CA2841960A1 - Novel compositions and methods for treating prostate cancer - Google Patents
Novel compositions and methods for treating prostate cancer Download PDFInfo
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- CA2841960A1 CA2841960A1 CA2841960A CA2841960A CA2841960A1 CA 2841960 A1 CA2841960 A1 CA 2841960A1 CA 2841960 A CA2841960 A CA 2841960A CA 2841960 A CA2841960 A CA 2841960A CA 2841960 A1 CA2841960 A1 CA 2841960A1
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Classifications
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- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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Landscapes
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- Dispersion Chemistry (AREA)
- Urology & Nephrology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201161508823P | 2011-07-18 | 2011-07-18 | |
| US61/508,823 | 2011-07-18 | ||
| PCT/US2012/047253 WO2013012959A1 (en) | 2011-07-18 | 2012-07-18 | Novel compositions and methods for treating prostate cancer |
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| CA2841960A1 true CA2841960A1 (en) | 2013-01-24 |
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| CA2841960A Abandoned CA2841960A1 (en) | 2011-07-18 | 2012-07-18 | Novel compositions and methods for treating prostate cancer |
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| US (3) | US20140288037A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2734207A4 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2014523445A (cg-RX-API-DMAC7.html) |
| CN (1) | CN103813794A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2012284053A1 (cg-RX-API-DMAC7.html) |
| BR (1) | BR112014001440A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2841960A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2013012959A1 (cg-RX-API-DMAC7.html) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014138881A1 (en) * | 2013-03-12 | 2014-09-18 | Patheon, Inc. | Drug delivery system |
| WO2016185485A3 (en) * | 2015-05-18 | 2017-01-19 | Msn Laboratories Private Limited | Process for the preparation of n-[4-[(3-chloro-4-fluoro phenyl) amino]-7-[[(3s)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4- (dimethyl amino)-(2e)-2-butenamide (2z)-2-butenedioate (1 :2) and its polymorphs thereof |
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| KR101538810B1 (ko) | 2007-02-09 | 2015-07-22 | 메타베이시스 테라퓨틱스, 인크. | 글루카곤 수용체의 길항제 |
| US20100048914A1 (en) | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal Cyp17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
| BRPI0918004B8 (pt) | 2008-08-13 | 2021-05-25 | Metabasis Therapeutics Inc | compostos antagonistas e agonistas inversos de receptores de glucagon, composição farmacêutica e uso dos compostos |
| BRPI1008745A2 (pt) | 2009-02-05 | 2019-09-17 | Tokai Pharmaceuticals Inc | pró-fármacos de inibidores esteroidais de cyp17/antiandrogênios |
| KR20230170108A (ko) | 2012-06-04 | 2023-12-18 | 파마싸이클릭스 엘엘씨 | 브루톤 타이로신 키나아제 저해제의 결정 형태 |
| SG11201507093WA (en) * | 2013-03-14 | 2015-10-29 | Univ Maryland Baltimore Office Of Technology Transfer | Androgen receptor down-regulating agents and uses thereof |
| KR20180021932A (ko) * | 2013-03-15 | 2018-03-05 | 아이슈티카 인코포레이티드 | 아비라테론 아세테이트 제제 |
| WO2014165815A2 (en) * | 2013-04-04 | 2014-10-09 | University Of Maryland, Baltimore | Nonsteroidal and steroidal compounds with potent androgen receptor down-regulation and anti prostate cancer activity |
| CA2920317A1 (en) | 2013-08-12 | 2015-02-19 | Tokai Pharmaceuticals, Inc. | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
| EP3080141A1 (en) * | 2013-12-12 | 2016-10-19 | Basf Se | Solid form of abiraterone acetate |
| WO2015191900A1 (en) * | 2014-06-12 | 2015-12-17 | Ligand Pharmaceuticals, Inc. | Glucagon antagonists |
| US9937259B2 (en) * | 2014-06-27 | 2018-04-10 | Zhuhai Beihai Biotech Co., Ltd. | Abiraterone derivatives and non-covalent complexes with albumin |
| CA2955747A1 (en) | 2014-08-07 | 2016-02-11 | Pharmacyclics Llc | Novel formulations of a bruton's tyrosine kinase inhibitor |
| AU2015330851B2 (en) * | 2014-10-08 | 2022-10-13 | Boston Biopharm, Inc. | Compositions and methods for increasing the bioavailability of one or more compounds |
| CN105616365B (zh) * | 2014-11-08 | 2019-04-05 | 山东新时代药业有限公司 | 一种依维莫司片剂 |
| CN105732759A (zh) * | 2015-01-29 | 2016-07-06 | 苏州晶云药物科技有限公司 | (3β)-17-(1H-苯并咪唑-1-基)雄甾-5，16-二烯-3-醇的盐及其制备方法 |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| US10722527B2 (en) | 2015-04-10 | 2020-07-28 | Capsugel Belgium Nv | Abiraterone acetate lipid formulations |
