IL98933A - History of N-biphenylmethyl-benzimidazole their preparation and pharmaceutical preparations containing them - Google Patents
History of N-biphenylmethyl-benzimidazole their preparation and pharmaceutical preparations containing themInfo
- Publication number
- IL98933A IL98933A IL9893391A IL9893391A IL98933A IL 98933 A IL98933 A IL 98933A IL 9893391 A IL9893391 A IL 9893391A IL 9893391 A IL9893391 A IL 9893391A IL 98933 A IL98933 A IL 98933A
- Authority
- IL
- Israel
- Prior art keywords
- group
- methyl
- butyl
- benzimidazol
- biphenyl
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- 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
- 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
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Toys (AREA)
- Instructional Devices (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4023369A DE4023369A1 (de) | 1990-07-23 | 1990-07-23 | Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
DE4031287A DE4031287A1 (de) | 1990-07-23 | 1990-10-04 | Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
DE4105324A DE4105324A1 (de) | 1990-07-23 | 1991-02-20 | Benzimidazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (2)
Publication Number | Publication Date |
---|---|
IL98933A0 IL98933A0 (en) | 1992-07-15 |
IL98933A true IL98933A (en) | 1995-12-31 |
Family
ID=27201487
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL9893391A IL98933A (en) | 1990-07-23 | 1991-07-23 | History of N-biphenylmethyl-benzimidazole their preparation and pharmaceutical preparations containing them |
Country Status (18)
Country | Link |
---|---|
EP (1) | EP0468470B1 (fr) |
JP (1) | JP2539113B2 (fr) |
AT (1) | ATE151766T1 (fr) |
AU (1) | AU640505B2 (fr) |
CA (1) | CA2047496C (fr) |
CS (1) | CS230491A3 (fr) |
DE (1) | DE59108658D1 (fr) |
DK (1) | DK0468470T3 (fr) |
ES (1) | ES2100907T3 (fr) |
FI (1) | FI105811B (fr) |
GR (1) | GR3024027T3 (fr) |
HU (1) | HUT58298A (fr) |
IE (1) | IE912563A1 (fr) |
IL (1) | IL98933A (fr) |
NO (1) | NO178927C (fr) |
NZ (1) | NZ239089A (fr) |
PT (1) | PT98414B (fr) |
RU (1) | RU1836357C (fr) |
Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8904174D0 (en) * | 1989-02-23 | 1989-04-05 | British Bio Technology | Compounds |
NZ232785A (en) * | 1989-03-15 | 1991-03-26 | Janssen Pharmaceutica Nv | 5-(1,2 benzisoxazol-, benzimidazol and benzisothiazol-3- yl)-1h-benzimadazol-2-yl carbamic acid ester derivatives preparatory processes, intermediates and anthelmintic compositions |
IE70593B1 (en) * | 1989-09-29 | 1996-12-11 | Eisai Co Ltd | Biphenylmethane derivative the use of it and pharmacological compositions containing same |
DE4224752A1 (de) * | 1992-04-11 | 1994-02-03 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5591762A (en) * | 1991-02-06 | 1997-01-07 | Dr. Karl Thomae Gmbh | Benzimidazoles useful as angiotensin-11 antagonists |
US5602127A (en) * | 1991-02-06 | 1997-02-11 | Karl Thomae Gmbh | (Alkanesultam-1-yl)-benzimidazol-1-yl)-1yl)-methyl-biphenyls useful as angiotensin-II antagonists |
SI9210098B (sl) * | 1991-02-06 | 2000-06-30 | Dr. Karl Thomae | Benzimidazoli, zdravila, ki te spojine vsebujejo, in postopek za njihovo pripravo |
DE4224133A1 (de) * | 1992-07-22 | 1994-01-27 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5594003A (en) * | 1991-02-06 | 1997-01-14 | Dr. Karl Thomae Gmbh | Tetrahydroimidazo[1,2-a]pyridin-2-yl-(benzimidazol-1-yl)-methyl-biphenyls useful as angiotensin-II antagonists |
DE4225756A1 (de) * | 1992-01-22 | 1994-03-10 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5798364A (en) * | 1992-03-26 | 1998-08-25 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Imidazopyridines |
