EE04938B1 - Orto-asendatud antraniilhappeamiidid ja nende kasutamine ravimitena - Google Patents
Orto-asendatud antraniilhappeamiidid ja nende kasutamine ravimitenaInfo
- Publication number
- EE04938B1 EE04938B1 EEP200200625A EEP200200625A EE04938B1 EE 04938 B1 EE04938 B1 EE 04938B1 EE P200200625 A EEP200200625 A EE P200200625A EE P200200625 A EEP200200625 A EE P200200625A EE 04938 B1 EE04938 B1 EE 04938B1
- Authority
- EE
- Estonia
- Prior art keywords
- acid amides
- anthranilic acid
- orthosubstituted
- medicaments
- ortho
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P3/08—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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- 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
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Surgery (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10023486A DE10023486C1 (de) | 2000-05-09 | 2000-05-09 | Ortho substituierte Anthranilsäureamide und deren Verwendung als Arzneimittel |
PCT/EP2001/005214 WO2001085719A1 (de) | 2000-05-09 | 2001-05-08 | Ortho substituierte anthranilsäureamide und deren verwendung als arzneimittel |
Publications (2)
Publication Number | Publication Date |
---|---|
EE200200625A EE200200625A (et) | 2004-04-15 |
EE04938B1 true EE04938B1 (et) | 2007-12-17 |
Family
ID=7641923
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EEP200200625A EE04938B1 (et) | 2000-05-09 | 2001-05-08 | Orto-asendatud antraniilhappeamiidid ja nende kasutamine ravimitena |
Country Status (31)
Country | Link |
---|---|
US (2) | US7081468B2 (et) |
EP (1) | EP1280799B1 (et) |
JP (1) | JP2003532725A (et) |
KR (1) | KR20020094024A (et) |
CN (1) | CN1237062C (et) |
AT (1) | ATE258174T1 (et) |
AU (2) | AU7400101A (et) |
BG (1) | BG107261A (et) |
BR (1) | BR0110621A (et) |
CA (1) | CA2407852A1 (et) |
CZ (1) | CZ20023677A3 (et) |
DE (2) | DE10023486C1 (et) |
DK (1) | DK1280799T3 (et) |
EE (1) | EE04938B1 (et) |
ES (1) | ES2214424T3 (et) |
HK (1) | HK1056728A1 (et) |
HR (1) | HRP20020977B1 (et) |
HU (1) | HUP0301954A2 (et) |
IL (2) | IL152578A0 (et) |
MX (1) | MXPA02010915A (et) |
NO (1) | NO323541B1 (et) |
NZ (1) | NZ521700A (et) |
PL (1) | PL358204A1 (et) |
PT (1) | PT1280799E (et) |
RU (1) | RU2264399C2 (et) |
SK (1) | SK15882002A3 (et) |
TR (1) | TR200400912T4 (et) |
UA (1) | UA73187C2 (et) |
WO (1) | WO2001085719A1 (et) |
YU (1) | YU82702A (et) |
ZA (1) | ZA200209896B (et) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10023484A1 (de) * | 2000-05-09 | 2001-11-22 | Schering Ag | Anthranylamide und deren Verwendung als Arzneimittel |
DE10023486C1 (de) * | 2000-05-09 | 2002-03-14 | Schering Ag | Ortho substituierte Anthranilsäureamide und deren Verwendung als Arzneimittel |
US7102009B2 (en) | 2001-01-12 | 2006-09-05 | Amgen Inc. | Substituted amine derivatives and methods of use |
US6878714B2 (en) * | 2001-01-12 | 2005-04-12 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
US20030134836A1 (en) * | 2001-01-12 | 2003-07-17 | Amgen Inc. | Substituted arylamine derivatives and methods of use |
US6995162B2 (en) | 2001-01-12 | 2006-02-07 | Amgen Inc. | Substituted alkylamine derivatives and methods of use |
US7105682B2 (en) | 2001-01-12 | 2006-09-12 | Amgen Inc. | Substituted amine derivatives and methods of use |
TW200306819A (en) * | 2002-01-25 | 2003-12-01 | Vertex Pharma | Indazole compounds useful as protein kinase inhibitors |
US7307088B2 (en) | 2002-07-09 | 2007-12-11 | Amgen Inc. | Substituted anthranilic amide derivatives and methods of use |
BR0313122A (pt) * | 2002-07-31 | 2005-07-05 | Schering Ag | Antranilamidopiridinas inibidoras de vegfr-2 e vegfr-3 |
