WO2004091515A3 - iRNA CONJUGATES - Google Patents

iRNA CONJUGATES Download PDF

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Publication number
WO2004091515A3
WO2004091515A3 PCT/US2004/011255 US2004011255W WO2004091515A3 WO 2004091515 A3 WO2004091515 A3 WO 2004091515A3 US 2004011255 W US2004011255 W US 2004011255W WO 2004091515 A3 WO2004091515 A3 WO 2004091515A3
Authority
WO
WIPO (PCT)
Prior art keywords
irna conjugates
irna
conjugates
enclosed
making
Prior art date
Application number
PCT/US2004/011255
Other languages
French (fr)
Other versions
WO2004091515A2 (en
Inventor
Muthiah Manoharan
Sayda Elbashir
Jens Harborth
Original Assignee
Alnylam Pharmaceuticals Inc
Muthiah Manoharan
Sayda Elbashir
Jens Harborth
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Alnylam Pharmaceuticals Inc, Muthiah Manoharan, Sayda Elbashir, Jens Harborth filed Critical Alnylam Pharmaceuticals Inc
Priority to CA2521464A priority Critical patent/CA2521464C/en
Priority to EP04750029A priority patent/EP1615611B1/en
Priority to AU2004229519A priority patent/AU2004229519B2/en
Priority to JP2006509942A priority patent/JP4912873B2/en
Priority to EP04759940A priority patent/EP1625138A4/en
Priority to EP13003405.1A priority patent/EP2669377A3/en
Priority to EP13003404.4A priority patent/EP2664672A1/en
Priority to EP13003406.9A priority patent/EP2666858A1/en
Priority to JP2006513077A priority patent/JP4597976B2/en
Priority to AU2004233092A priority patent/AU2004233092C9/en
Priority to CA002522349A priority patent/CA2522349A1/en
Priority to PCT/US2004/011822 priority patent/WO2004094345A2/en
Priority to PCT/US2004/011829 priority patent/WO2004094595A2/en
Priority to JP2006513075A priority patent/JP4991288B2/en
Priority to ES04759946T priority patent/ES2702942T3/en
Priority to EP13003403.6A priority patent/EP2660322A3/en
Priority to US10/553,659 priority patent/US20070179100A1/en
Priority to EP04759946.9A priority patent/EP1620544B1/en
Priority to CA2522637A priority patent/CA2522637C/en
Priority to DK04759946.9T priority patent/DK1620544T3/en
Priority to AU2004232964A priority patent/AU2004232964B2/en
Priority to US10/916,185 priority patent/US7745608B2/en
Priority to US10/936,115 priority patent/US20050119214A1/en
Priority to US10/946,873 priority patent/US20050164235A1/en
Publication of WO2004091515A2 publication Critical patent/WO2004091515A2/en
Priority to US10/985,426 priority patent/US7723509B2/en
Publication of WO2004091515A3 publication Critical patent/WO2004091515A3/en
Priority to US11/833,934 priority patent/US7851615B2/en
Priority to US12/510,050 priority patent/US8017762B2/en
Priority to AU2009213011A priority patent/AU2009213011B2/en
Priority to US12/619,382 priority patent/US8344125B2/en
Priority to US12/714,298 priority patent/US8507661B2/en
Priority to US12/724,267 priority patent/US8426377B2/en
Priority to US15/260,803 priority patent/US10119138B2/en
Priority to US15/906,908 priority patent/US10676740B2/en
Priority to US16/042,633 priority patent/US11015194B2/en
Priority to US17/243,503 priority patent/US20210254065A1/en
Priority to US17/697,685 priority patent/US20220403377A1/en

Links

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
    • C12N15/113—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
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Therapeutic iRNA agents and methods of making and using are enclosed.
PCT/US2004/011255 2003-04-09 2004-04-09 iRNA CONJUGATES WO2004091515A2 (en)

Priority Applications (36)

