TWI394748B - 新穎的雜環二苯基醚類化合物 - Google Patents
新穎的雜環二苯基醚類化合物 Download PDFInfo
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- TWI394748B TWI394748B TW096106502A TW96106502A TWI394748B TW I394748 B TWI394748 B TW I394748B TW 096106502 A TW096106502 A TW 096106502A TW 96106502 A TW96106502 A TW 96106502A TW I394748 B TWI394748 B TW I394748B
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- Prior art keywords
- pharmaceutically acceptable
- phenoxy
- compound
- acetic acid
- phenyl
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000847 severe hepatotoxicity Toxicity 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 231100000617 superantigen Toxicity 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 150000008494 α-glucosides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/359,657 US7781464B2 (en) | 2003-01-17 | 2006-02-21 | Heterocyclic diphenyl ethers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200812989A TW200812989A (en) | 2008-03-16 |
| TWI394748B true TWI394748B (zh) | 2013-05-01 |
Family
ID=38437869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW096106502A TWI394748B (zh) | 2006-02-21 | 2007-02-26 | 新穎的雜環二苯基醚類化合物 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7781464B2 (enExample) |
| EP (1) | EP2004185B1 (enExample) |
| JP (1) | JP5414280B2 (enExample) |
| CA (1) | CA2642650C (enExample) |
| ES (1) | ES2427726T3 (enExample) |
| PL (1) | PL2004185T3 (enExample) |
| TW (1) | TWI394748B (enExample) |
| WO (1) | WO2007097992A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7087576B2 (en) * | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
| US20090203744A1 (en) * | 2005-07-29 | 2009-08-13 | Pande Y Surendrakumar Satyanarayan | Novel pyridine derivatives |
| US7846953B2 (en) * | 2007-03-07 | 2010-12-07 | Janssen Pharmaceutica, Nv | Substituted phenoxy thiazolidinediones as estrogen related receptor-α modulators |
| JPWO2009025170A1 (ja) * | 2007-08-23 | 2010-11-25 | コニカミノルタオプト株式会社 | 長尺の位相差フィルム、長尺の楕円偏光フィルム、楕円偏光板、及び画像表示装置 |
| EP2300446B1 (en) * | 2008-05-20 | 2011-12-07 | Merck Sharp & Dohme Corp. | Efficient production of heterologous proteins using mannosyl transferase inhibitors |
| CN103108634B (zh) | 2010-07-28 | 2015-08-12 | 幽兰化学医药有限公司 | 用于治疗肝病、肺病、糖尿病并发症和心血管疾病的二苯醚化合物 |
| WO2012153775A1 (ja) | 2011-05-10 | 2012-11-15 | 国立大学法人神戸大学 | Ras機能阻害作用を有するチオキソチアゾリジン誘導体 |
| CN113396035A (zh) | 2019-02-27 | 2021-09-14 | 伯克希尔格雷股份有限公司 | 用于在可编程运动系统中的软管布线的系统和方法 |
| EP3959050B1 (en) | 2019-04-25 | 2024-04-17 | Berkshire Grey Operating Company, Inc. | System and method for maintaining vacuum hose life in hose routing systems in programmable motion systems |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030181494A1 (en) * | 1999-04-06 | 2003-09-25 | Partha Neogi | Novel heterocyclic analogs of diphenylethylene compounds |
| US20040142991A1 (en) * | 2003-01-17 | 2004-07-22 | Bishwajit Nag | Amino acid phenoxy ethers |
| US20050288341A1 (en) * | 2003-01-17 | 2005-12-29 | Bexel Pharmaceuticals, Inc. | Novel diphenyl ether derivatives |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20020049240A1 (en) * | 1994-12-19 | 2002-04-25 | Beecham Group P.1.C. | Novel compounds |
| US5166137A (en) * | 1991-03-27 | 1992-11-24 | Nobipols Forskningsstiftelse | Guluronic acid polymers and use of same for inhibition of cytokine production |
| US5441971A (en) * | 1991-04-11 | 1995-08-15 | The Upjohn Company | Thiazolidinedione derivatives, production and use thereof |
| TW268952B (enExample) * | 1993-02-26 | 1996-01-21 | Takeda Pharm Industry Co Ltd | |
| US6251928B1 (en) * | 1994-03-16 | 2001-06-26 | Eli Lilly And Company | Treatment of alzheimer's disease employing inhibitors of cathepsin D |
| US5527546A (en) * | 1994-08-10 | 1996-06-18 | Bayer Corporation | Human interleukin 6 inhibitor |
| DK0824588T3 (da) * | 1995-05-11 | 2004-08-16 | Applied Research Systems | Inhibitor af IL-6 aktivitet |
| TW577875B (en) * | 1997-01-31 | 2004-03-01 | Shionogi & Co | Pyrrolidine derivatives with inhibitory activity for phospholipase A2 |
| CA2289102A1 (en) * | 1997-05-07 | 1998-11-12 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| JP4398585B2 (ja) * | 1997-11-12 | 2010-01-13 | 有限会社ケムフィズ | レチノイドレセプター作用剤 |
| US7105552B2 (en) * | 1998-05-08 | 2006-09-12 | Theracos, Inc. | Heterocyclic analogs of diphenylethylene compounds |
