AR062575A1 - Metodo para la produccion de conjugados del factor de crecimiento similar a la insulina -1 y polietilenglicol - Google Patents
Metodo para la produccion de conjugados del factor de crecimiento similar a la insulina -1 y polietilenglicolInfo
- Publication number
- AR062575A1 AR062575A1 ARP070103823A ARP070103823A AR062575A1 AR 062575 A1 AR062575 A1 AR 062575A1 AR P070103823 A ARP070103823 A AR P070103823A AR P070103823 A ARP070103823 A AR P070103823A AR 062575 A1 AR062575 A1 AR 062575A1
- Authority
- AR
- Argentina
- Prior art keywords
- pro
- igf
- variant
- pegylated
- production
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 2
- 101710186630 Insulin-1 Proteins 0.000 title 1
- 239000002202 Polyethylene glycol Substances 0.000 title 1
- 239000003102 growth factor Substances 0.000 title 1
- 229920001223 polyethylene glycol Polymers 0.000 title 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 abstract 8
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 abstract 8
- 150000001413 amino acids Chemical class 0.000 abstract 4
- 108020001507 fusion proteins Proteins 0.000 abstract 3
- 102000037865 fusion proteins Human genes 0.000 abstract 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 abstract 2
- 239000004472 Lysine Substances 0.000 abstract 2
- WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 abstract 1
- 208000024827 Alzheimer disease Diseases 0.000 abstract 1
- LQJAALCCPOTJGB-YUMQZZPRSA-N Arg-Pro Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(O)=O LQJAALCCPOTJGB-YUMQZZPRSA-N 0.000 abstract 1
- 108010002231 IgA-specific serine endopeptidase Proteins 0.000 abstract 1
- RNKSNIBMTUYWSH-YFKPBYRVSA-N L-prolylglycine Chemical compound [O-]C(=O)CNC(=O)[C@@H]1CCC[NH2+]1 RNKSNIBMTUYWSH-YFKPBYRVSA-N 0.000 abstract 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 abstract 1
- FELJDCNGZFDUNR-WDSKDSINSA-N Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1 FELJDCNGZFDUNR-WDSKDSINSA-N 0.000 abstract 1
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 abstract 1
- RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 abstract 1
- GVUVRRPYYDHHGK-VQVTYTSYSA-N Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GVUVRRPYYDHHGK-VQVTYTSYSA-N 0.000 abstract 1
- QOLYAJSZHIJCTO-VQVTYTSYSA-N Thr-Pro Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O QOLYAJSZHIJCTO-VQVTYTSYSA-N 0.000 abstract 1
- 108010087924 alanylproline Proteins 0.000 abstract 1
- 108010060035 arginylproline Proteins 0.000 abstract 1
- 210000004899 c-terminal region Anatomy 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 abstract 1
- 238000012258 culturing Methods 0.000 abstract 1
- 239000013604 expression vector Substances 0.000 abstract 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 abstract 1
- 108010077515 glycylproline Proteins 0.000 abstract 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract 1
- 102000039446 nucleic acids Human genes 0.000 abstract 1
- 108020004707 nucleic acids Proteins 0.000 abstract 1
- 150000007523 nucleic acids Chemical class 0.000 abstract 1
- 108010029020 prolylglycine Proteins 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/65—Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Wood Science & Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Plant Pathology (AREA)
