EE04639B1 - Raku adhesiooni pärssiv ühend ja seda sisaldav farmatseutiline kompositsioon - Google Patents
Raku adhesiooni pärssiv ühend ja seda sisaldav farmatseutiline kompositsioonInfo
- Publication number
- EE04639B1 EE04639B1 EEP200000698A EEP200000698A EE04639B1 EE 04639 B1 EE04639 B1 EE 04639B1 EE P200000698 A EEP200000698 A EE P200000698A EE P200000698 A EEP200000698 A EE P200000698A EE 04639 B1 EE04639 B1 EE 04639B1
- Authority
- EE
- Estonia
- Prior art keywords
- cell adhesion
- pharmaceutical composition
- inhibiting compound
- adhesion inhibiting
- cell
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- 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
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- 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
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8706498P | 1998-05-28 | 1998-05-28 | |
| PCT/US1999/011924 WO1999061421A1 (en) | 1998-05-28 | 1999-05-28 | A NOVEL VLA-4 INHIBITOR: oMePUPA-V |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EE200000698A EE200000698A (et) | 2002-06-17 |
| EE04639B1 true EE04639B1 (et) | 2006-06-15 |
Family
ID=22202907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EEP200000698A EE04639B1 (et) | 1998-05-28 | 1999-05-28 | Raku adhesiooni pärssiv ühend ja seda sisaldav farmatseutiline kompositsioon |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6495525B1 (cs) |
| EP (1) | EP1082302B1 (cs) |
| JP (1) | JP2002516309A (cs) |
| KR (1) | KR100636713B1 (cs) |
| CN (1) | CN1148350C (cs) |
| AT (1) | ATE256659T1 (cs) |
| AU (1) | AU764108B2 (cs) |
| BG (1) | BG65021B1 (cs) |
| CA (1) | CA2333656C (cs) |
| CZ (1) | CZ298413B6 (cs) |
| DE (1) | DE69913687T2 (cs) |
| DK (1) | DK1082302T3 (cs) |
| EA (1) | EA002988B1 (cs) |
| EE (1) | EE04639B1 (cs) |
| ES (1) | ES2211096T3 (cs) |
| HU (1) | HUP0102255A3 (cs) |
| IL (1) | IL139967A (cs) |
| IS (1) | IS5737A (cs) |
| MX (1) | MXPA00011774A (cs) |
| NO (1) | NO317990B1 (cs) |
| NZ (1) | NZ509199A (cs) |
| PL (1) | PL198189B1 (cs) |
| PT (1) | PT1082302E (cs) |
| SI (1) | SI1082302T1 (cs) |
| SK (1) | SK285280B6 (cs) |
| TR (1) | TR200100190T2 (cs) |
| UA (1) | UA65623C2 (cs) |
| WO (1) | WO1999061421A1 (cs) |
| YU (1) | YU75500A (cs) |
| ZA (1) | ZA200007300B (cs) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6645939B1 (en) | 1997-11-24 | 2003-11-11 | Merck & Co., Inc. | Substituted β-alanine derivatives as cell adhesion inhibitors |
| CA2309341A1 (en) * | 1997-11-24 | 1999-06-03 | Merck & Co., Inc. | Substituted .beta.-alanine derivatives as cell adhesion inhibitors |
| TR200100734T2 (tr) * | 1998-09-14 | 2001-07-23 | Board Of Regents, The University Of Texas System | İntegrin antagonistlerini kullanarak multipl miyeloma ve miyeloma tarafından uyarılan kemik rezorpsiyonunun iyileştirilmesi |
| US7618630B2 (en) | 1998-09-14 | 2009-11-17 | Board Of Regents, The University Of Texas System | Methods of treating multiple myeloma and myeloma-induced bone resorption using integrin antagonists |
| US6525069B1 (en) * | 1998-12-18 | 2003-02-25 | Bristol-Myers Squibb Pharma Co. | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| ATE343383T1 (de) | 1999-08-13 | 2006-11-15 | Biogen Idec Inc | Hemmer der zelladhäsion |
| AP2002002565A0 (en) | 1999-12-28 | 2002-06-30 | Pfizer Prod Inc | Non-peptidyl inhibitors of VLA-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases. |
| EP1346982B1 (en) | 2000-12-28 | 2011-09-14 | Daiichi Pharmaceutical Co., Ltd. | Vla-4 inhibitors |
| ATE555106T1 (de) | 2003-07-24 | 2012-05-15 | Daiichi Sankyo Co Ltd | Cyclohexancarbonsäureverbindung |
| US7419666B1 (en) | 2004-02-23 | 2008-09-02 | Massachusetts Eye And Ear Infirmary | Treatment of ocular disorders |
