ATE247666T1 - Wasserlöslische prodrugs von 2,6- diisopropylphenol-analoga - Google Patents
Wasserlöslische prodrugs von 2,6- diisopropylphenol-analogaInfo
- Publication number
- ATE247666T1 ATE247666T1 AT99920385T AT99920385T ATE247666T1 AT E247666 T1 ATE247666 T1 AT E247666T1 AT 99920385 T AT99920385 T AT 99920385T AT 99920385 T AT99920385 T AT 99920385T AT E247666 T1 ATE247666 T1 AT E247666T1
- Authority
- AT
- Austria
- Prior art keywords
- propofol
- diisopropylphenol
- analogs
- water soluble
- soluble prodrugs
- Prior art date
Links
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical class CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 title abstract 7
- 229940002612 prodrug Drugs 0.000 title abstract 2
- 239000000651 prodrug Substances 0.000 title abstract 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title abstract 2
- 229960004134 propofol Drugs 0.000 abstract 4
- 150000002148 esters Chemical class 0.000 abstract 1
- 230000004770 neurodegeneration Effects 0.000 abstract 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
-
- 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
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P35/00—Antineoplastic 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/24—Halogenated derivatives
- C07C39/26—Halogenated derivatives monocyclic monohydroxylic containing halogen bound to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/24—Halogenated derivatives
- C07C39/26—Halogenated derivatives monocyclic monohydroxylic containing halogen bound to ring carbon atoms
- C07C39/27—Halogenated derivatives monocyclic monohydroxylic containing halogen bound to ring carbon atoms all halogen atoms being bound to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/017—Esters of hydroxy compounds having the esterified hydroxy group bound to a carbon atom of a six-membered aromatic ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Otolaryngology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/075,356 US6254853B1 (en) | 1998-05-08 | 1998-05-08 | Water soluble pro-drugs of propofol |
PCT/US1999/010013 WO1999058555A2 (en) | 1998-05-08 | 1999-05-07 | Water-soluble pro-drugs of 2,6-diisopropylphenol analogues |
Publications (1)
Publication Number | Publication Date |
---|---|
ATE247666T1 true ATE247666T1 (de) | 2003-09-15 |
Family
ID=22125164
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AT99920385T ATE247666T1 (de) | 1998-05-08 | 1999-05-07 | Wasserlöslische prodrugs von 2,6- diisopropylphenol-analoga |
Country Status (9)
Country | Link |
---|---|
US (1) | US6254853B1 (de) |
EP (1) | EP1075489B1 (de) |
JP (1) | JP2002514656A (de) |
AT (1) | ATE247666T1 (de) |
AU (1) | AU765569B2 (de) |
CA (1) | CA2331371A1 (de) |
DE (1) | DE69910560T2 (de) |
ES (1) | ES2204126T3 (de) |
WO (1) | WO1999058555A2 (de) |
Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6150423A (en) * | 1998-10-15 | 2000-11-21 | Phoenix Scientific, Inc. | Propofol-based anesthetic and method of making same |
US6362234B1 (en) * | 2000-08-15 | 2002-03-26 | Vyrex Corporation | Water-soluble prodrugs of propofol for treatment of migrane |
