ATE280234T1 - Expression eines fusionspolypeptides, das ohne leadersequenz aus dem cytoplasma transportiert wird - Google Patents
Expression eines fusionspolypeptides, das ohne leadersequenz aus dem cytoplasma transportiert wirdInfo
- Publication number
- ATE280234T1 ATE280234T1 AT94925175T AT94925175T ATE280234T1 AT E280234 T1 ATE280234 T1 AT E280234T1 AT 94925175 T AT94925175 T AT 94925175T AT 94925175 T AT94925175 T AT 94925175T AT E280234 T1 ATE280234 T1 AT E280234T1
- Authority
- AT
- Austria
- Prior art keywords
- polypeptide
- fusion
- cytoplasm
- expression
- leader sequence
- Prior art date
Links
- 229920001184 polypeptide Polymers 0.000 title abstract 8
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract 8
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract 8
- 230000004927 fusion Effects 0.000 title abstract 4
- 210000000805 cytoplasm Anatomy 0.000 title abstract 2
- 102000039446 nucleic acids Human genes 0.000 abstract 3
- 108020004707 nucleic acids Proteins 0.000 abstract 3
- 150000007523 nucleic acids Chemical class 0.000 abstract 3
- 102000037865 fusion proteins Human genes 0.000 abstract 2
- 108020001507 fusion proteins Proteins 0.000 abstract 2
- 210000004027 cell Anatomy 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
Classifications
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0036—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on NADH or NADPH (1.6)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/545—IL-1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- 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
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
- C07K2319/75—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/95—Fusion polypeptide containing a motif/fusion for degradation (ubiquitin fusions, PEST sequence)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/100,744 US5563046A (en) | 1993-08-02 | 1993-08-02 | Fusion polypeptides and proteins |
| PCT/US1994/008776 WO1995004076A1 (en) | 1993-08-02 | 1994-08-02 | Expression of fusion polypeptides transported out of the cytoplasm without leader sequences |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ATE280234T1 true ATE280234T1 (de) | 2004-11-15 |
Family
ID=22281315
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT94925175T ATE280234T1 (de) | 1993-08-02 | 1994-08-02 | Expression eines fusionspolypeptides, das ohne leadersequenz aus dem cytoplasma transportiert wird |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US5563046A (de) |
| EP (1) | EP0722461B1 (de) |
| JP (1) | JP3370094B2 (de) |
| AT (1) | ATE280234T1 (de) |
| AU (1) | AU688363B2 (de) |
| CA (1) | CA2168429C (de) |
| DE (1) | DE69434083T2 (de) |
| WO (1) | WO1995004076A1 (de) |
Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6221840B1 (en) * | 1991-02-14 | 2001-04-24 | The General Hospital Corporation | Intestinal trefoil proteins |
| US5914254A (en) * | 1993-08-02 | 1999-06-22 | Celtrix Pharmaceuticals, Inc. | Expression of fusion polypeptides transported out of the cytoplasm without leader sequences |
| US5948757A (en) * | 1996-03-01 | 1999-09-07 | Celtrix Pharmaceuticals, Inc. | High dose IGF-1 therapy |
| US6525018B1 (en) | 1999-05-17 | 2003-02-25 | The General Hospital Corp. | Treating eye disorders using intestinal trefoil proteins |
| US6025368A (en) * | 1997-02-25 | 2000-02-15 | Celtrix Pharmaceuticals, Inc. | Method for treating the symptoms of chronic stress-related disorders using IGF |
| US6514937B1 (en) | 1997-02-25 | 2003-02-04 | Celtrix Pharmaceuticals, Inc. | Method of treating psychological and metabolic disorders using IGF or IGF/IGFBP-3 |
| US6015786A (en) * | 1997-02-25 | 2000-01-18 | Celtrix Pharmaceuticals, Inc. | Method for increasing sex steroid levels using IGF or IGF/IGFBP-3 |
