CA2544502A1 - Vitamin d analogs for obesity prevention and treatment - Google Patents
Vitamin d analogs for obesity prevention and treatment Download PDFInfo
- Publication number
- CA2544502A1 CA2544502A1 CA002544502A CA2544502A CA2544502A1 CA 2544502 A1 CA2544502 A1 CA 2544502A1 CA 002544502 A CA002544502 A CA 002544502A CA 2544502 A CA2544502 A CA 2544502A CA 2544502 A1 CA2544502 A1 CA 2544502A1
- Authority
- CA
- Canada
- Prior art keywords
- analog
- straight
- carbon atoms
- branched chain
- vitamin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/592—9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P3/02—Nutrients, e.g. vitamins, minerals
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
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Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Cardiology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Nutrition Science (AREA)
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- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52481303P | 2003-11-25 | 2003-11-25 | |
| US52479803P | 2003-11-25 | 2003-11-25 | |
| US60/524,798 | 2003-11-25 | ||
| US60/524,813 | 2003-11-25 | ||
| PCT/US2004/039625 WO2005051323A2 (en) | 2003-11-25 | 2004-11-24 | Vitamin d analogs for obesity prevention and treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2544502A1 true CA2544502A1 (en) | 2005-06-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002544502A Abandoned CA2544502A1 (en) | 2003-11-25 | 2004-11-24 | Vitamin d analogs for obesity prevention and treatment |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8188064B2 (https=) |
| EP (1) | EP1689412A4 (https=) |
| JP (1) | JP2007512376A (https=) |
| AU (1) | AU2004293092A1 (https=) |
| CA (1) | CA2544502A1 (https=) |
| MX (1) | MXPA06005887A (https=) |
| WO (1) | WO2005051323A2 (https=) |
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| US7122533B2 (en) * | 1999-11-29 | 2006-10-17 | The United States Of America As Represented By The Department Of Health And Human Services | Cosalane compounds and methods for their use |
| US6627622B2 (en) * | 2002-02-18 | 2003-09-30 | Wisconsin Alumni Research Foundation | (20S)-1α-hydroxy-2-methylene-19-nor-bishomopregnacalciferol and its uses |
| AU2004266706B2 (en) * | 2003-08-20 | 2009-07-30 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-vitamin D2 compounds |
| US8404667B2 (en) * | 2006-12-29 | 2013-03-26 | Wisconsin Alumni Research Foundation | Compounds, compositions, kits and methods of use to orally and topically treat acne and other skin conditions by 19-Nor vitamin D analog |
| US7713951B2 (en) * | 2004-04-09 | 2010-05-11 | Wisconsin Alumni Research Foundation | 2-alkylidene-18,19-dinor-vitamin D compounds |
| JP5161582B2 (ja) * | 2004-11-22 | 2013-03-13 | ウィスコンシン・アルムニ・リサーチ・ファウンデーション | １７，２０（ｚ）−デヒドロビタミンｄ類似体およびそれらの使用 |
| JP2008520708A (ja) * | 2004-11-22 | 2008-06-19 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１９−ノル−（２０Ｒ）−１α−ヒドロキシ−ビスホモプレグナカルシフェロール |
| ATE467614T1 (de) * | 2004-11-22 | 2010-05-15 | Wisconsin Alumni Res Found | 2-methylen-19,26,27-trinor-(20s)-1-alpha- hydroxyvitamin d3 and dessen verwendungen |
| US7238681B2 (en) * | 2004-11-22 | 2007-07-03 | Wisconsin Alumni Research Foundation | 2-Methylene-18,19-dinor-1α-hydroxy-homopregnacalciferol and its uses |
| JP2008520689A (ja) | 2004-11-22 | 2008-06-19 | ウィスコンシン・アルムニ・リサーチ・ファウンデーション | １９，２６，２７−トリノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３の２α−メチルおよび２β−メチル類似体およびそれらの使用 |
| AU2005309804B9 (en) * | 2004-11-22 | 2011-12-08 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-(20S)-1alpha-hydroxy-bishomopregnacalciferol and its uses |