WO2003026632A2 (en) | 2001-09-26 | 2003-04-03 | Theravance, Inc. | Substituted phenol compounds useful for anesthesia and sedation |
GB0124071D0 (en) * | 2001-10-08 | 2001-11-28 | Kbig Ltd | Improvement in the administration of high boiling point aneasthetics |
CA2470500C (en) * | 2001-12-28 | 2012-05-15 | Guilford Pharmaceuticals, Inc. | Aqueous based pharmaceutical formulations of water-soluble prodrugs of propofol |
ITMI20020148A1 (it) * | 2002-01-29 | 2003-07-29 | Nicox Sa | Nuovi corticosteroidi |
US7312250B2 (en) | 2002-03-12 | 2007-12-25 | University Of Iowa Research Foundation | Fluorine-substituted alkyl phenol compounds and their uses |
PL373850A1 (en) * | 2002-04-08 | 2005-09-19 | Guilford Pharmaceuticals, Inc. | Pharmaceutical compositions containing water-soluble prodrugs of propofol and methods of administering same |
AU2002950713A0 (en) | 2002-08-09 | 2002-09-12 | Vital Health Sciences Pty Ltd | Carrier |
DE20215415U1 (de) * | 2002-10-08 | 2004-02-26 | Biotechnologie Gesellschaft Mittelhessen Mbh | Wasserlösliche Medikamentenvorstufen von Propofol |
ZA200504940B (en) * | 2003-01-28 | 2006-09-27 | Xenoport Inc | Amino acid derived prodrugs of propofol, compositions and uses thereof |
JP2006518384A (ja) * | 2003-01-31 | 2006-08-10 | チルドレンズ・ホスピタル・ロス・アンジエルス | 改善されたバイオアベイラビリティを有するフェンレチニドの経口組成物、およびその使用方法 |
US7468394B1 (en) * | 2003-03-11 | 2008-12-23 | Amphastar Pharmaceuticals, Inc. | Sterile pharmaceutical composition and process for a solution of propofol emulsion having microbial growth retardation |
AU2003901815A0 (en) * | 2003-04-15 | 2003-05-01 | Vital Health Sciences Pty Ltd | Phosphate derivatives |
US8546453B2 (en) | 2003-08-14 | 2013-10-01 | Rensheng Zhang | Propofol compositions and methods for reducing pain associated with propofol injection |
US7230003B2 (en) * | 2003-09-09 | 2007-06-12 | Xenoport, Inc. | Aromatic prodrugs of propofol, compositions and uses thereof |
WO2005033279A2 (en) * | 2003-09-29 | 2005-04-14 | University Of Virginia Patent Foundation | Discovery of novel soluble crystalline anesthetics |
AU2004286814A1 (en) * | 2003-10-24 | 2005-05-19 | Auspex Pharmaceuticals, Inc. | pH sensitive prodrugs of 2,6-diisopropylphenol |
WO2006017351A1 (en) * | 2004-07-12 | 2006-02-16 | Xenoport, Inc. | Prodrugs of propofol, compositions and uses thereof |
DE602005010270D1 (de) * | 2004-07-12 | 2008-11-20 | Xenoport Inc | Von aminosäuren abgeleitete prodrugs von propofolzusammensetzungen und anwendungen davon |
JP2008525501A (ja) * | 2004-12-23 | 2008-07-17 | ゼノポート,インコーポレイティド | セリンアミノ酸誘導のプロポフォールのプロドラッグ、その使用及び結晶体 |
CA2598159A1 (en) * | 2005-02-18 | 2006-08-24 | Abraxis Bioscience, Inc. | Compositions, methods of use and preparation of 2,6-diisopropyl phenol and analogs for ischemic injury |
WO2006133506A1 (en) | 2005-06-17 | 2006-12-21 | Vital Health Sciences Pty Ltd | A carrier comprising one or more di and/or mono-(electron transfer agent) phosphate derivatives or complexes thereof |
WO2007022437A2 (en) * | 2005-08-18 | 2007-02-22 | Auspex Pharmaceuticals, Inc. | Therapeutic agents for the treatment of cancer and metabolic disorders |