US7615565B2 (en) | 2002-07-31 | 2009-11-10 | Bayer Schering Pharma Aktiengesellschaft | VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridines |
EP1628661A2 (en) * | 2003-06-05 | 2006-03-01 | Vertex Pharmaceuticals Incorporated | Modulators of vr1 receptor |
US7202260B2 (en) | 2003-06-13 | 2007-04-10 | Schering Ag | VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridones |
DE10327719A1 (de) * | 2003-06-13 | 2005-01-20 | Schering Ag | VEGFR-2 und VEGFR-3 Inhibitorische Anthranylamidpyridone |
AU2004276341B2 (en) | 2003-09-23 | 2011-04-14 | Vertex Pharmaceuticals Incorporated | Pyrazolopyrrole derivatives as protein kinase inhibitors |
DE102004009238A1 (de) * | 2004-02-26 | 2005-09-08 | Merck Patent Gmbh | Arylamid-Derivate |
US7427390B2 (en) * | 2004-03-10 | 2008-09-23 | Schering Ag | Radiohalogenated benzamide derivatives and their use in tumor diagnosis and tumor therapy |
DE102004011720B4 (de) * | 2004-03-10 | 2008-04-03 | Bayer Schering Pharma Aktiengesellschaft | Radiohalogenierte Benzamidderivate und deren Verwendung in der Tumordiagnostik und Tumortherapie |
US7906533B2 (en) | 2004-11-03 | 2011-03-15 | Bayer Schering Pharma Ag | Nicotinamide pyridinureas as vascular endothelial growth factor (VEGF) receptor kinase inhibitors |
EP1655295A1 (en) * | 2004-11-03 | 2006-05-10 | Schering Aktiengesellschaft | Anthranilamide pyridinureas as VEGF receptor kinase inhibitors |
EP1657241A1 (en) * | 2004-11-03 | 2006-05-17 | Schering Aktiengesellschaft | Novel anthranilamide pyridinureas as VEGF receptor kinase inhibitors |
US8247556B2 (en) | 2005-10-21 | 2012-08-21 | Amgen Inc. | Method for preparing 6-substituted-7-aza-indoles |
US8106190B2 (en) | 2005-11-30 | 2012-01-31 | Astellas Pharma Inc. | 2-aminobenzamide derivatives |
NZ722019A (en) | 2014-01-13 | 2022-07-01 | Aurigene Discovery Tech Ltd | Bicyclic heterocyclyl derivatives as irak4 inhibitors |
SG11201610009XA (en) * | 2014-06-20 | 2017-01-27 | Aurigene Discovery Tech Ltd | Substituted indazole compounds as irak4 inhibitors |
WO2018178947A2 (en) | 2017-03-31 | 2018-10-04 | Aurigene Discovery Technologies Limited | Compounds and compositions for treating hematological disorders |
AU2018359248B2 (en) | 2017-10-31 | 2023-06-01 | Curis, Inc. | Compounds and compositions for treating hematological disorders |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3409668A (en) * | 1964-11-07 | 1968-11-05 | Palazzo Giuseppe | Substituted anthranilamides and process for the preparation thereof |
FR2689508B1 (fr) * | 1992-04-01 | 1994-06-17 | Fournier Ind & Sante | Derives de l'imidazole, leur procede de preparation et leur application en therapeutique. |
UA71587C2 (uk) * | 1998-11-10 | 2004-12-15 | Шерінг Акцієнгезелльшафт | Аміди антранілової кислоти та їхнє застосування як лікарських засобів |
GB9824579D0 (en) * | 1998-11-10 | 1999-01-06 | Novartis Ag | Organic compounds |
DE10023484A1 (de) * | 2000-05-09 | 2001-11-22 | Schering Ag | Anthranylamide und deren Verwendung als Arzneimittel |
DE10023492A1 (de) * | 2000-05-09 | 2001-11-22 | Schering Ag | Aza- und Polyazanthranylamide und deren Verwendung als Arzneimittel |
DE10023486C1 (de) * | 2000-05-09 | 2002-03-14 | Schering Ag | Ortho substituierte Anthranilsäureamide und deren Verwendung als Arzneimittel |
DE50213703D1 (de) * | 2001-05-08 | 2009-09-03 | Bayer Schering Pharma Ag | Selektive anthranylamidpyridinamide als vegfr-2 und vegfr-3 inhibitoren |
US20040039019A1 (en) * | 2002-06-19 | 2004-02-26 | Schering Ag | Selected anthranilaminde pyridinamides and their use as pharmaceutical agents |
US7517894B2 (en) * | 2002-07-31 | 2009-04-14 | Bayer Schering Pharma Ag | VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridines |
