JP2010507577A5 - - Google Patents
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- Publication number
- JP2010507577A5 JP2010507577A5 JP2009533536A JP2009533536A JP2010507577A5 JP 2010507577 A5 JP2010507577 A5 JP 2010507577A5 JP 2009533536 A JP2009533536 A JP 2009533536A JP 2009533536 A JP2009533536 A JP 2009533536A JP 2010507577 A5 JP2010507577 A5 JP 2010507577A5
- Authority
- JP
- Japan
- Prior art keywords
- receptor tyrosine
- tyrosine kinase
- cancer
- kinase
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims 7
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims 7
- 102000001253 Protein Kinase Human genes 0.000 claims 6
- 108060006633 protein kinase Proteins 0.000 claims 6
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 claims 4
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 claims 4
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 claims 4
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- 208000032839 leukemia Diseases 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims 2
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 claims 2
- 101000606129 Homo sapiens Tyrosine-protein kinase receptor TYRO3 Proteins 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 claims 2
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 claims 2
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 claims 2
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 claims 2
- 101150098329 Tyro3 gene Proteins 0.000 claims 2
- 102100039127 Tyrosine-protein kinase receptor TYRO3 Human genes 0.000 claims 2
- 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 claims 2
- 108010023337 axl receptor tyrosine kinase Proteins 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 239000012830 cancer therapeutic Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 102000047459 trkC Receptor Human genes 0.000 claims 2
- 108010064892 trkC Receptor Proteins 0.000 claims 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 claims 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 208000017604 Hodgkin disease Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 208000018142 Leiomyosarcoma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 claims 1
- 108091008556 ROS receptors Proteins 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 210000001185 bone marrow Anatomy 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 239000003607 modifier Substances 0.000 claims 1
- 210000002445 nipple Anatomy 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86255206P | 2006-10-23 | 2006-10-23 | |
| US87138406P | 2006-12-21 | 2006-12-21 | |
| US91375207P | 2007-04-24 | 2007-04-24 | |
| US95283307P | 2007-07-30 | 2007-07-30 | |
| PCT/US2007/081832 WO2008051805A2 (en) | 2006-10-23 | 2007-10-18 | Triazolo-pyridazine protein kinase modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010507577A JP2010507577A (ja) | 2010-03-11 |
| JP2010507577A5 true JP2010507577A5 (enExample) | 2010-12-02 |
Family
ID=39031065
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009533536A Withdrawn JP2010507577A (ja) | 2006-10-23 | 2007-10-18 | トリアゾロピリダジンタンパク質キナーゼモジュレーター |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8071581B2 (enExample) |
| EP (1) | EP2081937B1 (enExample) |
| JP (1) | JP2010507577A (enExample) |
| KR (1) | KR101083177B1 (enExample) |
| AU (1) | AU2007309237B2 (enExample) |
| BR (1) | BRPI0717317A2 (enExample) |
| CA (1) | CA2667453A1 (enExample) |
| DK (1) | DK2081937T3 (enExample) |
