DE69927495D1 - Verfahren zur regulierung der hematopoiese mit hilfe von cpg oligonukleotide - Google Patents
Verfahren zur regulierung der hematopoiese mit hilfe von cpg oligonukleotideInfo
- Publication number
- DE69927495D1 DE69927495D1 DE69927495T DE69927495T DE69927495D1 DE 69927495 D1 DE69927495 D1 DE 69927495D1 DE 69927495 T DE69927495 T DE 69927495T DE 69927495 T DE69927495 T DE 69927495T DE 69927495 D1 DE69927495 D1 DE 69927495D1
- Authority
- DE
- Germany
- Prior art keywords
- regulating
- hematopoiese
- cpg oligonucleotide
- relates
- hematopoiesis
- 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
- 230000001105 regulatory effect Effects 0.000 title abstract 4
- 108091034117 Oligonucleotide Proteins 0.000 title abstract 3
- 230000011132 hemopoiesis Effects 0.000 abstract 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 2
- 208000007502 anemia Diseases 0.000 abstract 1
- 210000000987 immune system Anatomy 0.000 abstract 1
- 230000035921 thrombopoiesis Effects 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
- 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
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- 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
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
-
- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8551698P | 1998-05-14 | 1998-05-14 | |
| US85516P | 1998-05-14 | ||
| US24165399A | 1999-02-02 | 1999-02-02 | |
| US241653 | 1999-02-02 | ||
| PCT/IB1999/001285 WO1999058118A2 (en) | 1998-05-14 | 1999-05-14 | METHODS FOR REGULATING HEMATOPOIESIS USING CpG-OLIGONUCLEOTIDES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69927495D1 true DE69927495D1 (de) | 2006-02-09 |
| DE69927495T2 DE69927495T2 (de) | 2006-07-06 |
Family
ID=26772811
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69927495T Expired - Lifetime DE69927495T2 (de) | 1998-05-14 | 1999-05-14 | Verfahren zur regulieren der hämatopoese mit hilfe von cpg-oligonukleotiden |
Country Status (10)
| Country | Link |
|---|---|
| US (5) | US20040030118A1 (de) |
| EP (2) | EP1674574A1 (de) |
| JP (1) | JP2002514397A (de) |
| AT (1) | ATE305507T1 (de) |
| AU (1) | AU760795B2 (de) |
| CA (1) | CA2328406A1 (de) |
| DE (1) | DE69927495T2 (de) |
| IL (3) | IL139646A0 (de) |
| NZ (1) | NZ508650A (de) |
| WO (1) | WO1999058118A2 (de) |
Families Citing this family (106)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US6429199B1 (en) * | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030026782A1 (en) * | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| US7935675B1 (en) * | 1994-07-15 | 2011-05-03 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| JP4359654B2 (ja) * | 1996-01-30 | 2009-11-04 | ザ リージェンツ オブ ザ ユニバーシティー オブ カリフォルニア | 抗原特異的免疫応答を生起させる遺伝子発現ベクターおよびその使用方法 |
| EP0855184A1 (de) * | 1997-01-23 | 1998-07-29 | Grayson B. Dr. Lipford | Pharmazeutisches Präparat das ein Polynukleotid und ein Antigen enthält, insbesondere zur Impfung |
| US6406705B1 (en) * | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| EP1003531B1 (de) | 1997-05-20 | 2007-08-22 | Ottawa Health Research Institute | Verfahren zur Herstellung von Nukleinsäurekonstrukten |
| WO1999051259A2 (en) * | 1998-04-03 | 1999-10-14 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| NZ508650A (en) * | 1998-05-14 | 2003-05-30 | Coley Pharm Gmbh | Regulating hematopoiesis using unmethylated C and G CpG-oligonucleotides with a phosphorothioate modification |
