HK1132262A1 - Amino-piperidine derivatives as cetp inhibitors - Google Patents
Amino-piperidine derivatives as cetp inhibitorsInfo
- Publication number
- HK1132262A1 HK1132262A1 HK09109684.3A HK09109684A HK1132262A1 HK 1132262 A1 HK1132262 A1 HK 1132262A1 HK 09109684 A HK09109684 A HK 09109684A HK 1132262 A1 HK1132262 A1 HK 1132262A1
- Authority
- HK
- Hong Kong
- Prior art keywords
- amino
- piperidine derivatives
- cetp inhibitors
- cetp
- inhibitors
- Prior art date
Links
Classifications
-
- 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
- C07D211/36—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 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- 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
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- 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
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06117541 | 2006-07-20 | ||
US88705807P | 2007-01-29 | 2007-01-29 | |
PCT/EP2007/006384 WO2008009435A1 (en) | 2006-07-20 | 2007-07-18 | Amino-piperidine derivatives as cetp inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HK1132262A1 true HK1132262A1 (en) | 2010-02-19 |
Family
ID=38695303
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HK09109684.3A HK1132262A1 (en) | 2006-07-20 | 2009-10-20 | Amino-piperidine derivatives as cetp inhibitors |
Country Status (23)
Country | Link |
---|---|
US (1) | US20090286790A1 (xx) |
EP (1) | EP2049517B1 (xx) |
JP (1) | JP5042311B2 (xx) |
KR (1) | KR101149274B1 (xx) |
AR (1) | AR061926A1 (xx) |
AU (1) | AU2007276433B2 (xx) |
CA (1) | CA2657258A1 (xx) |
CL (1) | CL2007002107A1 (xx) |
CO (1) | CO6150155A2 (xx) |
CR (1) | CR10478A (xx) |
EC (1) | ECSP099078A (xx) |
GT (1) | GT200900010A (xx) |
HK (1) | HK1132262A1 (xx) |
HR (1) | HRP20140183T1 (xx) |
IL (1) | IL195792A (xx) |
MA (1) | MA30638B1 (xx) |
MX (1) | MX2009000646A (xx) |
NO (1) | NO342106B1 (xx) |
PE (1) | PE20080404A1 (xx) |
PL (1) | PL2049517T3 (xx) |
TN (1) | TN2009000012A1 (xx) |
TW (1) | TWI387593B (xx) |
WO (1) | WO2008009435A1 (xx) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
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US20100144756A1 (en) * | 2007-07-13 | 2010-06-10 | Bolea Christelle | Novel heteroaromatic derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors |
EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
EP2207775B1 (en) * | 2007-11-05 | 2012-03-21 | Novartis AG | 4-benzylamino-1-carboxyacyl-piperidine derivatives as cetp inhibitors useful for the treatment of diseases such as hyperlipidemia or arteriosclerosis |
EP2229356B1 (en) * | 2007-12-03 | 2011-10-12 | Novartis AG | 1,2-disubstituted-4-benzylamino-pyrrolidine derivatives as cetp inhibitors useful for the treatment of diseases such as hyperli pidemia or arteriosclerosis |
JP2011506441A (ja) | 2007-12-12 | 2011-03-03 | アムジエン・インコーポレーテツド | グリシン輸送体−1阻害薬 |
WO2011157827A1 (de) | 2010-06-18 | 2011-12-22 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
WO2012005343A1 (ja) | 2010-07-09 | 2012-01-12 | 第一三共株式会社 | 置換ピリジン化合物 |
US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
US8673974B2 (en) | 2010-11-16 | 2014-03-18 | Novartis Ag | Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors |
