JP2009519289A - Hcvプロドラッグ処方 - Google Patents
Hcvプロドラッグ処方 Download PDFInfo
- Publication number
- JP2009519289A JP2009519289A JP2008544952A JP2008544952A JP2009519289A JP 2009519289 A JP2009519289 A JP 2009519289A JP 2008544952 A JP2008544952 A JP 2008544952A JP 2008544952 A JP2008544952 A JP 2008544952A JP 2009519289 A JP2009519289 A JP 2009519289A
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- solid suspension
- poloxamer
- solid
- compressed tablet
- 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.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
-
- 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
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2893—Tablet coating processes
Abstract
Description
以下の組成物は、重量%に基づく処方を表す。
以下の組成物を調製する:
Claims (14)
- イソ酪酸(2R,3S,4R,5R)−5−(4−アミノ−2−オキソ−2H−ピリミジン−1−イル)−2−アジド−3,4−ビス−イソ−ブチリルオキシ−テトラヒドロ−フラン−2−イルメチルエステル塩酸塩(I)とポリエチレングリコール(PEG)/ポリプロピレングリコール(PPG)ブロックコポリマーとのホットメルト押出により調製される固体懸濁物を含む薬剤組成物。
- 更に、少なくとも1種の希釈剤、担体及び/又は賦形剤を含む、請求項1記載の組成物。
- 該PEG/PPGブロックコポリマーが、ポロキサマーである、請求項1記載の薬剤組成物。
- 更に、少なくとも1種の希釈剤、担体及び/又は賦形剤を含む、請求項3記載の薬剤組成物。
- 該組成物が、カプセル又は圧縮錠に含まれ、かつ該錠剤又は該カプセルが、場合により1種以上の担体、希釈剤及び/又は賦形剤を含む、請求項3記載の薬剤組成物。
- 該固体懸濁物が、(I)及びポロキサマー188を含む、請求項5記載の薬剤組成物。
- 該固体懸濁物が、20〜40%(重量/重量)ポロキサマー188である、請求項6記載の薬剤組成物。
- 固体懸濁物が、圧縮錠に含まれ、該錠剤が、更に場合により、微結晶性セルロース、マンニトール、クロスポビドン、コロイド状二酸化ケイ素、トウモロコシデンプン(又はタルク)、ステアリン酸マグネシウム、重炭酸ナトリウム、アルギニン、マルトデキストリン及びコーティング材料よりなる群から選択される、1種以上の賦形剤を含む、請求項7記載の薬剤組成物。
- (I)、ポロキサマー188及び可塑剤のホットメルト押出により調製される固体懸濁物を含む薬剤組成物。
- (I)とPEG/PPGブロックコポリマーとの固体懸濁物の製造方法であって、
(i) ブレンダー中で固体を混合する工程;
(ii) 生じた固体混合物をホットメルト押出機の加熱域に導入する工程[ここで、加熱域の温度は、該ブロックコポリマーの融点より高く(I)の融点より低い範囲にある];
(iii) 生じた溶融物を押し出す工程;及び
(iv) 固体懸濁物を約20〜約2000ミクロンの間の粒度まで粉砕する工程
を含む方法。 - 固体懸濁物が、約100〜約600ミクロンの間まで粉砕される、請求項13記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US75014605P | 2005-12-14 | 2005-12-14 | |
US60/750,146 | 2005-12-14 | ||
US83059406P | 2006-07-12 | 2006-07-12 | |
US60/830,594 | 2006-07-12 | ||
PCT/EP2006/069262 WO2007068615A2 (en) | 2005-12-14 | 2006-12-04 | Hcv prodrug formulation |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009519289A true JP2009519289A (ja) | 2009-05-14 |
JP5649783B2 JP5649783B2 (ja) | 2015-01-07 |
Family
ID=37806115
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008544952A Expired - Fee Related JP5649783B2 (ja) | 2005-12-14 | 2006-12-04 | Hcvプロドラッグ処方 |
Country Status (21)
Country | Link |
---|---|
US (1) | US7795237B2 (ja) |
EP (1) | EP1962808B1 (ja) |
JP (1) | JP5649783B2 (ja) |
KR (1) | KR20080089344A (ja) |
AR (1) | AR058313A1 (ja) |
AT (1) | ATE482690T1 (ja) |
AU (1) | AU2006326130B2 (ja) |
BR (1) | BRPI0619890A2 (ja) |
CA (1) | CA2631498A1 (ja) |
CR (1) | CR10026A (ja) |
DE (1) | DE602006017257D1 (ja) |
DK (1) | DK1962808T3 (ja) |
EC (1) | ECSP088528A (ja) |
IL (1) | IL191791A (ja) |
MA (1) | MA30056B1 (ja) |
NO (1) | NO20082563L (ja) |
PL (1) | PL1962808T3 (ja) |
PT (1) | PT1962808E (ja) |
RU (1) | RU2435592C2 (ja) |
TW (1) | TWI382840B (ja) |
WO (1) | WO2007068615A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014500869A (ja) * | 2010-11-09 | 2014-01-16 | エフ.ホフマン−ラ ロシュ アーゲー | Hcv感染症を処置するための医薬組成物 |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2005072710A2 (en) * | 2004-01-28 | 2005-08-11 | Johns Hopkins University | Drugs and gene carrier particles that rapidly move through mucous barriers |
CN101516339B (zh) * | 2006-08-16 | 2012-06-13 | 诺瓦提斯公司 | 制备高度结晶的治疗化合物的固体分散体的方法 |
