) | 1981-04-17 | 1983-11-08 | Massachusetts Institute Of Technology | Methods of decreasing the hydrophobicity of fibroblast and other interferons |
| US5675941A (en) | 1983-12-09 | 1997-10-14 | Dykmans; Maximiliaan J. | Method and apparatus for constructing prestressed structures utilizing a membrane and floating dome assembly |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| DE3676670D1 (de) | 1985-06-26 | 1991-02-07 | Cetus Corp | Solubilisierung von proteinen fuer pharmazeutische zusammensetzungen mittels polymerkonjugierung. |
| US4810643A (en) | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| US6004548A (en) | 1985-08-23 | 1999-12-21 | Amgen, Inc. | Analogs of pluripotent granulocyte colony-stimulating factor |
| DE68929566D1 (de) | 1988-05-13 | 2010-01-28 | Amgen Inc | Verfahren zur Isolierung und Reinigung von G-CSF |
| US5218092A (en) | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
| JP2989002B2 (ja) | 1988-12-22 | 1999-12-13 | キリン―アムジエン・インコーポレーテツド | 化学修飾顆粒球コロニー刺激因子 |
| US6166183A (en) | 1992-11-30 | 2000-12-26 | Kirin-Amgen, Inc. | Chemically-modified G-CSF |
| GB9107846D0 (en) | 1990-04-30 | 1991-05-29 | Ici Plc | Polypeptides |
| US5399345A (en) | 1990-05-08 | 1995-03-21 | Boehringer Mannheim, Gmbh | Muteins of the granulocyte colony stimulating factor |
| DE4014750A1 (de) | 1990-05-08 | 1991-11-14 | Boehringer Mannheim Gmbh | Muteine des granulozyten-stimulierenden faktors (g-csf) |
| US6565841B1 (en) | 1991-03-15 | 2003-05-20 | Amgen, Inc. | Pulmonary administration of granulocyte colony stimulating factor |
| DE4126983A1 (de) * | 1991-08-15 | 1993-02-18 | Boehringer Mannheim Gmbh | Verfahren zur herstellung von humanprotein-enthaltenden, konservierten arzneimitteln fuer infusions- oder injektionszwecke |
| AU677789B2 (en) | 1992-07-02 | 1997-05-08 | Collagen Corporation | Biocompatible polymer conjugates |
| AU5098193A (en) | 1992-09-01 | 1994-03-29 | Berlex Laboratories, Inc. | Glycolation of glycosylated macromolecules |
| AU7097094A (en) | 1993-06-01 | 1994-12-20 | Enzon, Inc. | Carbohydrate-modified polymer conjugates with erythropoietic activity |
| US5874075A (en) | 1993-10-06 | 1999-02-23 | Amgen Inc. | Stable protein: phospholipid compositions and methods |
| DK1090645T3 (da) | 1994-02-08 | 2006-03-27 | Amgen Inc | Oral tilförsel af kemisk modificerede proteiner |
| ES2312166T3 (es) | 1994-02-23 | 2009-02-16 | Kyowa Hakko Kogyo Co., Ltd | Acelerador del crecimiento plaquetario. |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| JP2000506119A (ja) | 1996-02-15 | 2000-05-23 | ノボ ノルディスク アクティーゼルスカブ | ポリペプチドのコンジュゲーション |
| ES2218806T3 (es) | 1997-01-16 | 2004-11-16 | Neose Technologies, Inc. | Sialilacion practica in vitro de glicoproteinas recombinantes. |
| US6583267B2 (en) | 1997-06-06 | 2003-06-24 | Kyowa Hakko Kogyo Co., Ltd. | Chemically modified polypeptides |
| US6540672B1 (en) * | 1998-12-09 | 2003-04-01 | Novo Nordisk A/S | Medical system and a method of controlling the system for use by a patient for medical self treatment |
| FR2796071B1 (fr) | 1999-07-08 | 2001-09-07 | Hoechst Marion Roussel Inc | Procede de purification de facteur de stimulation de colonies de granulocytes |
| US6555660B2 (en) | 2000-01-10 | 2003-04-29 | Maxygen Holdings Ltd. | G-CSF conjugates |