AU2012282109B2 (en) * | 2011-07-08 | 2016-06-23 | Novartis Ag | Method of treating atherosclerosis in high triglyceride subjects |
CA2860601C (en) | 2012-01-06 | 2016-07-05 | Daiichi Sankyo Company, Limited | Acid addition salt of substituted pyridine compound |
UY35144A (es) | 2012-11-20 | 2014-06-30 | Novartis Ag | Miméticos lineales sintéticos de apelina para el tratamiento de insuficiencia cardiaca |
JP6295277B2 (ja) | 2013-02-14 | 2018-03-14 | ノバルティス アーゲー | Nep(中性エンドペプチダーゼ)阻害剤としての置換ビスフェニルブタン酸ホスホン酸誘導体 |
JP2014172851A (ja) * | 2013-03-07 | 2014-09-22 | Chiba Univ | ピラゾール誘導体の製造方法およびイソオキサゾール誘導体の製造方法 |
KR20160031551A (ko) | 2013-07-25 | 2016-03-22 | 노파르티스 아게 | 심부전의 치료를 위한 시클릭 폴리펩티드 |
AU2014293387B2 (en) | 2013-07-25 | 2017-04-20 | Novartis Ag | Bioconjugates of synthetic apelin polypeptides |
JP6402907B2 (ja) * | 2014-09-24 | 2018-10-10 | Jnc株式会社 | ピペリジン誘導体、液晶組成物および液晶表示素子 |
EA201791668A1 (ru) | 2015-01-23 | 2017-11-30 | Новартис Аг | Синтетические конъюгаты апелина с жирной кислотой с улучшенным периодом полураспада |
UY38072A (es) | 2018-02-07 | 2019-10-01 | Novartis Ag | Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos |
US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
WO2020223469A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | N-(1-(methylsulfonyl)piperidin-4-yl)-4,5-di hydro-1h-imidazo[4,5-h]quinazolin-8-amine derivatives and related compounds as cyclin-dependent kinase 2 (cdk2) inhibitors for treating cancer |
AR119765A1 (es) | 2019-08-14 | 2022-01-12 | Incyte Corp | Compuestos de imidazolil pirimidinilamina como inhibidores de cdk2 |
CN110508018B (zh) * | 2019-09-03 | 2022-02-25 | 中国石油大学(华东) | 生产聚甲氧基二甲醚的装置及方法 |
MX2022004390A (es) | 2019-10-11 | 2022-08-08 | Incyte Corp | Aminas biciclicas como inhibidores de la cinasa dependiente de ciclina 2 (cdk2). |
US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
Family Cites Families (14)
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PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
US4617307A (en) | 1984-06-20 | 1986-10-14 | Ciba-Geigy Corporation | Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors |
US4889861A (en) | 1982-12-21 | 1989-12-26 | Ciba-Geigy Corp. | Substituted imidazo[1,5-a]pyridine derivatives and other substituted bicyclic derivatives and their use as aromatase inhibitors |
RU2086544C1 (ru) | 1991-06-13 | 1997-08-10 | Хоффманн-Ля Рош АГ | Бензолсульфонамидные производные пиримидина или их соли, фармацевтическая композиция для лечения заболеваний, связанных с активностью эндотелина |
MY110227A (en) * | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
US5508272A (en) | 1993-06-15 | 1996-04-16 | Bristol-Myers Squibb Company | Compounds containing a fused bicycle ring and processes therefor |
MY119161A (en) | 1994-04-18 | 2005-04-30 | Novartis Ag | Delta-amino-gamma-hydroxy-omega-aryl-alkanoic acid amides with enzyme especially renin inhibiting activities |
TW313568B (xx) | 1994-12-20 | 1997-08-21 | Hoffmann La Roche | |
US6140342A (en) * | 1998-09-17 | 2000-10-31 | Pfizer Inc. | Oxy substituted 4-carboxyamino-2-methyl-1,2,3,4-tetrahydroquinolines |
JP3955180B2 (ja) | 1998-09-25 | 2007-08-08 | ファルマシア・コーポレーション | コレステリルエステル伝達タンパク質活性を阻害するのに有用な(R)−キラルなハロゲン化された1−置換アミノ−(n+1)−アルカノール |