US7589239B2 (en) * | 2005-09-02 | 2009-09-15 | Auspex Pharmaceuticals | Therapeutic agents for the treatment of cancer, metabolic diseases and skin disorders |
WO2007128866A2 (en) * | 2006-05-09 | 2007-11-15 | Novobion Oy | Novel chemical compositions |
WO2007143038A1 (en) * | 2006-05-30 | 2007-12-13 | Trustees Of Columbia University In The City Of New York | Method of mediating airway smooth muscle construction due to airway irritation |
US20080161400A1 (en) * | 2006-10-26 | 2008-07-03 | Xenoport, Inc. | Use of forms of propofol for treating diseases associated with oxidative stress |
AU2007313639A1 (en) * | 2006-10-31 | 2008-05-08 | Mgp Biotechnologies, Inc. | Butyrylcholinesterase inhibitors and their use in the treatment of neurodegenerative diseases |
US9757399B2 (en) | 2006-10-31 | 2017-09-12 | Jal Therapeutics, Inc. | Butyrylcholinesterase inhibitors |
NZ580752A (en) | 2007-05-09 | 2012-03-30 | Pharmacofore Inc | Stereoisomers propofol therapeutic compounds |
CA2685813A1 (en) | 2007-05-09 | 2008-11-20 | Pharmacofore, Inc. | Therapeutic compounds |
US20090005444A1 (en) * | 2007-06-21 | 2009-01-01 | Xenoport, Inc. | Use of propofol prodrugs for treating alcohol withdrawal, central pain, anxiety or pruritus |
US20090076141A1 (en) * | 2007-09-14 | 2009-03-19 | Xenoport, Inc. | Use of Propofol Prodrugs for Treating Neuropathic Pain |
US20090098209A1 (en) * | 2007-10-15 | 2009-04-16 | University Of Kansas | Pharmaceutical compositions containing water-soluble derivatives of propofol and methods of administering same via pulmonary administration |
GB0905834D0 (en) | 2009-04-03 | 2009-05-20 | Seps Pharma Nv | Phosphonyl-containing phenolic derivatives useful as medicaments |
CN101575349B (zh) * | 2009-06-11 | 2011-07-20 | 中国科学院广州化学研究所 | 一种丙泊酚磷酸酯二钠盐的制备方法 |
JP2011016777A (ja) * | 2009-07-10 | 2011-01-27 | Nipro Corp | 新規システイン誘導体 |
US10071030B2 (en) | 2010-02-05 | 2018-09-11 | Phosphagenics Limited | Carrier comprising non-neutralised tocopheryl phosphate |
MX2012011355A (es) | 2010-03-30 | 2012-11-30 | Phosphagenics Ltd | Parche de suministro transdermico. |
WO2012122586A1 (en) | 2011-03-15 | 2012-09-20 | Phosphagenics Limited | New composition |
US9023813B2 (en) * | 2011-04-13 | 2015-05-05 | NuTek Pharma Ltd. | Synthesis and use of glycoside derivatives of propofol |
CN102382005B (zh) * | 2011-09-08 | 2015-01-21 | 四川大学 | 含氨基羧酸酰胺结构的丙泊酚酯类衍生物、制备方法及其用途 |
GB201116271D0 (en) | 2011-09-21 | 2011-11-02 | Univ Cardiff | Dispersion anaesthetic device |
CN103880754A (zh) * | 2012-12-21 | 2014-06-25 | 西藏海思科药业集团股份有限公司 | 一种丙泊酚碱性氨基酸酯盐 |
WO2014180305A1 (zh) * | 2013-05-09 | 2014-11-13 | 四川海思科制药有限公司 | 苯酚衍生物及其制备方法和在医药上的应用 |
US9643917B2 (en) | 2014-02-17 | 2017-05-09 | Jiangsu Nhwaluokang Pharmceutical Research And Development Co., Ltd | Water-soluble propofol derivatives and uses thereof |
PT3189834T (pt) * | 2014-09-04 | 2024-03-15 | Sichuan Haisco Pharmaceutical Co Ltd | Utilização de agente de reforço do recetor gabaa na preparação de medicamento sedativo e anestésico |
JP6882321B2 (ja) | 2015-12-09 | 2021-06-02 | フォスファージニクス リミテッド | 医薬製剤 |