| US7196112B2 (en) | 2004-07-16 | 2007-03-27 | Biogen Idec Ma Inc. | Cell adhesion inhibitors |
| GT200500321A (es) * | 2004-11-09 | 2006-09-04 | Compuestos y composiciones como inhibidores de proteina kinase. | |
| US7685367B2 (en) * | 2006-03-08 | 2010-03-23 | Microsoft Corporation | Multi-cache cooperation for response output caching |
| JP2009545620A (ja) * | 2006-08-02 | 2009-12-24 | ジェンザイム・コーポレーション | 併用療法 |
| EP2124996A4 (en) | 2007-02-20 | 2010-03-24 | Merrimack Pharmaceuticals Inc | METHOD FOR TREATING MULTIPLE SCLEROSIS BY ADMINISTERING AN ALPHA FETOPROTEIN COMBINED WITH AN INTEGRINANT AGONIST |
| ES2525065T3 (es) | 2008-04-11 | 2014-12-17 | Merrimack Pharmaceuticals, Inc. | Ligadores de seroalbúmina humana y sus conjugados |
| CN102282168A (zh) | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| DK3202789T3 (da) | 2010-04-16 | 2020-05-18 | Biogen Ma Inc | Anti-vla-4-antistoffer |
| US9345766B2 (en) | 2012-08-30 | 2016-05-24 | Merrimack Pharmaceuticals, Inc. | Combination therapies comprising anti-ERBB3 agents |
| WO2019236417A1 (en) | 2018-06-04 | 2019-12-12 | Biogen Ma Inc. | Anti-vla-4 antibodies having reduced effector function |
| ES3013256T3 (en) | 2018-10-30 | 2025-04-11 | Gilead Sciences Inc | Imidazo[1,2-a]pyridine derivatives as alpha4beta7 integrin inhibitors for the treatment of inflammatory diseases |
| AU2019373245C1 (en) | 2018-10-30 | 2022-10-27 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4β7 integrin |
| AU2019373242B2 (en) | 2018-10-30 | 2023-07-13 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4 beta 7 integrin |
| JP7192139B2 (ja) | 2018-10-30 | 2022-12-19 | ギリアード サイエンシーズ， インコーポレイテッド | α４β７インテグリン阻害剤としてのキノリン誘導体 |
| US11578069B2 (en) | 2019-08-14 | 2023-02-14 | Gilead Sciences, Inc. | Compounds for inhibition of α4 β7 integrin |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1149971B (it) | 1979-06-11 | 1986-12-10 | Syntex Inc | Derivati nonapeptide e decapeptide dell'ormone che rilascia l'ormone luteinizzante |
| US4725583A (en) | 1985-01-23 | 1988-02-16 | Abbott Laboratories | Functionalized peptidylaminoalcohols |
| US4826815A (en) | 1985-05-17 | 1989-05-02 | Abbott Laboratories | Renin inhibiting compounds |
| DK163689A (da) | 1988-04-08 | 1989-10-30 | Sandoz Ag | Peptidderivater |
| WO1991009837A1 (en) | 1989-12-22 | 1991-07-11 | Commonwealth Scientific And Industrial Research Organisation | Amino acids, peptides or derivatives thereof coupled to fats |
| CA2043741C (en) | 1990-06-07 | 2003-04-01 | Kiyofumi Ishikawa | Endothelin antagonistic peptide derivatives |
| US5192746A (en) | 1990-07-09 | 1993-03-09 | Tanabe Seiyaku Co., Ltd. | Cyclic cell adhesion modulation compounds |
| US5260277A (en) * | 1990-09-10 | 1993-11-09 | Tanabe Seiyaku Co., Ltd. | Guanidinyl and related cell adhesion modulation compounds |
| WO1992008464A1 (en) | 1990-11-15 | 1992-05-29 | Tanabe Seiyaku Co. Ltd. | Substituted urea and related cell adhesion modulation compounds |
| DE69226820T2 (de) | 1991-06-21 | 1999-05-12 | Merck & Co., Inc., Rahway, N.J. | Peptidylderivate als Inhibitoren von Interleukin-1B-konvertierenden Enzymen |
| WO1993008823A1 (en) | 1991-11-06 | 1993-05-13 | Tanabe Seiyaku Co., Ltd. | Guanidinyl and related cell adhesion modulation compounds |
| JPH07503944A (ja) | 1991-11-22 | 1995-04-27 | イエダ リサーチ アンド デベロツプメント カンパニー リミテツド | Ａｒｇ−ｇｌｙ−ａｓｐ配列の非ペプチド代替物およびそれらからなる医薬組成物 |
| WO1993012809A1 (en) | 1991-12-24 | 1993-07-08 | Fred Hutchinson Cancer Research Center | Competitive inhibition of high-avidity alpha4-beta1 receptor using tripeptide ldv |
| DE4212304A1 (de) | 1992-04-13 | 1993-10-14 | Cassella Ag | Asparaginsäurederivate, ihre Herstellung und Verwendung |
| IL102646A (en) | 1992-07-26 | 1996-05-14 | Yeda Res & Dev | Non-peptidic surrogates of the ldv sequence and pharmaceutical compositions comprising them |
