HRP20041220A2 - Novi tiofen amidini, njihovi pripravci i postupci liječenja komplementom posredovanih bolesti i stanja - Google Patents
Novi tiofen amidini, njihovi pripravci i postupci liječenja komplementom posredovanih bolesti i stanjaInfo
- Publication number
- HRP20041220A2 HRP20041220A2 HR20041220A HRP20041220A HRP20041220A2 HR P20041220 A2 HRP20041220 A2 HR P20041220A2 HR 20041220 A HR20041220 A HR 20041220A HR P20041220 A HRP20041220 A HR P20041220A HR P20041220 A2 HRP20041220 A2 HR P20041220A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- thiophene
- methylsulfanyl
- compound
- sulfonyl
- Prior art date
Links
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- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 229940075931 sodium dithionate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
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- 239000012439 solid excipient Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- WKSMIPGYFCOFCQ-UHFFFAOYSA-N tert-butyl (nz)-n-[amino-[4-(3-bromo-5-hydroxyphenyl)sulfonyl-5-methylsulfanylthiophen-2-yl]methylidene]carbamate Chemical compound S1C(C(=N)NC(=O)OC(C)(C)C)=CC(S(=O)(=O)C=2C=C(Br)C=C(O)C=2)=C1SC WKSMIPGYFCOFCQ-UHFFFAOYSA-N 0.000 description 1
- HLMOCGQQXAOKPJ-UHFFFAOYSA-N tert-butyl (nz)-n-[amino-[4-[3-(2-ethenylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophen-2-yl]methylidene]carbamate Chemical compound S1C(C(=N)NC(=O)OC(C)(C)C)=CC(S(=O)(=O)C=2C=C(C=CC=2)C=2C(=CC=CC=2)C=C)=C1SC HLMOCGQQXAOKPJ-UHFFFAOYSA-N 0.000 description 1
- XDHUKTZRYRNQMH-UHFFFAOYSA-N tert-butyl 2-iodo-3-methylbenzoate Chemical compound CC1=CC=CC(C(=O)OC(C)(C)C)=C1I XDHUKTZRYRNQMH-UHFFFAOYSA-N 0.000 description 1
- LAVQGAKEILPGNN-UHFFFAOYSA-N tert-butyl 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound CC1=CC=C(C(=O)OC(C)(C)C)C(B2OC(C)(C)C(C)(C)O2)=C1 LAVQGAKEILPGNN-UHFFFAOYSA-N 0.000 description 1
- NVCXTANCBZKVQI-UHFFFAOYSA-N tert-butyl 5-chloro-6-methylbenzimidazole-1-carboxylate Chemical compound C1=C(Cl)C(C)=CC2=C1N=CN2C(=O)OC(C)(C)C NVCXTANCBZKVQI-UHFFFAOYSA-N 0.000 description 1
- DFUOVOKCFLCEIG-UHFFFAOYSA-N tert-butyl 5-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzimidazole-1-carboxylate Chemical compound CC1=CC=2N=CN(C(=O)OC(C)(C)C)C=2C=C1B1OC(C)(C)C(C)(C)O1 DFUOVOKCFLCEIG-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000006478 transmetalation reaction Methods 0.000 description 1
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- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- VOITXYVAKOUIBA-UHFFFAOYSA-N triethylaluminium Chemical compound CC[Al](CC)CC VOITXYVAKOUIBA-UHFFFAOYSA-N 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- PGAJYUDRKAPMPA-UHFFFAOYSA-N trimethylsilyl n-ethylcarbamate Chemical compound CCNC(=O)O[Si](C)(C)C PGAJYUDRKAPMPA-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- FKFXCROGBLLHFO-UHFFFAOYSA-M zinc;3-methyl-2h-pyridin-2-ide;bromide Chemical compound Br[Zn+].CC1=CC=CN=[C-]1 FKFXCROGBLLHFO-UHFFFAOYSA-M 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38313002P | 2002-05-28 | 2002-05-28 | |
PCT/US2003/016888 WO2003099805A1 (en) | 2002-05-28 | 2003-05-28 | Novel thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20041220A2 true HRP20041220A2 (hr) | 2006-04-30 |