| DE69932717T2 (de) | 1998-05-22 | 2007-08-09 | Ottawa Health Research Institute, Ottawa | Methoden und produkte zur induzierung mukosaler immunität |
| US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
| US6693086B1 (en) * | 1998-06-25 | 2004-02-17 | National Jewish Medical And Research Center | Systemic immune activation method using nucleic acid-lipid complexes |
| US7049302B1 (en) | 1998-08-10 | 2006-05-23 | Antigenics Inc. | Compositions of CPG and saponin adjuvants and uses thereof |
| ATE464907T1 (de) * | 1999-02-17 | 2010-05-15 | Csl Ltd | Immunogene komplexe und methoden in bezug auf diese |
| EP1176966B1 (de) * | 1999-04-12 | 2013-04-03 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Oligodeoxynukleotide und deren verwendung zur induktion einer immunreaktion |
| FR2795963A1 (fr) * | 1999-07-08 | 2001-01-12 | Pasteur Merieux Serums Vacc | Polynucleotide immunostimulant |
| EP1204425B1 (de) | 1999-08-19 | 2009-01-07 | Dynavax Technologies Corporation | Methode zur modulierung eines immunantwortes mit immunstimulierenden sequencen und zusammensetzungen dafür |
| AP2006003503A0 (en) * | 1999-09-25 | 2006-02-28 | Univ Iowa Res Found | Immunostimulatory nucleic acids. |
| US6949520B1 (en) * | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| EP1322655B1 (de) | 2000-01-14 | 2007-11-14 | The Government of the United States of America, as represented by the Secretary of the Department of Health and Human Services | Oligodeoxynukleotide und ihre verwendung zur induktion einer immunreaktion |
| AU3108001A (en) * | 2000-01-20 | 2001-12-24 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for inducing a th2 immune response |
| US7585847B2 (en) * | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
| US20040131628A1 (en) * | 2000-03-08 | 2004-07-08 | Bratzler Robert L. | Nucleic acids for the treatment of disorders associated with microorganisms |
| US20020028784A1 (en) * | 2000-03-10 | 2002-03-07 | Nest Gary Van | Methods of preventing and treating viral infections using immunomodulatory polynucleotide sequences |
| US20020107212A1 (en) * | 2000-03-10 | 2002-08-08 | Nest Gary Van | Methods of reducing papillomavirus infection using immunomodulatory polynucleotide sequences |
| US20020098199A1 (en) * | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences |
| US7157437B2 (en) * | 2000-03-10 | 2007-01-02 | Dynavax Technologies Corporation | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
| US20010046967A1 (en) * | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
| US6653467B1 (en) * | 2000-04-26 | 2003-11-25 | Jcr Pharmaceutical Co., Ltd. | Medicament for treatment of Duchenne muscular dystrophy |
| AU7013401A (en) * | 2000-06-22 | 2002-01-02 | Univ Iowa Res Found | Methods for enhancing antibody-induced cell lysis and treating cancer |
| WO2002002172A1 (en) * | 2000-06-30 | 2002-01-10 | Univ Jefferson | Dna palindrome - oligoguanylic acid compositions and uses thereof |
| KR100917101B1 (ko) * | 2000-08-04 | 2009-09-15 | 도요 보세키 가부시키가이샤 | 플렉시블 금속적층체 및 그 제조방법 |
| WO2002022809A2 (en) | 2000-09-15 | 2002-03-21 | Coley Pharmaceutical Gmbh | PROCESS FOR HIGH THROUGHPUT SCREENING OF CpG-BASED IMMUNO-AGONIST/ANTAGONIST |
| ES2307568T3 (es) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