EP0531874A1 (fr) * | 1991-09-10 | 1993-03-17 | Tanabe Seiyaku Co., Ltd. | Dérivés d'imidazopyridine et procédé de préparation |
EP0543263A3 (en) * | 1991-11-16 | 1993-08-25 | Dr. Karl Thomae Gmbh | Benziimidazoles, pharmaceuticals containing them and process for their preparation |
DE4219534A1 (de) * | 1992-02-19 | 1993-12-16 | Thomae Gmbh Dr K | Substituierte Biphenylylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
DE4207904A1 (de) * | 1992-03-12 | 1993-09-16 | Thomae Gmbh Dr K | Substituierte benzimidazolylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
US5612360A (en) * | 1992-06-03 | 1997-03-18 | Eli Lilly And Company | Angiotensin II antagonists |
DE4237656A1 (de) * | 1992-06-13 | 1993-12-16 | Merck Patent Gmbh | Benzimidazolderivate |
GB9218449D0 (en) | 1992-08-29 | 1992-10-14 | Boots Co Plc | Therapeutic agents |
DE4304455A1 (de) * | 1993-02-15 | 1994-08-18 | Bayer Ag | Heterocyclisch substituierte Phenyl-cyclohexan-carbonsäurederivate |
DE4408497A1 (de) * | 1994-03-14 | 1995-09-21 | Thomae Gmbh Dr K | Benzimidazole, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5753672A (en) * | 1994-04-19 | 1998-05-19 | Tanabe Seiyaku Co., Ltd. | Imidazopyridine derivatives and process for preparing the same |
JPH10504808A (ja) * | 1994-06-29 | 1998-05-12 | スミスクライン・ビーチャム・コーポレイション | ビトロネクチン受容体拮抗物質 |
TR199801249T2 (xx) * | 1995-12-28 | 1998-10-21 | Fujisawa Pharmaceutical Co,Ltd. | Benzimidazol t�revleri. |
TW453999B (en) | 1997-06-27 | 2001-09-11 | Fujisawa Pharmaceutical Co | Benzimidazole derivatives |
SE9903028D0 (sv) | 1999-08-27 | 1999-08-27 | Astra Ab | New use |
DE10314702A1 (de) * | 2003-03-31 | 2004-10-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung von Telmisartan |
WO2005037821A2 (fr) * | 2003-10-16 | 2005-04-28 | Teva Pharmaceutical Industries Ltd. | Preparation de candesartan cilexetil |
EP1699765A1 (fr) * | 2004-10-15 | 2006-09-13 | Teva Pharmaceutical Industries Ltd | Methode de preparation de telmisartan |
CA3089569C (fr) | 2007-06-04 | 2023-12-05 | Synergy Pharmaceuticals Inc. | Agonistes de guanylase cyclase utiles pour le traitement de troubles gastro-intestinaux, d'inflammation, de cancer et d'autres troubles |
US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
EP2321341B1 (fr) | 2008-07-16 | 2017-02-22 | Synergy Pharmaceuticals Inc. | Agonistes de guanylate cyclase utiles pour le traitement de troubles gastro-intestinaux, inflammatoires, cancéreux et autres |
AU2010253336A1 (en) * | 2009-05-29 | 2011-12-08 | Sumitomo Chemical Company, Limited | Agent for treatment or prevention of diseases associated with activity of neurotrophic factors |
US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
EP2970384A1 (fr) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonistes de la guanylate cyclase et leurs utilisations |
JP2016514670A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト |
RS65632B1 (sr) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Ltd | Ultra-prečišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i upotrebe |
ES2806135T3 (es) | 2013-06-21 | 2021-02-16 | Zenith Epigenetics Ltd | Nuevos inhibidores de bromodominios bicíclicos |
JP6599852B2 (ja) | 2013-06-21 | 2019-10-30 | ゼニス・エピジェネティクス・リミテッド | ブロモドメイン阻害剤としての新規の置換された二環式化合物 |
CN105593224B (zh) | 2013-07-31 | 2021-05-25 | 恒元生物医药科技(苏州)有限公司 | 作为溴结构域抑制剂的新型喹唑啉酮类化合物 |
US10035777B2 (en) * | 2014-08-05 | 2018-07-31 | Bristol-Myers Squibb Company | Heterocyclic kinase inhibitors |
CA2966298A1 (fr) | 2014-12-01 | 2016-06-09 | Zenith Epigenetics Ltd. | Pyridinones substituees utilisees comme inhibiteurs de bromodomaines |
