PL360248A1 - Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereof - Google Patents
Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereofInfo
- Publication number
- PL360248A1 PL360248A1 PL36024801A PL36024801A PL360248A1 PL 360248 A1 PL360248 A1 PL 360248A1 PL 36024801 A PL36024801 A PL 36024801A PL 36024801 A PL36024801 A PL 36024801A PL 360248 A1 PL360248 A1 PL 360248A1
- Authority
- PL
- Poland
- Prior art keywords
- compounds
- production
- methods
- medicaments containing
- bicyclic heterocycles
- Prior art date
Links
Classifications
-
- 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
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- 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
- 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
-
- 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
- A61P27/16—Otologicals
-
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- A61P37/08—Antiallergic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10042058A DE10042058A1 (en) | 2000-08-26 | 2000-08-26 | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| PCT/EP2001/009532 WO2002018351A1 (en) | 2000-08-26 | 2001-08-18 | Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL360248A1 true PL360248A1 (en) | 2004-09-06 |
Family
ID=7653945
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL36024801A PL360248A1 (en) | 2000-08-26 | 2001-08-18 | Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereof |
Country Status (31)
| Country | Link |
|---|---|
| EP (1) | EP1315705A1 (en) |
| JP (1) | JP4834282B2 (en) |
| KR (1) | KR100862873B1 (en) |
| CN (1) | CN100404517C (en) |
| AR (1) | AR033562A1 (en) |
| AU (2) | AU2001287694B2 (en) |
| BG (1) | BG107559A (en) |
| BR (1) | BR0113519A (en) |
| CA (1) | CA2417897C (en) |
| CZ (1) | CZ302567B6 (en) |
| DE (1) | DE10042058A1 (en) |
| EA (1) | EA005679B1 (en) |
| EC (1) | ECSP034464A (en) |
| EE (1) | EE05269B1 (en) |
| HK (1) | HK1057557A1 (en) |
| HR (1) | HRP20030138A2 (en) |
| HU (1) | HUP0300819A3 (en) |
| IL (2) | IL154602A0 (en) |
| ME (1) | MEP58708A (en) |
| MX (1) | MXPA03001483A (en) |
| MY (1) | MY126132A (en) |
| NO (1) | NO324866B1 (en) |
| NZ (1) | NZ524668A (en) |
| PL (1) | PL360248A1 (en) |
| RS (1) | RS52279B (en) |
| SK (1) | SK287747B6 (en) |
| TW (1) | TWI294422B (en) |
| UA (1) | UA73004C2 (en) |
| UY (1) | UY26903A1 (en) |
| WO (1) | WO2002018351A1 (en) |
| ZA (1) | ZA200300991B (en) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0201900A3 (en) | 1999-06-21 | 2003-02-28 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, pharmaceutical compositions containing them, their use and methods for the production thereof |
| DE10042059A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| TW200813014A (en) | 2002-03-28 | 2008-03-16 | Astrazeneca Ab | Quinazoline derivatives |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| CN1642552B (en) * | 2002-03-30 | 2010-05-12 | 贝林格尔英格海姆法玛两合公司 | 4-(N-phenylamino)-quinazolines / quinolines as tyrosine kinase inhibitors |
| DE10214412A1 (en) * | 2002-03-30 | 2003-10-09 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and process for their preparation |
| CA2491191C (en) | 2002-07-15 | 2014-02-04 | Exelixis, Inc. | Receptor-type kinase modulators and methods of use |
| DE10326186A1 (en) | 2003-06-06 | 2004-12-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| DE10334226A1 (en) * | 2003-07-28 | 2005-02-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of tyrosine kinase inhibitors for the treatment of inflammatory processes |
| GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
