ATE265436T1 - N-aryl substituierte tetrahydrochinoline ligande für retinoidrezeptoren mit agonist, antagonist oder inverser agonist wirkung - Google Patents
N-aryl substituierte tetrahydrochinoline ligande für retinoidrezeptoren mit agonist, antagonist oder inverser agonist wirkungInfo
- Publication number
- ATE265436T1 ATE265436T1 AT97913959T AT97913959T ATE265436T1 AT E265436 T1 ATE265436 T1 AT E265436T1 AT 97913959 T AT97913959 T AT 97913959T AT 97913959 T AT97913959 T AT 97913959T AT E265436 T1 ATE265436 T1 AT E265436T1
- Authority
- AT
- Austria
- Prior art keywords
- agonist
- antagonist
- tetrahydrocinoline
- ligands
- aryl substituted
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title abstract 2
- 239000000556 agonist Substances 0.000 title 1
- 229940125425 inverse agonist Drugs 0.000 title 1
- 239000003446 ligand Substances 0.000 title 1
- 102000027483 retinoid hormone receptors Human genes 0.000 title 1
- 108091008679 retinoid hormone receptors Proteins 0.000 title 1
- 150000004492 retinoid derivatives Chemical class 0.000 abstract 3
- 230000004071 biological effect Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- 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
- 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
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/744,210 US5739338A (en) | 1996-11-05 | 1996-11-05 | N-aryl substituted tetrahydroquinolines having retinoid agonist, retinoid antagonist or retinoid inverse agonist type biological activity |
| PCT/US1997/019915 WO1998019999A1 (en) | 1996-11-05 | 1997-10-29 | N-aryl substituted tetrahydroquinolines ligands for retinoid receptors having agonist, antagonist or inverse agonist type activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE265436T1 true ATE265436T1 (de) | 2004-05-15 |
Family
ID=24991892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT97913959T ATE265436T1 (de) | 1996-11-05 | 1997-10-29 | N-aryl substituierte tetrahydrochinoline ligande für retinoidrezeptoren mit agonist, antagonist oder inverser agonist wirkung |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5739338A (de) |
| EP (1) | EP0937045B1 (de) |
| JP (1) | JP2001504458A (de) |
| AT (1) | ATE265436T1 (de) |
| AU (1) | AU729997B2 (de) |
| CA (1) | CA2270893C (de) |
| DE (1) | DE69728893T2 (de) |
| ES (1) | ES2219760T3 (de) |
| WO (1) | WO1998019999A1 (de) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5958954A (en) | 1995-09-01 | 1999-09-28 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US6008204A (en) | 1995-09-01 | 1999-12-28 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US5952345A (en) | 1995-09-01 | 1999-09-14 | Allergan Sales, Inc. | Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities |
| US5763635A (en) | 1996-06-21 | 1998-06-09 | Allergan | Tetrahydronaphthalene derivatives substituted in the 8 position with alkyhidene groups having retinoid and/or retinoid antagonist-like biological activity |
| US6555690B2 (en) | 1996-06-21 | 2003-04-29 | Allergan, Inc. | Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity |
| US5773594A (en) | 1996-06-21 | 1998-06-30 | Allergan | Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity |
| US5728846A (en) | 1996-12-12 | 1998-03-17 | Allergan | Benzo 1,2-g!-chrom-3-ene and benzo 1,2-g!-thiochrom-3-ene derivatives |
| US6180640B1 (en) | 1998-06-25 | 2001-01-30 | Sepracor, Inc. | Di- and tetra-hydroquinoline-indole antimicrobial agents, uses and compositions related thereto |
| US6048873A (en) * | 1998-10-01 | 2000-04-11 | Allergan Sales, Inc. | Tetrahdroquinolin-2-one 6 or 7-yl, tetrahdroquinilin-2-thione 6 or 7-yl pentadienoic acid and related derivatives having retinoid-like biological activity |
| WO2000061182A2 (en) * | 1999-04-14 | 2000-10-19 | Allergan Sales, Inc. | Methods and compositions for the treatment and prevention of lung disease involving a selective rar-alpha agonist |