EP2277551B1 (en) | 2002-09-06 | 2013-05-08 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for delivering the therapeutic agents covalently bound thereto |
CA2554455A1 (en) | 2004-01-30 | 2005-08-11 | Japan Tobacco Inc. | Anorectic |
MY150958A (en) * | 2005-06-16 | 2014-03-31 | Astrazeneca Ab | Compounds for the treatment of multi-drug resistant bacterial infections |
EP2229356B1 (en) * | 2007-12-03 | 2011-10-12 | Novartis AG | 1,2-disubstituted-4-benzylamino-pyrrolidine derivatives as cetp inhibitors useful for the treatment of diseases such as hyperli pidemia or arteriosclerosis |
-
2007
- 2007-07-18 MX MX2009000646A patent/MX2009000646A/es active IP Right Grant
- 2007-07-18 CA CA002657258A patent/CA2657258A1/en not_active Abandoned
- 2007-07-18 AU AU2007276433A patent/AU2007276433B2/en not_active Ceased
- 2007-07-18 EP EP07786158.1A patent/EP2049517B1/en active Active
- 2007-07-18 WO PCT/EP2007/006384 patent/WO2008009435A1/en active Application Filing
- 2007-07-18 US US12/374,463 patent/US20090286790A1/en not_active Abandoned
- 2007-07-18 PL PL07786158T patent/PL2049517T3/pl unknown
- 2007-07-18 AR ARP070103209A patent/AR061926A1/es unknown
- 2007-07-18 KR KR1020097001089A patent/KR101149274B1/ko not_active IP Right Cessation
- 2007-07-18 JP JP2009519868A patent/JP5042311B2/ja not_active Expired - Fee Related
- 2007-07-19 TW TW096126359A patent/TWI387593B/zh not_active IP Right Cessation
- 2007-07-19 PE PE2007000936A patent/PE20080404A1/es not_active Application Discontinuation
- 2007-07-19 CL CL200702107A patent/CL2007002107A1/es unknown
-
2008
- 2008-12-02 CR CR10478A patent/CR10478A/es unknown
- 2008-12-08 IL IL195792A patent/IL195792A/en active IP Right Grant
-
2009
- 2009-01-16 TN TN2009000012A patent/TN2009000012A1/fr unknown
- 2009-01-16 GT GT200900010A patent/GT200900010A/es unknown
- 2009-01-19 EC EC2009009078A patent/ECSP099078A/es unknown
- 2009-01-20 CO CO09004534A patent/CO6150155A2/es unknown
- 2009-02-11 MA MA31630A patent/MA30638B1/fr unknown
- 2009-02-17 NO NO20090756A patent/NO342106B1/no not_active IP Right Cessation
- 2009-10-20 HK HK09109684.3A patent/HK1132262A1/xx not_active IP Right Cessation
-
2014
- 2014-02-27 HR HRP20140183TT patent/HRP20140183T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
MX2009000646A (es) | 2009-01-29 |
NO342106B1 (no) | 2018-03-26 |
TW200813022A (en) | 2008-03-16 |
PE20080404A1 (es) | 2008-06-27 |
AU2007276433A1 (en) | 2008-01-24 |
ECSP099078A (es) | 2009-02-27 |
CA2657258A1 (en) | 2008-01-24 |
HRP20140183T1 (hr) | 2014-04-11 |
EP2049517B1 (en) | 2013-11-27 |
TN2009000012A1 (en) | 2010-08-19 |
JP2009543827A (ja) | 2009-12-10 |
JP5042311B2 (ja) | 2012-10-03 |
WO2008009435A1 (en) | 2008-01-24 |
IL195792A0 (en) | 2009-09-01 |
CL2007002107A1 (es) | 2008-06-06 |
AU2007276433B2 (en) | 2011-06-16 |
PL2049517T3 (pl) | 2014-06-30 |
MA30638B1 (fr) | 2009-08-03 |
NO20090756L (no) | 2009-04-14 |
EP2049517A1 (en) | 2009-04-22 |
US20090286790A1 (en) | 2009-11-19 |
CR10478A (es) | 2009-02-02 |
CO6150155A2 (es) | 2010-04-20 |
AR061926A1 (es) | 2008-10-01 |
GT200900010A (es) | 2009-06-24 |
TWI387593B (zh) | 2013-03-01 |
IL195792A (en) | 2013-07-31 |
KR101149274B1 (ko) | 2012-05-29 |
KR20090031579A (ko) | 2009-03-26 |
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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: 20190723 |