FI120376B - Förfarande för producering av en biomodifierad polypeptid med hög affinitet - Google Patents
Förfarande för producering av en biomodifierad polypeptid med hög affinitet Download PDFInfo
- Publication number
- FI120376B FI120376B FI20075028A FI20075028A FI120376B FI 120376 B FI120376 B FI 120376B FI 20075028 A FI20075028 A FI 20075028A FI 20075028 A FI20075028 A FI 20075028A FI 120376 B FI120376 B FI 120376B
- Authority
- FI
- Finland
- Prior art keywords
- seq
- antigen
- peptide
- binding
- library
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 59
- 102000004196 processed proteins & peptides Human genes 0.000 title claims description 37
- 229920001184 polypeptide Polymers 0.000 title claims description 27
- 238000000034 method Methods 0.000 title claims description 19
- 239000000427 antigen Substances 0.000 claims description 42
- 102000036639 antigens Human genes 0.000 claims description 42
- 108091007433 antigens Proteins 0.000 claims description 42
- 230000027455 binding Effects 0.000 claims description 35
- 101710147327 Calcineurin B homologous protein 1 Proteins 0.000 claims description 19
- 101710205625 Capsid protein p24 Proteins 0.000 claims description 19
- 101710177166 Phosphoprotein Proteins 0.000 claims description 19
- 101710149279 Small delta antigen Proteins 0.000 claims description 19
- 239000002245 particle Substances 0.000 claims description 15
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 125000000539 amino acid group Chemical group 0.000 claims description 9
- 102000023732 binding proteins Human genes 0.000 claims description 9
- 108091008324 binding proteins Proteins 0.000 claims description 9
- 239000012634 fragment Substances 0.000 claims description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 5
- 108010027044 HIV Core Protein p24 Proteins 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002703 mutagenesis Methods 0.000 claims description 4
- 231100000350 mutagenesis Toxicity 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 2
- ZXVONLUNISGICL-UHFFFAOYSA-N 4,6-dinitro-o-cresol Chemical compound CC1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1O ZXVONLUNISGICL-UHFFFAOYSA-N 0.000 claims 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 12
- 239000000523 sample Substances 0.000 description 11
- 238000001514 detection method Methods 0.000 description 9
- 241000700605 Viruses Species 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 6
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- 238000004458 analytical method Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- 108090000565 Capsid Proteins Proteins 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 102100023321 Ceruloplasmin Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
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- 238000012552 review Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010048209 Human Immunodeficiency Virus Proteins Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000011225 antiretroviral therapy Methods 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000002967 competitive immunoassay Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000002773 nucleotide Chemical group 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000004896 polypeptide structure Anatomy 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000021309 simple sugar Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
- C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
- C07K16/1036—Retroviridae, e.g. leukemia viruses
- C07K16/1045—Lentiviridae, e.g. HIV, FIV, SIV
- C07K16/1054—Lentiviridae, e.g. HIV, FIV, SIV gag-pol, e.g. p17, p24
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1037—Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
-
- 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
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1058—Directional evolution of libraries, e.g. evolution of libraries is achieved by mutagenesis and screening or selection of mixed population of organisms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56983—Viruses
- G01N33/56988—HIV or HTLV
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/08—RNA viruses
- G01N2333/15—Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus
- G01N2333/155—Lentiviridae, e.g. visna-maedi virus, equine infectious virus, FIV, SIV
- G01N2333/16—HIV-1, HIV-2
- G01N2333/161—HIV-1, HIV-2 gag-pol, e.g. p55, p24/25, p17/18, p.7, p6, p66/68, p51/52, p31/34, p32, p40
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- AIDS & HIV (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pathology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Plant Pathology (AREA)
- Ecology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (6)
1. Förfarande för producering av en biomodifierad polypcptid med hög affinitet, vilken polypeptid kan bindas specifikt tili en 2-7 successiva eller icke-successiva aminosyror 5 läng konserverad epitop av HIV: s p24-antigen, vilket förfarande omfattar stegen: a) en ätminstone tvä aminosyror läng konserverad region väljs frän p24-antigenen genom en datoranalys pä p24-antigenens kända aminosyrasekvenser; 10 b) en peptid som baserar sig pä p24-antigenens valda konserverade region produceras; c) ett bibliotek pä partiklar som uttrycker bindningsproteiner bringas i kontakt med den nämnda peptiden; 15 d) de partiklar som uttrycker bindningsproteiner med bindningsaktivitet mot den nämnda peptiden isoleras; e) en nukleinsyra som har erhällits eller härletts frän den i steg d) isolerade partikeln eller de i steg d) isolerade partiklarna utsätts för mutagenes; 20 f) ett bibliotek pä partiklar som uttrycker bindningsproteiner produceras pä basis av de i steg e) erhällna partiklarna; g) det i steg f) erhällna biblioteket bringas i kontakt med den nämnda peptiden eller ett 25 fragment därav; h) de partiklar som uttrycker bindningsproteiner med en förbättrad bindningsaktivitet mot den nämnda peptiden eller ett fragment därav isoleras; 30 i) stegen e) - h) upprepas en eller Hera gänger; j) en biomodifierad polypeptid med hög affinitet som kan bindas specifikt till en 2-7 successiva eller icke-successiva aminosyror läng konserverad epitop av HIV:s p24-antigen tas frän de i steg i) erhällna partiklarna. 5