| EA (1) | EA016527B1 (enExample) |
| ES (1) | ES2393132T3 (enExample) |
| MX (1) | MX2009004060A (enExample) |
| PE (1) | PE20081256A1 (enExample) |
| PL (1) | PL2081937T3 (enExample) |
| PT (1) | PT2081937E (enExample) |
| TW (1) | TW200833692A (enExample) |
| WO (1) | WO2008051805A2 (enExample) |
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2008012945A (es) | 2006-04-07 | 2009-01-15 | Vertex Pharma | Moduladores de transportadores de cartucho de union a adenosina-trifosfato celular (atp). |
| US7645789B2 (en) | 2006-04-07 | 2010-01-12 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| USRE50453E1 (en) | 2006-04-07 | 2025-06-10 | Vertex Pharmaceuticals Incorporated | Indole derivatives as CFTR modulators |
| US10022352B2 (en) | 2006-04-07 | 2018-07-17 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| US8198448B2 (en) | 2006-07-14 | 2012-06-12 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| WO2008021781A1 (en) | 2006-08-07 | 2008-02-21 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
| US8563573B2 (en) | 2007-11-02 | 2013-10-22 | Vertex Pharmaceuticals Incorporated | Azaindole derivatives as CFTR modulators |
| CA2669991C (en) | 2006-11-22 | 2016-01-26 | Incyte Corporation | Imidazotriazines and imidazopyrimidines as kinase inhibitors |
| KR20100128305A (ko) | 2008-02-28 | 2010-12-07 | 노파르티스 아게 | C-met 티로신 키나제 매개 질환의 치료를 위한 이미다조[1,2-b]피리다진 유도체 |
| CA2724742C (en) * | 2008-05-21 | 2016-07-19 | Incyte Corporation | Salts of 2-fluoro-n-methyl-4-[7-(quinolin-6-yl-methyl)- imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide and processes related to preparing the same |
| DE102008028905A1 (de) * | 2008-06-18 | 2009-12-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo[4,3-b]pyridazinderivate |
| DE102008037790A1 (de) | 2008-08-14 | 2010-02-18 | Merck Patent Gmbh | Bicyclische Triazolderivate |
| DE102008038221A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | 7-Azaindolderivate |
| DE102008038222A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Indazol-5-carbonsäurehydrazid-derivate |
| DE102008038220A1 (de) | 2008-08-18 | 2010-02-25 | Merck Patent Gmbh | Oxadiazolderivate |
| EP2356116A1 (en) * | 2008-11-20 | 2011-08-17 | OSI Pharmaceuticals, Inc. | Substituted pyrroloý2,3-b¨-pyridines and-pyrazines |
| CA2744563A1 (en) * | 2008-12-12 | 2010-06-17 | Ariad Pharmaceuticals, Inc. | Azaindole derivatives as kinase inhibitors |
| DE102008063667A1 (de) * | 2008-12-18 | 2010-07-01 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-°[1,2,4]triazolo[4,3-b]pyrimidin-derivate |
| DE102008062825A1 (de) | 2008-12-23 | 2010-06-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo [4,3-b]pyridazin-derivate |
| SG172986A1 (en) * | 2009-02-10 | 2011-08-29 | Astrazeneca Ab | Triazolo [4,3-b] pyridazine derivatives and their uses for prostate cancer |
| EP2406264A4 (en) | 2009-03-09 | 2012-08-08 | Univ California | SUBSTITUTED HETEROCYCLES AND THEIR USE AS ALLOSTERIC MODULATORS OF NICOTINE AND GABAA RECEPTORS |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| EA201200260A1 (ru) | 2009-08-12 | 2012-09-28 | Новартис Аг | Гетероциклические гидразоны и их применение для лечения рака и воспаления |
| KR20120089463A (ko) | 2009-08-20 | 2012-08-10 | 노파르티스 아게 | 헤테로시클릭 옥심 화합물 |
| BR112012016129B1 (pt) * | 2009-12-31 | 2020-11-03 | Hutchison Medipharma Limited | composto, composição e uso dos ditos compostos |