| US20030185838A1 (en) * | 2001-11-28 | 2003-10-02 | Podolsky Daniel K. | Methods and compositions for treating lesions of the respiratory epithelium |
| US20030114384A1 (en) * | 2001-11-28 | 2003-06-19 | Podolsky Daniel K. | Methods and compositions for treating lesions of the respiratory epithelium |
| US20030186882A1 (en) * | 2001-07-31 | 2003-10-02 | Podolsky Daniel K. | Methods and compositions for treating and preventing distal bowel lesions |
| US6063600A (en) * | 1997-05-23 | 2000-05-16 | Uab Research Foundation | DNA encoding canine interleukin-1 receptor antagonist |
| DE69732378D1 (de) * | 1997-05-27 | 2005-03-03 | Hanil Synthetic Fiber Co Ltd | Verfahren zur herstellung von rekombinanten eiweissen durch verwendung von hocheffizienten expressionsvektoren aus saccharomyces cerevisiae |
| US7569674B2 (en) * | 1998-05-04 | 2009-08-04 | Innexus Biotechnology International Limited | Autophilic antibodies |
| US20050033033A1 (en) * | 1998-05-04 | 2005-02-10 | Heinz Kohler | Trans-membrane-antibody induced inhibition of apoptosis |
| US20040185039A1 (en) * | 2002-08-30 | 2004-09-23 | Heinz Kohler | Therapeutic applications of noncovalent dimerizing antibodies |
| US20030103984A1 (en) * | 1998-05-04 | 2003-06-05 | Heinz Kohler | Fusion proteins of biologically active peptides and antibodies |
| US6077689A (en) * | 1997-12-24 | 2000-06-20 | Amgen Inc. | Enhanced solubility of recombinant proteins |
| US6008329A (en) * | 1998-03-06 | 1999-12-28 | The United States Of America As Represented By The Secretary Of The Army | Method for purifying cholera toxin |
| US20090208418A1 (en) * | 2005-04-29 | 2009-08-20 | Innexus Biotechnology Internaltional Ltd. | Superantibody synthesis and use in detection, prevention and treatment of disease |
| US6417330B1 (en) * | 1998-06-01 | 2002-07-09 | Celtrix Pharmaceuticals, Inc. | Insulin-like growth factor binding protein variants |
| US6436897B2 (en) | 1998-06-01 | 2002-08-20 | Celtrix Pharmaceuticals, Inc. | Pharmaceutical formulations for IGF/IGFBP |
| US7288516B1 (en) | 1999-09-20 | 2007-10-30 | Celtrix Pharmaceuticals, Inc. | Null IGF for the treatment of cancer |
| US6040292A (en) * | 1999-06-04 | 2000-03-21 | Celtrix Pharmaceuticals, Inc. | Methods for treating diabetes |
| US7262005B1 (en) | 2000-02-04 | 2007-08-28 | Aurora Biosciences Corporation | Methods of protein destabilization and uses thereof |
| CN1328055A (zh) * | 2000-06-14 | 2001-12-26 | 上海博德基因开发有限公司 | 一种新的多肽——胰岛素类似生长因子结合蛋白16.17和编码这种多肽的多核苷酸 |
| GB0021303D0 (en) * | 2000-08-30 | 2000-10-18 | Medinnova Sf | Use |
| US6632638B1 (en) | 2000-11-17 | 2003-10-14 | Amgen, Inc. | Enhanced solubility of recombinant proteins using Uracil DNA glycosylase inhibitor |
| US7538082B2 (en) * | 2001-04-24 | 2009-05-26 | The General Hospital Corporation | Methods and compositions for treating oral and esophageal lesions |
| US20060189526A1 (en) * | 2002-04-24 | 2006-08-24 | Podolsky Daniel K | Compositions containing an intestinal trefoil peptide and a mucoadhesive |
| US20030105016A1 (en) * | 2001-09-06 | 2003-06-05 | Podolsky Daniel K. | Methods and compositions for treating vaginal, cervical, and uterine epithelial lesions |
| US20040171544A1 (en) * | 2001-04-24 | 2004-09-02 | Barker Nicholas P. | Trefoil domain-containing polypeptides and uses thereof |
| KR100535265B1 (ko) * | 2001-07-26 | 2005-12-08 | (주)에이피테크놀로지 | 융합 단백질로부터 목적 단백질을 분리하는 방법 |
| US20030181384A1 (en) * | 2001-09-06 | 2003-09-25 | Podolsky Daniel K. | Methods and compositions for treating vaginal, cervical, and uterine epithelial lesions |
| US20030185839A1 (en) * | 2001-10-05 | 2003-10-02 | Podolsky Daniel K. | Methods and compositions for treating dermal lesions |
| AU2002334886B2 (en) * | 2001-10-05 | 2008-07-31 | The General Hospital Corporation | Methods and compositions for treating dermal lesions |
| US8535908B2 (en) * | 2002-01-04 | 2013-09-17 | Brookhaven Science Associates, Llc | Facilitating protein solubility by use of peptide extensions |
