HK1074592A1 - 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases - Google Patents
17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseasesInfo
- Publication number
- HK1074592A1 HK1074592A1 HK05108331A HK05108331A HK1074592A1 HK 1074592 A1 HK1074592 A1 HK 1074592A1 HK 05108331 A HK05108331 A HK 05108331A HK 05108331 A HK05108331 A HK 05108331A HK 1074592 A1 HK1074592 A1 HK 1074592A1
- Authority
- HK
- Hong Kong
- Prior art keywords
- hydroxysteroid dehydrogenase
- inhibitors
- treatment
- beta
- compounds
- Prior art date
Links
Classifications
-
- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- A61P17/08—Antiseborrheics
-
- 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
- A61P17/10—Anti-acne agents
-
- 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
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/28—Antiandrogens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43410102P | 2002-12-17 | 2002-12-17 | |
PCT/US2003/039863 WO2004060488A1 (en) | 2002-12-17 | 2003-12-15 | 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
Publications (1)
Publication Number | Publication Date |
---|---|
HK1074592A1 true HK1074592A1 (en) | 2005-11-18 |
Family
ID=32713010
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HK05108331A HK1074592A1 (en) | 2002-12-17 | 2005-09-22 | 17 beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
Country Status (12)
Country | Link |
---|---|
US (3) | US7053091B2 (de) |
EP (1) | EP1572299B1 (de) |
JP (1) | JP4585320B2 (de) |
CN (1) | CN1744930A (de) |
AT (1) | ATE409065T1 (de) |
AU (1) | AU2003293555A1 (de) |
CA (1) | CA2509758A1 (de) |
DE (1) | DE60323765D1 (de) |
ES (1) | ES2312845T3 (de) |
HK (1) | HK1074592A1 (de) |
MX (1) | MXPA05006485A (de) |
WO (1) | WO2004060488A1 (de) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4585320B2 (ja) * | 2002-12-17 | 2010-11-24 | シェーリング コーポレイション | 男性ホルモン依存性疾患の処置のための17β−ヒドロキシステロイドデヒドロゲナーゼ3型インヒビター |
MXPA06011722A (es) * | 2004-04-13 | 2007-01-25 | Incyte Corp | Derivados de piperazinilpiperidina como antagonistas del receptor de quimiocina. |
US7598259B2 (en) * | 2004-06-15 | 2009-10-06 | Schering Corporation | mGluR1 antagonists as therapeutic agents |
JP4091095B2 (ja) * | 2004-08-06 | 2008-05-28 | シャープ株式会社 | 送信機、受信機、通信システム、通信方法、通信プログラム |
WO2006105109A2 (en) * | 2005-03-29 | 2006-10-05 | The Trustees Of The University Of Pennsylvania | Methods for generating new hair follicles, treating baldness, and hair removal |
GB0513702D0 (en) * | 2005-07-04 | 2005-08-10 | Sterix Ltd | Compound |
US20070197590A1 (en) * | 2006-01-31 | 2007-08-23 | Demong Duane E | Substituted dipiperidine ccr2 antagonists |
US20080051380A1 (en) | 2006-08-25 | 2008-02-28 | Auerbach Alan H | Methods and compositions for treating cancer |
US8080540B2 (en) | 2006-09-19 | 2011-12-20 | Abbott Products Gmbh | Therapeutically active triazoles and their use |
US8288367B2 (en) | 2006-11-30 | 2012-10-16 | Solvay Pharmaceuticals Gmbh | Substituted estratriene derivatives as 17BETA HSD inhibitors |