DE602007012559D1 (de) * | 2006-09-08 | 2011-03-31 | Univ Johns Hopkins | H die schleimhaut |
WO2008119659A2 (en) * | 2007-03-29 | 2008-10-09 | F. Hoffmann-La Roche Ag | Pharmaceutical composition and process |
ES2513415T3 (es) * | 2009-01-21 | 2014-10-27 | F. Hoffmann-La Roche Ag | Composiciones farmacéuticas que comprenden un profármaco inhibidor de la polimerasa del VHC |
AR075180A1 (es) * | 2009-01-29 | 2011-03-16 | Novartis Ag | Formulaciones orales solidas de una pirido-pirimidinona |
GB0909680D0 (en) | 2009-06-05 | 2009-07-22 | Euro Celtique Sa | Dosage form |
CN102725303B (zh) | 2010-01-28 | 2015-05-27 | 里博科学有限责任公司 | 作为抗hcv化合物的4’-叠氮基-核苷 |
KR101858797B1 (ko) | 2010-05-10 | 2018-05-16 | 유로-셀티큐 에스.에이. | 히드로모르폰 및 날록손을 포함하는 제약 조성물 |
CA2798885C (en) | 2010-05-10 | 2014-11-18 | Euro-Celtique S.A. | Combination of active loaded granules with additional actives |
KR20130030261A (ko) | 2010-05-10 | 2013-03-26 | 유로-셀티큐 에스.에이. | 활성제-무함유 과립 및 그를 포함하는 정제의 제조 |
EP2635254B1 (en) * | 2010-11-05 | 2019-05-15 | The John Hopkins University | Compositions and methods relating to reduced mucoadhesion |
WO2012062691A1 (en) * | 2010-11-09 | 2012-05-18 | F. Hoffmann-La Roche Ag | Pharmaceutical compositions for treating hcv infections |
JP5917964B2 (ja) * | 2012-03-19 | 2016-05-18 | 富士ゼロックス株式会社 | 錠剤、錠剤の製造方法、錠剤管理装置、錠剤照合装置及びプログラム |
US9827191B2 (en) | 2012-05-03 | 2017-11-28 | The Johns Hopkins University | Compositions and methods for ophthalmic and/or other applications |
EP4008355A1 (en) * | 2012-05-03 | 2022-06-08 | Kala Pharmaceuticals, Inc. | Pharmaceutical nanoparticles showing improved mucosal transport |
JP6360040B2 (ja) | 2012-05-03 | 2018-07-18 | カラ ファーマシューティカルズ インコーポレイテッド | 粘液浸透性被覆粒子、組成物、医薬組成物、医薬製剤、及びそれらの形成方法 |
US11596599B2 (en) | 2012-05-03 | 2023-03-07 | The Johns Hopkins University | Compositions and methods for ophthalmic and/or other applications |
WO2014127214A1 (en) | 2013-02-15 | 2014-08-21 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
AU2014219024B2 (en) | 2013-02-20 | 2018-04-05 | KALA BIO, Inc. | Therapeutic compounds and uses thereof |
US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
AU2014342042B2 (en) | 2013-11-01 | 2017-08-17 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
CN112716955A (zh) | 2013-11-13 | 2021-04-30 | 欧洲凯尔特公司 | 用于治疗疼痛和阿片样物质肠功能障碍综合征的氢***酮和纳洛酮 |
CA3036336A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
BR112019004463A2 (pt) | 2016-09-08 | 2019-05-28 | Kala Pharmaceuticals Inc | formas cristalinas de compostos terapêuticos, seus processos de obtenção e seus métodos de uso |
US10392399B2 (en) | 2016-09-08 | 2019-08-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
EP3381479A1 (de) * | 2017-03-29 | 2018-10-03 | ARTOSS GmbH | Trägerzusammensetzung für knochenersatzmaterialien |
Citations (2)
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JP2001520984A (ja) * | 1997-10-27 | 2001-11-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 水難溶性薬剤の固態溶剤及び固体分散体 |
WO2004046159A1 (en) * | 2002-11-19 | 2004-06-03 | F. Hoffmann-La-Roche Ag | Antiviral nucleoside derivatives |
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PT1014941E (pt) * | 1996-06-26 | 2009-07-08 | Univ Texas | Formulação farmacêutica extrudível por termofusão |
CZ20033211A3 (cs) * | 2001-05-03 | 2004-09-15 | F. Hoffmann-La Roche Ag | Farmaceutická léková forma amorfního nelfinavir mesylátu |
DE10208344A1 (de) * | 2002-02-27 | 2003-09-04 | Roehm Gmbh | Schmelzextrusion von Wirkstoffsalzen |