| EP1667992B1 (en) | 2003-09-19 | 2007-01-24 | Astrazeneca AB | Quinazoline derivatives |
| ES2925655T3 (en) | 2003-09-26 | 2022-10-19 | Exelixis Inc | c-Met modulators and methods of use |
| DE10345875A1 (en) * | 2003-09-30 | 2005-04-21 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, pharmaceutical compositions containing them, their use and methods of preparation |
| US7456189B2 (en) | 2003-09-30 | 2008-11-25 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
| DE10350717A1 (en) * | 2003-10-30 | 2005-06-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of tyrosine kinase inhibitors for the treatment of inflammatory processes |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| PE20060777A1 (en) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | INDOLINONE DERIVATIVES FOR THE TREATMENT OR PREVENTION OF FIBROTIC DISEASES |
| MX2007010399A (en) | 2005-02-26 | 2007-09-25 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors. |
| KR100673775B1 (en) * | 2005-04-08 | 2007-01-24 | 엘지전자 주식회사 | Home bar door of refrigerator |
| WO2007023073A2 (en) * | 2005-08-22 | 2007-03-01 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles medicaments comprising said compounds use and method for production thereof |
| CA2833706C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| EP1996561A1 (en) * | 2006-03-09 | 2008-12-03 | Boehringer Ingelheim International GmbH | Bicyclic heterocycles, medicaments containing these compounds, their use and process for preparing them |
| AU2007299080B2 (en) | 2006-09-18 | 2013-04-18 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
| EP1921070A1 (en) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclic heterocycles, medicaments comprising them, their use and process for their preparation |
| JP5377332B2 (en) | 2007-02-06 | 2013-12-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Bicyclic heterocycles, drugs containing these compounds, their use and their preparation |
| EA019709B1 (en) | 2008-02-07 | 2014-05-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Spirocyclic heterocycles and use thereof as medicaments |
| CA2723989C (en) | 2008-05-13 | 2017-04-25 | Astrazeneca Ab | Fumarate salt of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(n-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline |
| CA2733153C (en) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
| TWI447108B (en) | 2009-01-16 | 2014-08-01 | Exelixis Inc | Malate salts of n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof |
| DK2451445T3 (en) | 2009-07-06 | 2019-06-24 | Boehringer Ingelheim Int | PROCEDURE FOR DRYING BIBW2992, IT'S SALTS AND SOLID PHARMACEUTICAL FORMULATIONS INCLUDING THIS ACTIVE INGREDIENT |
| UA108618C2 (en) | 2009-08-07 | 2015-05-25 | APPLICATION OF C-MET-MODULATORS IN COMBINATION WITH THEMOSOLOMID AND / OR RADIATION THERAPY FOR CANCER TREATMENT | |
| KR101317809B1 (en) | 2011-06-07 | 2013-10-16 | 한미약품 주식회사 | Pharmaceutical composition comprising amide derivative inhibiting the growth of cancer cell and non-metalic salt lubricant |
| KR20140096571A (en) | 2013-01-28 | 2014-08-06 | 한미약품 주식회사 | Method for preparing 1-(4-(4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)piperidin-1-yl)prop-2-en-1-one |
| PE20152000A1 (en) | 2013-03-06 | 2016-01-22 | Astrazeneca Ab | QUINAZOLINE INHIBITORS OF MUTATED FORMS ACTIVATING THE RECEPTOR OF THE EPIDERMAL GROWTH FACTOR |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
| US10005764B2 (en) * | 2014-04-04 | 2018-06-26 | H. Lundbeck A/S | Halogenated quinazolin-THF-amines as PDE1 inhibitors |
