TW200407147A - Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH) / prostatic hypertrophy - Google Patents
Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH) / prostatic hypertrophy Download PDFInfo
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- TW200407147A TW200407147A TW092112331A TW92112331A TW200407147A TW 200407147 A TW200407147 A TW 200407147A TW 092112331 A TW092112331 A TW 092112331A TW 92112331 A TW92112331 A TW 92112331A TW 200407147 A TW200407147 A TW 200407147A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
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|---|---|---|---|
| DE10221018A DE10221018A1 (de) | 2002-05-11 | 2002-05-11 | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
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| TW092112331A TW200407147A (en) | 2002-05-11 | 2003-05-06 | Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH) / prostatic hypertrophy |
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| EP (1) | EP1505981B1 (https=) |
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| CA (1) | CA2483590C (https=) |
| DE (1) | DE10221018A1 (https=) |
| PE (1) | PE20040400A1 (https=) |
| TW (1) | TW200407147A (https=) |
| UY (1) | UY27800A1 (https=) |
| WO (1) | WO2003094921A2 (https=) |
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| EE04748B1 (et) * | 1999-06-21 | 2006-12-15 | Boehringer Ingelheim Pharma Kg | Bitsüklilised heterotsüklilised ühendid, neid ühendeid sisaldavad ravimid, nende kasutamine ja meetodid nende valmistamiseks |
| US7019012B2 (en) * | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| US20050043233A1 (en) | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| ES2305844T3 (es) | 2003-09-16 | 2008-11-01 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de tirosina cinasa. |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| CN1972688B (zh) * | 2004-05-06 | 2012-06-27 | 沃尼尔·朗伯有限责任公司 | 4-苯胺基-喹唑啉-6-基-酰胺类化合物 |
| CA2833706C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| PL1948180T3 (pl) * | 2005-11-11 | 2013-09-30 | Boehringer Ingelheim Int | Terapia skojarzona raka polegająca na podawaniu inhibitorów EGFR/HER2 |
| JP5241513B2 (ja) | 2006-01-26 | 2013-07-17 | 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 | アミノクロトニルアミノ置換キナゾリン誘導体の合成方法 |
| AU2007299080B2 (en) | 2006-09-18 | 2013-04-18 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
| PE20100252A1 (es) | 2008-06-06 | 2010-04-12 | Boehringer Ingelheim Int | Nuevas formulaciones farmaceuticas solidas que comprenden dimaleato de 4-[(3-cloro-4-fluorofenil) amino]-6-{[4-(n,n-dimetilamino)-1-oxo-2-buten-1-il] amino}-7-((s)-tetrahidrofuran-3-iloxi)-quinazolina |
| KR101703941B1 (ko) | 2008-11-10 | 2017-02-07 | 내셔날 헬스 리서치 인스티튜트 | 티로신 키나아제 억제제로서의 접합 이환 및 삼환 피리미딘 화합물 |
| PL2451445T3 (pl) | 2009-07-06 | 2019-09-30 | Boehringer Ingelheim International Gmbh | Sposób suszenia BIBW2992, jego soli i stałych preparatów farmaceutycznych zawierających tę substancję czynną |
| US8828391B2 (en) | 2011-05-17 | 2014-09-09 | Boehringer Ingelheim International Gmbh | Method for EGFR directed combination treatment of non-small cell lung cancer |
| CN103254183B (zh) * | 2013-05-10 | 2015-11-11 | 苏州明锐医药科技有限公司 | 阿法替尼的制备方法 |
| WO2014180271A1 (zh) * | 2013-05-10 | 2014-11-13 | 苏州明锐医药科技有限公司 | 阿法替尼及其中间体的制备方法 |
| EP3061459B1 (en) * | 2013-10-23 | 2019-12-11 | Gemvax & Kael Co., Ltd. | Composition for treating and preventing benign prostatic hyperplasia |
| 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 |
| KR20180086187A (ko) | 2015-10-05 | 2018-07-30 | 더 트러스티이스 오브 콜롬비아 유니버시티 인 더 시티 오브 뉴욕 | 자가포식 유동의 활성체 및 포스포리파제 d 및 타우를 포함하는 단백질 응집물의 클리어런스 및 단백질질환의 치료 |
| CN105669658B (zh) * | 2016-04-05 | 2018-06-29 | 北京民康百草医药科技有限公司 | 一种阿法替尼的精制方法 |
| CN107488172B (zh) * | 2016-06-10 | 2020-06-12 | 山东新时代药业有限公司 | 一种阿法替尼的制备方法 |
Family Cites Families (62)
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| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| MX9707453A (es) | 1995-03-30 | 1997-12-31 | Pfizer | Derivados de quinazolina. |
| GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| MX9800215A (es) | 1995-07-06 | 1998-03-31 | Novartis Ag | Pirrolopirimidas y procesos para su preparacion. |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| IL120302A0 (en) * | 1996-03-27 | 1997-06-10 | Pfizer | Use of alpha1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia |
| HU228446B1 (en) | 1996-04-12 | 2013-03-28 | Warner Lambert Co | Kinazoline derivatives as irreversible inhibitors of protein-kinase, pharmaceutical compositions containing these compounds and use thereof |
| GB9718972D0 (en) * | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| UA73073C2 (uk) | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| ZA986729B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitors of tyrosine kinases |
| ZA986732B (en) * | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
| US6251912B1 (en) * | 1997-08-01 | 2001-06-26 | American Cyanamid Company | Substituted quinazoline derivatives |
| TW436485B (en) | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| WO1999033980A2 (en) | 1997-12-30 | 1999-07-08 | Chiron Corporation | Members of tnf and tnfr families |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| DE19825591A1 (de) * | 1998-06-09 | 1999-12-23 | Jenapharm Gmbh | Pharmazeutische Kombinationen zum Ausgleich eines Testosteron-Defizits beim Mann mit gleichzeitigem Schutz der Prostata |
| WO2000031048A1 (en) | 1998-11-19 | 2000-06-02 | Warner-Lambert Company | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
| TR200102505T2 (tr) * | 1999-02-27 | 2003-01-21 | Boehringer Ingelheim Pharma Kg | 4-amino-kinazolin ve kinolin türevleri. |
| DE19911366A1 (de) | 1999-03-15 | 2000-09-21 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| EE04748B1 (et) | 1999-06-21 | 2006-12-15 | Boehringer Ingelheim Pharma Kg | Bitsüklilised heterotsüklilised ühendid, neid ühendeid sisaldavad ravimid, nende kasutamine ja meetodid nende valmistamiseks |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| IL141235A (en) * | 2000-02-09 | 2012-04-30 | Novartis Int Pharm Ltd | Combined use of an alpha-adrenoceptor antagonist and a muscarinic antagonist in the preparation of a drug for the treatment of non-malignant prostatic hyperplasia |
| KR100817423B1 (ko) | 2000-03-13 | 2008-03-27 | 와이어쓰 홀딩스 코포레이션 | 시아노퀴놀린을 포함하는 결장 폴립의 치료 또는 억제를 위한 약제학적 조성물 |
| US20060063752A1 (en) * | 2000-03-14 | 2006-03-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
| ES2267748T3 (es) * | 2000-04-07 | 2007-03-16 | Astrazeneca Ab | Compuestos de quinazolina. |
| ATE350378T1 (de) * | 2000-04-08 | 2007-01-15 | Boehringer Ingelheim Pharma | Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| DE10017539A1 (de) * | 2000-04-08 | 2001-10-11 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbingungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US6627634B2 (en) * | 2000-04-08 | 2003-09-30 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
| US7084136B2 (en) * | 2000-06-02 | 2006-08-01 | Shionogi & Co., Ltd. | Drug composition antagonistic to both PGD2/TXA2 receptors |
| US6656946B2 (en) * | 2000-08-26 | 2003-12-02 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US6617329B2 (en) * | 2000-08-26 | 2003-09-09 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines and their use as medicaments |
| US6740651B2 (en) * | 2000-08-26 | 2004-05-25 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US6403580B1 (en) * | 2000-08-26 | 2002-06-11 | Boehringer Ingelheim Pharma Kg | Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| DE10042064A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Chinazoline, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE10042060A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US20020082270A1 (en) * | 2000-08-26 | 2002-06-27 | Frank Himmelsbach | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US6653305B2 (en) * | 2000-08-26 | 2003-11-25 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