| WO2000061233A2 (en) * | 1999-04-14 | 2000-10-19 | Allergan Sales, Inc. | Methods and compositions for the treatment and prevention of lung disease involving a specific rar-gamma agonist |
| WO2000061232A2 (en) * | 1999-04-14 | 2000-10-19 | Allergan Sales, Inc. | Methods and compositions for the treatment and prevention of lung disease involving a specific rar-beta antagonist |
| WO2000066595A1 (en) | 1999-04-28 | 2000-11-09 | Institute Of Medicinal Molecular Design. Inc. | Heterocyclic carboxylic acid derivatives |
| US7268148B2 (en) * | 1999-05-20 | 2007-09-11 | Regents Of The University Of Michigan | Compositions and methods for use against acne-induced inflammation and dermal matrix-degrading enzymes |
| US20040235950A1 (en) * | 1999-05-20 | 2004-11-25 | Voorhees John J. | Compositions and methods for use against acne-induced inflammation and dermal matrix-degrading enzymes |
| AU6228000A (en) * | 1999-07-23 | 2001-02-13 | Allergan Sales, Inc. | The use of retinoid receptor antagonists in the treatment of prostate carcinoma |
| US6127382A (en) * | 1999-08-16 | 2000-10-03 | Allergan Sales, Inc. | Amines substituted with a tetrahydroquinolinyl group an aryl or heteroaryl group and an alkyl group, having retinoid-like biological activity |
| US6313168B1 (en) * | 1999-12-15 | 2001-11-06 | Allergan Sales, Inc. | Use of retinoid receptor antagonists in the treatment of cartilage and bone pathologies |
| US20030114482A1 (en) * | 1999-12-15 | 2003-06-19 | Maurizio Pacifici | Use of retinoid receptor antagonists or agonists in the treatment of cartilage and bone pathologies |
| US6291677B1 (en) | 2000-08-29 | 2001-09-18 | Allergan Sales, Inc. | Compounds having activity as inhibitors of cytochrome P450RAI |
| US6313107B1 (en) | 2000-08-29 | 2001-11-06 | Allergan Sales, Inc. | Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI |
| CA2420869A1 (en) * | 2000-08-29 | 2002-03-07 | Allergan, Inc. | Compounds having activity as inhibitors of cytochrome p450rai |
| ES2283649T3 (es) * | 2001-10-31 | 2007-11-01 | F. Hoffmann-La Roche Ag | Compuesto retinoides heterociclicos. |
| US6620963B1 (en) | 2002-09-19 | 2003-09-16 | Allergan, Inc. | TRICYCLO[6.2.202,7]DODECA-2(7),3,5-TRIEN-4-CARBONYLAMINO-PHENYL AND TRICYCLO[6.2.202,7]DODECA-2(7),3,5-TRIEN-4-CARBONYLAMINO-HETEROARYL AND RELATED COMPOUNDS HAVING RARα RECEPTOR SELECTIVE BIOLOGICAL ACTIVITY |
| US6683092B1 (en) | 2003-04-09 | 2004-01-27 | Allergan, Inc. | [3-(c5-14alkyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-3-oxo-propenyl]-phenyl and [3-(c5-14alkyl-2-oxo-1,2,3,4- tetrahydro-quinolin-6-yl)-3-oxo-propenyl]-heteroaryl derivatives having anti-tumor activity |
| US6734193B1 (en) | 2003-06-03 | 2004-05-11 | Allergan, Inc. | (1,2,3,4-tetrahydroquinolin-8-yl)-heptatrienoic acid derivatives having serum glucose reducing activity |
| EP1701934B1 (de) * | 2003-12-26 | 2009-02-25 | Allergan, Inc. | DISUBSTITUIERTE CHALCOGENOXIME MIT ANTAGONISTISCHER WIRKUNG AM RAR(Gamma)-RETINOIDREZEPTOR |
| US7476673B2 (en) * | 2003-12-30 | 2009-01-13 | Allergan, Inc. | Disubstituted chalcone oximes as selective agonists of RARγ retinoid receptors |
| LT1937244T (lt) | 2005-09-30 | 2018-11-12 | Io Therapeutics, Llc | Vėžio gydymas specifiniais rxr agonistais |
| CN101316821A (zh) * | 2005-09-30 | 2008-12-03 | 詹森药业有限公司 | 作为rxr激动剂用于治疗异常脂肪血症、高胆固醇血症和糖尿病的二氢-[1h]-喹啉-2-酮衍生物 |
| WO2007041077A2 (en) * | 2005-09-30 | 2007-04-12 | Janssen Pharmaceutica N.V. | Heterocyclic amide derivatives as rxr agonists for the treatment of dyslipidemia, hypercholesterolemia and diabetes |
| CN101472572B (zh) * | 2006-05-16 | 2012-10-10 | Io治疗有限责任公司 | Rar拮抗剂或反向激动剂在治疗化学疗法和/或放射疗法副作用中的用途 |