| ES2608329T3 (es) | 2010-02-03 | 2017-04-07 | Incyte Holdings Corporation | Imidazo[1,2-b][1,2,4]triazinas como inhibidores de c-Met |
| US8802868B2 (en) | 2010-03-25 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide |
| MX342288B (es) | 2010-04-22 | 2016-09-23 | Vertex Pharma | Proceso para producir compuestos de cicloalquilcarboxamido-indol. |
| AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
| EP2569315A1 (en) | 2010-05-14 | 2013-03-20 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| JP5960688B2 (ja) | 2010-05-17 | 2016-08-02 | インコゼン セラピューティクス プライベート リミテッド | プロテインキナーゼ調節物質としての新規3,5−二置換−3h−[1,2,3]トリアゾロ[4,5−b]ピリジン化合物 |
| US10414760B2 (en) | 2016-11-29 | 2019-09-17 | Angion Biomedica Corp. | Cytochrome P450 inhibitors and uses thereof |
| WO2011153192A2 (en) * | 2010-06-01 | 2011-12-08 | Angion Biomedica Corp. | Cytochrome p450 inhibitors and uses thereof |
| AR085183A1 (es) | 2010-07-30 | 2013-09-18 | Lilly Co Eli | Compuesto 6-(1-metil-1h-pirazol-4-il)-3-(2-metil-2h-indazol-5-iltio)-[1,2,4]triazol[4,3-b]piridazina, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para tratar cancer |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| EP2710003A1 (en) | 2011-05-16 | 2014-03-26 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
| AU2012310168B2 (en) | 2011-09-15 | 2015-07-16 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
| CA2848518C (en) | 2011-09-27 | 2019-06-18 | Genfit | Derivatives of 6-substituted triazolopyridazines as rev-erb agonists |
| KR101869534B1 (ko) * | 2012-03-05 | 2018-06-20 | 한국화학연구원 | 신규한 트리아졸로 피리다진 유도체 및 그의 용도 |
| BR112014024251A8 (pt) | 2012-03-30 | 2018-01-23 | Rhizen Pharmaceuticals S A | novos compostos piridina 3,5-dissubstituída-3h-imidazo [4,5-b] e piridina 3,5-dissubstituída -3h-[1,2,3]triazolo[4,5-b] como moduladores de quinases de proteína c-met |
| US9012496B2 (en) | 2012-07-16 | 2015-04-21 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof |
| CN103122000B (zh) * | 2012-09-03 | 2013-12-25 | 中美冠科生物技术(太仓)有限公司 | 用作抗肿瘤药物的高选择性的c-Met激酶抑制剂 |
| ME02794B (me) | 2012-10-16 | 2018-01-20 | Janssen Pharmaceutica Nv | Metilen vezani hinolinil modulatori ror-gama-t |
| AU2013331493A1 (en) | 2012-10-16 | 2015-04-09 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORyt |
| EP2909193B1 (en) | 2012-10-16 | 2017-04-19 | Janssen Pharmaceutica NV | Phenyl linked quinolinyl modulators of ror-gamma-t |
| US9846345B2 (en) | 2013-02-28 | 2017-12-19 | Empire Technology Development Llc | Colored pigment particles for electrophoretic displays |
| BR112015020716A2 (pt) * | 2013-03-13 | 2017-07-18 | Hoffmann La Roche | processo para a preparação de (2-(4-(2-(1-isopropil-3-metil-1h-1,2,4-triazol-5-il)-5,6-diidrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-il)-1h-pirazol-1-il)-2-metilpropanamida (i) e composto |
| US20140303121A1 (en) * | 2013-03-15 | 2014-10-09 | Plexxikon Inc. | Heterocyclic compounds and uses thereof |
| NZ630875A (en) * | 2013-03-15 | 2017-12-22 | Plexxikon Inc | Heterocyclic compounds and uses thereof |
| AU2014334619A1 (en) | 2013-10-15 | 2016-04-21 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORyt |
| US9328095B2 (en) | 2013-10-15 | 2016-05-03 | Janssen Pharmaceutica Nv | Heteroaryl linked quinolinyl modulators of RORgammat |
| US9221804B2 (en) | 2013-10-15 | 2015-12-29 | Janssen Pharmaceutica Nv | Secondary alcohol quinolinyl modulators of RORγt |
| US10555941B2 (en) | 2013-10-15 | 2020-02-11 | Janssen Pharmaceutica Nv | Alkyl linked quinolinyl modulators of RORγt |