| CA2475388A1 (en) * | 2002-02-14 | 2003-08-21 | William J. Rutter | Chimeric molecules for cleavage in a treated host |
| CA2480372A1 (en) * | 2002-03-26 | 2003-10-09 | The General Hospital Corporation | Combination therapy using trefoil peptides |
| US7208594B2 (en) * | 2002-06-29 | 2007-04-24 | Aquanova Ag | Isoflavone concentrates as well as methods for their production |
| KR100890579B1 (ko) * | 2002-08-19 | 2009-04-27 | 프로테온 주식회사 | Rna 결합 단백질의 유전자를 융합파트너로 이용한재조합 단백질의 제조방법 |
| US7598224B2 (en) * | 2002-08-20 | 2009-10-06 | Biosurface Engineering Technologies, Inc. | Dual chain synthetic heparin-binding growth factor analogs |
| US7166574B2 (en) | 2002-08-20 | 2007-01-23 | Biosurface Engineering Technologies, Inc. | Synthetic heparin-binding growth factor analogs |
| US8227411B2 (en) | 2002-08-20 | 2012-07-24 | BioSurface Engineering Technologies, Incle | FGF growth factor analogs |
| US20060188471A1 (en) * | 2002-10-31 | 2006-08-24 | Podolsky Daniel K | Methods of treating epithelial lesions |
| EP1646650B9 (de) * | 2003-06-13 | 2010-02-03 | Insmed, Inc. | Recombinante igf expressionssysteme |
| US7985564B2 (en) * | 2003-11-21 | 2011-07-26 | Pfenex, Inc. | Expression systems with sec-system secretion |
| DK2275556T3 (da) | 2004-01-17 | 2013-07-08 | Korea Res Inst Of Bioscience | Hurtig fremgangsmåde til screening af translationsfusionspartnere til fremstilling af rekombinante proteiner og translationsfusionpartnere screenet derfra |
| US7414028B1 (en) | 2004-02-04 | 2008-08-19 | Biosurface Engineering Technologies, Inc. | Growth factor analogs |
| US20080227696A1 (en) | 2005-02-22 | 2008-09-18 | Biosurface Engineering Technologies, Inc. | Single branch heparin-binding growth factor analogs |
| US7528105B1 (en) | 2004-02-10 | 2009-05-05 | Biosurface Engineering Technologies | Heterodimeric chain synthetic heparin-binding growth factor analogs |
| US7671012B2 (en) | 2004-02-10 | 2010-03-02 | Biosurface Engineering Technologies, Inc. | Formulations and methods for delivery of growth factor analogs |
| US20060024347A1 (en) * | 2004-02-10 | 2006-02-02 | Biosurface Engineering Technologies, Inc. | Bioactive peptide coatings |
| EP1725576B1 (de) * | 2004-02-20 | 2010-09-22 | Biosurface Engineering Technologies, Inc. | Positiver modulator des knochenmorphogenetisches protein-2 (bmp-2) |
| US8211648B2 (en) * | 2005-07-22 | 2012-07-03 | Kalobios Pharmaceuticals, Inc. | Secretion of antibodies without signal peptides from bacteria |
| US7820172B1 (en) | 2006-06-01 | 2010-10-26 | Biosurface Engineering Technologies, Inc. | Laminin-derived multi-domain peptides |
| EP2046350A4 (de) | 2006-06-22 | 2011-09-14 | Biosurface Eng Tech Inc | Zusammensetzungen und verfahren zur freisetzung eines bmp-2-amplifikators/coaktivators für verstärkte osteogenese |
| EP2468869B1 (de) * | 2007-01-31 | 2015-03-18 | Pfenex Inc. | Bakterielle Leader-Sequenzen für erhöhte Expression |
| CN101969983B (zh) | 2007-04-18 | 2014-11-05 | 普利玛库尔公司 | 治疗和/或预防早产并发症的方法和产品 |
| JP5524977B2 (ja) * | 2008-12-04 | 2014-06-18 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 高分泌性蛋白質のスクリーニングおよび組換え蛋白質の生産のための融合パートナーとしてのその用途 |
| KR101291241B1 (ko) | 2010-11-04 | 2013-08-01 | 한국생명공학연구원 | 효모에서 인체 상피세포 성장인자를 대량 생산하는 방법 |
| JP5918295B2 (ja) * | 2014-04-14 | 2016-05-18 | 佛教慈濟醫療財團法人大林慈濟醫院 | 融合蛋白質、その製造方法、及び融合蛋白質により抗原ペプチドを小胞体に輸送する方法 |
| KR101634380B1 (ko) * | 2015-06-23 | 2016-06-28 | 한국생산기술연구원 | Tlr5 아고니스트 단백질의 생산방법 |
| WO2017118752A1 (en) * | 2016-01-07 | 2017-07-13 | Novo Nordisk A/S | Modified enterokinase light chain and its preparation method |
| KR101744297B1 (ko) | 2016-06-21 | 2017-06-07 | 한국생산기술연구원 | Tlr5 아고니스트 단백질의 생산방법 |
| GB201708277D0 (en) * | 2017-05-24 | 2017-07-05 | Ge Healthcare | A Recombinant protein |