| US20090197878A1 (en) * | 2008-02-01 | 2009-08-06 | Wyeth | SUBSTITUTED BENZO[d][1,3]OXAZIN-2(4H)-ONES AND RELATED DERIVATIVES AND THEIR USES FOR MODULATING THE PROGESTERONE RECEPTOR |
| CN110151745A (zh) | 2011-12-13 | 2019-08-23 | Io治疗公司 | 使用rxr激动剂的自身免疫紊乱的治疗 |
| US10653650B2 (en) | 2011-12-13 | 2020-05-19 | Io Therapeutics, Inc. | Treatment of diseases by concurrently eliciting remyelination effects and immunomodulatory effects using selective RXR agonists |
| WO2013159095A1 (en) | 2012-04-20 | 2013-10-24 | Anderson Gaweco | Ror modulators and their uses |
| WO2013166013A1 (en) * | 2012-04-30 | 2013-11-07 | Anderson Gaweco | Ror modulators and their uses |
| EP2844260A4 (de) * | 2012-04-30 | 2016-06-29 | Anderson Gaweco | Ror-modulatoren und deren verwendungen |
| CN106660998B (zh) * | 2014-10-31 | 2019-10-25 | 豪夫迈·罗氏有限公司 | 吡唑基-3,4-二氢喹啉-2-酮醛固酮合酶抑制剂 |
| EP3212630B1 (de) * | 2014-10-31 | 2022-05-18 | F. Hoffmann-La Roche AG | Neue dihydrochinolinpyrazolylverbindungen |
| KR102149321B1 (ko) | 2015-10-31 | 2020-08-28 | 아이오 테라퓨틱스, 인크. | Rxr 아고니스트와 갑상선 호르몬의 조합을 사용한 신경계 질환의 치료 |
| WO2017091762A1 (en) | 2015-11-25 | 2017-06-01 | Io Therapeutics, Inc. | Use of cyp26-resistant rar alpha selective agonists in the treatment of cancer |
| KR102549273B1 (ko) | 2016-03-10 | 2023-06-28 | 아이오 테라퓨틱스, 인크. | Rxr 작용제 및 갑상선 호르몬의 조합을 사용한 자가면역 질환의 치료 |
| NZ745704A (en) | 2016-03-10 | 2019-04-26 | Io Therapeutics Inc | Treatment of muscular disorders with combinations of rxr agonists and thyroid hormones |
| CA3026563C (en) | 2016-06-10 | 2023-11-28 | Io Therapeutics, Inc. | Receptor selective retinoid and rexinoid compounds and immune modulators for cancer immunotherapy |
| CA3069672A1 (en) | 2017-07-13 | 2019-01-17 | Io Therapeutics, Inc. | Receptor subtype and function selective retinoid and rexinoid compounds in combination with immune modulators for cancer immunotherapy |
| CA3073953A1 (en) | 2017-08-31 | 2019-03-07 | Io Therapeutics, Inc. | Rar selective agonists in combination with immune modulators for cancer immunotherapy |
| EP3684348A4 (de) | 2017-09-20 | 2021-08-18 | IO Therapeutics, Inc. | Behandlung von krankheiten mit estern von selektiven rxr-agonisten |
| US10966950B2 (en) | 2019-06-11 | 2021-04-06 | Io Therapeutics, Inc. | Use of an RXR agonist in treating HER2+ cancers |
| EP4444287A4 (de) | 2021-12-07 | 2025-05-28 | Io Therapeutics, Inc. | Verwendung eines rxr-agonisten und taxanen zur behandlung von her2+-krebs |
| KR20240115316A (ko) | 2021-12-07 | 2024-07-25 | 아이오 테라퓨틱스, 인크. | 약물 내성 her2+ 암 치료에서의 rxr 작용제의 용도 |
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-
1996
- 1996-11-05 US US08/744,210 patent/US5739338A/en not_active Expired - Fee Related
-
1997
- 1997-10-29 WO PCT/US1997/019915 patent/WO1998019999A1/en not_active Ceased
- 1997-10-29 AU AU51011/98A patent/AU729997B2/en not_active Ceased
- 1997-10-29 EP EP97913959A patent/EP0937045B1/de not_active Expired - Lifetime
- 1997-10-29 AT AT97913959T patent/ATE265436T1/de not_active IP Right Cessation
- 1997-10-29 JP JP52163798A patent/JP2001504458A/ja not_active Withdrawn
- 1997-10-29 CA CA002270893A patent/CA2270893C/en not_active Expired - Fee Related
- 1997-10-29 DE DE69728893T patent/DE69728893T2/de not_active Expired - Fee Related
- 1997-10-29 ES ES97913959T patent/ES2219760T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69728893T2 (de) | 2005-04-21 |
| ES2219760T3 (es) | 2004-12-01 |
| AU5101198A (en) | 1998-05-29 |
| AU729997B2 (en) | 2001-02-22 |
| US5739338A (en) | 1998-04-14 |
| CA2270893A1 (en) | 1998-05-14 |
| EP0937045B1 (de) | 2004-04-28 |
| DE69728893D1 (de) | 2004-06-03 |
| JP2001504458A (ja) | 2001-04-03 |
| WO1998019999A1 (en) | 1998-05-14 |
| EP0937045A1 (de) | 1999-08-25 |
| CA2270893C (en) | 2008-10-21 |
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| RER | Ceased as to paragraph 5 lit. 3 law introducing patent treaties |