Family
ID=29584510
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20041220A HRP20041220A2 (hr) | 2002-05-28 | 2004-12-28 | Novi tiofen amidini, njihovi pripravci i postupci liječenja komplementom posredovanih bolesti i stanja |
Country Status (23)
Country | Link |
---|---|
US (2) | US7109354B2 (ru) |
EP (1) | EP1549632A4 (ru) |
JP (1) | JP2005538953A (ru) |
KR (1) | KR20050009720A (ru) |
CN (1) | CN100412073C (ru) |
AR (1) | AR039891A1 (ru) |
AU (1) | AU2003251384B2 (ru) |
BR (1) | BR0311419A (ru) |
CA (1) | CA2484822A1 (ru) |
CO (1) | CO5640081A2 (ru) |
HK (1) | HK1081187A1 (ru) |
HR (1) | HRP20041220A2 (ru) |
IL (1) | IL164890A0 (ru) |
MX (1) | MX249034B (ru) |
MY (1) | MY137509A (ru) |
NO (1) | NO20045403L (ru) |
NZ (1) | NZ537346A (ru) |
PL (1) | PL372246A1 (ru) |
RU (1) | RU2359967C2 (ru) |
TW (1) | TW200406395A (ru) |
UA (1) | UA80131C2 (ru) |
WO (1) | WO2003099805A1 (ru) |
ZA (1) | ZA200408711B (ru) |
Families Citing this family (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1401825E (pt) * | 2001-06-11 | 2009-10-23 | Virochem Pharma Inc | Compostos e métodos para o tratamento ou para a prevenção de infecções com flavivírus |
DE10162114A1 (de) * | 2001-12-12 | 2003-06-26 | Schering Ag | Neue Amidin-Derivate und deren Verwendung in Arzneimitteln |
US7109354B2 (en) | 2002-05-28 | 2006-09-19 | 3-Dimensional Pharmaceuticals, Inc. | Thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions |
ES2345438T3 (es) | 2002-12-10 | 2010-09-23 | Virochem Pharma Inc. | Compuestos y metodos para el tratamiento o prevencion de infecciones por flavivirus. |
GB0305575D0 (en) * | 2003-03-11 | 2003-04-16 | Glaxo Group Ltd | Novel compounds |
US7482376B2 (en) * | 2003-07-03 | 2009-01-27 | 3-Dimensional Pharmaceuticals, Inc. | Conjugated complement cascade inhibitors |
EP2289560B1 (en) | 2004-07-08 | 2015-04-22 | Novo Nordisk A/S | Polypeptide protracting tags comprising a tetrazole moiety |
NZ554555A (en) * | 2004-10-20 | 2011-09-30 | Univ California | Cyclohexyl-urea derivatives as improved inhibitors for the soluble epoxide hydrolase |
RS54876B1 (sr) | 2005-05-10 | 2016-10-31 | Incyte Holdings Corp | Modulatori indoleamina 2,3-dioksigenaze i metode za upotrebu istih |
JP5030947B2 (ja) | 2005-05-13 | 2012-09-19 | ヴァイロケム・ファーマ・インコーポレーテッド | フラビウイルス感染の治療及び予防のための化合物及び方法 |
JP5294874B2 (ja) * | 2005-12-20 | 2013-09-18 | インサイト・コーポレイション | インドールアミン2,3−ジオキシゲナーゼのモジュレーターとしてのn−ヒドロキシアミジノヘテロ環 |
CN102532180B (zh) * | 2005-12-30 | 2016-06-29 | 安纳考尔医药公司 | 含硼的小分子 |
DK2719388T3 (da) | 2006-02-16 | 2019-05-13 | Anacor Pharmaceuticals Inc | Borholdige små molekyler som antiinflammatoriske midler |
US20080146624A1 (en) * | 2006-09-19 | 2008-06-19 | Incyte Corporation | Amidines as modulators of indoleamine 2,3-dioxygenase |
US20080125470A1 (en) | 2006-09-19 | 2008-05-29 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
CL2007002650A1 (es) | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
KR20090086081A (ko) * | 2006-11-15 | 2009-08-10 | 바이로켐 파마 인코포레이티드 | 플라비바이러스 감염의 치료 또는 예방용 티오펜 유사체 |
US8580735B2 (en) | 2007-02-05 | 2013-11-12 | Apellis Pharmaceuticals, Inc. | Local complement inhibition for treatment of complement-mediated disorders |