| JPH08505628A (ja) | 1993-01-08 | 1996-06-18 | 田辺製薬株式会社 | ペプチド型細胞接着阻害薬 |
| US5314902A (en) | 1993-01-27 | 1994-05-24 | Monsanto Company | Urea derivatives useful as platelet aggregation inhibitors |
| DE4309867A1 (de) | 1993-03-26 | 1994-09-29 | Cassella Ag | Neue Harnstoffderivate, ihre Herstellung und Verwendung |
| WO1994023714A1 (en) | 1993-04-09 | 1994-10-27 | Toyama Chemical Co., Ltd. | Immunomodulator, cell adhesion inhibitor, and agent for treating and preventing autoimmune diseases |
| WO1995015973A1 (en) | 1993-12-06 | 1995-06-15 | Cytel Corporation | Cs-1 peptidomimetics, compositions and methods of using the same |
| US5770573A (en) | 1993-12-06 | 1998-06-23 | Cytel Corporation | CS-1 peptidomimetics, compositions and methods of using the same |
| US5434188A (en) | 1994-03-07 | 1995-07-18 | Warner-Lambert Company | 1-ether and 1-thioether-naphthalene-2-carboxamides as inhibitors of cell adhesion and as inhibitors of the activation of HIV |
| US6306840B1 (en) * | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
| US6248713B1 (en) | 1995-07-11 | 2001-06-19 | Biogen, Inc. | Cell adhesion inhibitors |
| NZ333904A (en) * | 1996-07-25 | 2000-06-23 | Biogen Inc | VLA-4 and IIb/IIIa cell adhesion inhibitors |
-
1999
- 1999-05-28 TR TR2001/00190T patent/TR200100190T2/xx unknown
- 1999-05-28 CN CNB998080020A patent/CN1148350C/zh not_active Expired - Fee Related
- 1999-05-28 JP JP2000550827A patent/JP2002516309A/ja active Pending
- 1999-05-28 WO PCT/US1999/011924 patent/WO1999061421A1/en active IP Right Grant
- 1999-05-28 CZ CZ20004425A patent/CZ298413B6/cs not_active IP Right Cessation
- 1999-05-28 AU AU42192/99A patent/AU764108B2/en not_active Ceased
- 1999-05-28 EP EP99926019A patent/EP1082302B1/en not_active Expired - Lifetime
- 1999-05-28 EA EA200001236A patent/EA002988B1/ru not_active IP Right Cessation
- 1999-05-28 EE EEP200000698A patent/EE04639B1/xx not_active IP Right Cessation
- 1999-05-28 AT AT99926019T patent/ATE256659T1/de not_active IP Right Cessation
- 1999-05-28 NZ NZ509199A patent/NZ509199A/en unknown
- 1999-05-28 IL IL13996799A patent/IL139967A/xx not_active IP Right Cessation
- 1999-05-28 HU HU0102255A patent/HUP0102255A3/hu unknown
- 1999-05-28 YU YU75500A patent/YU75500A/sh unknown
- 1999-05-28 CA CA002333656A patent/CA2333656C/en not_active Expired - Fee Related
- 1999-05-28 DK DK99926019T patent/DK1082302T3/da active
- 1999-05-28 UA UA2000127603A patent/UA65623C2/uk unknown
- 1999-05-28 PL PL344440A patent/PL198189B1/pl not_active IP Right Cessation
- 1999-05-28 SI SI9930526T patent/SI1082302T1/xx unknown
- 1999-05-28 ES ES99926019T patent/ES2211096T3/es not_active Expired - Lifetime
- 1999-05-28 PT PT99926019T patent/PT1082302E/pt unknown
- 1999-05-28 DE DE69913687T patent/DE69913687T2/de not_active Expired - Fee Related
- 1999-05-28 KR KR1020007013421A patent/KR100636713B1/ko not_active Expired - Fee Related
- 1999-05-28 MX MXPA00011774A patent/MXPA00011774A/es not_active IP Right Cessation
- 1999-05-28 SK SK1810-2000A patent/SK285280B6/sk not_active IP Right Cessation
-
2000
- 2000-11-28 IS IS5737A patent/IS5737A/is unknown
- 2000-11-28 NO NO20006023A patent/NO317990B1/no unknown
- 2000-11-28 US US09/724,107 patent/US6495525B1/en not_active Expired - Fee Related
- 2000-12-08 ZA ZA200007300A patent/ZA200007300B/en unknown
- 2000-12-18 BG BG105060A patent/BG65021B1/bg unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HC1A | Change of owner name | ||
| KB4A | Valid patent at the end of a year |
Effective date: 20061231 |
|
| KB4A | Valid patent at the end of a year |
Effective date: 20071231 |
|
| KB4A | Valid patent at the end of a year |
Effective date: 20081231 |
|
| MM4A | Lapsed by not paying the annual fees |
Effective date: 20090528 |