JP4405594B2 - 改良型固相ペプチド合成及びかかる合成において利用するための試薬 - Google Patents
改良型固相ペプチド合成及びかかる合成において利用するための試薬 Download PDFInfo
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- JP4405594B2 JP4405594B2 JP51316698A JP51316698A JP4405594B2 JP 4405594 B2 JP4405594 B2 JP 4405594B2 JP 51316698 A JP51316698 A JP 51316698A JP 51316698 A JP51316698 A JP 51316698A JP 4405594 B2 JP4405594 B2 JP 4405594B2
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
- C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Prostheses (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK97196 | 1996-09-09 | ||
| DK0971/96 | 1996-09-09 | ||
| PCT/DK1997/000375 WO1998011125A1 (en) | 1996-09-09 | 1997-09-09 | Improved solid-phase peptide synthesis and agent for use in such synthesis |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001500134A JP2001500134A (ja) | 2001-01-09 |
| JP2001500134A5 JP2001500134A5 (https=) | 2005-06-16 |
| JP4405594B2 true JP4405594B2 (ja) | 2010-01-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51316698A Expired - Fee Related JP4405594B2 (ja) | 1996-09-09 | 1997-09-09 | 改良型固相ペプチド合成及びかかる合成において利用するための試薬 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7348404B2 (https=) |
| EP (1) | EP0929567B1 (https=) |
| JP (1) | JP4405594B2 (https=) |
| AT (1) | ATE290014T1 (https=) |
| AU (1) | AU723268B2 (https=) |
| CA (1) | CA2265900C (https=) |
| CZ (1) | CZ295838B6 (https=) |
| DE (1) | DE69732640T2 (https=) |
| DK (1) | DK0929567T3 (https=) |
| ES (1) | ES2239364T3 (https=) |
| HU (1) | HU230354B1 (https=) |
| IL (1) | IL128829A (https=) |
| PT (1) | PT929567E (https=) |
| WO (1) | WO1998011125A1 (https=) |
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| US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
| US7550425B2 (en) | 2000-06-16 | 2009-06-23 | Zealand Pharma A/S | Diuretic peptide conjugates |
| DK1737889T3 (da) | 2004-10-19 | 2011-01-03 | Lonza Ag | Fremgangsmåde til fastfase-peptidsyntese |
| DE602006020123D1 (de) | 2005-05-04 | 2011-03-31 | Zealand Pharma As | Glucagon-like-peptide-2- (glp-2-) analoga |
| GB0514071D0 (en) | 2005-07-07 | 2005-08-17 | Zealand Pharma As | N- or C- terminally modified small peptides |
| US20090171097A1 (en) * | 2005-11-22 | 2009-07-02 | Hiroshi Sugiyama | Automated solid phase synthesis of pyrrole-imidazole polyamide |
| UA96283C2 (uk) | 2005-12-23 | 2011-10-25 | Зіланд Фарма А/С | Модифіковані міметики лізину |
| KR100859972B1 (ko) | 2006-02-20 | 2008-09-25 | 이화여자대학교 산학협력단 | 막투과 단백질 도메인 펩타이드 |
| JP5328345B2 (ja) * | 2006-03-29 | 2013-10-30 | 株式会社糖鎖工学研究所 | ペプチドのチオエステル化合物の製造方法 |
| AU2007319066B2 (en) | 2006-11-08 | 2013-09-19 | Zealand Pharma A/S | Selective glucagon-like-peptide-2 (GLP-2) analogues |
| JP5385266B2 (ja) | 2007-06-15 | 2014-01-08 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| US8685919B2 (en) | 2008-12-15 | 2014-04-01 | Zealand Pharma A/S | Glucagon analogues |
| WO2010070255A1 (en) | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| KR20110126592A (ko) | 2008-12-15 | 2011-11-23 | 질랜드 파마 에이/에스 | 글루카곤 유사체 |
| JP5635531B2 (ja) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン類似体 |