| ATE369894T1 (de) | 2000-11-22 | 2007-09-15 | Novartis Pharma Gmbh | Kombination enthaltend ein mittel zur verminderung von vegf-aktivität und ein mittel zur verminderung von egf-aktivität |
| US7019012B2 (en) * | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| DE10063435A1 (de) * | 2000-12-20 | 2002-07-04 | Boehringer Ingelheim Pharma | Chinazolinderviate,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| SE0100902D0 (sv) * | 2001-03-15 | 2001-03-15 | Astrazeneca Ab | Compounds |
| TWI324597B (en) * | 2002-03-28 | 2010-05-11 | 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 |
| US20040044014A1 (en) * | 2002-04-19 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| US20030225079A1 (en) * | 2002-05-11 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy |
| US7223749B2 (en) * | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| US20050043233A1 (en) * | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| DE10326186A1 (de) * | 2003-06-06 | 2004-12-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| 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 |
| DE10349113A1 (de) | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| US20060058311A1 (en) * | 2004-08-14 | 2006-03-16 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| PL1948180T3 (pl) * | 2005-11-11 | 2013-09-30 | Boehringer Ingelheim Int | Terapia skojarzona raka polegająca na podawaniu inhibitorów EGFR/HER2 |
| CA2833706C (en) | 2005-11-11 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
| JP5241513B2 (ja) * | 2006-01-26 | 2013-07-17 | 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 | アミノクロトニルアミノ置換キナゾリン誘導体の合成方法 |
| AU2007299080B2 (en) | 2006-09-18 | 2013-04-18 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
| PE20100252A1 (es) * | 2008-06-06 | 2010-04-12 | Boehringer Ingelheim Int | Nuevas formulaciones farmaceuticas solidas que comprenden dimaleato de 4-[(3-cloro-4-fluorofenil) amino]-6-{[4-(n,n-dimetilamino)-1-oxo-2-buten-1-il] amino}-7-((s)-tetrahidrofuran-3-iloxi)-quinazolina |
| CN102227434B (zh) * | 2008-09-30 | 2015-02-18 | 马林克罗特有限公司 | 选择性胺化酮吗啡喃的方法 |
| JP2012515184A (ja) * | 2009-01-14 | 2012-07-05 | 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 | 大腸がんの治療方法 |
| PL2451445T3 (pl) | 2009-07-06 | 2019-09-30 | Boehringer Ingelheim International Gmbh | Sposób suszenia BIBW2992, jego soli i stałych preparatów farmaceutycznych zawierających tę substancję czynną |
| JP2013512882A (ja) | 2009-12-07 | 2013-04-18 | 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 | トリプルネガティブ乳癌の治療に使用するｂｉｂｗ２９９２ |
-
2002
- 2002-05-11 DE DE10221018A patent/DE10221018A1/de not_active Withdrawn
-
2003
- 2003-05-02 WO PCT/EP2003/004606 patent/WO2003094921A2/de not_active Ceased
- 2003-05-02 CA CA2483590A patent/CA2483590C/en not_active Expired - Fee Related
- 2003-05-02 EP EP03727422A patent/EP1505981B1/de not_active Expired - Lifetime
- 2003-05-02 AU AU2003233223A patent/AU2003233223A1/en not_active Abandoned
- 2003-05-02 JP JP2004503006A patent/JP4630659B2/ja not_active Expired - Fee Related
- 2003-05-06 TW TW092112331A patent/TW200407147A/zh unknown
- 2003-05-09 AR ARP030101622A patent/AR039987A1/es not_active Application Discontinuation
- 2003-05-09 UY UY27800A patent/UY27800A1/es not_active Application Discontinuation
- 2003-05-09 PE PE2003000451A patent/PE20040400A1/es not_active Application Discontinuation
-
2010
- 2010-02-17 US US12/706,819 patent/US8431585B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| UY27800A1 (es) | 2003-12-31 |
| DE10221018A1 (de) | 2003-11-27 |
| CA2483590A1 (en) | 2003-11-20 |
| JP2005526123A (ja) | 2005-09-02 |
| AU2003233223A1 (en) | 2003-11-11 |
| CA2483590C (en) | 2011-01-04 |
| US8431585B2 (en) | 2013-04-30 |
| WO2003094921A2 (de) | 2003-11-20 |
| US20100144639A1 (en) | 2010-06-10 |
| JP4630659B2 (ja) | 2011-02-09 |
| AR039987A1 (es) | 2005-03-09 |
| EP1505981A2 (de) | 2005-02-16 |
| PE20040400A1 (es) | 2004-08-02 |
| WO2003094921A3 (de) | 2004-03-18 |
| EP1505981B1 (de) | 2012-07-11 |
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