| SK11672002A3 (sk) | 2000-01-10 | 2002-12-03 | Maxygen Holdings Ltd. | Polypeptidový konjugát, spôsob jeho výroby, farmaceutický prostriedok s jeho obsahom a jeho použitie |
| AU2001236005A1 (en) * | 2000-02-29 | 2001-09-12 | Chugai Seiyaku Kabushiki Kaisha | Preparations stabilized over long time |
| EP1285072A2 (en) | 2000-05-12 | 2003-02-26 | Neose Technologies, Inc. | In vitro fucosylation recombinant glycopeptides |
| ATE291436T2 (de) | 2000-05-15 | 2005-04-15 | Hoffmann La Roche | Flüssige arzneizubereitung enthaltend ein erythropoietin derivat |
| CN1318443C (zh) | 2000-05-16 | 2007-05-30 | 博尔德生物技术公司 | 含游离半胱氨酸残基的蛋白重折叠的方法 |
| KR100396983B1 (ko) | 2000-07-29 | 2003-09-02 | 이강춘 | 고반응성의 가지 달린 고분자 유도체 및 고분자와 단백질또는 펩타이드의 접합체 |
| WO2002011753A1 (en) | 2000-08-04 | 2002-02-14 | Chugai Seiyaku Kabushiki Kaisha | Protein injection preparations |
| KR20030027077A (ko) * | 2000-09-01 | 2003-04-03 | 쥬가이 세이야쿠 가부시키가이샤 | 장기 안정화 용액 제제 |
| US7265085B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycoconjugation methods and proteins/peptides produced by the methods |
| US7157277B2 (en) | 2001-11-28 | 2007-01-02 | Neose Technologies, Inc. | Factor VIII remodeling and glycoconjugation of Factor VIII |
| US7265084B2 (en) | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycopegylation methods and proteins/peptides produced by the methods |
| EP2305312B1 (en) | 2001-10-10 | 2015-03-04 | ratiopharm GmbH | Remodelling and glycoconjugation of follicle-stimulating hormone (FSH) |
| SI21102A (sl) | 2001-12-19 | 2003-06-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Postopek za izolacijo biološko aktivnega granulocitne kolonije stimulirajočega dejavnika |
| DE10209821A1 (de) | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
| SI21273A (sl) | 2002-07-31 | 2004-02-29 | LEK farmacevtska dru�ba d.d. | Priprava inkluzijskih teles z visokim deležem pravilno zvitega prekurzorja heterolognega proteina |
| EP1660134B1 (en) | 2003-08-08 | 2010-12-29 | Fresenius Kabi Deutschland GmbH | Conjugates of hydroxyalkyl starch and g-csf |
| WO2005014655A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| DE10348550A1 (de) * | 2003-10-20 | 2005-06-16 | Hexal Biotech Forschungsgmbh | Stabile wässrige G-CSF-haltige Zusammensetzungen |
| EP1682184B1 (en) | 2003-11-04 | 2013-10-16 | LEK Pharmaceuticals d.d. | Stable pharmaceutical composition comprising granulocyte-colony stimulating factor |
| EP1694274B1 (en) | 2003-12-03 | 2013-04-24 | BioGeneriX AG | Glycopegylated granulocyte colony stimulating factor |
| US8361961B2 (en) * | 2004-01-08 | 2013-01-29 | Biogenerix Ag | O-linked glycosylation of peptides |
| CN102302787A (zh) | 2004-03-11 | 2012-01-04 | 费森尤斯卡比德国有限公司 | 羟烷基淀粉和蛋白质的接合物 |
| CA2558738C (en) | 2004-03-11 | 2013-02-05 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein, prepared by reductive amination |
| DE102004036909B4 (de) | 2004-07-29 | 2007-04-05 | Infineon Technologies Ag | Halbleiterbasisbauteil mit Verdrahtungssubstrat und Zwischenverdrahtungsplatte für einen Halbleiterbauteilstapel sowie Verfahren zu deren Herstellung |
| EP1869078A2 (en) | 2005-03-17 | 2007-12-26 | Zenotech Laboratories Limited | Process for the purification of recombinant granulocyte-colony stimulating factor |