| AP3329A (en) | 2009-07-13 | 2015-06-30 | Zealand Pharma As | Acylated glucagon analogues |
| EA023925B1 (ru) | 2010-04-27 | 2016-07-29 | Зилэнд Фарма А/С | Пептидные конъюгаты агонистов рецептора glp-1 и их применение |
| UY33462A (es) | 2010-06-23 | 2012-01-31 | Zealand Pharma As | Analogos de glucagon |
| PH12012502472A1 (en) | 2010-06-24 | 2013-03-25 | Zealand Pharma As | Glucagon analogues |
| KR20140043709A (ko) | 2011-01-20 | 2014-04-10 | 질랜드 파마 에이/에스 | 아실화 글루카곤 유사체와 인슐린 유사체의 조합 |
| MX2014005351A (es) | 2011-11-03 | 2014-05-28 | Zealand Pharma As | Conjugados de gastrina peptidicos de agonistas de receptor glp-1. |
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| WO2013098408A1 (en) | 2011-12-30 | 2013-07-04 | Zealand Pharma A/S | Glucagon and cck receptor agonist peptide conjugates |
| TW201336864A (zh) | 2012-02-03 | 2013-09-16 | Zealand Pharma As | 胃飢餓素（ｇｈｒｅｌｉｎ）類似物 |
| JP6228187B2 (ja) | 2012-05-03 | 2017-11-08 | ジーランド ファーマ アクティーゼルスカブ | Ｇｉｐ−ｇｌｐ−１デュアルアゴニスト化合物及び方法 |
| AU2013255752B2 (en) | 2012-05-03 | 2017-11-09 | Zealand Pharma A/S | Glucagon-like-peptide-2 (GLP-2) analogues |
| AU2013295035B2 (en) | 2012-07-23 | 2017-08-03 | Zealand Pharma A/S | Glucagon analogues |
| TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
| RS60280B1 (sr) | 2013-03-12 | 2020-06-30 | Molecular Templates Inc | Citotoksični proteini koji sadrže ciljane vezujuće regione za ćelije i regioni shiga toksina a podjedinice za selektivno ubijanje određenih vrsta ćelija |
| US9695214B2 (en) | 2013-03-15 | 2017-07-04 | Massachusetts Institute Of Technology | Solid phase peptide synthesis processes and associated systems |
| US9169287B2 (en) | 2013-03-15 | 2015-10-27 | Massachusetts Institute Of Technology | Solid phase peptide synthesis processes and associated systems |
| WO2014147129A1 (en) | 2013-03-21 | 2014-09-25 | Sanofi-Aventis Deutschland Gmbh | Synthesis of cyclic imide containing peptide products |
| CN105189465B (zh) | 2013-03-21 | 2019-02-26 | 赛诺菲-安万特德国有限公司 | 合成含有乙内酰脲的肽产物 |
| US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
| WO2015055801A1 (en) | 2013-10-17 | 2015-04-23 | Zealand Pharma A/S | Acylated glucagon analogues |
| MX2016005556A (es) | 2013-11-06 | 2016-07-15 | Zealand Pharma As | Compuestos agonistas duales de gip-glp-1 y procedimientos. |
| AU2014345570B2 (en) | 2013-11-06 | 2019-01-24 | Zealand Pharma A/S | Glucagon-GLP-1-GIP triple agonist compounds |
| WO2015100246A1 (en) | 2013-12-24 | 2015-07-02 | Ossianix, Inc. | Baff selective binding compounds and related methods |
| CN111909278B (zh) | 2014-01-27 | 2024-04-09 | 分子模板公司 | Mhc i类表位递送多肽 |
| WO2017019623A2 (en) | 2015-07-26 | 2017-02-02 | Molecular Templates, Inc. | Cell-targeting molecules comprising shiga toxin a subunit effectors and cd8+ t-cell epitopes |
| AU2015229583B2 (en) | 2014-03-11 | 2020-07-09 | Molecular Templates, Inc. | Proteins comprising amino-terminal proximal Shiga toxin A Subunit effector regions and cell-targeting immunoglobulin-type binding regions |
| ES2723774T3 (es) | 2014-03-11 | 2019-09-02 | Molecular Templates Inc | Proteínas que comprenden regiones de unión, regiones efectoras de la subunidad A de toxina Shiga y motivos señal de localización de retículo endoplasmático carboxi terminal |
