JP4987022B2 - デコイを含む薬学的組成物およびその使用方法 - Google Patents
デコイを含む薬学的組成物およびその使用方法 Download PDFInfo
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- JP4987022B2 JP4987022B2 JP2009026797A JP2009026797A JP4987022B2 JP 4987022 B2 JP4987022 B2 JP 4987022B2 JP 2009026797 A JP2009026797 A JP 2009026797A JP 2009026797 A JP2009026797 A JP 2009026797A JP 4987022 B2 JP4987022 B2 JP 4987022B2
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/13—Decoys
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- Genetics & Genomics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Microbiology (AREA)
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- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Plant Pathology (AREA)
- Marine Sciences & Fisheries (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
JAら、Mol Pathol 1998 Apr;51(2):55−61);NF−κBデコイは、慢性関節リウマチ患者由来の滑膜細胞におけるサイトカインおよび接着分子の発現を阻害する(Tomita Tら、Rheumatology(Oxford) 2000 Jul;39(7):749−57);NF−κBを含む複数の転写因子間の協力作用の抑制は、種々の癌の悪性表現型を変える(Denhardt DT、Crit Rev Oncog 1996;7(3−4):261−91);緑茶ポリフェノールによるNF−κB活性のダウンレギュレーションは、一酸化窒素合成酵素の誘導をブロックし、A431ヒト類表皮癌細胞を抑制する(Lin JKら、Biochem Pharmacol 1999 Sep 15;58(6):911−5);アルツハイマー病患者の脳で見られるアミロイドβペプチドは、神経芽腫細胞において、75kD神経栄養因子レセプター(p75NTR)に結合することにより、NF−κBを時間依存性様式および用量依存性様式で活性化する(Kuper Pら、J
Neurosci Res 1998 Dec 15;54(6):798−804);NF−κBで活性化されるTNFαは、糸球体腎炎の発症に重要な役割を演じる(Ardaillouら、Bull Acad Natl Med 1995 Jan;179(1)103−15)。
Aug;7(15)1326−32);など。
glomerular mesangial cells is mediated by increased activities of NF−kappaB and
activating protein−1 and involves activation of the mitogen−activated protein kinase pathways. Eberhardt W、 Huwiler A、 Beck KF、 Walpen S、 Pfeilschifter J. J Immunol 2000 Nov 15、165(10)、5788−97;Nuclea
r factor kappaB activity is essential for matrix metalloproteinase−1 and −3 upregulation in rabbit dermal fibroblasts. Biochem Biophys Res Commun.Bond M、Baker AH、 Newby AC. 1999 Oct 22、264(2)、561−7;Synergistic upregulation of metalloproteinase−9 by growth factors and inflammatory
cytokines: an absolute requirement for transcription factor NF−kappa B.Bond M、 Fabunmi RP、 Baker AH、 Newby AC. FEBS Lett 1998 Sep 11、435(1)、29−34;およびLipopolysaccharide activates matrix metalloproteinase−2 in endothelial cells through an NF−kappaB−dependent pathway. Kim H、Koh G.Biochem Biophys Res Commun. 2000 Mar 16、269(2)、401−5)。
Vestergaardら.J Clin Invest 1999 104、1097−1105;Involvement of nuclear factor−kappa B activation in IgE synthesis in human B cells.Yanagihara Y、 Basaki Y、Ikizawa
K、Kajiwara K、Koshio
T、Akiyama K.J Allergy Clin Immunol 1996
Dec、98(6 Pt 2):S224−9)。
endothelial cells by the common haptens
nickel and cobalt.Goebeler M、Roth J、Brocker EB、Sorg C、Schulze−Osthoff K. J Immunol 1995 Sep 1;155(5):2459−67)。
Allergy
Clin Immunol 2000 Jun 105(6Pt1)、1146−52; Inhibition of allergic inflammation in
a murine model of asthma by
expression of a dominant−negative mutant of GATA−3、Zhang DH、Yang L、Cohn
L、Parkyn L、Homer R、Ray P、Ray A、Immunity
1999 Oct 11(4)、473−82)。
S、Okumura Y、Akiyama K、Okudaira H. J
Allergy Clin Immunol 1999 May 103(5Pt2)、S429−36; The glucocorticoid receptor gene as a candidate for gene therapy in asthma、Mathieu M、Gougat C、Jaffuel D、Danielsen M、Godard P、Bousquet J、Demoly P、Gene Ther 1999 Feb、6(2)、245−52)。