Application Number Priority Date Filing Date Title
CA2521464A CA2521464C (en) 2003-04-09 2004-04-09 Irna conjugates
EP04750029A EP1615611B1 (en) 2003-04-09 2004-04-09 iRNA CONJUGATES
AU2004229519A AU2004229519B2 (en) 2003-04-09 2004-04-09 iRNA conjugates
JP2006509942A JP4912873B2 (en) 2003-04-09 2004-04-09 iRNA complex
EP04759946.9A EP1620544B1 (en) 2003-04-17 2004-04-16 MODIFIED iRNA AGENTS
EP13003405.1A EP2669377A3 (en) 2003-04-17 2004-04-16 Modified iRNA agents
EP13003404.4A EP2664672A1 (en) 2003-04-17 2004-04-16 Modified iRNA agents
EP13003406.9A EP2666858A1 (en) 2003-04-17 2004-04-16 Modified iRNA agents
JP2006513077A JP4597976B2 (en) 2003-04-17 2004-04-16 Modified iRNA agent
AU2004233092A AU2004233092C9 (en) 2003-04-17 2004-04-16 Modified iRNA agents
CA002522349A CA2522349A1 (en) 2003-04-17 2004-04-16 Protected monomers
PCT/US2004/011822 WO2004094345A2 (en) 2003-04-17 2004-04-16 Protected monomers
PCT/US2004/011829 WO2004094595A2 (en) 2003-04-17 2004-04-16 MODIFIED iRNA AGENTS
JP2006513075A JP4991288B2 (en) 2003-04-17 2004-04-16 A double-stranded iRNA agent and a method of modulating the stability of a pair of double-stranded iRNA agents.
ES04759946T ES2702942T3 (en) 2003-04-17 2004-04-16 Modified RNAi agents
EP13003403.6A EP2660322A3 (en) 2003-04-17 2004-04-16 Modified iRNA agents
US10/553,659 US20070179100A1 (en) 2003-04-09 2004-04-16 Protected monomers
EP04759940A EP1625138A4 (en) 2003-04-17 2004-04-16 Protected monomers
CA2522637A CA2522637C (en) 2003-04-17 2004-04-16 Modified irna agents
DK04759946.9T DK1620544T3 (en) 2003-04-17 2004-04-16 MODIFIED iRNA AGENTS
AU2004232964A AU2004232964B2 (en) 2003-04-17 2004-04-16 Protected monomers
US10/916,185 US7745608B2 (en) 2003-04-17 2004-08-10 Modified iRNA agents
US10/936,115 US20050119214A1 (en) 2003-04-17 2004-09-07 Nuclease resistant double-stranded ribonucleic acid
US10/946,873 US20050164235A1 (en) 2003-04-17 2004-09-21 Modified iRNA agents
US10/985,426 US7723509B2 (en) 2003-04-17 2004-11-09 IRNA agents with biocleavable tethers
US11/833,934 US7851615B2 (en) 2003-04-17 2007-08-03 Lipophilic conjugated iRNA agents
US12/510,050 US8017762B2 (en) 2003-04-17 2009-07-27 Modified iRNA agents
AU2009213011A AU2009213011B2 (en) 2003-04-17 2009-09-07 Modified iRNA agents
US12/619,382 US8344125B2 (en) 2003-04-17 2009-11-16 Modified iRNA agents
US12/714,298 US8507661B2 (en) 2003-04-17 2010-02-26 Modified iRNA agents
US12/724,267 US8426377B2 (en) 2003-04-17 2010-03-15 iRNA agents with biocleavable tethers
US15/260,803 US10119138B2 (en) 2003-04-17 2016-09-09 iRNA agents with biocleavable tethers
US15/906,908 US10676740B2 (en) 2003-04-17 2018-02-27 Modified iRNA agents
US16/042,633 US11015194B2 (en) 2003-04-17 2018-07-23 iRNA agents with biocleavable tethers
US17/243,503 US20210254065A1 (en) 2003-04-17 2021-04-28 iRNA AGENTS WITH BIOCLEAVABLE TETHERS
US17/697,685 US20220403377A1 (en) 2003-04-17 2022-03-17 MODIFIED iRNA AGENTS

Applications Claiming Priority (30)

