DE69841549D1 - Verfahren und zubereitungen zur zerstörung bestimmter proteine - Google Patents
Verfahren und zubereitungen zur zerstörung bestimmter proteineInfo
- Publication number
- DE69841549D1 DE69841549D1 DE69841549T DE69841549T DE69841549D1 DE 69841549 D1 DE69841549 D1 DE 69841549D1 DE 69841549 T DE69841549 T DE 69841549T DE 69841549 T DE69841549 T DE 69841549T DE 69841549 D1 DE69841549 D1 DE 69841549D1
- Authority
- DE
- Germany
- Prior art keywords
- ansamycin
- compounds
- targeting
- alone
- moiety
- 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.)
- Expired - Lifetime
Links
- 108090000623 proteins and genes Proteins 0.000 title abstract 5
- 102000004169 proteins and genes Human genes 0.000 title abstract 5
- 230000006378 damage Effects 0.000 title 1
- 238000000034 method Methods 0.000 title 1
- 238000002360 preparation method Methods 0.000 title 1
- ATEBXHFBFRCZMA-VXTBVIBXSA-N rifabutin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC(=C2N3)C(=O)C=4C(O)=C5C)C)OC)C5=C1C=4C2=NC13CCN(CC(C)C)CC1 ATEBXHFBFRCZMA-VXTBVIBXSA-N 0.000 abstract 4
- 229960000885 rifabutin Drugs 0.000 abstract 4
- 230000008685 targeting Effects 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 3
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 abstract 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 abstract 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 abstract 1
- 208000024827 Alzheimer disease Diseases 0.000 abstract 1
- 208000023275 Autoimmune disease Diseases 0.000 abstract 1
- 101100016370 Danio rerio hsp90a.1 gene Proteins 0.000 abstract 1
- 101100285708 Dictyostelium discoideum hspD gene Proteins 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 101100071627 Schizosaccharomyces pombe (strain 972 / ATCC 24843) swo1 gene Proteins 0.000 abstract 1
- 239000000427 antigen Substances 0.000 abstract 1
- 102000036639 antigens Human genes 0.000 abstract 1
- 108091007433 antigens Proteins 0.000 abstract 1
- 230000003115 biocidal effect Effects 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 230000015556 catabolic process Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000012829 chemotherapy agent Substances 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 229960005309 estradiol Drugs 0.000 abstract 1
- 229930182833 estradiol Natural products 0.000 abstract 1
- 239000003550 marker Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000008506 pathogenesis Effects 0.000 abstract 1
- 230000001717 pathogenic effect Effects 0.000 abstract 1
- 230000008684 selective degradation Effects 0.000 abstract 1
- 229960001603 tamoxifen Drugs 0.000 abstract 1
- 229960003604 testosterone Drugs 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 abstract 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D225/06—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/554—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4645197P | 1997-05-14 | 1997-05-14 | |
| PCT/US1998/009805 WO1998051702A1 (en) | 1997-05-14 | 1998-05-14 | Methods and compositions for destruction of selected proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE69841549D1 true DE69841549D1 (de) | 2010-04-22 |
Family
ID=21943529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69841549T Expired - Lifetime DE69841549D1 (de) | 1997-05-14 | 1998-05-14 | Verfahren und zubereitungen zur zerstörung bestimmter proteine |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6670348B1 (de) |