| CA2588412A1 (en) * | 2004-11-22 | 2006-06-01 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-1alpha-hydroxy-homopregnacalciferol and its uses |
| US7541348B2 (en) * | 2004-11-22 | 2009-06-02 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-(20S)-1α-hydroxy-trishomopregnacalciferol |
| EP1827452B1 (en) * | 2004-11-22 | 2011-03-02 | Wisconsin Alumni Research Foundation | 2-methylene-19,21-dinor-1alpha-hydroxy-bishomopregnacalciferol |
| NZ561076A (en) * | 2005-02-11 | 2010-01-29 | Wisconsin Alumni Res Found | 2-methylene-19-nor-(20S-24EPI)-1alpha,25-dihydroxyvitamin-D2 |
| US8114393B2 (en) * | 2005-09-14 | 2012-02-14 | Wisconsin Alumni Research Foundation | Methods and compositions for phosphate binding |
| WO2007038094A1 (en) * | 2005-09-22 | 2007-04-05 | Wisconsin Alumni Research Foundation | 19,23,24,25,26,27-hexanor-1alpha-hydroxyvitamin d3 |
| US7803789B2 (en) | 2006-02-02 | 2010-09-28 | Wisconsin Alumni Research Foundation | Vitamin D analog—RAK, methods and uses thereof |
| US7528122B2 (en) * | 2006-02-02 | 2009-05-05 | Wisconsin Alumni Research Foundation | Vitamin D analog—NEL, methods and uses thereof |
| US20090281340A1 (en) * | 2006-04-05 | 2009-11-12 | Deluca Hector F | 1alpha-hydroxy-2-(3'-hydroxypropylidene)-19-nor-vitamin d compounds and methods of making and treatment thereof |
| EP2010483A2 (en) * | 2006-04-05 | 2009-01-07 | Wisconsin Alumni Research Foundation | 1.alpha.-hydroxy-2-(3'-hydroxypropylidene)-19-nor-vitamin d compounds and methods of making and use thereof |
| AU2007298651A1 (en) * | 2006-04-06 | 2008-03-27 | Wisconsin Alumni Research Foundation | 2-methylene-1 alpha-hydroxy-18,19,21-trinorvitamin D3 analogs and uses thereof |
| CA2646909A1 (en) * | 2006-04-06 | 2008-03-27 | Hector F. Deluca | 2-methylene-1alpha-hydroxy-19,21-dinorvitamin d3 analogs and uses thereof |
| MX2008012671A (es) | 2006-04-06 | 2008-10-15 | Wisconsin Alumni Res Found | Analogos 1 a,25-dihidroxi- 19, 26,27-trinor vitamina d 2-sustituidos y sus usos. |
| JP2009533483A (ja) * | 2006-04-06 | 2009-09-17 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１α，２５−ジヒドロキシ−１８，１９，２１−トリノルビタミンＤ３およびその使用 |
| US7648973B2 (en) * | 2006-04-06 | 2010-01-19 | Wisconsin Alumni Research Foundation | 2-methylene-1α,25-dihydroxy-19,21-dinorvitamin D3 analogs and uses thereof |
| WO2008026078A2 (en) * | 2006-04-06 | 2008-03-06 | Wisconsin Alumni Research Foundation | 19-nor-vitamin d analogs with 1,2,or 3,2 heterocyclic ring |
| DE602007012216D1 (de) * | 2006-04-10 | 2011-03-10 | Wisconsin Alumni Res Found | 1-alpha-hydroxy-2-(3'-hydroxypropyliden)-19-nor-vitamin-d-verbindungen mit einer 1,1-dimethylpropyl-seitenkette |
| MX2009003241A (es) | 2006-09-28 | 2009-05-05 | Wisconsin Alumni Res Found | Analogos de 2-metilen-(20r,25s)-19,27-dinor-(22e)-vitamina d. |
| ATE552238T1 (de) * | 2006-09-28 | 2012-04-15 | Wisconsin Alumni Res Found | 2-methylen-(20s,25s)-19,27-dinor-(22e)-vitamin- - analoga |
| ATE552239T1 (de) * | 2007-12-28 | 2012-04-15 | Wisconsin Alumni Res Found | 2-methylen-20-methyl-19,24,25,26,27-pentanor- vitamin-d-analoga |
| CA2710954C (en) * | 2007-12-28 | 2015-07-21 | Wisconsin Alumni Research Foundation | (20s)-23,23-difluoro-2-methylene-19-nor-bishomopregnacalciferol-vitamin d analogs |
| AU2009221717A1 (en) * | 2008-03-06 | 2009-09-11 | Wisconsin Alumni Research Foundation | Methods of increasing epidermal skin thickness by topical administration of A 19-nor containing vitamin D compound |
| US7648974B1 (en) * | 2008-07-10 | 2010-01-19 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D analogs with 3,2-dihydrofuran ring |
