CA2696594C - Liquid formulation of g-csf conjugate - Google Patents
Liquid formulation of g-csf conjugate Download PDFInfo
- Publication number
- CA2696594C CA2696594C CA2696594A CA2696594A CA2696594C CA 2696594 C CA2696594 C CA 2696594C CA 2696594 A CA2696594 A CA 2696594A CA 2696594 A CA2696594 A CA 2696594A CA 2696594 C CA2696594 C CA 2696594C
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- Canada
- Prior art keywords
- csf
- aqueous preparation
- preparation according
- polymer
- conjugate
- Prior art date
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- 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
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- 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
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- 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
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- 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
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- 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
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- 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)
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- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Immunology (AREA)
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- Hematology (AREA)
- Genetics & Genomics (AREA)
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- Neurology (AREA)
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- Biophysics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (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 | ||
| PCT/EP2008/061232 WO2009027437A1 (en) | 2007-08-27 | 2008-08-27 | Liquid formulation of g-csf conjugate |
Publications (2)
| Publication Number | Publication Date |
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| CA2696594A1 CA2696594A1 (en) | 2009-03-05 |
| CA2696594C true CA2696594C (en) | 2019-03-19 |
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|---|---|---|---|
| CA2696594A Expired - Fee Related CA2696594C (en) | 2007-08-27 | 2008-08-27 | Liquid formulation of g-csf conjugate |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US8546328B2 (OSRAM) |
| EP (2) | EP2578235A3 (OSRAM) |
| JP (2) | JP5570988B2 (OSRAM) |
| KR (1) | KR20100052501A (OSRAM) |
| CN (2) | CN104689333B (OSRAM) |
| AU (1) | AU2008292186B9 (OSRAM) |
| BR (1) | BRPI0815975B8 (OSRAM) |
| CA (1) | CA2696594C (OSRAM) |
| CY (1) | CY1115908T1 (OSRAM) |
| DE (1) | DE202008017456U1 (OSRAM) |
| DK (1) | DK2197919T3 (OSRAM) |
| EA (1) | EA020069B1 (OSRAM) |
| ES (1) | ES2476915T3 (OSRAM) |
| HR (1) | HRP20140590T1 (OSRAM) |
| IL (1) | IL204190A (OSRAM) |
| MX (1) | MX2010002448A (OSRAM) |
| NZ (1) | NZ583276A (OSRAM) |
| PL (1) | PL2197919T3 (OSRAM) |
| PT (1) | PT2197919E (OSRAM) |
| RS (1) | RS53404B (OSRAM) |
| SI (1) | SI2197919T1 (OSRAM) |
| UA (1) | UA98001C2 (OSRAM) |
| WO (1) | WO2009027437A1 (OSRAM) |
| ZA (1) | ZA201000798B (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2654102T3 (es) * | 2010-01-19 | 2018-02-12 | Hanmi Science Co., Ltd. | Formulaciones líquidas para conjugado de C-CSF de acción prolongada |
| AU2011229491B2 (en) | 2010-03-17 | 2015-02-05 | Ratiopharm 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 |
| CN108368512B (zh) * | 2016-04-18 | 2020-03-27 | 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. |
| CN112312890A (zh) * | 2018-05-04 | 2021-02-02 | 伊尔科根医药工业和贸易有限公司 | 稳定的杂合fc融合g-csf制剂 |
| 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 |
| AU2023325906A1 (en) * | 2022-08-19 | 2025-02-13 | Evive Biotechnology (Shanghai) Ltd | Formulations comprising g-csf and uses thereof |
Family Cites Families (63)
| 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 (OSRAM) | 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 |
| WO1987000056A1 (en) | 1985-06-26 | 1987-01-15 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US6004548A (en) | 1985-08-23 | 1999-12-21 | Amgen, Inc. | Analogs of pluripotent granulocyte colony-stimulating factor |
| US4810643A (en) | 1985-08-23 | 1989-03-07 | Kirin- Amgen Inc. | Production of pluripotent granulocyte colony-stimulating factor |
| NZ229098A (en) | 1988-05-13 | 1992-10-28 | Amgen Inc | (bg-csf) bovine granulocyte colony stimulating factor, recombinant methods and pharmaceuticals |
| US5218092A (en) | 1988-09-29 | 1993-06-08 | Kyowa Hakko Kogyo Co., Ltd. | Modified granulocyte-colony stimulating factor polypeptide with added carbohydrate chains |
| US6166183A (en) | 1992-11-30 | 2000-12-26 | Kirin-Amgen, Inc. | Chemically-modified G-CSF |
| DE68925966T2 (de) | 1988-12-22 | 1996-08-29 | Kirin Amgen Inc | Chemisch modifizierte granulocytenkolonie erregender faktor |
| 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 |
| WO1994001483A1 (en) | 1992-07-02 | 1994-01-20 | 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 |