このような親水性ポリマーの例として、ヒドロキシプロピルセルロース、ポリエチレングリコールが挙げられる。本発明のデコイ化合物を、適切な溶媒中のこのような親水性ポリマーと混合し、溶媒を、風乾などの方法により除去して、所望の形態、例えば、シート状に成型した後、標的部位に付与し得る。このような親水性ポリマーを含む製剤は、水分含量が少ないので、保存性に優れ、使用の際には、水分を吸収してゲル状になるので、デコイ化合物の貯留性に優れる。このようなシートは上記の組成以外にも類似物として、セルロース、デンプン及びその誘導体あるいは合成高分子化合物などに多価アルコールを混合し硬度を調整して形成した親水性シートも利用できる。
さらに具体的な例としては、例えば、臓器梗塞等でPTCAを行う場合には、同時またはその前後に患部血管に投与することができ、また臓器移植等では移植する臓器を予め本願で用いられる製剤で処置して用いてもよい。また、例えば、慢性関節リウマチ等では、直接関節内に注入して用いることもできる。
NF−κBデコイ 10mg、ステアリルアルコール 30mg、
ワセリン 0.6g。
コントロールデコイ10 mg、ステアリルアルコール 30mg、
ワセリン 0.6g
プロトコール1:
マウス一匹あたり約1mgのNF−kBデコイまたはコントロールデコイを、上記軟膏を塗布することによって投与する;生後4週〜2週間に1度の割合で合計4回塗布し、生後12週で評価する。
マウス一匹あたり約2mgのNF−kBデコイまたはコントロールデコイを、上記軟膏を塗布することによって投与する;生後29週目に1回だけ塗布、生後30週で評価する。
Claims (7)
- 有棘層肥厚を改善するための薬学的組成物であって、少なくとも1つのNF−κBのデコイ、および薬学的に受容可能なキャリアを含む組成物であって、該デコイは2本鎖オリゴヌクレオチドまたはそのS-オリゴである組成物。
- 前記NF−κBのデコイが、NF−κBが結合し得る核酸配列を少なくとも1つ含む2本鎖オリゴヌクレオチドまたはそのS-オリゴである、請求項1に記載の組成物。
- 前記NF−κBのデコイが、配列番号1に記載された配列の一部が置換、挿入または欠失した配列を含み、かつ、NF−κB核酸結合部位と特異的に拮抗する2本鎖オリゴヌクレオチドまたはそのS-オリゴである、請求項1に記載の組成物。
- 前記NF−κBのデコイが、配列番号1に記載された配列およびその相補体を含む二本鎖核酸を含む、請求項1に記載の組成物。
- 前記少なくとも1つのNF−κBのデコイが、NF−κBに結合し得る核酸配列を1つ以上含むオリゴヌクレオチドである、請求項1に記載の組成物。
- 前記薬学的に受容可能なキャリアがワセリンを含む、請求項1〜5のいずれか1項に記載の組成物。
- 前記薬学的に受容可能なキャリアが、ワセリン、5%ステアリルアルコールを含むワセリン、または流動パラフィンを含むワセリンである、請求項1〜5のいずれか1項に記載の組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009026797A JP4987022B2 (ja) | 2001-02-20 | 2009-02-06 | デコイを含む薬学的組成物およびその使用方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001044350 | 2001-02-20 | ||
JP2001044350 | 2001-02-20 | ||
JP2009026797A JP4987022B2 (ja) | 2001-02-20 | 2009-02-06 | デコイを含む薬学的組成物およびその使用方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2005128753A Division JP4305857B2 (ja) | 2001-02-20 | 2005-04-26 | デコイを含む薬学的組成物およびその使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009102428A JP2009102428A (ja) | 2009-05-14 |
JP4987022B2 true JP4987022B2 (ja) | 2012-07-25 |
Family
ID=18906362
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2002565628A Expired - Lifetime JP3778357B2 (ja) | 2001-02-20 | 2002-02-06 | デコイを含む薬学的組成物およびその使用方法 |
JP2009026797A Expired - Lifetime JP4987022B2 (ja) | 2001-02-20 | 2009-02-06 | デコイを含む薬学的組成物およびその使用方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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JP2002565628A Expired - Lifetime JP3778357B2 (ja) | 2001-02-20 | 2002-02-06 | デコイを含む薬学的組成物およびその使用方法 |
Country Status (11)
Country | Link |
---|---|
US (2) | US9012417B2 (ja) |
EP (2) | EP1362600B1 (ja) |
JP (2) | JP3778357B2 (ja) |
AT (1) | ATE390938T1 (ja) |
CY (1) | CY1108165T1 (ja) |
DE (1) | DE60225899T2 (ja) |
DK (1) | DK1362600T3 (ja) |
ES (1) | ES2307733T3 (ja) |
PT (1) | PT1362600E (ja) |
TW (1) | TWI308492B (ja) |
WO (1) | WO2002066070A1 (ja) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT732929E (pt) * | 1993-10-29 | 2008-08-26 | Brigham & Womens Hospital | Utilização terapêutica de ''engodos'' de elementos cis in vivo |
ES2307733T3 (es) * | 2001-02-20 | 2008-12-01 | Anges Mg, Inc. | Uso topico de compuestos señuelo nf-kb para tratar la dermatitis atopica. |