| ES2919749T3 (es) | 2014-06-11 | 2022-07-28 | Molecular Templates Inc | Moléculas dirigidas a células citotóxicas resistentes a la escisión por proteasa |
| US10479990B2 (en) | 2014-06-26 | 2019-11-19 | Ossianix, Inc. | Semi-synthetic nurse shark VNAR libraries for making and using selective binding compounds |
| US10253078B2 (en) | 2014-10-29 | 2019-04-09 | Zealand Pharma A/S | GIP agonist compounds and methods |
| WO2016077840A2 (en) | 2014-11-14 | 2016-05-19 | Ossianix, Inc. | TfR SELECTIVE BINDING COMPOUNDS AND RELATED METHODS |
| MX2017010072A (es) | 2015-02-05 | 2017-11-09 | Molecular Templates Inc | Moleculas multivalentes que se enlazan a cd20, las cuales comprenden regiones efectoras de la subunidad a de la toxina shiga, y composiciones enriquecidas de las mismas. |
| AR103954A1 (es) | 2015-03-18 | 2017-06-14 | Zealand Pharma As | Análogos de amilina |
| GB201506380D0 (en) | 2015-04-15 | 2015-05-27 | Serodus Asa | Materials and methods for treatment of pulmonary hypertension |
| US10336802B2 (en) | 2015-04-16 | 2019-07-02 | Zealand Pharma A/S | Acylated glucagon analogue |
| AU2016271124C1 (en) | 2015-05-30 | 2020-05-14 | Molecular Templates, Inc. | De-immunized, Shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same |
| JP2018530543A (ja) | 2015-09-17 | 2018-10-18 | マサチューセッツ インスティテュート オブ テクノロジー | 固相ペプチド合成のための方法およびシステム |
| CA3033082A1 (en) | 2016-08-06 | 2018-02-15 | Ossianix, Inc. | In vivo methods for selecting peptides that cross the blood brain barrier, related compositions and methods of use |
| TWI784968B (zh) | 2016-09-09 | 2022-12-01 | 丹麥商西蘭製藥公司 | 澱粉素類似物 |
| WO2018104558A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Acylated glp-1/glp-2 dual agonists |
| WO2018104559A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Glp-1/glp-2 dual agonists |
| JP2020500890A (ja) | 2016-12-09 | 2020-01-16 | ジーランド・ファーマ・ア／エス | Ｇｌｐ−１／ｇｌｐ−２二重アゴニスト |
| AU2017371516C1 (en) | 2016-12-09 | 2021-09-02 | Zealand Pharma A/S | Acylated GLP-1/GLP-2 dual agonists |
| WO2018103868A1 (en) | 2016-12-09 | 2018-06-14 | Zealand Pharma A/S | Acylated glp-1/glp-2 dual agonists |
| EP3573648B1 (en) | 2017-01-25 | 2023-11-22 | Molecular Templates, Inc. | Cell-targeting molecules comprising de-immunized, shiga toxin a subunit effectors and cd8+ t-cell epitopes |
| BR112019026711A2 (pt) | 2017-06-16 | 2020-06-30 | Zealand Pharma A/S | regimes de dosagem para a administração de análogos de peptídeo semelhante a glucagon- 2 (glp-2) |
| CA3080351A1 (en) | 2017-11-02 | 2019-05-09 | Ossianix, Inc. | Improved tfr-selective binding peptides capable of crossing the blood brain barrier |
| PE20201254A1 (es) | 2018-02-27 | 2020-11-16 | Zp Spv 3 K/S | Analogos de compstatina y sus usos medicos |
| AU2019257343A1 (en) | 2018-04-17 | 2020-09-10 | Molecular Templates, Inc. | HER2-targeting molecules comprising de-immunized, Shiga toxin A Subunit scaffolds |
| WO2019246288A1 (en) | 2018-06-22 | 2019-12-26 | Ossianix, Inc. | Anti-cd98hc vnars for crossing the blood brain barrier and type iv vnar libraries |