| EP (1) | EP1023315B1 (de) |
| JP (2) | JP4903922B2 (de) |
| AT (1) | ATE460423T1 (de) |
| CA (1) | CA2287387C (de) |
| DE (1) | DE69841549D1 (de) |
| WO (1) | WO1998051702A1 (de) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2330611A1 (en) * | 1998-05-22 | 1999-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and therapies based thereon |
| WO2000045805A2 (en) * | 1999-02-08 | 2000-08-10 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Methods of inhibiting the hgf-met-upa-plasmin network with geldanamycin derivates |
| EP1169319A4 (de) * | 1999-04-09 | 2005-02-09 | Sloan Kettering Institutefor C | Methoden und zusammensetzungen zum abbau und /oder zur hemmung von tyrosin-kinasen der her-familie |
| US6887842B1 (en) | 1999-11-19 | 2005-05-03 | The Board Of Trustees Of The Leland Stanford Junior University | Modulating a pharmacokinetic property of a drug by administering a bifunctional molecule containing the drug |
| AU2044001A (en) | 1999-11-19 | 2001-05-30 | Board Of Trustees Of The Leland Stanford Junior University | Targeted bifunctional molecules and therapies based thereon |
| US7220552B1 (en) | 1999-11-19 | 2007-05-22 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and their use in the disruption of protein-protein interactions |
| WO2002009696A1 (en) * | 2000-07-28 | 2002-02-07 | Sloan-Kettering Institute For Cancer Research | Methods for treating cell proliferative disorders and viral infections |
| CN1501928A (zh) | 2000-11-02 | 2004-06-02 | 斯隆-凯特林癌症研究所 | 结合hsp90的小分子组合物 |
| CA2447066A1 (en) | 2001-05-23 | 2002-11-28 | Sloan Kettering Institute For Cancer Research | Method of treatment for cancers associated with elevated |
| GB0117645D0 (en) * | 2001-07-19 | 2001-09-12 | Isis Innovation | Therapeutic stratergies for prevention and treatment of alzheimers disease |
| US6872715B2 (en) | 2001-08-06 | 2005-03-29 | Kosan Biosciences, Inc. | Benzoquinone ansamycins |
| CA2464031A1 (en) | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| EP1472230B1 (de) | 2002-02-08 | 2009-06-17 | Conforma Therapeutic Corporation | Ansamycine mit verbesserten pharmakologischen und biologischen eigenschaften |
| US7230139B2 (en) | 2002-12-05 | 2007-06-12 | Gemin X Biotechnologies | Diterpenoid compounds, compositions thereof and their use as anti-cancer or anti-fungal agents |
| CN100567242C (zh) | 2003-06-27 | 2009-12-09 | 协和发酵麒麟株式会社 | Hsp90家族蛋白质阻断剂 |
| WO2005028434A2 (en) | 2003-09-18 | 2005-03-31 | Conforma Therapeutics Corporation | Novel heterocyclic compounds as hsp90-inhibitors |
| US7259156B2 (en) * | 2004-05-20 | 2007-08-21 | Kosan Biosciences Incorporated | Geldanamycin compounds and method of use |
| WO2006034147A2 (en) * | 2004-09-16 | 2006-03-30 | Abraxis Bioscience, Inc. | Compositions and methods for the preparation and administration of poorly water soluble drugs |
| EP1799699A1 (de) * | 2004-10-13 | 2007-06-27 | Wyeth | 17-hydroxywortmannin-analoga als pi3k-hemmer |
| AU2005295788A1 (en) * | 2004-10-13 | 2006-04-27 | Wyeth | N-benzenesulfonyl substituted anilino-pyrimidine analogs |
| KR20080004550A (ko) | 2005-03-30 | 2008-01-09 | 콘포마 세러퓨틱스 코포레이션 | Ｈｓｐ９０-억제제로서 알키닐 피롤로피리미딘 및 관련유사체 |
| WO2007086943A2 (en) * | 2005-09-01 | 2007-08-02 | Beth Israel Deaconess Medical Center | Wortmannin conjugates and uses thereof |
| US20070259820A1 (en) * | 2006-05-03 | 2007-11-08 | The Regents Of The University Of Michigan | Methods and reagents for activating heat shock protein 70 |
