BRPI0517135B1 - Composições e métodos para tratar doenças neoplásticas - Google Patents
Composições e métodos para tratar doenças neoplásticas Download PDFInfo
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- BRPI0517135B1 BRPI0517135B1 BRPI0517135-0A BRPI0517135A BRPI0517135B1 BR PI0517135 B1 BRPI0517135 B1 BR PI0517135B1 BR PI0517135 A BRPI0517135 A BR PI0517135A BR PI0517135 B1 BRPI0517135 B1 BR PI0517135B1
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- 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
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- Veterinary Medicine (AREA)
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| US63316104P | 2004-12-03 | 2004-12-03 | |
| US60/633,161 | 2004-12-03 | ||
| PCT/US2005/043668 WO2006060676A1 (en) | 2004-12-03 | 2005-12-02 | Compositions and methods for treating neoplastic diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BRPI0517135A BRPI0517135A (pt) | 2008-09-30 |
| BRPI0517135B1 true BRPI0517135B1 (pt) | 2022-04-19 |
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Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6777217B1 (en) | 1996-03-26 | 2004-08-17 | President And Fellows Of Harvard College | Histone deacetylases, and uses related thereto |
| US20030129724A1 (en) | 2000-03-03 | 2003-07-10 | Grozinger Christina M. | Class II human histone deacetylases, and uses related thereto |
| ES2402045T3 (es) * | 2000-11-16 | 2013-04-26 | The Regents Of The University Of California | Taxón de actionomiceto marino para el descubrimiento de fármacos y de productos de fermentación |
| US7244853B2 (en) | 2001-05-09 | 2007-07-17 | President And Fellows Of Harvard College | Dioxanes and uses thereof |
| US7176232B2 (en) | 2002-06-24 | 2007-02-13 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| US8217072B2 (en) * | 2003-06-20 | 2012-07-10 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| JP2007523862A (ja) * | 2003-06-20 | 2007-08-23 | ネレアス ファーマシューティカルズ インコーポレイテッド | 癌、炎症及び感染性疾患の治療のための、［３．２．０］複素環式化合物およびそれらの類縁体の使用 |
| US7579371B2 (en) | 2004-04-30 | 2009-08-25 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| US7276530B2 (en) * | 2004-04-30 | 2007-10-02 | Nereus Pharmaceuticals, Inc. | [3.2.0] Heterocyclic compounds and methods of using the same |
| JP2008522975A (ja) * | 2004-12-03 | 2008-07-03 | ネレアス ファーマシューティカルズ インコーポレイテッド | ［３．２．０］複素環式化合物及びそれらのアナログを使用する方法 |
| CN103230394B (zh) | 2004-12-03 | 2016-04-20 | 达纳-法伯癌症研究公司 | 治疗肿瘤性疾病的化合物及其用途 |
| SG171690A1 (en) * | 2005-03-22 | 2011-06-29 | Harvard College | Treatment of protein degradation disorders |
| CA2628110A1 (en) * | 2005-11-04 | 2007-05-18 | The Regents Of The University Of California | Methods of sensitizing cancer to therapy-induced cytotoxicity |
| WO2008091349A1 (en) | 2006-02-14 | 2008-07-31 | The President And Fellows Of Harvard College | Bifunctional histone deacetylase inhibitors |
| DK2010168T3 (da) | 2006-02-14 | 2014-07-21 | Harvard College | Histondeacetylase-inhibitore |
| NZ596653A (en) | 2006-04-06 | 2012-10-26 | Nereus Pharmaceuticals Inc | Total synthesis of salinosporamide a and analogs thereof |
| WO2007130429A2 (en) | 2006-05-03 | 2007-11-15 | The President And Fellows Of Harvard College | Histone deacetylase and tubulin deacetylase inhibitors |
| WO2008095195A2 (en) * | 2007-02-02 | 2008-08-07 | Nereus Pharmaceuticals, Inc. | Lyophilized formulations of salinosporamide a |
| WO2008124699A1 (en) * | 2007-04-06 | 2008-10-16 | Nereus Pharmaceuticals, Inc. | A method of using proteasome inhibitors in combination with histone deacetylase inhibitors to treat cancer |
| WO2008137780A2 (en) * | 2007-05-04 | 2008-11-13 | Nereus Pharmaceuticals, Inc. | Use of [3.2.0] heterocyclic compounds and analogs thereof for treating infectious diseases |