| RU2007149238A (ru) * | 2005-06-01 | 2009-07-20 | Максиджен Холдингз Лтд. (Ky) | Пегилированные полипептиды гксф и способы их получения |
| EP1762250A1 (en) | 2005-09-12 | 2007-03-14 | Fresenius Kabi Deutschland GmbH | Conjugates of hydroxyalkyl starch and an active substance, prepared by chemical ligation via thiazolidine |
| DE202006020194U1 (de) | 2006-03-01 | 2007-12-06 | Bioceuticals Arzneimittel Ag | G-CSF-Flüssigformulierung |
| ITMI20061624A1 (it) | 2006-08-11 | 2008-02-12 | Bioker Srl | Mono-coniugati sito-specifici di g-csf |
| CN101796063B (zh) | 2007-04-03 | 2017-03-22 | 拉蒂奥法姆有限责任公司 | 使用糖聚乙二醇化g‑csf的治疗方法 |
| US8207112B2 (en) * | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
-
2008
- 2008-08-27 MX MX2010002448A patent/MX2010002448A/es unknown
- 2008-08-27 DK DK08787525.8T patent/DK2197919T3/da active
- 2008-08-27 AU AU2008292186A patent/AU2008292186B9/en active Active
- 2008-08-27 US US12/675,749 patent/US8546328B2/en active Active
- 2008-08-27 PL PL08787525T patent/PL2197919T3/pl unknown
- 2008-08-27 JP JP2010522361A patent/JP5570988B2/ja not_active Expired - Fee Related
- 2008-08-27 BR BRPI0815975A patent/BRPI0815975B8/pt not_active IP Right Cessation
- 2008-08-27 CN CN201510065114.9A patent/CN104689333B/zh not_active Expired - Fee Related
- 2008-08-27 DE DE202008017456U patent/DE202008017456U1/de not_active Expired - Lifetime
- 2008-08-27 CA CA2696594A patent/CA2696594C/en not_active Expired - Fee Related
- 2008-08-27 PT PT87875258T patent/PT2197919E/pt unknown
- 2008-08-27 HR HRP20140590AT patent/HRP20140590T1/hr unknown
- 2008-08-27 UA UAA201003493A patent/UA98001C2/uk unknown
- 2008-08-27 RS RS20140361A patent/RS53404B/sr unknown
- 2008-08-27 WO PCT/EP2008/061232 patent/WO2009027437A1/en not_active Ceased
- 2008-08-27 EP EP08787525.8A patent/EP2197919B1/en active Active
- 2008-08-27 NZ NZ583276A patent/NZ583276A/en not_active IP Right Cessation
- 2008-08-27 ES ES08787525.8T patent/ES2476915T3/es active Active
- 2008-08-27 SI SI200831235T patent/SI2197919T1/sl unknown
- 2008-08-27 EA EA201070315A patent/EA020069B1/ru not_active IP Right Cessation
- 2008-08-27 EP EP12194213.0A patent/EP2578235A3/en not_active Withdrawn
- 2008-08-27 CN CN200880104971A patent/CN101827864A/zh active Pending
- 2008-08-27 KR KR1020107004576A patent/KR20100052501A/ko not_active Ceased
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2010
- 2010-02-03 ZA ZA201000798A patent/ZA201000798B/xx unknown
- 2010-02-25 IL IL204190A patent/IL204190A/en active IP Right Grant
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2013
- 2013-11-05 JP JP2013229688A patent/JP5836351B2/ja not_active Expired - Fee Related
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2014
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006074467A2 (en) * | 2005-01-10 | 2006-07-13 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
Non-Patent Citations (2)
| Title |
|---|
| 《A Role for G-CSF (Granulocyte-colony Stimulating Factor) in the Central Nervous System》;Armin Schneider et al.;《Cell Cycle》;20051231;第4卷(第12期);第1753-1757页 * |
| Deirdre Murphy Piedmonte et al..《Formulation of Neulasta®;(pegfilgrastim)》.《Advanced Drug Delivery Reviews》.2007, * |
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