DE10148886A1 (de) * | 2001-10-04 | 2003-04-30 | Avontec Gmbh | Inhibition von STAT-1 |
EP1647292A4 (en) * | 2003-05-09 | 2011-02-23 | Ryuichi Morishita | NADELLOSIS SYRINGE WITH MEDICINES RECEIVED IN IT |
AU2003252493A1 (en) * | 2003-07-09 | 2005-01-28 | Anges Mg, Inc. | Pharmaceutical composition containing decoy and method of using the same |
JPWO2005021045A1 (ja) * | 2003-08-29 | 2006-10-26 | アンジェスMg株式会社 | 針無注射器を用いた皮膚疾患の遺伝子治療 |
EP1691817A2 (en) * | 2003-12-02 | 2006-08-23 | Corgentech, Inc. | NF-kB OLIGONUCLEOTIDE DECOY MOLECULES |
US8372966B2 (en) | 2003-12-19 | 2013-02-12 | University Of Cincinnati | Oligonucleotide decoys and methods of use |
WO2006034433A2 (en) * | 2004-09-21 | 2006-03-30 | Anesiva, Inc. | Delivery of polynucleotides |
JP4921975B2 (ja) | 2004-10-22 | 2012-04-25 | アンジェスMg株式会社 | キメラ(ダブル)デコイ |
US20090214630A1 (en) * | 2005-05-10 | 2009-08-27 | Warren Strober | Compositions and Methods for the Treatment of Inflammatory Bowel Disease Utilizing NF-KappaB Decoy Polynucleotides |
US20060258604A1 (en) * | 2005-05-10 | 2006-11-16 | Warren Strober | Compositions and methods for the treatment of inflammatory bowel disease utilizing NF-kappaB decoy polynucleotides |
CA2614295A1 (en) | 2005-06-06 | 2006-12-14 | Anges Mg, Inc. | Transcription factor decoy |
WO2007013852A1 (en) * | 2005-07-27 | 2007-02-01 | Agency For Science, Technology & Research | Modulators |
WO2007072909A1 (ja) | 2005-12-22 | 2007-06-28 | Anges Mg, Inc. | 新規オリゴヌクレオチド及びそれから成るNF-κBデコイ |
WO2007071069A1 (en) * | 2005-12-22 | 2007-06-28 | Institut De Cardiologie De Montreal | Transcription factor decoy oligodeoxynucleotides having multiple cis elements |
JP4602298B2 (ja) * | 2006-08-31 | 2010-12-22 | ホソカワミクロン株式会社 | 医薬製剤 |
JP5384120B2 (ja) | 2007-02-16 | 2014-01-08 | アンジェスMg株式会社 | 歯周病、及び外科手術による歯槽骨欠損の治療剤 |
US20080249044A1 (en) * | 2007-04-03 | 2008-10-09 | Masaya Tanaka | Nucleic acid external skin formulation |
JP5646320B2 (ja) | 2007-05-11 | 2014-12-24 | アダイニクス, インコーポレイテッド | 遺伝子発現と疼痛 |
JP5674020B2 (ja) * | 2008-03-28 | 2015-02-18 | アンジェスMg株式会社 | 転写因子デコイを有効成分とする外用剤組成物 |
WO2013170086A2 (en) | 2012-05-10 | 2013-11-14 | Adynxx, Inc. | Formulations for the delivery of active ingredients |
ES2750689T3 (es) | 2014-08-15 | 2020-03-26 | Adynxx Inc | Señuelos oligonucleotídicos para el tratamiento del dolor |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2361756A (en) * | 1942-03-31 | 1944-10-31 | George W Fiero | Ointments and the like |
JPS56135416A (en) * | 1980-03-27 | 1981-10-22 | Mitsubishi Chem Ind Ltd | Pharmaceutical preparation for skin |
US4301145A (en) * | 1980-07-28 | 1981-11-17 | Cestari Joseph E | Antiseptic skin cream |
US6410516B1 (en) * | 1986-01-09 | 2002-06-25 | President & Fellows Of Harvard College | Nuclear factors associated with transcriptional regulation |
JPH05331066A (ja) * | 1992-05-25 | 1993-12-14 | Toko Yakuhin Kogyo Kk | 尋常性ざ瘡治療用組成物 |
PT732929E (pt) * | 1993-10-29 | 2008-08-26 | Brigham & Womens Hospital | Utilização terapêutica de ''engodos'' de elementos cis in vivo |
US6399376B1 (en) * | 1993-11-05 | 2002-06-04 | Isis Pharmaceuticals, Inc. | Modulation of vascular cell adhesive molecule expression through oligonucleotide interactions |