| US8394816B2 (en) * | 2007-12-07 | 2013-03-12 | Irene Ghobrial | Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia |
| BRPI0909661A2 (pt) | 2008-03-07 | 2015-08-11 | Nereus Pharmaceuticals Inc | Composto e métodos de síntese química e de formação ou preparação de compostos |
| US7910616B2 (en) | 2008-05-12 | 2011-03-22 | Nereus Pharmaceuticals, Inc. | Proteasome inhibitors |
| US20110144155A1 (en) * | 2008-06-06 | 2011-06-16 | Schimmer Aaron D | 8-hydroxyquinoline derivatives for the treatment of hematological malignancies |
| EP2321264B1 (en) | 2008-07-23 | 2016-05-04 | President and Fellows of Harvard College | Deacetylase inhibitors and uses thereof |
| US20110207627A1 (en) * | 2008-08-13 | 2011-08-25 | George Mason University | Ex vivo therapeutics screening of living bone marrow cells for multiple myeloma |
| WO2010099601A1 (en) * | 2009-03-05 | 2010-09-10 | University Health Network | Use of 5ahq and bortezomib for the treatment of hematological diseases |
| US8716344B2 (en) | 2009-08-11 | 2014-05-06 | President And Fellows Of Harvard College | Class- and isoform-specific HDAC inhibitors and uses thereof |
| US20130173294A1 (en) * | 2011-12-30 | 2013-07-04 | Elwha LLC, a limited liability company of the State of Delaware | Evidence-based healthcare information management protocols |
| US10475142B2 (en) | 2011-12-30 | 2019-11-12 | Elwha Llc | Evidence-based healthcare information management protocols |
| US10552581B2 (en) | 2011-12-30 | 2020-02-04 | Elwha Llc | Evidence-based healthcare information management protocols |
| US10528913B2 (en) | 2011-12-30 | 2020-01-07 | Elwha Llc | Evidence-based healthcare information management protocols |
| US10559380B2 (en) | 2011-12-30 | 2020-02-11 | Elwha Llc | Evidence-based healthcare information management protocols |
| US10679309B2 (en) | 2011-12-30 | 2020-06-09 | Elwha Llc | Evidence-based healthcare information management protocols |
| CN104884637A (zh) * | 2012-11-05 | 2015-09-02 | 普隆奈治疗公司 | 利用生物标志物通过bcl2表达的调节治疗癌症的方法 |
| EP3370709A4 (en) * | 2015-11-06 | 2019-12-18 | Accuitis Pharmaceuticals, Inc. | USE OF PROTEASOME INHIBITORS FOR THE TREATMENT OF EYE DISEASES |
| US10703760B2 (en) | 2016-08-19 | 2020-07-07 | Celgene International Ii Sàrl | Morphic forms of marizomib and uses thereof |
| CN110402144A (zh) * | 2017-01-31 | 2019-11-01 | 小利兰斯坦福大学托管委员会 | 抑制ngly1的剂及其使用方法 |
| JP7498475B2 (ja) * | 2020-01-31 | 2024-06-12 | 株式会社セラバイオファーマ | 多発性骨髄腫の治療剤 |
| WO2021183789A1 (en) | 2020-03-11 | 2021-09-16 | Trader Darci J | Activity-based probes with unnatural amino acids to monitor the proteasome activity |
| CN113750215B (zh) * | 2021-09-24 | 2023-06-23 | 暨南大学 | 用于治疗肿瘤的联合药物 |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US5276182A (en) * | 1990-07-09 | 1994-01-04 | The Dow Chemical Company | Process for preparing polyurea oligomers |
| DE4039602A1 (de) * | 1990-12-12 | 1992-06-17 | Bauer Kurt Heinz Prof Dr | Pharmazeutische formulierungen |
| KR100221695B1 (ko) * | 1991-08-12 | 1999-09-15 | 그린 마틴, 브라이언 쥐 테슬리 | 약학적 구상 제형 |
| US5653962A (en) * | 1991-12-12 | 1997-08-05 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicaments |
| CA2149150C (en) * | 1992-11-27 | 2000-08-01 | David R. Carver | Injectable taxol composition with improved stability |
| US5654286A (en) * | 1993-05-12 | 1997-08-05 | Hostetler; Karl Y. | Nucleotides for topical treatment of psoriasis, and methods for using same |
| PL177323B1 (pl) * | 1993-10-01 | 1999-10-29 | Syntex Inc | Kompozycja farmaceutyczna zawierająca mykofenolan mofetylu lub kwas mykofenolowy i sposób wytwarzania kompozycji farmaceutycznej zawierającej mykofenolan mofetylu lub kwas mykofenolowy |