| US6331633B1 (en) * | 1998-05-08 | 2001-12-18 | Calyx Therapeutics Inc. | Heterocyclic analogs of diphenylethylene compounds |
| US6699896B1 (en) | 1998-05-12 | 2004-03-02 | Wyeth | Oxazole-aryl-carboxylic acids useful in the treatment of insulin resistance and hyperglycemia |
| KR20010052615A (ko) * | 1998-06-05 | 2001-06-25 | 다비드 에 질레스 | 옥사졸리디논 유도체, 이것의 제조 방법 및 이것을함유하는 약학 조성물 |
| WO2000000194A1 (en) * | 1998-06-27 | 2000-01-06 | Photogenesis, Inc. | Ophthalmic uses of ppargamma agonists and ppargamma antagonists |
| AU5443499A (en) * | 1998-08-27 | 2000-03-21 | Ono Pharmaceutical Co. Ltd. | Carboxylic acid derivatives and drugs containing the same as the active ingredient |
| PL351878A1 (en) * | 1999-04-07 | 2003-06-30 | Sankyo Co | Amino compound derivatives |
| IL145922A0 (en) | 1999-04-28 | 2002-07-25 | Aventis Pharma Gmbh | Di-aryl acid derivatives as ppar receptor ligands |
| TWI284533B (en) * | 1999-05-24 | 2007-08-01 | Sankyo Co | Pharmaceutical composition for treating hyperglycemia, impaired glucose tolerance, diabetes complications and for improving insulin resistant |
| JP2001072592A (ja) * | 1999-07-01 | 2001-03-21 | Kyowa Hakko Kogyo Co Ltd | テロメラーゼ阻害剤 |
| AU6340600A (en) | 1999-07-01 | 2001-01-22 | Geron Corporation | Telomerase inhibitors and methods of their use |
| SE514748C2 (sv) * | 1999-08-03 | 2001-04-09 | Sahlin Gjutteknik Ab | Spolsten |
| WO2001014349A1 (en) * | 1999-08-23 | 2001-03-01 | Kyorin Pharmaceutical Co., Ltd. | Substituted benzylthiazolidine-2,4-dione derivatives |
| BR0013671A (pt) * | 1999-08-31 | 2003-06-10 | Maxia Pharmaceuticals Inc | Derivados heterocìclicos para o tratamento do diabetes e outras doenças |
| JP2001199888A (ja) * | 2000-01-24 | 2001-07-24 | Fujimoto Brothers:Kk | 糖尿病治療剤 |
| JP2001308814A (ja) | 2000-04-19 | 2001-11-02 | Hitachi Ltd | フレーム構成自動識別通信装置 |
| US6620830B2 (en) * | 2000-04-21 | 2003-09-16 | Pfizer, Inc. | Thyroid receptor ligands |
| ATE310733T1 (de) | 2000-04-21 | 2005-12-15 | Pfizer Prod Inc | Thyroid-rezeptorliganden |
| US6680387B2 (en) * | 2000-04-24 | 2004-01-20 | Aryx Therapeutics | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| MXPA04002404A (es) | 2001-09-14 | 2004-05-31 | Novo Nordisk As | Ligandos novedosos para los sitios hisb10zn2+ del hexamero de insulina en estado r. |
| JP2007523842A (ja) | 2003-03-11 | 2007-08-23 | ノボ ノルディスク アクティーゼルスカブ | 酸安定化されたインスリンを含有する薬学的製剤 |
| US7087576B2 (en) * | 2003-10-07 | 2006-08-08 | Bexel Pharmaceuticals, Inc. | Dipeptide phenyl ethers |
| CA2601884A1 (en) * | 2005-03-18 | 2006-09-21 | Surendrakumar Satyanarayan Pandey | Novel tyrosine derivatives |
-
2006
- 2006-02-21 US US11/359,657 patent/US7781464B2/en not_active Expired - Fee Related
-
2007
- 2007-02-15 JP JP2008556356A patent/JP5414280B2/ja not_active Expired - Fee Related
- 2007-02-15 WO PCT/US2007/004007 patent/WO2007097992A2/en not_active Ceased
- 2007-02-15 EP EP07750819.0A patent/EP2004185B1/en not_active Not-in-force
- 2007-02-15 ES ES07750819T patent/ES2427726T3/es active Active
- 2007-02-15 PL PL07750819T patent/PL2004185T3/pl unknown
- 2007-02-15 CA CA2642650A patent/CA2642650C/en not_active Expired - Fee Related
- 2007-02-26 TW TW096106502A patent/TWI394748B/zh not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030181494A1 (en) * | 1999-04-06 | 2003-09-25 | Partha Neogi | Novel heterocyclic analogs of diphenylethylene compounds |
| US20040142991A1 (en) * | 2003-01-17 | 2004-07-22 | Bishwajit Nag | Amino acid phenoxy ethers |
| US20050288341A1 (en) * | 2003-01-17 | 2005-12-29 | Bexel Pharmaceuticals, Inc. | Novel diphenyl ether derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2004185A2 (en) | 2008-12-24 |
| PL2004185T3 (pl) | 2013-11-29 |
| WO2007097992A3 (en) | 2008-11-06 |
| WO2007097992A2 (en) | 2007-08-30 |
| US20060247285A1 (en) | 2006-11-02 |
| CA2642650A1 (en) | 2007-08-30 |
| EP2004185B1 (en) | 2013-06-26 |
| US7781464B2 (en) | 2010-08-24 |
| JP5414280B2 (ja) | 2014-02-12 |
| TW200812989A (en) | 2008-03-16 |
| CA2642650C (en) | 2015-04-14 |
| EP2004185A4 (en) | 2012-02-29 |
| JP2009528997A (ja) | 2009-08-13 |
| ES2427726T3 (es) | 2013-10-31 |
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| MM4A | Annulment or lapse of patent due to non-payment of fees |