| MY204234A (en) | 2018-08-27 | 2024-08-16 | Regeneron Pharma | Use of raman spectroscopy in downstream purification |
| US12351642B2 (en) | 2018-09-14 | 2025-07-08 | Ossianix, Inc. | TFR-specific binding moieties and transcytosis method to select VNARs that cross cellular barriers |
| WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
| AR119677A1 (es) | 2019-01-23 | 2022-01-05 | Millennium Pharm Inc | Dominios de unión anti-cd38 |
| CN113454108B (zh) | 2019-01-23 | 2025-02-14 | 米伦纽姆医药公司 | 包含去免疫化志贺菌毒素a亚基效应子的cd38结合蛋白 |
| BR112021020941A2 (pt) | 2019-06-14 | 2021-12-21 | Zealand Pharma As | Composição farmacêutica parenteral isotônica, método para melhoria da estabilidade química da dita composição e uso de manitol |
| ES3049784T3 (en) | 2019-08-27 | 2025-12-18 | Zp Spv 3 K/S | Compstatin analogues and their medical uses |
| WO2021055816A1 (en) | 2019-09-18 | 2021-03-25 | Molecular Templates, Inc. | Pd-l1 binding molecules comprising shiga toxin a subunit scaffolds |
| EP4031162A1 (en) | 2019-09-20 | 2022-07-27 | Zealand Pharma A/S | Kv1.3 blockers |
| WO2021102445A1 (en) | 2019-11-24 | 2021-05-27 | Molecular Templates, Inc. | Uses of cd20-binding molecules and additional therapeutic agents |
| EP4126003A1 (en) | 2020-03-30 | 2023-02-08 | Zealand Pharma A/S | Glp-1/glp-2 dual agonists |
| EP4126004A1 (en) | 2020-03-30 | 2023-02-08 | Zealand Pharma A/S | Agonist combination |
| MX2023000679A (es) | 2020-07-16 | 2023-04-18 | Zp Spv 3 K/S | Inhibidores del factor c3 del complemento y sus usos medicos. |
| WO2022103769A1 (en) | 2020-11-11 | 2022-05-19 | Ossianix, Inc. | High affinity human and monkey specific tfr-1 vnars |
| TW202241491A (zh) | 2020-12-16 | 2022-11-01 | 丹麥商西蘭製藥公司 | Ｇｌｐ－１／ｇｌｐ－２雙重促效劑之醫藥組合物 |
| TW202241492A (zh) | 2020-12-16 | 2022-11-01 | 丹麥商西蘭製藥公司 | Ｇｌｐ－１／ｇｌｐ－２雙重促效劑之醫藥組合物 |
| JP7809117B2 (ja) | 2020-12-16 | 2026-01-30 | ジーランド ファーマ エー／エス | Ｇｌｐ－１／ｇｌｐ－２デュアルアゴニストの医薬組成物 |
| US20240316155A1 (en) | 2021-02-18 | 2024-09-26 | Zealand Pharma A/S | Composition for treating short bowel syndrome |
| WO2022197945A1 (en) | 2021-03-17 | 2022-09-22 | Molecular Templates, Inc. | Pd-l1 binding proteins comprising shiga toxin a subunit scaffolds and cd8+ t cell antigens |
| CA3208713A1 (en) | 2021-03-23 | 2022-09-29 | Henrik Fischer MUNCH | Kv1.3 blockers |
| WO2022260877A1 (en) | 2021-06-07 | 2022-12-15 | Ossianix, Inc. | Shark vnars for treating covid-19 |
| TW202317606A (zh) | 2021-06-18 | 2023-05-01 | 大陸商北京拓界生物醫藥科技有限公司 | 胰高血糖素類似物及其醫藥用途 |
| EP4388001A1 (en) | 2021-08-17 | 2024-06-26 | Ossianix, Inc. | Deimmunized vnar domains and scaffolds |
| AU2022339044A1 (en) | 2021-09-03 | 2024-03-14 | Zealand Pharma A/S | Dosage regime |
| CN118354781A (zh) | 2021-12-01 | 2024-07-16 | 西兰制药公司 | 白介素-23受体的肽抑制剂 |
| WO2024068848A1 (en) | 2022-09-28 | 2024-04-04 | Zealand Pharma A/S | Methods for treating obesity |
| CN120265307A (zh) | 2022-10-18 | 2025-07-04 | 西兰制药公司 | 抑制剂 |
| WO2024168411A1 (pt) * | 2023-02-15 | 2024-08-22 | Proteimax Bio Technology Israel Ltd | Aditivo de alimento e/ou suplemento alimentar, processo de obtenção, formulação de alimento funcional e/ou suplemento alimentar, uso |