| US5707641A (en) * | 1994-10-13 | 1998-01-13 | Pharmaderm Research & Development Ltd. | Formulations comprising therapeutically-active proteins or polypeptides |
| IE80468B1 (en) * | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
| US6838477B2 (en) * | 1995-04-12 | 2005-01-04 | President And Fellows Of Harvard College | Lactacystin analogs |
| US6335358B1 (en) * | 1995-04-12 | 2002-01-01 | President And Fellows Of Harvard College | Lactacystin analogs |
| US5653987A (en) * | 1995-05-16 | 1997-08-05 | Modi; Pankaj | Liquid formulations for proteinic pharmaceuticals |
| US5726181A (en) * | 1995-06-05 | 1998-03-10 | Bionumerik Pharmaceuticals, Inc. | Formulations and compositions of poorly water soluble camptothecin derivatives |
| US5667809A (en) * | 1995-06-07 | 1997-09-16 | Alliance Pharmaceutical Corp. | Continuous fluorochemical microdispersions for the delivery of lipophilic pharmaceutical agents |
| US5874443A (en) * | 1995-10-19 | 1999-02-23 | Trega Biosciences, Inc. | Isoquinoline derivatives and isoquinoline combinatorial libraries |
| US5886210A (en) * | 1996-08-22 | 1999-03-23 | Rohm And Haas Company | Method for preparing aromatic compounds |
| US6271199B2 (en) | 1997-02-15 | 2001-08-07 | Millennium Pharmaceuticals, Inc. | Treatment of infarcts |
| US5922683A (en) * | 1997-05-29 | 1999-07-13 | Abbott Laboratories | Multicyclic erythromycin derivatives |
| DE69809063T2 (de) * | 1997-08-04 | 2003-06-12 | Nihon Nohyaku Co., Ltd. | Aryloxyanilin-derivate |
| NZ503169A (en) | 1997-08-15 | 2001-12-21 | Millennium Pharm Inc | Synthesis of clasto-lactacystin beta-lactone whereupon the process relies upon a stereoselective addition of a formyl amide to an oxazoline |
| US6133308A (en) * | 1997-08-15 | 2000-10-17 | Millennium Pharmaceuticals, Inc. | Synthesis of clasto-lactacystin beta-lactone and analogs thereof |
| AU9580098A (en) | 1997-09-25 | 1999-04-12 | Millennium Pharmaceuticals, Inc. | Proteasome inhibitors, ubiquitin pathway inhibitors or agents that interfere with the activation of nf-(k)b via the ubiquitin proteasome pathway to treat inflammatory and autoimmune diseases |
| US20010051654A1 (en) * | 1997-09-25 | 2001-12-13 | Elliott Peter J. | Treatment of inflammatory and autoimmune diseases |
| US6831057B2 (en) | 1997-10-28 | 2004-12-14 | The University Of North Carolina At Chapel Hill | Use of NF-κB inhibition in combination therapy for cancer |
| EP2201945B1 (en) * | 1997-11-21 | 2013-03-06 | Purdue Neuroscience Company | Use of substituted 2-aminoacetamides for treating or ameliorating anxiety |
| US6617171B2 (en) | 1998-02-27 | 2003-09-09 | The General Hospital Corporation | Methods for diagnosing and treating autoimmune disease |
| IL137974A0 (en) * | 1998-03-26 | 2001-10-31 | Shionogi & Co | Indole derivatives having antiviral activity |
| US6509331B1 (en) * | 1998-06-22 | 2003-01-21 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| AU762373B2 (en) | 1998-10-20 | 2003-06-26 | Millennium Pharmaceuticals, Inc. | Method for monitoring proteasome inhibitor drug action |
| FR2784988B1 (fr) * | 1998-10-23 | 2002-09-20 | Adir | Nouveaux composes dihydro et tetrahydroquinoleiniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US20020049157A1 (en) | 1999-08-25 | 2002-04-25 | Jiangping Wu | Use of proteasome inhibitors for treating cancer, inflammation, autoimmune disease, graft rejection and septic shock |
| ES2272558T3 (es) | 2000-10-12 | 2007-05-01 | Viromics Gmbh | Inhibidores del proteasoma para el tratamiento de infecciones causadas por virus de la hepatitis. |
| ES2402045T3 (es) | 2000-11-16 | 2013-04-26 | The Regents Of The University Of California | Taxón de actionomiceto marino para el descubrimiento de fármacos y de productos de fermentación |