| WO2019051474A1 (en) | 2017-09-11 | 2019-03-14 | Shire Human Genetic Therapies, Inc. | METHODS AND COMPOSITIONS FOR TREATING CHRONIC PULMONARY DISEASES |
| WO2021005604A1 (en) | 2019-07-11 | 2021-01-14 | Opko Biologics Ltd. | Long-acting igf-1 or igf-1 variants and methods of producing same |
| JP7827315B2 (ja) | 2020-10-19 | 2026-03-10 | オーク ヒル バイオ リミテッド | 新生児における使用に好適な組成物 |
| AU2023210427A1 (en) | 2022-01-19 | 2024-08-22 | Oak Hill Bio Limited | Compositions and methods for reducing oxidation of igf‐1/igfbp |
| US20250102495A1 (en) | 2022-01-24 | 2025-03-27 | Oak Hill Bio Ltd | Lot release assays for igf-1/igfbp complexes |
| WO2023242440A1 (en) | 2022-06-17 | 2023-12-21 | Oak Hill Bio Limited | Treament of lungs in infants |
| WO2023242439A1 (en) | 2022-06-17 | 2023-12-21 | Oak Hill Bio Limited | Vascular stabilisation (preterm infants) |
| WO2023242442A1 (en) | 2022-06-17 | 2023-12-21 | Oak Hill Bio Limited | Method of maturing/differentiating neurons and/or modulating the vagus nerve |
| EP4665383A1 (de) | 2023-02-14 | 2025-12-24 | Oak Hill Bio Limited | Behandlung von heilungsdysregulation in gi-gewebe |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4595658A (en) * | 1982-09-13 | 1986-06-17 | The Rockefeller University | Method for facilitating externalization of proteins synthesized in bacteria |
| US4801536A (en) * | 1985-10-11 | 1989-01-31 | Genetics Institute, Inc. | Method for producing heterologous proteins |
| US5496924A (en) * | 1985-11-27 | 1996-03-05 | Hoechst Aktiengesellschaft | Fusion protein comprising an interleukin-2 fragment ballast portion |
| GB8611832D0 (en) * | 1986-05-15 | 1986-06-25 | Holland I B | Polypeptide |
| US5132213A (en) * | 1986-10-02 | 1992-07-21 | Massachusetts Institute Of Technology | Method for producing proteins and polypeptides using ubiquitin fusions |
| ATE247708T1 (de) * | 1986-10-02 | 2003-09-15 | Massachusetts Inst Technology | Verfahren zur regulierung der metabolischen stabilität von proteinen |
| US5084384A (en) * | 1987-04-23 | 1992-01-28 | Monsanto Company | Secretion of insulin-like growth factor-I |
| US5108919A (en) * | 1988-06-24 | 1992-04-28 | Genentech, Inc. | Dna sequences encoding yeast ubiquitin hydrolase |
| ATE103292T1 (de) * | 1990-01-24 | 1994-04-15 | Upjohn Co | Verfahren zur reinigung rekombinanter polypeptide. |
| US5270181A (en) * | 1991-02-06 | 1993-12-14 | Genetics Institute, Inc. | Peptide and protein fusions to thioredoxin and thioredoxin-like molecules |
-
1993
- 1993-08-02 US US08/100,744 patent/US5563046A/en not_active Expired - Lifetime
-
1994
- 1994-08-02 JP JP50606995A patent/JP3370094B2/ja not_active Expired - Fee Related
- 1994-08-02 WO PCT/US1994/008776 patent/WO1995004076A1/en not_active Ceased
- 1994-08-02 DE DE69434083T patent/DE69434083T2/de not_active Expired - Fee Related
- 1994-08-02 US US08/284,784 patent/US5629172A/en not_active Expired - Lifetime
- 1994-08-02 AT AT94925175T patent/ATE280234T1/de not_active IP Right Cessation
- 1994-08-02 CA CA002168429A patent/CA2168429C/en not_active Expired - Fee Related
- 1994-08-02 EP EP94925175A patent/EP0722461B1/de not_active Expired - Lifetime
- 1994-08-02 AU AU75194/94A patent/AU688363B2/en not_active Ceased
-
1995
- 1995-06-05 US US08/460,915 patent/US5830706A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO1995004076A1 (en) | 1995-02-09 |
| US5563046A (en) | 1996-10-08 |
| CA2168429C (en) | 2001-06-05 |
| US5629172A (en) | 1997-05-13 |
| JPH09504166A (ja) | 1997-04-28 |
| DE69434083T2 (de) | 2006-02-09 |
| AU7519494A (en) | 1995-02-28 |
| EP0722461A4 (de) | 1997-02-26 |
| EP0722461A1 (de) | 1996-07-24 |
| EP0722461B1 (de) | 2004-10-20 |
| AU688363B2 (en) | 1998-03-12 |
| DE69434083D1 (de) | 2004-11-25 |
| US5830706A (en) | 1998-11-03 |
| CA2168429A1 (en) | 1995-02-09 |
| JP3370094B2 (ja) | 2003-01-27 |
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