ES2422718T3 (es) * | 2009-04-02 | 2013-09-13 | Merck Patent Gmbh | Derivados de piperidina y piperazina como inhibidores de la autotaxina |
US20140079686A1 (en) | 2010-12-06 | 2014-03-20 | Shikha P. Barman | Methods For Treating Baldness And Promoting Hair Growth |
US10377791B2 (en) | 2013-06-25 | 2019-08-13 | Forendo Pharma Ltd. | Therapeutically active estratrienthiazole derivatives as inhibitors of 17 B-hydroxysteroid dehydrogenase, type 1 |
US9663549B2 (en) | 2013-06-25 | 2017-05-30 | Forendo Pharma Ltd. | Therapeutically active 17-nitrogen substituted estratreinthiazole derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase |
US9850272B2 (en) | 2013-06-25 | 2017-12-26 | Forendo Pharma Ltd. | Therapeutically active estratrienthiazole derivatives as inhibitors of 17.beta-hydroxy-steroid dehydrogenase, type 1 |
DE102014005129A1 (de) | 2014-04-08 | 2014-11-06 | Daimler Ag | Verfahren und Fahrerassistenzvorrichtung zur Unterstützung eines Fahrers beim Führen eines Fahrzeugs |
CN107207562B (zh) | 2014-12-23 | 2020-03-06 | 佛恩多制药有限公司 | 17β-HSD1抑制剂的前药 |
CN107207561B (zh) | 2014-12-23 | 2020-03-31 | 佛恩多制药有限公司 | 17β-HSD1–抑制剂的前药 |
CN105461705B (zh) * | 2015-11-30 | 2018-04-10 | 中国医科大学 | 二苯并氮杂卓二酮类抗肿瘤化合物及其制备方法 |
US20180028521A1 (en) | 2016-07-29 | 2018-02-01 | Janssen Pharmaceutica Nv | Methods of Treating Prostate Cancer |
UA126342C2 (uk) | 2017-06-08 | 2022-09-21 | Форендо Фарма Лтд | 15-бета-[3-пропанамідо]-заміщені естра-1,3,5(10)-трієн-17-он-сполуки і їх 17-оксими для використання в інгібуванні 17-бета-гідроксистероїддегідрогеназ |
SG11202105795XA (en) | 2018-12-05 | 2021-06-29 | Forendo Pharma Ltd | Estra-1,3,5(10)-triene compounds condensed in position 16(17) with a pyrazole ring as inhibitors of 17-hsd1 |
CN112321515A (zh) * | 2020-10-21 | 2021-02-05 | 上海馨远医药科技有限公司 | 一种手性1-叔丁基-3-甲基-6-甲基哌嗪-1,3-二甲酸酯的制备方法 |
CN112321538A (zh) * | 2020-10-28 | 2021-02-05 | 都创(上海)医药开发有限公司 | 一种合成单胺保护的哌嗪-(r/s)2-甲酸酯的方法 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU594309B2 (en) | 1984-08-02 | 1990-03-08 | Fernand Labrie | Pharmaceutical composition for combination therapy of hormonedependent cancers |
HU221589B (hu) | 1989-03-10 | 2002-11-28 | Endorecherche Inc. | Emlő- és méhrák kezelésére alkalmas kombinációs gyógyszerkészítmény és eljárás előállítására |
CA2062792C (en) | 1989-07-07 | 2006-03-21 | Fernard Labrie | Treatment of androgen-related diseases |
WO1991000731A1 (en) | 1989-07-07 | 1991-01-24 | Endorecherche Inc. | Combination therapy for prophylaxis and/or treatment of benign prostatic hyperplasia |
US6060503A (en) | 1991-12-02 | 2000-05-09 | Endorecherche, Inc. | Benzopyran-containing compounds and method for their use |
ATE197458T1 (de) | 1993-05-17 | 2000-11-11 | Endorech Inc | Verbesserte antiandrogene |
US6124115A (en) | 1995-09-22 | 2000-09-26 | Endorecherche Inc. | Production and use of isolated type 5 17β-hydroxysteroid dehydrogenase |
US6162804A (en) * | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