| WO2016172517A1 (en) * | 2015-04-24 | 2016-10-27 | Tokai Pharmaceuticals, Inc. | Methods of treating prostate cancer |
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| CZ2019168A3 (cs) | 2019-03-20 | 2020-09-30 | Zentiva, K.S. | Farmaceutická kompozice obsahující abirateron acetát |
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Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0901786B1 (en) * | 1997-08-11 | 2007-06-13 | Pfizer Products Inc. | Solid pharmaceutical dispersions with enhanced bioavailability |
| US20030059471A1 (en) * | 1997-12-15 | 2003-03-27 | Compton Bruce Jon | Oral delivery formulation |
| CN1183154C (zh) * | 1998-04-10 | 2005-01-05 | 三菱化学株式会社 | 含有唾液酸衍生物的固体分散体 |
| UA80393C2 (uk) * | 2000-12-07 | 2007-09-25 | Алтана Фарма Аг | Фармацевтична композиція, яка містить інгібітор фде 4, диспергований в матриці |
| SE0103424D0 (sv) * | 2001-10-15 | 2001-10-15 | Astrazeneca Ab | Pharmaceutical formulation |
| WO2005053660A2 (en) * | 2003-12-03 | 2005-06-16 | Lifecycle Pharma A/S | Pharmaceutical compositions comprising danazol |
| US20060013873A1 (en) * | 2004-07-16 | 2006-01-19 | Chih-Chiang Yang | Bioadhesive dosage form of steroids |
| PT2206719E (pt) * | 2005-03-02 | 2015-02-05 | Univ Maryland | Composição farmacêutica compreendendo 3-beta-hidroxi-17- (1-h-benzimidazol-1-il)androsta-5,16-dieno |
| US20060204588A1 (en) * | 2005-03-10 | 2006-09-14 | Elan Pharma International Limited | Formulations of a nanoparticulate finasteride, dutasteride or tamsulosin hydrochloride, and mixtures thereof |
| DE102005011786A1 (de) * | 2005-03-11 | 2006-09-14 | Pharmasol Gmbh | Verfahren zur Herstellung ultrafeiner Submicron-Suspensionen |
| WO2010089763A2 (en) * | 2008-06-30 | 2010-08-12 | Reliance Life Sciences Pvt. Ltd. | Poly(n-vinyl caprolactam-co-acrylamide) microparticles for controlled release applications |
| BRPI1008745A2 (pt) * | 2009-02-05 | 2019-09-17 | Tokai Pharmaceuticals Inc | pró-fármacos de inibidores esteroidais de cyp17/antiandrogênios |
| US8791094B2 (en) * | 2009-08-07 | 2014-07-29 | Tokai Pharmaceuticals, Inc. | Treatment of prostate cancer |
-
2012
- 2012-07-18 BR BR112014001440A patent/BR112014001440A2/pt not_active IP Right Cessation
- 2012-07-18 AU AU2012284053A patent/AU2012284053A1/en not_active Abandoned
- 2012-07-18 WO PCT/US2012/047253 patent/WO2013012959A1/en not_active Ceased
- 2012-07-18 JP JP2014521743A patent/JP2014523445A/ja active Pending
- 2012-07-18 CN CN201280045417.9A patent/CN103813794A/zh active Pending
- 2012-07-18 US US14/233,335 patent/US20140288037A1/en not_active Abandoned
- 2012-07-18 EP EP12814940.8A patent/EP2734207A4/en not_active Withdrawn
- 2012-07-18 CA CA2841960A patent/CA2841960A1/en not_active Abandoned
-
2015
- 2015-07-23 US US14/807,013 patent/US20150320770A1/en not_active Abandoned
- 2015-09-15 US US14/854,513 patent/US20160002283A1/en not_active Abandoned
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014138881A1 (en) * | 2013-03-12 | 2014-09-18 | Patheon, Inc. | Drug delivery system |
| US9138425B2 (en) | 2013-03-12 | 2015-09-22 | Patheon Inc. | Drug delivery system to increase bioavailability |
| US9579387B2 (en) | 2013-03-12 | 2017-02-28 | Arno Therapeutics, Inc. | Drug delivery system to increase bioavailability |
| US10039833B2 (en) | 2013-03-12 | 2018-08-07 | Ohio State Innovation Foundation | Drug delivery system to increase bioavailability |
| WO2016185485A3 (en) * | 2015-05-18 | 2017-01-19 | Msn Laboratories Private Limited | Process for the preparation of n-[4-[(3-chloro-4-fluoro phenyl) amino]-7-[[(3s)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4- (dimethyl amino)-(2e)-2-butenamide (2z)-2-butenedioate (1 :2) and its polymorphs thereof |
| US10550107B2 (en) | 2015-05-18 | 2020-02-04 | Msn Laboratories Private Limited | Process for the preparation of N-[4-[(3-chloro-4-fluoro phenyl) amino]-7-[[(3s-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethyl amino)-(2E)-2-butenamide (2Z)-2-butenedioate (1:2) and its polymorphs thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014523445A (ja) | 2014-09-11 |
| AU2012284053A1 (en) | 2014-01-23 |
| US20140288037A1 (en) | 2014-09-25 |
| BR112014001440A2 (pt) | 2017-02-21 |
| CN103813794A (zh) | 2014-05-21 |
| US20150320770A1 (en) | 2015-11-12 |
| WO2013012959A1 (en) | 2013-01-24 |
| US20160002283A1 (en) | 2016-01-07 |
| EP2734207A4 (en) | 2015-06-17 |
| EP2734207A1 (en) | 2014-05-28 |
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