US7615565B2 (en) * | 2002-07-31 | 2009-11-10 | Bayer Schering Pharma Aktiengesellschaft | VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridines |
US7202260B2 (en) * | 2003-06-13 | 2007-04-10 | Schering Ag | VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridones |
US7659242B2 (en) * | 2004-07-19 | 2010-02-09 | Thia Medica As | Composition comprising protein material and compounds comprising non-oxidizable fatty acid entities |
EP1655295A1 (en) * | 2004-11-03 | 2006-05-10 | Schering Aktiengesellschaft | Anthranilamide pyridinureas as VEGF receptor kinase inhibitors |
US7906533B2 (en) * | 2004-11-03 | 2011-03-15 | Bayer Schering Pharma Ag | Nicotinamide pyridinureas as vascular endothelial growth factor (VEGF) receptor kinase inhibitors |
EP1657241A1 (en) * | 2004-11-03 | 2006-05-17 | Schering Aktiengesellschaft | Novel anthranilamide pyridinureas as VEGF receptor kinase inhibitors |
US20060266770A1 (en) * | 2005-05-26 | 2006-11-30 | Fitzgerald Robert M | Portable dispensers comprising a mobile dispenser and mobile storage cartridge |
-
2000
- 2000-05-09 DE DE10023486A patent/DE10023486C1/de not_active Expired - Fee Related
-
2001
- 2001-05-08 EP EP01940416A patent/EP1280799B1/de not_active Expired - Lifetime
- 2001-05-08 YU YU82702A patent/YU82702A/sh unknown
- 2001-05-08 HU HU0301954A patent/HUP0301954A2/hu unknown
- 2001-05-08 NZ NZ521700A patent/NZ521700A/en unknown
- 2001-05-08 TR TR2004/00912T patent/TR200400912T4/xx unknown
- 2001-05-08 WO PCT/EP2001/005214 patent/WO2001085719A1/de active IP Right Grant
- 2001-05-08 CA CA002407852A patent/CA2407852A1/en not_active Abandoned
- 2001-05-08 SK SK1588-2002A patent/SK15882002A3/sk unknown
- 2001-05-08 EE EEP200200625A patent/EE04938B1/et not_active IP Right Cessation
- 2001-05-08 RU RU2002131887/04A patent/RU2264399C2/ru not_active IP Right Cessation
- 2001-05-08 AT AT01940416T patent/ATE258174T1/de not_active IP Right Cessation
- 2001-05-08 MX MXPA02010915A patent/MXPA02010915A/es active IP Right Grant
- 2001-05-08 IL IL15257801A patent/IL152578A0/xx unknown
- 2001-05-08 DE DE50101364T patent/DE50101364D1/de not_active Expired - Fee Related
- 2001-05-08 BR BR0110621-0A patent/BR0110621A/pt not_active IP Right Cessation
- 2001-05-08 CN CNB018091369A patent/CN1237062C/zh not_active Expired - Fee Related
- 2001-05-08 KR KR1020027014966A patent/KR20020094024A/ko active IP Right Grant
- 2001-05-08 JP JP2001582320A patent/JP2003532725A/ja active Pending
- 2001-05-08 DK DK01940416T patent/DK1280799T3/da active
- 2001-05-08 AU AU7400101A patent/AU7400101A/xx active Pending
- 2001-05-08 PL PL01358204A patent/PL358204A1/xx unknown
- 2001-05-08 PT PT01940416T patent/PT1280799E/pt unknown
- 2001-05-08 CZ CZ20023677A patent/CZ20023677A3/cs unknown
- 2001-05-08 ES ES01940416T patent/ES2214424T3/es not_active Expired - Lifetime
- 2001-05-08 US US10/275,480 patent/US7081468B2/en not_active Expired - Fee Related
- 2001-05-08 AU AU2001274001A patent/AU2001274001B2/en not_active Ceased
- 2001-08-05 UA UA2002129865A patent/UA73187C2/uk unknown
-
2002
- 2002-10-31 IL IL152578A patent/IL152578A/en not_active IP Right Cessation
- 2002-11-08 BG BG107261A patent/BG107261A/bg unknown
- 2002-11-08 NO NO20025358A patent/NO323541B1/no unknown
- 2002-12-05 ZA ZA200209896A patent/ZA200209896B/en unknown
- 2002-12-09 HR HR20020977A patent/HRP20020977B1/xx not_active IP Right Cessation
-
2003
- 2003-12-13 HK HK03109101A patent/HK1056728A1/xx not_active IP Right Cessation
-
2005
- 2005-09-06 US US11/218,423 patent/US20060014747A1/en not_active Abandoned
Also Published As
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
KB4A | Valid patent at the end of a year |
Effective date: 20081231 |
|
MM4A | Lapsed by not paying the annual fees |
Effective date: 20090508 |