| US20170176028A1 (en) | 2015-12-18 | 2017-06-22 | Lg Electronics Inc. | Air conditioner |
| CA3044432A1 (en) | 2016-11-17 | 2018-05-24 | Board Of Regents, The University Of Texas System | Compounds with anti-tumor activity against cancer cells bearing egfr or her2 exon 20 mutations |
| CN112321814B (en) * | 2020-12-30 | 2021-03-23 | 广州初曲科技有限公司 | Preparation and application of gefitinib idebenone conjugate |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| HUP9901155A3 (en) * | 1996-02-13 | 2003-04-28 | Astrazeneca Ab | Quinazoline derivatives as vegf inhibitors |
| GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| KR100489174B1 (en) * | 1996-03-05 | 2005-09-30 | 제네카-파마 소시에떼아노님 | 4-anilinoquinazoline derivatives |
| CA2249446C (en) * | 1996-04-12 | 2008-06-17 | Warner-Lambert Company | Irreversible inhibitors of tyrosine kinases |
| GB9718972D0 (en) * | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| DE19911509A1 (en) * | 1999-03-15 | 2000-09-21 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
-
2000
- 2000-08-26 DE DE10042058A patent/DE10042058A1/en not_active Ceased
-
2001
- 2001-08-18 UA UA2003032533A patent/UA73004C2/en unknown
- 2001-08-18 AU AU2001287694A patent/AU2001287694B2/en not_active Ceased
- 2001-08-18 RS YU14003A patent/RS52279B/en unknown
- 2001-08-18 SK SK231-2003A patent/SK287747B6/en not_active IP Right Cessation
- 2001-08-18 EP EP01967285A patent/EP1315705A1/en not_active Ceased
- 2001-08-18 CZ CZ20030870A patent/CZ302567B6/en not_active IP Right Cessation
- 2001-08-18 KR KR1020037002744A patent/KR100862873B1/en not_active IP Right Cessation
- 2001-08-18 NZ NZ524668A patent/NZ524668A/en not_active IP Right Cessation
- 2001-08-18 HU HU0300819A patent/HUP0300819A3/en unknown
- 2001-08-18 IL IL15460201A patent/IL154602A0/en unknown
- 2001-08-18 EA EA200300219A patent/EA005679B1/en not_active IP Right Cessation
- 2001-08-18 JP JP2002523469A patent/JP4834282B2/en not_active Expired - Fee Related
- 2001-08-18 BR BR0113519-8A patent/BR0113519A/en active Pending
- 2001-08-18 ME MEP-587/08A patent/MEP58708A/en unknown
- 2001-08-18 EE EEP200300077A patent/EE05269B1/en not_active IP Right Cessation
- 2001-08-18 CA CA002417897A patent/CA2417897C/en not_active Expired - Fee Related
- 2001-08-18 PL PL36024801A patent/PL360248A1/en not_active Application Discontinuation
- 2001-08-18 CN CNB01814635XA patent/CN100404517C/en not_active Expired - Fee Related
- 2001-08-18 MX MXPA03001483A patent/MXPA03001483A/en active IP Right Grant
- 2001-08-18 AU AU8769401A patent/AU8769401A/en active Pending
- 2001-08-18 WO PCT/EP2001/009532 patent/WO2002018351A1/en active Application Filing
- 2001-08-23 UY UY26903A patent/UY26903A1/en not_active Application Discontinuation
- 2001-08-24 TW TW090120905A patent/TWI294422B/en not_active IP Right Cessation
- 2001-08-24 MY MYPI20013985A patent/MY126132A/en unknown
- 2001-08-24 AR ARP010104041A patent/AR033562A1/en not_active Suspension/Interruption
-
2003
- 2003-02-03 EC EC2003004464A patent/ECSP034464A/en unknown
- 2003-02-05 ZA ZA200300991A patent/ZA200300991B/en unknown
- 2003-02-14 BG BG107559A patent/BG107559A/en active Pending
- 2003-02-24 IL IL154602A patent/IL154602A/en not_active IP Right Cessation
- 2003-02-24 HR HR20030138A patent/HRP20030138A2/en not_active Application Discontinuation
- 2003-02-25 NO NO20030870A patent/NO324866B1/en not_active IP Right Cessation
-
2004
- 2004-01-21 HK HK04100462A patent/HK1057557A1/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| REFS | Decisions on refusal to grant patents (taken after the publication of the particulars of the applications) |