JO3396B1 (ar) * | 2007-06-20 | 2019-10-20 | Anacor Pharmaceuticals Inc | جزيئات صغيرة تحتوي على البورون |
CA2709664A1 (en) * | 2007-12-26 | 2009-07-02 | Eisai R&D Management Co., Ltd. | Method for manufacturing heterocycle substituted pyridine derivatives |
MY171866A (en) | 2008-07-08 | 2019-11-05 | Incyte Holdings Corp | 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase |
US8481549B2 (en) | 2010-01-19 | 2013-07-09 | Theravance, Inc. | Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents |
US10039802B2 (en) | 2011-06-22 | 2018-08-07 | Apellis Pharmaceuticals, Inc. | Methods of treating chronic disorders with complement inhibitors |
AU2013292519B2 (en) | 2012-07-19 | 2017-12-07 | Drexel University | Sigma receptor ligands for modulating cellular protein homeostasis |
CN104619683B (zh) | 2012-09-27 | 2017-05-10 | 拜耳农作物科学股份公司 | 用于制备任选地取代的苯基和吡啶基吡咯烷类的方法 |
SI2953942T1 (en) | 2013-02-06 | 2018-03-30 | Bayer Cropscience Ag | Halogen-substituted pyrazole derivatives such as pesticides |
EP3628661A1 (en) * | 2013-06-27 | 2020-04-01 | Lg Chem, Ltd. | Biaryl derivatives as gpr120 agonists |
BR112016009786B1 (pt) | 2013-11-08 | 2021-01-05 | Incyte Holdings Corporation | compostos inibidores de indoleamina 2,3-dioxigenase e seus processos de síntese |
MA47440B1 (fr) | 2015-02-16 | 2021-08-31 | The Provost Fellows Found Scholars And The Other Members Of Board Of The College Of The Holy & Undiv | Sulfonylurées, composés apparentés, et leur utilisation |
JP7235742B2 (ja) | 2017-07-07 | 2023-03-08 | インフレイゾーム リミテッド | 新規なスルホンアミドカルボキサミド化合物 |
US11370776B2 (en) | 2017-07-07 | 2022-06-28 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as NLRP3 inhibitors |
US11518739B2 (en) | 2017-08-15 | 2022-12-06 | Inflazome Limited | Sulfonamide carboxamide compounds |
TW201910314A (zh) * | 2017-08-15 | 2019-03-16 | 愛爾蘭商英弗雷佐姆有限公司 | 新穎化合物 |
WO2019034693A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3 |
EP3668842A1 (en) | 2017-08-15 | 2020-06-24 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as nlrp3 inhibitors |
CA3071150A1 (en) | 2017-08-15 | 2019-02-21 | Inflazome Limited | Sulfonylureas and sulfonylthioureas as nlrp3 inhibitors |
WO2019089902A1 (en) | 2017-11-01 | 2019-05-09 | Drexel University | Compounds, compositions, and methods for treating diseases |
WO2019092170A1 (en) | 2017-11-09 | 2019-05-16 | Inflazome Limited | Novel sulfonamide carboxamide compounds |
EP3759077A1 (en) | 2018-03-02 | 2021-01-06 | Inflazome Limited | Novel compounds |
WO2021067526A1 (en) | 2019-10-02 | 2021-04-08 | Alexion Pharmaceuticals, Inc. | Complement inhibitors for treating drug-induced complement-mediated response |
EP4150338A1 (en) | 2020-05-15 | 2023-03-22 | Alexion Pharmaceuticals, Inc. | Method of using extracellular vesicles to detect complement activation, and uses thereof to assess and/or monitor treatment of a complement-mediated disease |
KR20230058660A (ko) | 2020-09-01 | 2023-05-03 | 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 | 융합된 이미다졸 유도체, 이의 제조 방법, 및 이의 의학적 용도 |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS59139357A (ja) * | 1983-01-28 | 1984-08-10 | Torii Yakuhin Kk | アミジン誘導体 |
US4510130A (en) | 1983-05-20 | 1985-04-09 | Genetic Diagnostics Corporation | Promoting animal and plant growth with leupeptin |