| US8222236B2 (en) | 2008-07-10 | 2012-07-17 | Wisconsin Alumni Research Foundation | 2-methylene-(20E)-20(22)-dehydro-19-nor-vitamin D analogs |
| US8399439B2 (en) * | 2008-07-10 | 2013-03-19 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs |
| US8193170B2 (en) * | 2008-07-10 | 2012-06-05 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20R,22E,25R)-vitamin D analogs |
| US7888339B2 (en) | 2008-07-10 | 2011-02-15 | Wisconsin Alumni Research Foundation | 2-methylene-20(21)-dehydro-19-nor-vitamin D analogs |
| US7893043B2 (en) | 2008-07-10 | 2011-02-22 | Wisconsin Alumni Research Foundation | 2-methylene-(17Z)-17(20)-dehydro-19,21-dinor-vitamin D analogs |
| JP2013512259A (ja) * | 2009-11-30 | 2013-04-11 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１９，２６−ノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３ |
| US8664206B2 (en) | 2010-03-23 | 2014-03-04 | Wisconsin Alumni Research Foundation | Diastereomers of 2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin D3 |
| JP5931845B2 (ja) * | 2010-03-23 | 2016-06-08 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１９−ノル−２２−メチル−１α，２５−ジヒドロキシビタミンＤ３のジアステレオマー |
| AU2011232633B2 (en) * | 2010-03-23 | 2014-05-29 | Wisconsin Alumni Research Foundation | (20S)-2-methylene-19-nor-22-dimethyl-1alpha,25- dihydroxyvitamin D3 and (20R)-2-methylene-19-nor-22- dimethyl-1alpha,25-hydroxyvitamin D3 |
| US8420839B1 (en) * | 2011-10-05 | 2013-04-16 | Wisconsin Alumni Research Foundation | Crystallization of 1α-hydroxy-2-methylene-18,19-dinor-homopregnacalciferol |
| US9416102B2 (en) * | 2013-01-23 | 2016-08-16 | Wisconsin Alumni Research Foundation | (22E)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D3 analogs |
| CN104211579B (zh) * | 2014-09-04 | 2016-01-06 | 上海皓元生物医药科技有限公司 | 一种用于制备维生素d及其类似物的中间体化合物ii的方法 |
| US9616109B2 (en) | 2014-10-22 | 2017-04-11 | Extend Biosciences, Inc. | Insulin vitamin D conjugates |
| WO2016065042A1 (en) | 2014-10-22 | 2016-04-28 | Extend Biosciences, Inc. | Therapeutic vitamin d conjugates |
| CN104447211A (zh) * | 2014-12-12 | 2015-03-25 | 重庆华邦制药有限公司 | 维生素d类药物的中间体化合物及制备方法 |
| US10494337B2 (en) * | 2015-05-26 | 2019-12-03 | Wisconsin Alumni Research Foundation | (20S)-1-α,25-dihydroxy-24,24-difluoro-19-nor-vitamin D3 analogs and their pharmaceutical uses |
| JP2019533022A (ja) | 2016-10-24 | 2019-11-14 | ユマニティ セラピューティクス，インコーポレーテッド | 化合物及びその使用 |
| EP3566055B1 (en) | 2017-01-06 | 2025-03-12 | Janssen Pharmaceutica NV | Scd inhibitor for the treatment of neurological disorders |
| CA3083000A1 (en) | 2017-10-24 | 2019-05-02 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| WO2019183587A1 (en) | 2018-03-23 | 2019-09-26 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| WO2020154571A1 (en) | 2019-01-24 | 2020-07-30 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
| EA202192047A1 (ru) | 2019-11-13 | 2021-12-08 | Юманити Терапьютикс, Инк. | Соединения и их применение |
| KR20250075704A (ko) | 2022-09-30 | 2025-05-28 | 익스텐드 바이오사이언시즈, 인크. | 장기-지속형 부갑상선 호르몬 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1333616C (en) | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
| US5246925A (en) | 1989-03-09 | 1993-09-21 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D compounds for use in treating hyperparathyroidism |
| US5086191A (en) | 1991-05-28 | 1992-02-04 | Wisconsin Alumni Research Foundation | Intermediates for the synthesis of 19-nor vitamin D compounds |
| DE69400495T2 (de) | 1993-04-05 | 1997-04-30 | Wisconsin Alumni Res Found | 19-Nor-vitamin-D3-Verbindung mit einem Substituent an die 2. Stelle |