PL343862A1 (en) * | 1998-03-11 | 2001-09-10 | Endorech | Inhibitors of type 5 and type 3 17β−hydroxysteroid dehydrogenase and methods for their use |
US6673799B1 (en) * | 1998-09-22 | 2004-01-06 | Yamanouchi Pharmaceutical Co. Ltd. | Cyanophenyl derivative |
US6362188B1 (en) * | 1998-12-18 | 2002-03-26 | Schering Corporation | Farnesyl protein transferase inhibitors |
CO5160344A1 (es) * | 1998-12-18 | 2002-05-30 | Schering Corp | Inhibidores de transferasa de proteina farnesilo |
DK1423381T3 (da) | 2001-09-06 | 2007-05-07 | Schering Corp | 17beta-hydroxysteroid-dehydrogenase type 3-inhibitorer til behandling af androgenafhængige sygdomme |
AR036812A1 (es) | 2001-10-17 | 2004-10-06 | Schering Corp | Inhibidores de la 17beta-hidroxiesteroide deshidrogenasa tipo 3, composiciones farmaceuticas y el uso de dichos compuestos para la fabricacion de medicamentos para el tratamiento de enfermedades androgeno-dependientes |
CA2506290C (en) | 2002-11-18 | 2012-04-24 | Schering Corporation | 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases |
JP4585320B2 (ja) * | 2002-12-17 | 2010-11-24 | シェーリング コーポレイション | 男性ホルモン依存性疾患の処置のための17β−ヒドロキシステロイドデヒドロゲナーゼ3型インヒビター |
-
2003
- 2003-12-15 JP JP2004565490A patent/JP4585320B2/ja not_active Expired - Fee Related
- 2003-12-15 US US10/735,983 patent/US7053091B2/en not_active Expired - Fee Related
- 2003-12-15 AT AT03790505T patent/ATE409065T1/de not_active IP Right Cessation
- 2003-12-15 MX MXPA05006485A patent/MXPA05006485A/es active IP Right Grant
- 2003-12-15 ES ES03790505T patent/ES2312845T3/es not_active Expired - Lifetime
- 2003-12-15 CN CNA2003801094364A patent/CN1744930A/zh active Pending
- 2003-12-15 WO PCT/US2003/039863 patent/WO2004060488A1/en active Application Filing
- 2003-12-15 EP EP03790505A patent/EP1572299B1/de not_active Expired - Lifetime
- 2003-12-15 CA CA002509758A patent/CA2509758A1/en not_active Abandoned
- 2003-12-15 AU AU2003293555A patent/AU2003293555A1/en not_active Abandoned
- 2003-12-15 DE DE60323765T patent/DE60323765D1/de not_active Expired - Lifetime
-
2005
- 2005-09-22 HK HK05108331A patent/HK1074592A1/xx not_active IP Right Cessation
-
2006
- 2006-02-23 US US11/360,711 patent/US7271175B2/en not_active Expired - Fee Related
-
2007
- 2007-08-09 US US11/836,530 patent/US7485645B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US7271175B2 (en) | 2007-09-18 |
US20060142338A1 (en) | 2006-06-29 |
MXPA05006485A (es) | 2005-08-26 |
WO2004060488A1 (en) | 2004-07-22 |
US20040138226A1 (en) | 2004-07-15 |
ES2312845T3 (es) | 2009-03-01 |
US7053091B2 (en) | 2006-05-30 |
JP2006514054A (ja) | 2006-04-27 |
US20080004248A1 (en) | 2008-01-03 |
EP1572299B1 (de) | 2008-09-24 |
US7485645B2 (en) | 2009-02-03 |
JP4585320B2 (ja) | 2010-11-24 |
EP1572299A1 (de) | 2005-09-14 |
CA2509758A1 (en) | 2004-07-22 |
ATE409065T1 (de) | 2008-10-15 |
DE60323765D1 (de) | 2008-11-06 |
CN1744930A (zh) | 2006-03-08 |
AU2003293555A1 (en) | 2004-07-29 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PC | Patent ceased (i.e. patent has lapsed due to the failure to pay the renewal fee) |
Effective date: 20121215 |