US20050044529A1 (en) * | 2003-08-20 | 2005-02-24 | Microsoft Corporation | Task library of task data for a plurality of components on a computer system |
US20050048112A1 (en) * | 2003-08-28 | 2005-03-03 | Jorg Breitenbach | Solid pharmaceutical dosage form |
-
2006
- 2006-12-04 WO PCT/EP2006/069262 patent/WO2007068615A2/en active Application Filing
- 2006-12-04 RU RU2008128361/15A patent/RU2435592C2/ru not_active IP Right Cessation
- 2006-12-04 EP EP06830328A patent/EP1962808B1/en active Active
- 2006-12-04 AU AU2006326130A patent/AU2006326130B2/en not_active Ceased
- 2006-12-04 AT AT06830328T patent/ATE482690T1/de active
- 2006-12-04 PL PL06830328T patent/PL1962808T3/pl unknown
- 2006-12-04 CA CA002631498A patent/CA2631498A1/en not_active Abandoned
- 2006-12-04 BR BRPI0619890-2A patent/BRPI0619890A2/pt not_active IP Right Cessation
- 2006-12-04 KR KR1020087014073A patent/KR20080089344A/ko not_active Application Discontinuation
- 2006-12-04 DE DE602006017257T patent/DE602006017257D1/de active Active
- 2006-12-04 JP JP2008544952A patent/JP5649783B2/ja not_active Expired - Fee Related
- 2006-12-04 PT PT06830328T patent/PT1962808E/pt unknown
- 2006-12-04 DK DK06830328.8T patent/DK1962808T3/da active
- 2006-12-12 TW TW095146501A patent/TWI382840B/zh not_active IP Right Cessation
- 2006-12-12 AR ARP060105459A patent/AR058313A1/es not_active Application Discontinuation
- 2006-12-13 US US11/637,999 patent/US7795237B2/en not_active Expired - Fee Related
-
2008
- 2008-05-28 CR CR10026A patent/CR10026A/es not_active Application Discontinuation
- 2008-05-28 IL IL191791A patent/IL191791A/en not_active IP Right Cessation
- 2008-06-02 NO NO20082563A patent/NO20082563L/no not_active Application Discontinuation
- 2008-06-12 EC EC2008008528A patent/ECSP088528A/es unknown
- 2008-06-16 MA MA31038A patent/MA30056B1/fr unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2001520984A (ja) * | 1997-10-27 | 2001-11-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 水難溶性薬剤の固態溶剤及び固体分散体 |
WO2004046159A1 (en) * | 2002-11-19 | 2004-06-03 | F. Hoffmann-La-Roche Ag | Antiviral nucleoside derivatives |
Non-Patent Citations (1)
Title |
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JPN6012023447; JOURNAL OF PHARMACEUTICAL SCIENCES VOL.94, NO.11, 200511, P.2463-2474 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014500869A (ja) * | 2010-11-09 | 2014-01-16 | エフ.ホフマン−ラ ロシュ アーゲー | Hcv感染症を処置するための医薬組成物 |
Also Published As
Publication number | Publication date |
---|---|
RU2435592C2 (ru) | 2011-12-10 |
JP5649783B2 (ja) | 2015-01-07 |
US20070202175A1 (en) | 2007-08-30 |
PL1962808T3 (pl) | 2011-03-31 |
AR058313A1 (es) | 2008-01-30 |
TW200803873A (en) | 2008-01-16 |
EP1962808B1 (en) | 2010-09-29 |
IL191791A0 (en) | 2008-12-29 |
TWI382840B (zh) | 2013-01-21 |
MA30056B1 (fr) | 2008-12-01 |
IL191791A (en) | 2011-06-30 |
US7795237B2 (en) | 2010-09-14 |
AU2006326130A1 (en) | 2007-06-21 |
DK1962808T3 (da) | 2010-11-08 |
ECSP088528A (es) | 2008-07-30 |
KR20080089344A (ko) | 2008-10-06 |
WO2007068615A3 (en) | 2007-09-07 |
NO20082563L (no) | 2008-07-03 |
ATE482690T1 (de) | 2010-10-15 |
DE602006017257D1 (de) | 2010-11-11 |
PT1962808E (pt) | 2010-10-29 |
CA2631498A1 (en) | 2007-06-21 |
AU2006326130B2 (en) | 2011-09-22 |
CR10026A (es) | 2008-07-29 |
RU2008128361A (ru) | 2010-01-20 |
BRPI0619890A2 (pt) | 2011-10-25 |
EP1962808A2 (en) | 2008-09-03 |
WO2007068615A2 (en) | 2007-06-21 |
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