| WO2003084551A1 (de) * | 2002-04-05 | 2003-10-16 | Viromics Gmbh | Mittel zur behandlung von flaviviridae-infektionen |
| US7179834B2 (en) * | 2002-06-24 | 2007-02-20 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| US7176232B2 (en) * | 2002-06-24 | 2007-02-13 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| WO2004043374A2 (en) | 2002-11-06 | 2004-05-27 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for treating cancer using proteasome inhibitors |
| KR20050098928A (ko) * | 2003-02-14 | 2005-10-12 | 바이엘 헬스케어 아게 | 치환된 헤테로사이클 |
| US8217072B2 (en) * | 2003-06-20 | 2012-07-10 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| JP2007523862A (ja) * | 2003-06-20 | 2007-08-23 | ネレアス ファーマシューティカルズ インコーポレイテッド | 癌、炎症及び感染性疾患の治療のための、［３．２．０］複素環式化合物およびそれらの類縁体の使用 |
| WO2005094423A2 (en) | 2004-02-26 | 2005-10-13 | President And Fellows Of Harvard College | Selective inhibition of proteasomes of tuberculosis and other bacteria |
| US7371875B2 (en) * | 2004-03-12 | 2008-05-13 | Miikana Therapeutics, Inc. | Cytotoxic agents and methods of use |
| WO2005099687A2 (en) | 2004-04-09 | 2005-10-27 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| US7183417B2 (en) * | 2004-04-09 | 2007-02-27 | President And Fellows Of Harvard College | Simple stereocontrolled synthesis of salinosporamide A |
| US7232818B2 (en) | 2004-04-15 | 2007-06-19 | Proteolix, Inc. | Compounds for enzyme inhibition |
| US7276530B2 (en) * | 2004-04-30 | 2007-10-02 | Nereus Pharmaceuticals, Inc. | [3.2.0] Heterocyclic compounds and methods of using the same |
| US20060264495A1 (en) * | 2004-04-30 | 2006-11-23 | Michael Palladino | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| US7579371B2 (en) * | 2004-04-30 | 2009-08-25 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| EP1771411A1 (en) | 2004-07-12 | 2007-04-11 | Bayer CropScience Aktiengesellschaft | Substituted 2-pyrrolidone derivatives as fungicides and insecticides |
| CN103230394B (zh) * | 2004-12-03 | 2016-04-20 | 达纳-法伯癌症研究公司 | 治疗肿瘤性疾病的化合物及其用途 |
| WO2006060609A1 (en) | 2004-12-03 | 2006-06-08 | Honeywell International Inc. | Gas jet control for inertial measurement unit |
| WO2006060819A2 (en) | 2004-12-03 | 2006-06-08 | The Regents Of The University Of California | Dhmeq as a sensitizing agent for chemotherapy and immunotherapy of resistant cancer cells |
| JP2008522975A (ja) * | 2004-12-03 | 2008-07-03 | ネレアス ファーマシューティカルズ インコーポレイテッド | ［３．２．０］複素環式化合物及びそれらのアナログを使用する方法 |
| WO2006118973A2 (en) | 2005-04-29 | 2006-11-09 | Nereus Pharmaceuticals, Inc. | Methods of using heterobyclic compounds for treatment of rectal cancer |
| US20060287520A1 (en) * | 2005-05-16 | 2006-12-21 | Danishefsky Samuel J | Synthesis of salinosporamide A and analogues thereof |
| WO2007021897A1 (en) | 2005-08-10 | 2007-02-22 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| WO2007030662A1 (en) * | 2005-09-09 | 2007-03-15 | Nereus Pharmaceuticals, Inc. | Biosynthesis of salinosporamide a and its analogs |
| US7465720B2 (en) | 2005-09-12 | 2008-12-16 | President And Fellows Of Harvard College | Proteasome inhibiting β-lactam compounds |
| CA2628110A1 (en) * | 2005-11-04 | 2007-05-18 | The Regents Of The University Of California | Methods of sensitizing cancer to therapy-induced cytotoxicity |
| GB0605217D0 (en) | 2006-03-15 | 2006-04-26 | Novartis Ag | Method and compositions for assessing acute rejection |
| NZ596653A (en) | 2006-04-06 | 2012-10-26 | Nereus Pharmaceuticals Inc | Total synthesis of salinosporamide a and analogs thereof |
| WO2007130404A1 (en) | 2006-05-03 | 2007-11-15 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof for the treatment of lung cancer |