| EP4471048A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| EP4471049A1 (en) | 2023-06-01 | 2024-12-04 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| WO2025056677A1 (en) | 2023-09-15 | 2025-03-20 | Zealand Pharma A/S | Dasiglucagon for use in the treatment of congenital hyperinsulinism |
| TW202530247A (zh) | 2023-12-04 | 2025-08-01 | 丹麥商西蘭製藥公司 | 方法 |
| TW202528338A (zh) | 2023-12-04 | 2025-07-16 | 丹麥商西蘭製藥公司 | 方法 |
| WO2025248124A1 (en) | 2024-05-31 | 2025-12-04 | Zealand Pharma A/S | Dapiglutide for use in treating a sub-group of subjects |
| US20250381242A1 (en) | 2024-06-12 | 2025-12-18 | Invaio Sciences, Inc. | Antimicrobial peptides against citrus greening |
| US20250382332A1 (en) | 2024-06-12 | 2025-12-18 | Invaio Sciences, Inc. | Novel alpha-factor based peptides with antifungal activity |
| WO2025262301A1 (en) | 2024-06-20 | 2025-12-26 | Zealand Pharma A/S | Petrelintide for use in the treatment of obesity, diabetes or a disease linked to obesity or diabetes, or of reducing body weight, inhibiting weight gain or reducing food intake |
| WO2026003546A1 (en) | 2024-06-27 | 2026-01-02 | Vrg Miniprotein Zrt | Potassium ion kv1.3 channel inhibitors |
| WO2026013260A1 (en) | 2024-07-12 | 2026-01-15 | Zealand Pharma A/S | Peptide inhibitors of interleukin-23 receptor |
| WO2026052859A1 (en) | 2024-09-09 | 2026-03-12 | Zealand Pharma A/S | Treatment with dapiglutide |
| WO2026052861A1 (en) | 2024-09-09 | 2026-03-12 | Zealand Pharma A/S | Treatment with dapiglutide |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5116666A (https=) * | 1974-07-30 | 1976-02-10 | Shionogi Seiyaku Kk | |
| US5021550A (en) * | 1986-10-07 | 1991-06-04 | Thomas Jefferson University | Method for preventing deletion sequences in solid phase synthesis |
| JP2807287B2 (ja) * | 1989-10-13 | 1998-10-08 | 株式会社医学生物学研究所 | ペプチドおよびその用途 |
| CA2170030A1 (en) * | 1993-09-14 | 1995-03-23 | Robert A. Lazarus | Pharmaceutical compositions containing ecotin and homologs thereof |
| US7176282B1 (en) * | 1996-09-09 | 2007-02-13 | Zealand Pharma A/S | Solid-phase peptide synthesis and agent for use in such synthesis |
| JP4394279B2 (ja) * | 1998-03-09 | 2010-01-06 | ジーランド ファーマ アクティーゼルスカブ | 酵素加水分解に対する傾向が減少した薬理学的に活性なペプチド複合体 |
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- 1997-09-09 DK DK97939974T patent/DK0929567T3/da active
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| AU723268B2 (en) | 2000-08-24 |
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| ATE290014T1 (de) | 2005-03-15 |
| US20070004905A1 (en) | 2007-01-04 |
| EP0929567B1 (en) | 2005-03-02 |
| ES2239364T3 (es) | 2005-09-16 |
| CZ295838B6 (cs) | 2005-11-16 |
| PT929567E (pt) | 2005-07-29 |
| HUP0102900A3 (en) | 2002-02-28 |
| CA2265900C (en) | 2007-07-31 |
| DE69732640D1 (de) | 2005-04-07 |
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| CA2265900A1 (en) | 1998-03-19 |
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| US7348404B2 (en) | 2008-03-25 |
| DK0929567T3 (da) | 2005-06-27 |
| HU230354B1 (hu) | 2016-02-29 |
| CZ80399A3 (cs) | 1999-08-11 |
| AU4199397A (en) | 1998-04-02 |
| EP0929567A1 (en) | 1999-07-21 |
| HUP0102900A2 (hu) | 2002-01-28 |
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