US4727064A (en) | 1984-04-25 | 1988-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Pharmaceutical preparations containing cyclodextrin derivatives |
GB8506792D0 (en) | 1985-03-15 | 1985-04-17 | Janssen Pharmaceutica Nv | Derivatives of y-cyclodextrin |
US4916219A (en) | 1985-03-28 | 1990-04-10 | University Of Iowa Research Foundation | Oligosaccharide heparin fragments as inhibitors of complement cascade |
US4722890A (en) | 1985-08-27 | 1988-02-02 | The United States Of America As Represented By The Department Of Health And Human Services | Quantitative assay for human terminal complement cascade activation |
US5002935A (en) | 1987-12-30 | 1991-03-26 | University Of Florida | Improvements in redox systems for brain-targeted drug delivery |
US5256642A (en) | 1988-04-01 | 1993-10-26 | The Johns Hopkins University | Compositions of soluble complement receptor 1 (CR1) and a thrombolytic agent, and the methods of use thereof |
US5268363A (en) | 1989-09-12 | 1993-12-07 | The Beth Israel Hospital Association | Method of treatment to inhibit the undesirable activation of the complement cascade with factor J, an inhibitor of complement C1 |
ZA928276B (en) * | 1991-10-31 | 1993-05-06 | Daiichi Seiyaku Co | Aromatic amidine derivates and salts thereof. |
US5466811A (en) | 1994-07-18 | 1995-11-14 | Merck & Co., Inc. | Dioxolenylmethyl carbamates pro moieties for amine drugs |
DE19650196A1 (de) * | 1996-12-04 | 1998-06-10 | Bayer Ag | Thienylsulfonylamino(thio)carbonylverbindungen |
AU6959898A (en) | 1997-04-11 | 1998-11-11 | David J. Grainger | Compounds and therapies for the prevention of vascular and non-vascular pathol ogies |
GB9721964D0 (en) | 1997-10-16 | 1997-12-17 | Pfizer Ltd | Isoquinolines |
US6291514B1 (en) | 1998-02-09 | 2001-09-18 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors |
CA2321025A1 (en) * | 1998-02-09 | 1999-08-12 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines as protease inhibitors, in particular as urokinase inhibitors |
US6727238B2 (en) * | 1998-06-11 | 2004-04-27 | Pfizer Inc. | Sulfonylbenzene compounds as anti-inflammatory/analgesic agents |
DE19840319A1 (de) | 1998-09-04 | 2000-03-09 | Bayer Ag | Verfahren zur Herstellung von aromatischen oder heteroaromatischen Sulfonsäurechloriden |
FR2783519B1 (fr) * | 1998-09-23 | 2003-01-24 | Sod Conseils Rech Applic | Nouveaux derives d'amidines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
JP3450724B2 (ja) * | 1998-11-06 | 2003-09-29 | キヤノン株式会社 | 画像形成装置 |
EP1152759A2 (en) * | 1999-02-09 | 2001-11-14 | 3-Dimensional Pharmaceuticals, Inc. | METHODS OF TREATING C1s-MEDIATED DISEASES AND CONDITIONS, AND COMPOUNDS AND COMPOSITIONS THEREFOR |
EP1150979A1 (en) * | 1999-02-09 | 2001-11-07 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines as protease inhibitors |
AU2001288819A1 (en) | 2000-09-11 | 2002-03-26 | Genentech, Inc. | Amidine inhibitors of serine proteases |
DE10112041A1 (de) * | 2001-03-14 | 2002-09-26 | Aventis Pharma Gmbh | p-Thienylbenzyl-Amide als Agonisten von Angiotensin-(1-7)-Rezeptoren, Verfahren zu ihrer Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