WO1996012495A1 (fr) * | 1994-10-24 | 1996-05-02 | Nikken Chemicals Co., Ltd | Preparation administrable par voie percutanee |
ATE357922T1 (de) * | 1995-05-12 | 2007-04-15 | Anges Mg Inc | Heilung und vorbeugung von durch nf-kappab verursachten erkrankungen |
KR19990071523A (ko) * | 1995-11-21 | 1999-09-27 | 해리 에이. 루스제 | Il-8 및 il-8 수용체에 대한 안티센스올리고누클레오티드에 의한 종양 성장의 억제방법 |
DE69834038D1 (de) * | 1997-07-01 | 2006-05-18 | Isis Pharmaceutical Inc | Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre |
JP2001055331A (ja) | 1999-06-11 | 2001-02-27 | Toyama Chem Co Ltd | アトピー性皮膚炎治療剤 |
CA2369491C (en) * | 2000-02-02 | 2008-09-02 | Yasufumi Kaneda | Virus envelope vector for gene transfer |
DE10049549A1 (de) * | 2000-10-06 | 2002-05-02 | Markus Hecker | Modulation der Transkription pro-inflammatorischer Genprodukte |
ES2307733T3 (es) | 2001-02-20 | 2008-12-01 | Anges Mg, Inc. | Uso topico de compuestos señuelo nf-kb para tratar la dermatitis atopica. |
DE60231063D1 (de) * | 2002-02-01 | 2009-03-19 | Anges Mg Inc | N zur behandlung von aneurysmen |
JP4971609B2 (ja) | 2004-08-27 | 2012-07-11 | アンジェスMg株式会社 | 核酸皮膚外用製剤 |
JP2006111591A (ja) | 2004-10-15 | 2006-04-27 | Anges Mg Inc | 核酸医薬を標的特異的に細胞内送達するための製剤 |
-
2002
- 2002-02-06 ES ES02711351T patent/ES2307733T3/es not_active Expired - Lifetime
- 2002-02-06 EP EP02711351A patent/EP1362600B1/en not_active Expired - Lifetime
- 2002-02-06 TW TW091102095A patent/TWI308492B/zh not_active IP Right Cessation
- 2002-02-06 WO PCT/JP2002/000990 patent/WO2002066070A1/ja active IP Right Grant
- 2002-02-06 JP JP2002565628A patent/JP3778357B2/ja not_active Expired - Lifetime
- 2002-02-06 DE DE60225899T patent/DE60225899T2/de not_active Expired - Lifetime
- 2002-02-06 DK DK02711351T patent/DK1362600T3/da active
- 2002-02-06 PT PT02711351T patent/PT1362600E/pt unknown
- 2002-02-06 AT AT02711351T patent/ATE390938T1/de active
- 2002-02-06 EP EP06004446.8A patent/EP1690544B1/en not_active Expired - Lifetime
- 2002-02-06 US US10/468,717 patent/US9012417B2/en not_active Expired - Fee Related
-
2008
- 2008-06-30 CY CY20081100682T patent/CY1108165T1/el unknown
- 2008-12-02 US US12/314,009 patent/US20090105183A1/en not_active Abandoned
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2009
- 2009-02-06 JP JP2009026797A patent/JP4987022B2/ja not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
EP1690544A2 (en) | 2006-08-16 |
WO2002066070A1 (fr) | 2002-08-29 |
EP1690544A3 (en) | 2012-03-07 |
EP1690544B1 (en) | 2017-09-13 |
EP1362600A1 (en) | 2003-11-19 |
US20090105183A1 (en) | 2009-04-23 |
ATE390938T1 (de) | 2008-04-15 |
EP1362600A4 (en) | 2005-09-21 |
DE60225899D1 (de) | 2008-05-15 |
JP2009102428A (ja) | 2009-05-14 |
JP3778357B2 (ja) | 2006-05-24 |
ES2307733T3 (es) | 2008-12-01 |
US9012417B2 (en) | 2015-04-21 |
TWI308492B (ja) | 2009-04-11 |
JPWO2002066070A1 (ja) | 2004-06-17 |
CY1108165T1 (el) | 2014-02-12 |
EP1362600B1 (en) | 2008-04-02 |
DE60225899T2 (de) | 2009-04-09 |
PT1362600E (pt) | 2008-07-09 |
DK1362600T3 (da) | 2008-07-28 |
US20040162251A1 (en) | 2004-08-19 |
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