| US20030055014A1 (en) * | 2000-12-14 | 2003-03-20 | Bratzler Robert L. | Inhibition of angiogenesis by nucleic acids |
| US7087586B2 (en) * | 2001-04-24 | 2006-08-08 | Bioniche Life Sciences, Inc. | Oligonucleotide compositions and their use to induce differentiation of cells |
| CN100334228C (zh) | 2001-06-21 | 2007-08-29 | 戴纳瓦克斯技术公司 | 嵌合免疫调制化合物及其使用方法 |
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| CA2517839A1 (en) * | 2003-03-26 | 2004-10-07 | Martin F. Bachmann | Melan-a peptide analogue-virus-like-particle conjugates |
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| EP1720568A2 (de) * | 2004-02-19 | 2006-11-15 | Coley Pharmaceutical Group, Inc. | Immunstimulatorische virale rna-oligonucleotide |
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| CN101160401A (zh) * | 2005-02-24 | 2008-04-09 | 科勒制药集团公司 | 免疫刺激寡核苷酸 |
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| US20060241076A1 (en) * | 2005-04-26 | 2006-10-26 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
| DK2179737T3 (da) | 2005-07-01 | 2013-11-11 | Index Pharmaceuticals Ab | Modulering af respons på steroider |
| ATE476193T1 (de) | 2005-07-01 | 2010-08-15 | Index Pharmaceuticals Ab | Immunstimulatorisches verfahren |
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-
1999
- 1999-05-14 NZ NZ508650A patent/NZ508650A/en unknown
- 1999-05-14 DE DE69927495T patent/DE69927495T2/de not_active Expired - Lifetime
- 1999-05-14 EP EP05108933A patent/EP1674574A1/de not_active Withdrawn
- 1999-05-14 EP EP99928176A patent/EP1078053B1/de not_active Expired - Lifetime
- 1999-05-14 IL IL13964699A patent/IL139646A0/xx active IP Right Grant
- 1999-05-14 WO PCT/IB1999/001285 patent/WO1999058118A2/en active Application Filing
- 1999-05-14 JP JP2000547969A patent/JP2002514397A/ja active Pending
- 1999-05-14 AU AU45288/99A patent/AU760795B2/en not_active Ceased
- 1999-05-14 CA CA002328406A patent/CA2328406A1/en not_active Abandoned
- 1999-05-14 AT AT99928176T patent/ATE305507T1/de not_active IP Right Cessation
-
2000
- 2000-11-13 IL IL139646A patent/IL139646A/en not_active IP Right Cessation
-
2003
- 2003-02-24 US US10/373,381 patent/US20040030118A1/en not_active Abandoned
-
2004
- 2004-06-25 US US10/876,892 patent/US20040235777A1/en not_active Abandoned
- 2004-06-25 US US10/877,369 patent/US20040234512A1/en not_active Abandoned
- 2004-06-25 US US10/876,965 patent/US20040235778A1/en not_active Abandoned
-
2006
- 2006-11-10 US US11/595,823 patent/US20070184465A1/en not_active Abandoned
-
2007
- 2007-12-06 IL IL187987A patent/IL187987A0/en unknown
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|---|---|
| IL139646A0 (en) | 2002-02-10 |
| ATE305507T1 (de) | 2005-10-15 |
| NZ508650A (en) | 2003-05-30 |
| EP1674574A1 (de) | 2006-06-28 |
| DE69927495T2 (de) | 2006-07-06 |
| WO1999058118A3 (en) | 2000-01-13 |
| IL139646A (en) | 2008-03-20 |
| IL187987A0 (en) | 2008-03-20 |
| US20040234512A1 (en) | 2004-11-25 |
| US20040235777A1 (en) | 2004-11-25 |
| AU760795B2 (en) | 2003-05-22 |
| CA2328406A1 (en) | 1999-11-18 |
| AU4528899A (en) | 1999-11-29 |
| EP1078053B1 (de) | 2005-09-28 |
| US20070184465A1 (en) | 2007-08-09 |
| JP2002514397A (ja) | 2002-05-21 |
| US20040030118A1 (en) | 2004-02-12 |
| US20040235778A1 (en) | 2004-11-25 |
| EP1078053A2 (de) | 2001-02-28 |
| WO1999058118A2 (en) | 1999-11-18 |
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