- Neurosurgery (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Un método para la produccion de IGF-I o variante de IGF-l PEGilado en la lisina, y dicha variante comprende uno o dos aminoácido(s) seleccionados del grupo que consiste en lisina 27, 65 y/o 68 sustituidos independientemente por otro aminoácido polar, que se caracteriza por cultivar una célula huésped procariota que comprende un vector de expresion que contiene un ácido nucleico que codifica una proteína de fusion que comprende dicho IGF-I o variante de IGF-I unido en el extremo N-terminal al extremo C-terminal de un propéptido en el que dicho propéptido finaliza en el C-terminal con los aminoácidos -Y-Pro, en el que Y se selecciona del grupo que consiste en Pro, Pro-Ala, Pro-Gly, Pro-Thr, Ala-Pro, Gly-Pro, Thr-Pro, Arg-Pro, o Pro-Arg- Pro, recuperando y PEGilando dicha proteína de fusion, escindiendo dicha proteína de fusion PEGilada con la proteasa IgA, y recuperando dicho IGF-I o variante de IGF-I PEGilado. El IGF-I o variante de IGF-I PEGilado es util para el tratamiento de trastornos neurodegenerativos como la enfermedad de Alzheimer.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06018170 | 2006-08-31 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR062575A1 true AR062575A1 (es) | 2008-11-19 |
Family
ID=37667695
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP070103823A AR062575A1 (es) | 2006-08-31 | 2007-08-29 | Metodo para la produccion de conjugados del factor de crecimiento similar a la insulina -1 y polietilenglicol |
Country Status (21)
Country | Link |
---|---|
US (4) | US7625996B2 (es) |
EP (1) | EP2059261B1 (es) |
JP (1) | JP5184532B2 (es) |
KR (1) | KR101106931B1 (es) |
CN (1) | CN101511390B (es) |
AR (1) | AR062575A1 (es) |
AU (1) | AU2007291502B2 (es) |
BR (1) | BRPI0715943A2 (es) |
CA (1) | CA2662062C (es) |
CL (1) | CL2007002502A1 (es) |
CO (1) | CO6251278A2 (es) |
CR (1) | CR10591A (es) |
ES (1) | ES2397660T3 (es) |
IL (1) | IL196736A (es) |
MA (1) | MA30660B1 (es) |
MX (1) | MX2009002011A (es) |
NO (1) | NO20090451L (es) |
PE (1) | PE20080912A1 (es) |
RU (1) | RU2009106118A (es) |
TW (1) | TW200819468A (es) |
WO (1) | WO2008025528A1 (es) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
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EP1674113A1 (en) | 2004-12-22 | 2006-06-28 | F. Hoffmann-La Roche Ag | Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol) |
US8168181B2 (en) | 2006-02-13 | 2012-05-01 | Alethia Biotherapeutics, Inc. | Methods of impairing osteoclast differentiation using antibodies that bind siglec-15 |
DK1994155T4 (da) | 2006-02-13 | 2022-07-25 | Daiichi Sankyo Co Ltd | Polynukleotid- og polypeptidsekvenser involveret i fremgangsmåden med knogleremodellering |
EP2059530B1 (en) | 2006-08-31 | 2012-08-29 | F.Hoffmann-La Roche Ag | Method for the production of insulin-like growth factor-i |
CL2007002502A1 (es) | 2006-08-31 | 2008-05-30 | Hoffmann La Roche | Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer. |
WO2009099763A1 (en) | 2008-01-30 | 2009-08-13 | Indiana University Research And Technology Corporation | Ester-based peptide prodrugs |
WO2009121759A2 (en) * | 2008-04-03 | 2009-10-08 | F. Hoffmann-La Roche Ag | Use of pegylated igf-i variants for the treatment of neuromuscular disorders |