| US5552392A (en) | 1993-11-03 | 1996-09-03 | Wisconsin Alumni Research Foundation | Method of treating hypoparathyroidism with (20S) vitamin D compounds |
| US5843928A (en) | 1997-03-17 | 1998-12-01 | Wisconsin Alumni Research Foundation | 2-alkylidene-19-nor-vitamin D compounds |
| US5945410A (en) | 1997-03-17 | 1999-08-31 | Wisconsin Alumni Research Foundation | 2-alkyl-19-nor-vitamin D compounds |
| US6392071B1 (en) | 1997-03-17 | 2002-05-21 | Wisconsin Alumni: Research Foundation | 26,27-homologated-20-EPI-2-alkylidene-19-nor-vitamin D compounds |
| EP1745787B1 (en) * | 1999-04-01 | 2016-11-09 | Johns Hopkins University | NON-CALCEMIC, ANTIPROLIFERATIVE, TRANSCRIPTIONALLY ACTIVE SULFUR-CONTAINING ANALOGS OF 1-alpha 25-DIHYDROXY VITAMIN D3 |
| US7704979B2 (en) * | 2000-09-01 | 2010-04-27 | The University Of Tennessee Research Foundation | Materials and methods for the treatment or prevention of obesity |
| US6384087B1 (en) * | 2000-09-01 | 2002-05-07 | University Of Tennesseee Research Corporation, Inc. | Materials and methods for the treatment or prevention of obesity |
| WO2002020021A1 (en) | 2000-09-08 | 2002-03-14 | Wisconsin Alumni Research Foundation | 1alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol and its therapeutic applications |
| US6627622B2 (en) | 2002-02-18 | 2003-09-30 | Wisconsin Alumni Research Foundation | (20S)-1α-hydroxy-2-methylene-19-nor-bishomopregnacalciferol and its uses |
| US6566352B1 (en) | 2002-02-18 | 2003-05-20 | Wisconsin Alumni Research Foudation | 1 α-hydroxy-2-methylene-19-nor-pregnacalciferol and its uses |
| BR0307896A (pt) | 2002-03-29 | 2004-12-07 | Wisconsin Alumni Res Found | Método de produção de 1(alfa)-hidroxi-2-metileno-19-nor-homopregnacalcif erol |
| AU2004266706B2 (en) | 2003-08-20 | 2009-07-30 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-vitamin D2 compounds |
| CA2539361A1 (en) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an estrogen agonist/antagonist |
| WO2005027913A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a growth hormone secretagogue |
| WO2005027929A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an estrogen |
| WO2005027931A1 (en) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an ep2 or ep4 selective agonist |
| KR20060058133A (ko) * | 2003-09-19 | 2006-05-29 | 화이자 프로덕츠 인코포레이티드 | 2-알킬리덴-19-노르-비타민 ｄ 유도체 및 부갑상선호르몬의 조합을 포함하는 약학 조성물 및 방법 |
| AU2005309804B9 (en) * | 2004-11-22 | 2011-12-08 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-(20S)-1alpha-hydroxy-bishomopregnacalciferol and its uses |
| JP2008520689A (ja) * | 2004-11-22 | 2008-06-19 | ウィスコンシン・アルムニ・リサーチ・ファウンデーション | １９，２６，２７−トリノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３の２α−メチルおよび２β−メチル類似体およびそれらの使用 |
-
2004
- 2004-11-24 CA CA002544502A patent/CA2544502A1/en not_active Abandoned
- 2004-11-24 WO PCT/US2004/039625 patent/WO2005051323A2/en not_active Ceased
- 2004-11-24 AU AU2004293092A patent/AU2004293092A1/en not_active Abandoned
- 2004-11-24 US US10/997,698 patent/US8188064B2/en not_active Expired - Fee Related
- 2004-11-24 EP EP04812196A patent/EP1689412A4/en not_active Withdrawn
- 2004-11-24 JP JP2006541728A patent/JP2007512376A/ja not_active Abandoned
- 2004-11-24 MX MXPA06005887A patent/MXPA06005887A/es active IP Right Grant
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|---|---|
| EP1689412A2 (en) | 2006-08-16 |
| US20050119242A1 (en) | 2005-06-02 |
| WO2005051323A3 (en) | 2005-07-07 |
| WO2005051323A2 (en) | 2005-06-09 |
| AU2004293092A1 (en) | 2005-06-09 |
| EP1689412A4 (en) | 2009-03-11 |
| MXPA06005887A (es) | 2006-06-27 |
| JP2007512376A (ja) | 2007-05-17 |
| US8188064B2 (en) | 2012-05-29 |
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