| EP2034839B1 (de) | 2006-06-30 | 2017-08-23 | Sloan-Kettering Institute for Cancer Research | Behandlung neurodegenerativer krankheiten durch hemmung von hsp90 |
| EP2111409B1 (de) * | 2007-02-13 | 2012-06-27 | Council of Scientific & Industrial Research | Neue kationische 17-alpha-substituierte estradiolderivate als mittel gegen krebs |
| TW200845960A (en) * | 2007-04-05 | 2008-12-01 | Wyeth Corp | Wortmannin-rapalog conjugate and uses thereof |
| JP2010523566A (ja) * | 2007-04-05 | 2010-07-15 | ワイス エルエルシー | ワートマニン−ラパマイシンコンジュゲートおよびその使用 |
| NZ625593A (en) | 2009-10-07 | 2016-03-31 | Sloan Kettering Inst Cancer | Purine derivatives useful as hsp90 inhibitors |
| EP2588129A4 (de) * | 2010-06-30 | 2014-07-09 | Univ Brandeis | Auf kleine moleküle zielender proteinabbau |
| BR112013025634A2 (pt) | 2011-04-05 | 2016-07-19 | Sloan Kettering Inst Cancer | inibidores de hsp90 |
| BR112013025761A2 (pt) | 2011-04-05 | 2018-05-29 | Sloan Kettering Inst Cancer Res | inibidores de hsp90 |
| CA2861066C (en) | 2012-01-12 | 2024-01-02 | Yale University | Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase |
| EP2846784A4 (de) * | 2012-05-11 | 2016-03-09 | Univ Yale | Verbindungen zur förderung des proteinabbaus und verfahren damit |
| GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| WO2016118666A1 (en) | 2015-01-20 | 2016-07-28 | Arvinas, Inc. | Compounds and methods for the targeted degradation of the androgen receptor |
| US20170327469A1 (en) | 2015-01-20 | 2017-11-16 | Arvinas, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| CA2979070A1 (en) | 2015-03-18 | 2016-09-22 | Arvinas, Inc. | Compounds and methods for the enhanced degradation of targeted proteins |
| US20180147202A1 (en) | 2015-06-05 | 2018-05-31 | Arvinas, Inc. | TANK-BINDING KINASE-1 PROTACs AND ASSOCIATED METHODS OF USE |
| US10772962B2 (en) | 2015-08-19 | 2020-09-15 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of bromodomain-containing proteins |
| WO2018053354A1 (en) | 2016-09-15 | 2018-03-22 | Arvinas, Inc. | Indole derivatives as estrogen receptor degraders |
| AU2017341723B2 (en) | 2016-10-11 | 2021-12-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| WO2018102067A2 (en) | 2016-11-01 | 2018-06-07 | Arvinas, Inc. | Tau-protein targeting protacs and associated methods of use |
| RS64976B1 (sr) | 2016-12-01 | 2024-01-31 | Arvinas Operations Inc | Derivati tetrahidronaftalena i tetrahidroizohinolina kao degradatori estrogenih receptora |
| WO2018118598A1 (en) | 2016-12-23 | 2018-06-28 | Arvinas, Inc. | Compounds and methods for the targeted degradation of fetal liver kinase polypeptides |
| US11173211B2 (en) | 2016-12-23 | 2021-11-16 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of rapidly accelerated Fibrosarcoma polypeptides |
| AU2017382436C1 (en) | 2016-12-23 | 2021-05-27 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of Rapidly Accelerated Fibrosarcoma polypeptides |
| JP2020505327A (ja) | 2016-12-23 | 2020-02-20 | アルビナス・オペレーションズ・インコーポレイテッドＡｒｖｉｎａｓ Ｏｐｅｒａｔｉｏｎｓ， Ｉｎｃ． | Ｅｇｆｒタンパク質分解標的化キメラ分子およびその関連する使用方法 |
| US11191741B2 (en) | 2016-12-24 | 2021-12-07 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide |
| BR112019015312A2 (pt) | 2017-01-26 | 2020-03-10 | Arvinas Operations, Inc. | Moduladores da proteólise pelo receptor de estrogênio e métodos de uso associados |
| US11065231B2 (en) | 2017-11-17 | 2021-07-20 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of interleukin-1 receptor- associated kinase 4 polypeptides |