Application Number Priority Date Filing Date Title
US46209703P 2003-04-09 2003-04-09
US60/462,097 2003-04-09
US46191503P 2003-04-10 2003-04-10
US60/461,915 2003-04-10
US46289403P 2003-04-14 2003-04-14
US60/462,894 2003-04-14
US46377203P 2003-04-17 2003-04-17
US60/463,772 2003-04-17
US46580203P 2003-04-25 2003-04-25
US46566503P 2003-04-25 2003-04-25
US60/465,665 2003-04-25
US60/465,802 2003-04-25
US46961203P 2003-05-09 2003-05-09
US60/469,612 2003-05-09
US49398603P 2003-08-08 2003-08-08
US60/493,986 2003-08-08
US49459703P 2003-08-11 2003-08-11
US60/494,597 2003-08-11
US50634103P 2003-09-26 2003-09-26
US60/506,341 2003-09-26
US51024603P 2003-10-09 2003-10-09
US60/510,246 2003-10-09
US51031803P 2003-10-10 2003-10-10
US60/510,318 2003-10-10
US51845303P 2003-11-07 2003-11-07
US60/518,453 2003-11-07
US40707004A 2004-03-08 2004-03-08
USUS04/07070 2004-03-08
US41058604A 2004-04-05 2004-04-05
USUS04/10586 2004-04-05

Publications (2)

Publication Number Publication Date
WO2004091515A2 WO2004091515A2 (en) 2004-10-28
WO2004091515A3 true WO2004091515A3 (en) 2007-07-26

Family

ID=39524922

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/011255 WO2004091515A2 (en) 2003-04-09 2004-04-09 iRNA CONJUGATES

Country Status (3)

Country Link
AU (1) AU2004229519B2 (en)
CA (1) CA2521464C (en)
WO (1) WO2004091515A2 (en)

Cited By (5)

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Publication number Priority date Publication date Assignee Title
US7834171B2 (en) 2003-04-02 2010-11-16 Dharmacon, Inc. Modified polynucleotides for reducing off-target effects in RNA interference
US7923206B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Method of determining a cellular response to a biological agent
US7923207B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Apparatus and system having dry gene silencing pools
US7935811B2 (en) 2004-11-22 2011-05-03 Dharmacon, Inc. Apparatus and system having dry gene silencing compositions
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation

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* Cited by examiner, † Cited by third party
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US8017762B2 (en) 2003-04-17 2011-09-13 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
EP1620544B1 (en) 2003-04-17 2018-09-19 Alnylam Pharmaceuticals Inc. MODIFIED iRNA AGENTS
US8796436B2 (en) 2003-04-17 2014-08-05 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
CN101133074B (en) 2004-09-24 2012-05-30 阿尔尼拉姆医药品有限公司 RNAi modulation of APOB and uses thereof
CA2587411A1 (en) * 2004-11-17 2006-05-26 Protiva Biotherapeutics, Inc. Sirna silencing of apolipoprotein b
EP1931778A2 (en) * 2005-09-15 2008-06-18 Santaris Pharma A/S RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-Bl00 EXPRESSION
JP5336853B2 (en) 2005-11-02 2013-11-06 プロチバ バイオセラピューティクス インコーポレイティッド Modified siRNA molecules and methods of use thereof
GB0608838D0 (en) 2006-05-04 2006-06-14 Novartis Ag Organic compounds
JP5076374B2 (en) * 2006-06-28 2012-11-21 東レ株式会社 Pharmaceutical composition
WO2008113830A1 (en) * 2007-03-22 2008-09-25 Santaris Pharma A/S Rna antagonist compounds for the inhibition of apo-b100 expression
KR101141544B1 (en) 2009-03-13 2012-05-03 한국과학기술원 Multi-conjugate of siRNA and preparing method thereof
ES2804764T3 (en) 2009-06-01 2021-02-09 Halo Bio Rnai Therapeutics Inc Polynucleotides for multivalent RNA interference, compositions and methods of use thereof
CN102802637A (en) * 2009-06-12 2012-11-28 桑塔里斯制药公司 New potent anti APOB antisense compounds
CA2767129C (en) 2009-07-01 2015-01-06 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein b
EP2449114B9 (en) 2009-07-01 2017-04-19 Protiva Biotherapeutics Inc. Novel lipid formulations for delivery of therapeutic agents to solid tumors
JP5976643B2 (en) 2010-07-06 2016-08-24 ダイセルナ ファーマシューティカルズ， インコーポレイテッドＤｉｃｅｒｎａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Methods and compositions for specific inhibition of beta-catenin by double stranded RNA
US10023862B2 (en) 2012-01-09 2018-07-17 Arrowhead Pharmaceuticals, Inc. Organic compositions to treat beta-catenin-related diseases
ES2702874T3 (en) 2012-02-24 2019-03-06 Arbutus Biopharma Corp Cationic trialkyl lipids and methods for their use
US9133461B2 (en) * 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
US10676737B2 (en) 2014-12-17 2020-06-09 Proqr Therapeutics Ii B.V. Targeted RNA editing
KR20180039621A (en) 2015-06-15 2018-04-18 엠펙 엘에이, 엘엘씨 The defined multijunctional oligonucleotides
EP3340967B1 (en) 2015-08-24 2024-05-22 Halo-Bio Rnai Therapeutics, Inc. Polynucleotide nanoparticles for the modulation of gene expression and uses thereof
WO2017220751A1 (en) 2016-06-22 2017-12-28 Proqr Therapeutics Ii B.V. Single-stranded rna-editing oligonucleotides
CA3035293A1 (en) 2016-09-01 2018-03-08 Proqr Therapeutics Ii B.V. Chemically modified single-stranded rna-editing oligonucleotides
CA3043768A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
EP3571300A1 (en) 2017-01-19 2019-11-27 ProQR Therapeutics II B.V. Oligonucleotide complexes for use in rna editing
KR20240010750A (en) 2017-02-06 2024-01-24 엠펙 엘에이, 엘.엘.씨. Multimeric oligonucleotides having decreased kidney clearance
CN115667531A (en) 2020-03-24 2023-01-31 世代生物公司 Non-viral DNA vectors and their use for expressing Gaucher (Gaucher) therapeutics
MX2022011805A (en) 2020-03-24 2023-01-11 Generation Bio Co Non-viral dna vectors and uses thereof for expressing factor ix therapeutics.
CN117881786A (en) 2021-04-27 2024-04-12 世代生物公司 Non-viral DNA vectors expressing therapeutic antibodies and uses thereof
WO2022232286A1 (en) 2021-04-27 2022-11-03 Generation Bio Co. Non-viral dna vectors expressing anti-coronavirus antibodies and uses thereof
CN113862268A (en) * 2021-10-20 2021-12-31 厦门甘宝利生物医药有限公司 AGT inhibitors and uses thereof
AU2023235112A1 (en) 2022-03-14 2024-10-17 Generation Bio Co. Heterologous prime boost vaccine compositions and methods of use
WO2024040222A1 (en) 2022-08-19 2024-02-22 Generation Bio Co. Cleavable closed-ended dna (cedna) and methods of use thereof
CN118011012A (en) * 2024-02-19 2024-05-10 中国科学院昆明动物研究所 LL-37-ApoB-100 biomarker and application thereof

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Publication number Priority date Publication date Assignee Title
US6133246A (en) * 1997-08-13 2000-10-17 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the modulation of JNK proteins
US6506559B1 (en) * 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
US20030007956A1 (en) * 2000-12-18 2003-01-09 Pierre Legrain Proteins that interact with betaTrCP
WO2003097662A1 (en) * 2002-05-15 2003-11-27 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
US20050080246A1 (en) * 2002-11-05 2005-04-14 Charles Allerson Compositions comprising alternating 2'-modified nucleosides for use in gene modulation

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7834171B2 (en) 2003-04-02 2010-11-16 Dharmacon, Inc. Modified polynucleotides for reducing off-target effects in RNA interference
US7923206B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Method of determining a cellular response to a biological agent
US7923207B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Apparatus and system having dry gene silencing pools
US7935811B2 (en) 2004-11-22 2011-05-03 Dharmacon, Inc. Apparatus and system having dry gene silencing compositions
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation

Also Published As

Publication number Publication date
AU2004229519B2 (en) 2011-07-21
WO2004091515A2 (en) 2004-10-28
CA2521464A1 (en) 2004-10-28
AU2004229519A1 (en) 2004-10-28
CA2521464C (en) 2013-02-05

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