2. Förfarande enligt patentkrav 1, varvid det nämnda biblioteket är ett fagbibliotek pä enkelkedjiga antikroppar.
3. Förfarande enligt patentkrav 1, varvid den nämnda biomodifierade polypeptiden med hög affinitet har en affinitet pä 10"12 -10'15 M i förhällande tili epitopen. 10
4. Förfarande enligt patentkrav 1, varvid den nämnda peptiden har valts frän en grupp som bestär av följande peptider: RTLNAWVK (SEQ ID NO:l),
15 VGGHQAAMQ (SEQ ID NO:2), WDRLHP (SEQ ID NO:3), P R G S D IA G (SEQ ID NO:4), G L N KIV (SEQ ID NO:5), V R M Y S P (SEQ ID NO:6),
20. G P K E (SEQ ID NO:7), FRDYVDRF (SEQ ID NO:8), L R A E Q (SEQ ID NO:9), WMTETLL (SEQ ID NO:10), WMTDTLL (SEQ ID NO:ll),
25 QN A N P D C (SEQ ID NO: 12), E E M M T A C (SEQ ID NO:13), och ACQGVGGP (SEQ ID NO:14).
5. Förfarande enligt patentkrav 4, varvid epitopen bestär av 2 - 3, 2 - 4, 2 - 5, 2 - 6, 3 - 4, 30 3-5 eller 3-6 successiva eller icke-successiva aminosyrarester.
6. Förfarande enligt patentkrav 4, varvid epitopen bestär av 2, 3, 4, 5 eller 6 successiva eller icke-successiva aminosyrarester.
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI20075028A FI120376B (sv) | 2007-01-17 | 2007-01-17 | Förfarande för producering av en biomodifierad polypeptid med hög affinitet |
AU2008206881A AU2008206881A1 (en) | 2007-01-17 | 2008-01-17 | Method for detection of human immunodeficiency virus |
US12/522,838 US20100048407A1 (en) | 2007-01-17 | 2008-01-17 | Method for detection of human immunodeficiency virus |
EP08701712A EP2109772A4 (en) | 2007-01-17 | 2008-01-17 | METHOD FOR DETECTING HUMAN IMMUNE DISEASE VIRUS |
CN200880002505A CN101646944A (zh) | 2007-01-17 | 2008-01-17 | 检测人免疫缺陷病毒的方法 |
PCT/FI2008/050012 WO2008087254A2 (en) | 2007-01-17 | 2008-01-17 | Method for detection of human immunodeficiency virus |
JP2009545963A JP2010516660A (ja) | 2007-01-17 | 2008-01-17 | ヒト免疫不全ウイルスの検出方法 |
CA002675122A CA2675122A1 (en) | 2007-01-17 | 2008-01-17 | Method for detection of human immunodeficiency virus |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI20075028A FI120376B (sv) | 2007-01-17 | 2007-01-17 | Förfarande för producering av en biomodifierad polypeptid med hög affinitet |
FI20075028 | 2007-01-17 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI20075028A0 FI20075028A0 (sv) | 2007-01-17 |
FI20075028A FI20075028A (sv) | 2008-07-18 |
FI120376B true FI120376B (sv) | 2009-09-30 |
Family
ID=37745720
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI20075028A FI120376B (sv) | 2007-01-17 | 2007-01-17 | Förfarande för producering av en biomodifierad polypeptid med hög affinitet |
Country Status (8)
Country | Link |
---|---|
US (1) | US20100048407A1 (sv) |
EP (1) | EP2109772A4 (sv) |
JP (1) | JP2010516660A (sv) |
CN (1) | CN101646944A (sv) |
AU (1) | AU2008206881A1 (sv) |
CA (1) | CA2675122A1 (sv) |
FI (1) | FI120376B (sv) |
WO (1) | WO2008087254A2 (sv) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO314588B1 (no) * | 2000-09-04 | 2003-04-14 | Bionor Immuno As | HIV-peptider, antigener, vaksinesammensetning, immunoassay- testsett og en fremgangsmåte for å påvise antistoffer indusert av HIV |
US6818392B2 (en) * | 2000-12-06 | 2004-11-16 | Abbott Laboratories | Monoclonal antibodies to human immunodeficiency virus and uses thereof |
US6833441B2 (en) * | 2001-08-01 | 2004-12-21 | Abmaxis, Inc. | Compositions and methods for generating chimeric heteromultimers |
-
2007
- 2007-01-17 FI FI20075028A patent/FI120376B/sv not_active IP Right Cessation
-
2008
- 2008-01-17 WO PCT/FI2008/050012 patent/WO2008087254A2/en active Application Filing
- 2008-01-17 AU AU2008206881A patent/AU2008206881A1/en not_active Abandoned
- 2008-01-17 CA CA002675122A patent/CA2675122A1/en not_active Abandoned
- 2008-01-17 US US12/522,838 patent/US20100048407A1/en not_active Abandoned
- 2008-01-17 JP JP2009545963A patent/JP2010516660A/ja active Pending
- 2008-01-17 EP EP08701712A patent/EP2109772A4/en not_active Withdrawn
- 2008-01-17 CN CN200880002505A patent/CN101646944A/zh active Pending
Also Published As
Publication number | Publication date |
---|---|
WO2008087254A2 (en) | 2008-07-24 |
FI20075028A0 (sv) | 2007-01-17 |
JP2010516660A (ja) | 2010-05-20 |
FI20075028A (sv) | 2008-07-18 |
AU2008206881A1 (en) | 2008-07-24 |
EP2109772A1 (en) | 2009-10-21 |
US20100048407A1 (en) | 2010-02-25 |
CN101646944A (zh) | 2010-02-10 |
CA2675122A1 (en) | 2008-07-24 |
EP2109772A4 (en) | 2010-09-29 |
WO2008087254A8 (en) | 2009-07-30 |
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