US11331271B2 (en) | 2016-05-27 | 2022-05-17 | The Johns Hopkins University | Buccal, sublingual and intranasal delivery of fospropofol |
CN107556167A (zh) * | 2016-06-30 | 2018-01-09 | 陕西合成药业股份有限公司 | 一种麻醉类化合物及其制备方法和用途 |
NZ754168A (en) | 2016-12-21 | 2024-08-30 | Avecho Biotechnology Ltd | Process for phosphorylating a complex alcohol |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4839464A (de) * | 1971-09-25 | 1973-06-09 | ||
US4170614A (en) * | 1977-09-06 | 1979-10-09 | Ppg Industries, Inc. | Process for preparing halogenated diaryl hydrogen phosphates |
DE3342109A1 (de) * | 1983-11-18 | 1985-05-30 | Toyo Jozo K.K., Tagata, Shizuoka | Enzymatische pruefmethode |
US5262439A (en) * | 1992-04-30 | 1993-11-16 | The Regents Of The University Of California | Soluble analogs of probucol |
US5607691A (en) * | 1992-06-12 | 1997-03-04 | Affymax Technologies N.V. | Compositions and methods for enhanced drug delivery |
US5308874A (en) | 1992-06-26 | 1994-05-03 | Vyrex Corporation | Airborne protectants against oxidative tissue damage |
US5478857A (en) | 1993-12-23 | 1995-12-26 | Eli Lilly And Company | Use of PLA2 inhibitors as treatment for alzheimer's disease |
GB9405593D0 (en) | 1994-03-22 | 1994-05-11 | Zeneca Ltd | Pharmaceutical compositions |
US5561122A (en) * | 1994-12-22 | 1996-10-01 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Combretastatin A-4 prodrug |
US5529989A (en) * | 1995-01-09 | 1996-06-25 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Pancratistatin prodrug |
US5496537A (en) * | 1995-03-23 | 1996-03-05 | Henry; Richard A. | Propofol hydrofluorocarbon propellant formulations |
IT1281876B1 (it) * | 1995-05-10 | 1998-03-03 | Fidia Advanced Biopolymers Srl | Acido ialuronico e suoi derivati esterei per la preparazione di matrici per il rilascio controllato di farmaci. |
US5637625A (en) * | 1996-03-19 | 1997-06-10 | Research Triangle Pharmaceuticals Ltd. | Propofol microdroplet formulations |
-
1998
- 1998-05-08 US US09/075,356 patent/US6254853B1/en not_active Expired - Lifetime
-
1999
- 1999-05-07 JP JP2000548357A patent/JP2002514656A/ja active Pending
- 1999-05-07 DE DE69910560T patent/DE69910560T2/de not_active Expired - Lifetime
- 1999-05-07 WO PCT/US1999/010013 patent/WO1999058555A2/en active IP Right Grant
- 1999-05-07 ES ES99920385T patent/ES2204126T3/es not_active Expired - Lifetime
- 1999-05-07 AU AU37894/99A patent/AU765569B2/en not_active Ceased
- 1999-05-07 EP EP99920385A patent/EP1075489B1/de not_active Expired - Lifetime
- 1999-05-07 CA CA002331371A patent/CA2331371A1/en not_active Abandoned
- 1999-05-07 AT AT99920385T patent/ATE247666T1/de not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
WO1999058555A3 (en) | 2000-03-02 |
DE69910560D1 (de) | 2003-09-25 |
ES2204126T3 (es) | 2004-04-16 |
EP1075489A2 (de) | 2001-02-14 |
WO1999058555A2 (en) | 1999-11-18 |
DE69910560T2 (de) | 2004-06-09 |
JP2002514656A (ja) | 2002-05-21 |
AU3789499A (en) | 1999-11-29 |
AU765569B2 (en) | 2003-09-25 |
CA2331371A1 (en) | 1999-11-18 |
US6254853B1 (en) | 2001-07-03 |
EP1075489B1 (de) | 2003-08-20 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
RER | Ceased as to paragraph 5 lit. 3 law introducing patent treaties |