US7109354B2 (en) | 2002-05-28 | 2006-09-19 | 3-Dimensional Pharmaceuticals, Inc. | Thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions |
TWI299664B (en) * | 2003-01-06 | 2008-08-11 | Osi Pharm Inc | (2-carboxamido)(3-amino)thiophene compounds |
-
2003
- 2003-05-28 US US10/445,817 patent/US7109354B2/en not_active Expired - Fee Related
- 2003-05-28 TW TW092114404A patent/TW200406395A/zh unknown
- 2003-05-28 CN CNB038161168A patent/CN100412073C/zh not_active Expired - Fee Related
- 2003-05-28 MX MXPA04011671 patent/MX249034B/es active IP Right Grant
- 2003-05-28 UA UA20041209867A patent/UA80131C2/uk unknown
- 2003-05-28 CA CA002484822A patent/CA2484822A1/en not_active Abandoned
- 2003-05-28 AU AU2003251384A patent/AU2003251384B2/en not_active Ceased
- 2003-05-28 PL PL03372246A patent/PL372246A1/xx not_active Application Discontinuation
- 2003-05-28 BR BR0311419-8A patent/BR0311419A/pt not_active IP Right Cessation
- 2003-05-28 NZ NZ537346A patent/NZ537346A/en not_active IP Right Cessation
- 2003-05-28 AR ARP030101873A patent/AR039891A1/es unknown
- 2003-05-28 JP JP2004507462A patent/JP2005538953A/ja active Pending
- 2003-05-28 MY MYPI20031975A patent/MY137509A/en unknown
- 2003-05-28 ZA ZA200408711A patent/ZA200408711B/en unknown
- 2003-05-28 US US10/515,554 patent/US7138530B2/en not_active Expired - Fee Related
- 2003-05-28 KR KR10-2004-7019227A patent/KR20050009720A/ko not_active Application Discontinuation
- 2003-05-28 WO PCT/US2003/016888 patent/WO2003099805A1/en active Application Filing
- 2003-05-28 RU RU2004138787/04A patent/RU2359967C2/ru not_active IP Right Cessation
- 2003-05-28 EP EP03755527A patent/EP1549632A4/en not_active Withdrawn
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2004
- 2004-10-17 IL IL16489004A patent/IL164890A0/xx unknown
- 2004-12-10 NO NO20045403A patent/NO20045403L/no not_active Application Discontinuation
- 2004-12-20 CO CO04126948A patent/CO5640081A2/es not_active Application Discontinuation
- 2004-12-28 HR HR20041220A patent/HRP20041220A2/hr not_active Application Discontinuation
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- 2006-01-26 HK HK06101171.3A patent/HK1081187A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CO5640081A2 (es) | 2006-05-31 |
ZA200408711B (en) | 2006-10-25 |
WO2003099805A1 (en) | 2003-12-04 |
MX249034B (es) | 2007-09-14 |
BR0311419A (pt) | 2005-04-05 |
US7138530B2 (en) | 2006-11-21 |
JP2005538953A (ja) | 2005-12-22 |
CN1665800A (zh) | 2005-09-07 |
TW200406395A (en) | 2004-05-01 |
RU2359967C2 (ru) | 2009-06-27 |
EP1549632A4 (en) | 2005-11-09 |
IL164890A0 (en) | 2005-12-18 |
US20050234081A1 (en) | 2005-10-20 |
AU2003251384B2 (en) | 2009-01-29 |
EP1549632A1 (en) | 2005-07-06 |
US20040009995A1 (en) | 2004-01-15 |
CN100412073C (zh) | 2008-08-20 |
AU2003251384A1 (en) | 2003-12-12 |
NZ537346A (en) | 2006-12-22 |
UA80131C2 (en) | 2007-08-27 |
PL372246A1 (en) | 2005-07-11 |
NO20045403L (no) | 2004-12-10 |
AR039891A1 (es) | 2005-03-09 |
RU2004138787A (ru) | 2005-07-10 |
KR20050009720A (ko) | 2005-01-25 |
MY137509A (en) | 2009-02-27 |
MXPA04011671A (es) | 2005-03-07 |
US7109354B2 (en) | 2006-09-19 |
CA2484822A1 (en) | 2003-12-04 |
HK1081187A1 (en) | 2006-05-12 |
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