AU2009335713A1 (en) * | 2008-12-19 | 2010-07-15 | Indiana University Research And Technology Corporation | YL-based insulin-like growth factors exhibiting high activity at the insulin receptor |
US8697632B2 (en) | 2008-12-19 | 2014-04-15 | Indiana University Research And Technology Corporation | Amide based insulin prodrugs |
JP5789515B2 (ja) | 2008-12-19 | 2015-10-07 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation | インスリン類似体 |
US20110152188A1 (en) | 2009-12-23 | 2011-06-23 | Hanns-Christian Mahler | Pharmaceutical compositions of igf/i proteins |
BR112012019992A2 (pt) * | 2010-02-11 | 2020-08-18 | F. Hoffmann-La Roche Ag. | conjugados de igf-i poli (etileno glicol) |
CA2802485C (en) | 2010-06-16 | 2019-09-17 | Indiana University Research And Technology Corporation | Single chain insulin agonists exhibiting high activity at the insulin receptor |
US8946147B2 (en) | 2010-06-24 | 2015-02-03 | Indiana University Research And Technology Corporation | Amide-based insulin prodrugs |
GB201012784D0 (en) | 2010-07-29 | 2010-09-15 | Ucb Pharma Sa | Method |
BR112014015156A2 (pt) | 2011-12-20 | 2020-10-27 | Indiana University Research And Technology Corporation | análogos de insulina à base de ctp, seus métodos de produção e uso no tratamento de hiperglicemia, bem como sequência de ácido nucleico e célula hospedeira |
ES2723885T3 (es) | 2012-07-19 | 2019-09-03 | Daiichi Sankyo Co Ltd | Anticuerpos anti-Siglec-15 |
WO2014052451A2 (en) | 2012-09-26 | 2014-04-03 | Indiana University Research And Technology Corporation | Insulin analog dimers |
KR20150131213A (ko) | 2013-03-14 | 2015-11-24 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 인슐린-인크레틴 접합체들 |
WO2014205617A1 (en) * | 2013-06-24 | 2014-12-31 | Shandong University | Lanthanide labeled peptide and use thereof |
EP3052123A1 (en) | 2013-10-02 | 2016-08-10 | Novartis Ag | Insulin-like growth factor mimetics for use in therapy |
UY35874A (es) | 2013-12-12 | 2015-07-31 | Novartis Ag | Un proceso para la preparación de una composición de proteínas pegiladas |
EP3206710B1 (en) | 2014-09-24 | 2020-05-06 | Indiana University Research & Technology Corporation | Incretin-insulin conjugates |
JP6701208B2 (ja) | 2014-09-24 | 2020-05-27 | インディアナ ユニヴァーシティ リサーチ アンド テクノロジー コーポレイション | 脂質化アミド系インスリンプロドラッグ |
WO2017147298A1 (en) | 2016-02-23 | 2017-08-31 | The Regents Of The University Of Colorado, A Body Corporate | Peptide-based methods for treating neurological injury |
EP3911668A1 (en) | 2019-01-18 | 2021-11-24 | The Regents of the University of Colorado, a body corporate | Amphipathic alpha-helical antimicrobial peptides treat infections by gram-negative pathogens |
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JP2006519170A (ja) * | 2002-12-26 | 2006-08-24 | マウンテン ビュー ファーマシューティカルズ,インコーポレイテッド | サイトカイン、ケモカイン、増殖因子、ポリペプチドホルモン、およびレセプター結合活性が保存されたそのアンタゴニストのポリマー結合体 |
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HUE027645T2 (en) | 2005-01-07 | 2016-10-28 | Regeneron Pharma | IGF-1 fusion proteins and therapeutic applications |
BRPI0709843A2 (pt) * | 2006-03-28 | 2011-07-26 | Biogen Idec Inc | anticorpos de anti-igf-1r e usos dos mesmos |
CL2007002502A1 (es) | 2006-08-31 | 2008-05-30 | Hoffmann La Roche | Variantes del factor de crecimiento similar a insulina-1 humano (igf-1) pegilados en lisina; metodo de produccion; proteina de fusion que la comprende; y su uso para tratar la enfermedad de alzheimer. |