| JP2021512153A (ja) | 2018-01-26 | 2021-05-13 | イエール ユニバーシティ | タンパク質分解のイミド系モジュレーターおよび使用方法 |
| MX2020010420A (es) | 2018-04-04 | 2020-12-11 | Arvinas Operations Inc | Moduladores de la proteólisis y métodos asociados de uso. |
| WO2020041331A1 (en) | 2018-08-20 | 2020-02-27 | Arvinas Operations, Inc. | Proteolysis targeting chimeric (protac) compound with e3 ubiquitin ligase binding activity and targeting alpha-synuclein protein for treating neurodegenerative diseases |
| EP3999182A1 (de) | 2019-07-17 | 2022-05-25 | Arvinas Operations, Inc. | Gegen tau-protein gerichtete verbindungen und zugehörige verfahren zur verwendung |
| WO2021127443A1 (en) | 2019-12-19 | 2021-06-24 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of androgen receptor |
| MX2023011940A (es) | 2021-04-16 | 2023-12-07 | Arvinas Operations Inc | Moduladores de la proteolisis bcl6 y metodos de uso asociados. |
| US11957759B1 (en) | 2022-09-07 | 2024-04-16 | Arvinas Operations, Inc. | Rapidly accelerated fibrosarcoma (RAF) degrading compounds and associated methods of use |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4261989A (en) | 1979-02-19 | 1981-04-14 | Kaken Chemical Co. Ltd. | Geldanamycin derivatives and antitumor drug |
| DE3907290A1 (de) * | 1989-03-07 | 1990-09-13 | Gerhard Prof Dr Eisenbrand | Steroidhormonrezeptoraffine antitumorwirkstoffe |
| US5650430A (en) | 1990-06-06 | 1997-07-22 | Sankyo Company, Limited | Radicicol derivatives, their preparation and their anti-tumor activity |
| AU6803494A (en) * | 1993-06-07 | 1995-01-03 | British Technology Group Limited | Anticancer compounds |
| US5932566A (en) | 1994-06-16 | 1999-08-03 | Pfizer Inc. | Ansamycin derivatives as antioncogene and anticancer agents |
| US5911995A (en) * | 1994-08-19 | 1999-06-15 | Regents Of The University Of Minnesota | EGF-genistein conjugates for the treatment of cancer |
| EP0831880A4 (de) * | 1995-06-07 | 2004-12-01 | Imclone Systems Inc | Antikörper und deren fragmente zur hemmung von tumorwachstum |
| ES2216130T3 (es) | 1996-10-25 | 2004-10-16 | Kyowa Hakko Kogyo Co., Ltd. | Derivados de radicicol. |
| US5968921A (en) * | 1997-10-24 | 1999-10-19 | Orgegon Health Sciences University | Compositions and methods for promoting nerve regeneration |
-
1998
- 1998-05-14 EP EP98923415A patent/EP1023315B1/de not_active Expired - Lifetime
- 1998-05-14 CA CA2287387A patent/CA2287387C/en not_active Expired - Fee Related
- 1998-05-14 AT AT98923415T patent/ATE460423T1/de not_active IP Right Cessation
- 1998-05-14 WO PCT/US1998/009805 patent/WO1998051702A1/en active Application Filing
- 1998-05-14 JP JP54951698A patent/JP4903922B2/ja not_active Expired - Fee Related
- 1998-05-14 US US09/403,434 patent/US6670348B1/en not_active Expired - Fee Related
- 1998-05-14 DE DE69841549T patent/DE69841549D1/de not_active Expired - Lifetime
-
2009
- 2009-08-11 JP JP2009186660A patent/JP2009256388A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2009256388A (ja) | 2009-11-05 |
| CA2287387C (en) | 2010-02-16 |
| JP4903922B2 (ja) | 2012-03-28 |
| WO1998051702A1 (en) | 1998-11-19 |
| EP1023315A4 (de) | 2004-12-29 |
| US6670348B1 (en) | 2003-12-30 |
| JP2001525824A (ja) | 2001-12-11 |
| EP1023315A1 (de) | 2000-08-02 |
| ATE460423T1 (de) | 2010-03-15 |
| CA2287387A1 (en) | 1998-11-19 |
| EP1023315B1 (de) | 2010-03-10 |
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