| EP3057422B1 (en) | 2013-10-15 | 2019-05-15 | Janssen Pharmaceutica NV | Quinolinyl modulators of ror(gamma)t |
| US9284308B2 (en) | 2013-10-15 | 2016-03-15 | Janssen Pharmaceutica Nv | Methylene linked quinolinyl modulators of RORγt |
| US9403816B2 (en) | 2013-10-15 | 2016-08-02 | Janssen Pharmaceutica Nv | Phenyl linked quinolinyl modulators of RORγt |
| GB201321745D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| WO2015134854A2 (en) * | 2014-03-06 | 2015-09-11 | Oyagen, Inc. | Small molecule vif dimerization antagonists as anti-hiv agents and for use as hiv/aids therapeutics |
| KR102447581B1 (ko) | 2014-04-15 | 2022-09-28 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막전도 조절자 매개 질환 치료용 약제학적 조성물 |
| JP6578349B2 (ja) | 2014-08-11 | 2019-09-18 | アンジオン バイオメディカ コーポレーション | チトクロームp450阻害剤およびその使用 |
| CN107531631B (zh) | 2014-12-31 | 2021-09-03 | 安吉昂生物医药公司 | 用于治疗疾病的方法和药剂 |
| HUE053903T2 (hu) * | 2015-04-13 | 2021-07-28 | Five Prime Therapeutics Inc | Kombinációs terápia rák ellen |
| CR20180109A (es) | 2015-07-20 | 2018-05-03 | Genzyme Corp | Inhibidores de receptor del factor estimulador de colonias 1 (csf-1r) |
| AU2018348241B2 (en) | 2017-10-13 | 2023-01-12 | Opna Bio SA | Solid forms of a compound for modulating kinases |
| GB201905721D0 (en) | 2019-04-24 | 2019-06-05 | Univ Dundee | Compounds |
| CN113861198B (zh) * | 2020-06-30 | 2024-08-02 | 上海医药集团股份有限公司 | 咪唑并[4,5-b]吡嗪类化合物、其制备方法及应用 |
| EP4267573A1 (en) | 2020-12-23 | 2023-11-01 | Genzyme Corporation | Deuterated colony stimulating factor-1 receptor (csf-1r) inhibitors |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002251266A1 (en) | 2001-04-10 | 2002-10-28 | Merck Sharp And Dohme Limited | Inhibitors of akt activity |
| WO2002083139A1 (en) | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| WO2003014649A1 (en) * | 2001-08-10 | 2003-02-20 | Yokohama Tlo Company Ltd. | Heat transfer device |
| UA98297C2 (en) * | 2005-12-21 | 2012-05-10 | Янссен Фармацевтика, Н.В. | Triazolopyridazines as tyrosine kinase modulators |
| JP2009538899A (ja) * | 2006-05-30 | 2009-11-12 | ファイザー・プロダクツ・インク | トリアゾロピリダジン誘導体 |
| PE20121506A1 (es) * | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
-
2007
- 2007-10-18 AU AU2007309237A patent/AU2007309237B2/en not_active Ceased
- 2007-10-18 BR BRPI0717317-2A2A patent/BRPI0717317A2/pt not_active IP Right Cessation
- 2007-10-18 EA EA200970402A patent/EA016527B1/ru not_active IP Right Cessation
- 2007-10-18 ES ES07854193T patent/ES2393132T3/es active Active
- 2007-10-18 EP EP07854193A patent/EP2081937B1/en active Active
- 2007-10-18 MX MX2009004060A patent/MX2009004060A/es not_active Application Discontinuation
- 2007-10-18 PL PL07854193T patent/PL2081937T3/pl unknown
- 2007-10-18 PT PT07854193T patent/PT2081937E/pt unknown
- 2007-10-18 JP JP2009533536A patent/JP2010507577A/ja not_active Withdrawn
- 2007-10-18 CA CA002667453A patent/CA2667453A1/en not_active Abandoned
- 2007-10-18 DK DK07854193.5T patent/DK2081937T3/da active
- 2007-10-18 WO PCT/US2007/081832 patent/WO2008051805A2/en not_active Ceased
- 2007-10-18 US US12/442,987 patent/US8071581B2/en not_active Expired - Fee Related
- 2007-10-18 KR KR1020097007986A patent/KR101083177B1/ko not_active Expired - Fee Related
- 2007-10-22 TW TW096139481A patent/TW200833692A/zh unknown
- 2007-10-23 PE PE2007001436A patent/PE20081256A1/es not_active Application Discontinuation
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