| DE102006026464A1 (de) | 2006-06-01 | 2007-12-06 | Virologik Gmbh Innovationszentrum Medizintechnik Und Pharma | Pharmazeutische Zusammensetzung zur Behandlung von Virusinfektionen und / oder Tumorerkrankungen durch Inhibition der Proteinfaltung und des Proteinabbaus |
| US8088923B2 (en) * | 2006-07-07 | 2012-01-03 | The Texas A&M University System | Cyclic-fused beta-lactones and their synthesis |
| WO2008137780A2 (en) | 2007-05-04 | 2008-11-13 | Nereus Pharmaceuticals, Inc. | Use of [3.2.0] heterocyclic compounds and analogs thereof for treating infectious diseases |
| US7442830B1 (en) | 2007-08-06 | 2008-10-28 | Millenium Pharmaceuticals, Inc. | Proteasome inhibitors |
| US8394816B2 (en) * | 2007-12-07 | 2013-03-12 | Irene Ghobrial | Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia |
| BRPI0909661A2 (pt) | 2008-03-07 | 2015-08-11 | Nereus Pharmaceuticals Inc | Composto e métodos de síntese química e de formação ou preparação de compostos |
| US7910616B2 (en) | 2008-05-12 | 2011-03-22 | Nereus Pharmaceuticals, Inc. | Proteasome inhibitors |
| US8772724B2 (en) | 2011-01-05 | 2014-07-08 | Intel-Ge Care Innovations Llc | Low power, inexpensive velocity detection using a PIR array |
-
2005
- 2005-12-02 CN CN201310024563.XA patent/CN103230394B/zh not_active Expired - Lifetime
- 2005-12-02 AU AU2005311709A patent/AU2005311709B2/en not_active Expired
- 2005-12-02 CA CA2588923A patent/CA2588923C/en not_active Expired - Lifetime
- 2005-12-02 WO PCT/US2005/043668 patent/WO2006060676A1/en not_active Ceased
- 2005-12-02 ES ES05852783T patent/ES2396762T3/es not_active Expired - Lifetime
- 2005-12-02 SG SG200907327-1A patent/SG157365A1/en unknown
- 2005-12-02 EP EP05852783A patent/EP1830838B1/en not_active Expired - Lifetime
- 2005-12-02 US US11/293,354 patent/US20070225350A1/en not_active Abandoned
- 2005-12-02 PL PL05852783T patent/PL1830838T3/pl unknown
- 2005-12-02 MX MX2007006526A patent/MX2007006526A/es active IP Right Grant
- 2005-12-02 CN CN2005800466157A patent/CN101155582B/zh not_active Expired - Lifetime
- 2005-12-02 NZ NZ555439A patent/NZ555439A/en not_active IP Right Cessation
- 2005-12-02 BR BRPI0517135-0A patent/BRPI0517135B1/pt active IP Right Grant
- 2005-12-02 KR KR1020077015299A patent/KR101282191B1/ko not_active Expired - Fee Related
- 2005-12-02 JP JP2007544545A patent/JP5676071B2/ja not_active Expired - Lifetime
- 2005-12-02 DK DK05852783.9T patent/DK1830838T3/da active
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- 2007-05-29 IL IL183506A patent/IL183506A/en active IP Right Grant
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2008
- 2008-07-30 US US12/183,007 patent/US8722724B2/en not_active Expired - Fee Related
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2012
- 2012-09-10 JP JP2012198263A patent/JP5837469B2/ja not_active Expired - Fee Related
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2014
- 2014-03-25 US US14/224,965 patent/US10610517B2/en not_active Expired - Lifetime
- 2014-11-11 JP JP2014228602A patent/JP5963830B2/ja not_active Expired - Fee Related
- 2014-12-24 IL IL23642614A patent/IL236426B/en active IP Right Grant
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- 2020-02-25 US US16/800,570 patent/US20200206190A1/en not_active Abandoned
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2022
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| B06A | Patent application procedure suspended [chapter 6.1 patent gazette] | ||
| B09A | Decision: intention to grant [chapter 9.1 patent gazette] | ||
| B16A | Patent or certificate of addition of invention granted [chapter 16.1 patent gazette] |
Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 02/12/2005, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME ADI 5.529/DF, QUE DETERMINA A ALTERACAO DO PRAZO DE CONCESSAO. |