WO2009121759A2 (en) | 2008-04-03 | 2009-10-08 | F. Hoffmann-La Roche Ag | Use of pegylated igf-i variants for the treatment of neuromuscular disorders |
-
2007
- 2007-08-28 CL CL200702502A patent/CL2007002502A1/es unknown
- 2007-08-29 AU AU2007291502A patent/AU2007291502B2/en not_active Ceased
- 2007-08-29 JP JP2009525971A patent/JP5184532B2/ja not_active Expired - Fee Related
- 2007-08-29 RU RU2009106118/10A patent/RU2009106118A/ru not_active Application Discontinuation
- 2007-08-29 EP EP07801961A patent/EP2059261B1/en active Active
- 2007-08-29 AR ARP070103823A patent/AR062575A1/es not_active Application Discontinuation
- 2007-08-29 BR BRPI0715943-9A patent/BRPI0715943A2/pt not_active IP Right Cessation
- 2007-08-29 ES ES07801961T patent/ES2397660T3/es active Active
- 2007-08-29 CN CN2007800319871A patent/CN101511390B/zh not_active Expired - Fee Related
- 2007-08-29 TW TW096132101A patent/TW200819468A/zh unknown
- 2007-08-29 PE PE2007001177A patent/PE20080912A1/es not_active Application Discontinuation
- 2007-08-29 MX MX2009002011A patent/MX2009002011A/es active IP Right Grant
- 2007-08-29 WO PCT/EP2007/007540 patent/WO2008025528A1/en active Application Filing
- 2007-08-29 KR KR1020097003975A patent/KR101106931B1/ko not_active IP Right Cessation
- 2007-08-29 CA CA2662062A patent/CA2662062C/en not_active Expired - Fee Related
- 2007-08-29 US US11/846,857 patent/US7625996B2/en not_active Expired - Fee Related
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2009
- 2009-01-26 IL IL196736A patent/IL196736A/en active IP Right Grant
- 2009-01-29 CR CR10591A patent/CR10591A/es not_active Application Discontinuation
- 2009-01-29 NO NO20090451A patent/NO20090451L/no not_active Application Discontinuation
- 2009-01-30 CO CO09008773A patent/CO6251278A2/es not_active Application Discontinuation
- 2009-02-25 MA MA31660A patent/MA30660B1/fr unknown
- 2009-10-09 US US12/576,266 patent/US20100035817A1/en not_active Abandoned
-
2010
- 2010-04-27 US US12/767,829 patent/US20100210547A1/en not_active Abandoned
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2012
- 2012-08-21 US US13/590,549 patent/US8476232B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN101511390B (zh) | 2013-04-24 |
US20100035817A1 (en) | 2010-02-11 |
MA30660B1 (fr) | 2009-08-03 |
EP2059261A1 (en) | 2009-05-20 |
WO2008025528A1 (en) | 2008-03-06 |
TW200819468A (en) | 2008-05-01 |
JP2010501192A (ja) | 2010-01-21 |
IL196736A0 (en) | 2009-11-18 |
US20100210547A1 (en) | 2010-08-19 |
JP5184532B2 (ja) | 2013-04-17 |
KR20090046875A (ko) | 2009-05-11 |
MX2009002011A (es) | 2009-03-05 |
CL2007002502A1 (es) | 2008-05-30 |
RU2009106118A (ru) | 2010-10-10 |
AU2007291502A1 (en) | 2008-03-06 |
ES2397660T3 (es) | 2013-03-08 |
AU2007291502B2 (en) | 2012-05-31 |
PE20080912A1 (es) | 2008-07-19 |
CR10591A (es) | 2009-04-03 |
KR101106931B1 (ko) | 2012-01-25 |
US8476232B2 (en) | 2013-07-02 |
US7625996B2 (en) | 2009-12-01 |
US20130065831A1 (en) | 2013-03-14 |
CO6251278A2 (es) | 2011-02-21 |
IL196736A (en) | 2013-10-31 |
NO20090451L (no) | 2009-02-26 |
EP2059261B1 (en) | 2012-10-24 |
US20080119409A1 (en) | 2008-05-22 |
CN101511390A (zh) | 2009-08-19 |
BRPI0715943A2 (pt) | 2013-07-30 |
CA2662062C (en) | 2015-06-23 |
CA2662062A1 (en) | 2008-03-06 |
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