JP2017537946A (ja) | 2014-12-11 | 2017-12-21 | ゼニス・エピジェネティクス・リミテッドZenith Epigenetics Ltd. | ブロモドメイン阻害剤としての置換複素環 |
CA2966450A1 (fr) | 2014-12-17 | 2016-06-23 | Olesya KHARENKO | Inhibiteurs de bromodomaines |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4820843A (en) * | 1987-05-22 | 1989-04-11 | E. I. Du Pont De Nemours And Company | Tetrazole intermediates to antihypertensive compounds |
US4880804A (en) * | 1988-01-07 | 1989-11-14 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking benzimidazoles |
EP0400835A1 (fr) * | 1989-05-15 | 1990-12-05 | Merck & Co. Inc. | Benzimidazoles substitués comme antagoniste d'angiotensine II |
SG50669A1 (en) * | 1989-06-30 | 1998-07-20 | Du Pont | Fused-ring aryl subtituted imidazoles |
IE70593B1 (en) * | 1989-09-29 | 1996-12-11 | Eisai Co Ltd | Biphenylmethane derivative the use of it and pharmacological compositions containing same |
IL95975A (en) * | 1989-10-24 | 1997-06-10 | Takeda Chemical Industries Ltd | N-benzyl- 2-alkylbenzimidazole derivatives, their production and pharmaceutical compositions containing them |
IL96019A0 (en) * | 1989-10-31 | 1991-07-18 | Fujisawa Pharmaceutical Co | Imidazole derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same |
-
1991
- 1991-07-04 RU SU915001010A patent/RU1836357C/ru active
- 1991-07-22 ES ES91112404T patent/ES2100907T3/es not_active Expired - Lifetime
- 1991-07-22 EP EP91112404A patent/EP0468470B1/fr not_active Expired - Lifetime
- 1991-07-22 DE DE59108658T patent/DE59108658D1/de not_active Expired - Lifetime
- 1991-07-22 NO NO912859A patent/NO178927C/no not_active IP Right Cessation
- 1991-07-22 AT AT91112404T patent/ATE151766T1/de not_active IP Right Cessation
- 1991-07-22 FI FI913503A patent/FI105811B/fi not_active IP Right Cessation
- 1991-07-22 JP JP3181033A patent/JP2539113B2/ja not_active Expired - Lifetime
- 1991-07-22 DK DK91112404.8T patent/DK0468470T3/da active
- 1991-07-22 HU HU912456A patent/HUT58298A/hu unknown
- 1991-07-22 IE IE256391A patent/IE912563A1/en not_active IP Right Cessation
- 1991-07-22 PT PT98414A patent/PT98414B/pt not_active IP Right Cessation
- 1991-07-22 CA CA002047496A patent/CA2047496C/fr not_active Expired - Lifetime
- 1991-07-23 NZ NZ23908991A patent/NZ239089A/en not_active IP Right Cessation
- 1991-07-23 CS CS912304A patent/CS230491A3/cs unknown
- 1991-07-23 IL IL9893391A patent/IL98933A/en not_active IP Right Cessation
- 1991-07-23 AU AU81227/91A patent/AU640505B2/en not_active Expired
-
1997
- 1997-07-09 GR GR970401682T patent/GR3024027T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
NO178927C (no) | 1996-07-03 |
FI913503A (fi) | 1992-01-24 |
GR3024027T3 (en) | 1997-10-31 |
NO912859D0 (no) | 1991-07-22 |
FI105811B (fi) | 2000-10-13 |
CA2047496C (fr) | 2001-10-23 |
ATE151766T1 (de) | 1997-05-15 |
AU8122791A (en) | 1992-01-30 |
NO912859L (no) | 1992-01-24 |
NO178927B (no) | 1996-03-25 |
JP2539113B2 (ja) | 1996-10-02 |
NZ239089A (en) | 1994-07-26 |
HUT58298A (en) | 1992-02-28 |
PT98414A (pt) | 1992-05-29 |
IL98933A0 (en) | 1992-07-15 |
DK0468470T3 (da) | 1997-09-22 |
CS230491A3 (en) | 1992-02-19 |
HU912456D0 (en) | 1991-12-30 |
DE59108658D1 (de) | 1997-05-22 |
RU1836357C (ru) | 1993-08-23 |
ES2100907T3 (es) | 1997-07-01 |
IE912563A1 (en) | 1992-01-29 |
CA2047496A1 (fr) | 1992-01-24 |
JPH04253966A (ja) | 1992-09-09 |
EP0468470B1 (fr) | 1997-04-16 |
FI913503A0 (fi) | 1991-07-22 |
AU640505B2 (en) | 1993-08-26 |
PT98414B (pt) | 1999-01-29 |
EP0468470A1 (fr) | 1992-01-29 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
FF | Patent granted | ||
KB | Patent renewed | ||
KB | Patent renewed | ||
KB | Patent renewed | ||
KB | Patent renewed | ||
EXP | Patent expired |