| WO1995021629A1 (en) | 1994-02-08 | 1995-08-17 | Amgen Inc. | Oral delivery of chemically modified proteins |
| JP4011106B2 (ja) | 1994-02-23 | 2007-11-21 | 協和醗酵工業株式会社 | 血小板増殖促進剤 |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| AU725287B2 (en) | 1996-02-15 | 2000-10-12 | Novozymes A/S | Conjugation of polypeptides |
| WO1998031826A1 (en) | 1997-01-16 | 1998-07-23 | Cytel Corporation | Practical in vitro sialylation of recombinant glycoproteins |
| JP4011124B2 (ja) | 1997-06-06 | 2007-11-21 | 協和醗酵工業株式会社 | 化学修飾ポリペプチド |
| 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 |
| DK1250154T3 (da) | 2000-01-10 | 2009-08-17 | Maxygen Holdings Ltd | G-CSF-konjugater |
| JP4683810B2 (ja) | 2000-02-29 | 2011-05-18 | 中外製薬株式会社 | 長期安定化製剤 |
| HUP0302299A2 (hu) | 2000-05-12 | 2003-10-28 | Neose Technologies, Inc. | Rekombináns glikopeptidek glikozilezési mintázatának in vitro módosítása |
| DE60109625T3 (de) | 2000-05-15 | 2017-08-03 | F. Hoffmann-La Roche Ag | Flüssige arzneizubereitung enthaltend ein erythropoietin derivat |
| ATE367398T1 (de) | 2000-05-16 | 2007-08-15 | Bolder Biotechnology Inc | Verfahren zur rückfaltung von proteinen mit freien cysteinresten |
| KR100396983B1 (ko) | 2000-07-29 | 2003-09-02 | 이강춘 | 고반응성의 가지 달린 고분자 유도체 및 고분자와 단백질또는 펩타이드의 접합체 |
| JP5490972B2 (ja) | 2000-08-04 | 2014-05-14 | 中外製薬株式会社 | タンパク質注射製剤 |
| WO2002017957A1 (en) | 2000-09-01 | 2002-03-07 | Chugai Seiyaku Kabushiki Kaisha | Solution preparations stabilized over long time |
| EP2305313B1 (en) | 2001-10-10 | 2014-03-26 | ratiopharm GmbH | Remodelling and glycoconjugation of interferon-alpha (IFNa) |
| 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 |
| 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 |
| WO2005014655A2 (en) | 2003-08-08 | 2005-02-17 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| PL1660134T3 (pl) | 2003-08-08 | 2011-05-31 | Fresenius Kabi Deutschland Gmbh | Koniugaty hydroksyalkiloskrobi i G-CSF |
| DE10348550A1 (de) * | 2003-10-20 | 2005-06-16 | Hexal Biotech Forschungsgmbh | Stabile wässrige G-CSF-haltige Zusammensetzungen |
| CA2544432C (en) | 2003-11-04 | 2011-06-28 | 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 |
| ES2560657T3 (es) * | 2004-01-08 | 2016-02-22 | Ratiopharm Gmbh | Glicosilación con unión en O de péptidos G-CSF |
| WO2005092391A2 (en) | 2004-03-11 | 2005-10-06 | Fresenius Kabi Deutschland Gmbh | Conjugates of hydroxyalkyl starch and a protein |
| CN1946742A (zh) | 2004-03-11 | 2007-04-11 | 弗雷泽纽斯卡比德国有限公司 | 通过还原氨基化制备的羟烷基淀粉和蛋白质的偶联物 |
| DE102004036909B4 (de) | 2004-07-29 | 2007-04-05 | Infineon Technologies Ag | Halbleiterbasisbauteil mit Verdrahtungssubstrat und Zwischenverdrahtungsplatte für einen Halbleiterbauteilstapel sowie Verfahren zu deren Herstellung |
| WO2006074467A2 (en) | 2005-01-10 | 2006-07-13 | Neose Technologies, Inc. | Glycopegylated granulocyte colony stimulating factor |
| 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 |
| CA2682897C (en) | 2007-04-03 | 2016-11-22 | Biogenerix Ag | Methods of treatment using glycopegylated g-csf |
| US8207112B2 (en) * | 2007-08-29 | 2012-06-26 | Biogenerix Ag | Liquid formulation of G-CSF conjugate |
-
2008
- 2008-08-27 AU AU2008292186A patent/AU2008292186B9/en active Active
- 2008-08-27 MX MX2010002448A patent/MX2010002448A/es unknown
- 2008-08-27 UA UAA201003493A patent/UA98001C2/uk unknown
- 2008-08-27 EA EA201070315A patent/EA020069B1/ru not_active IP Right Cessation
- 2008-08-27 PL PL08787525T patent/PL2197919T3/pl unknown
- 2008-08-27 EP EP12194213.0A patent/EP2578235A3/en not_active Withdrawn
- 2008-08-27 JP JP2010522361A patent/JP5570988B2/ja not_active Expired - Fee Related
- 2008-08-27 PT PT87875258T patent/PT2197919E/pt unknown
- 2008-08-27 SI SI200831235T patent/SI2197919T1/sl unknown
- 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 CN CN200880104971A patent/CN101827864A/zh active Pending
- 2008-08-27 ES ES08787525.8T patent/ES2476915T3/es active Active
- 2008-08-27 EP EP08787525.8A patent/EP2197919B1/en active Active
- 2008-08-27 HR HRP20140590AT patent/HRP20140590T1/hr unknown
- 2008-08-27 US US12/675,749 patent/US8546328B2/en active Active
- 2008-08-27 RS RS20140361A patent/RS53404B/sr unknown
- 2008-08-27 BR BRPI0815975A patent/BRPI0815975B8/pt not_active IP Right Cessation
- 2008-08-27 DK DK08787525.8T patent/DK2197919T3/da active
- 2008-08-27 NZ NZ583276A patent/NZ583276A/en not_active IP Right Cessation
- 2008-08-27 KR KR1020107004576A patent/KR20100052501A/ko not_active Ceased
- 2008-08-27 WO PCT/EP2008/061232 patent/WO2009027437A1/en not_active Ceased
- 2008-08-27 CA CA2696594A patent/CA2696594C/en not_active Expired - Fee Related
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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
- 2014-07-03 CY CY20141100501T patent/CY1115908T1/el unknown
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