RU2007125644A - Отбор пациентов для терапии ингибитором her - Google Patents
Отбор пациентов для терапии ингибитором her Download PDFInfo
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- RU2007125644A RU2007125644A RU2007125644/13A RU2007125644A RU2007125644A RU 2007125644 A RU2007125644 A RU 2007125644A RU 2007125644/13 A RU2007125644/13 A RU 2007125644/13A RU 2007125644 A RU2007125644 A RU 2007125644A RU 2007125644 A RU2007125644 A RU 2007125644A
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- her2
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- 239000003112 inhibitor Substances 0.000 title claims 8
- 238000002560 therapeutic procedure Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims 41
- 239000000523 sample Substances 0.000 claims 19
- 206010028980 Neoplasm Diseases 0.000 claims 14
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 11
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 11
- 201000011510 cancer Diseases 0.000 claims 11
- 102000005962 receptors Human genes 0.000 claims 11
- 108020003175 receptors Proteins 0.000 claims 11
- 239000003446 ligand Substances 0.000 claims 10
- 102000007299 Amphiregulin Human genes 0.000 claims 8
- 108010033760 Amphiregulin Proteins 0.000 claims 8
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 6
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 6
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 6
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 claims 5
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 claims 5
- 230000004913 activation Effects 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 229940127089 cytotoxic agent Drugs 0.000 claims 4
- 230000026731 phosphorylation Effects 0.000 claims 4
- 238000006366 phosphorylation reaction Methods 0.000 claims 4
- 206010033128 Ovarian cancer Diseases 0.000 claims 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 3
- 238000003752 polymerase chain reaction Methods 0.000 claims 3
- 101800001382 Betacellulin Proteins 0.000 claims 2
- 206010055113 Breast cancer metastatic Diseases 0.000 claims 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 2
- 239000004010 HER dimerization inhibitor Substances 0.000 claims 2
- 102100029837 Probetacellulin Human genes 0.000 claims 2
- 230000001399 anti-metabolic effect Effects 0.000 claims 2
- 239000012472 biological sample Substances 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 2
- 239000012188 paraffin wax Substances 0.000 claims 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 2
- 101800000155 Epiregulin Proteins 0.000 claims 1
- 201000001342 Fallopian tube cancer Diseases 0.000 claims 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 1
- 102100025498 Proepiregulin Human genes 0.000 claims 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 claims 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 238000006471 dimerization reaction Methods 0.000 claims 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
- 229960005277 gemcitabine Drugs 0.000 claims 1
- 238000005734 heterodimerization reaction Methods 0.000 claims 1
- 239000013610 patient sample Substances 0.000 claims 1
- 229960002087 pertuzumab Drugs 0.000 claims 1
- 238000004445 quantitative analysis Methods 0.000 claims 1
- 238000003753 real-time PCR Methods 0.000 claims 1
- 238000011897 real-time detection Methods 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- 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
- G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
-
- 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
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57449—Specifically defined cancers of ovaries
-
- 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
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/5748—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving oncogenic proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- 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
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/485—Epidermal growth factor [EGF] (urogastrone)
-
- 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
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
- G01N2333/9121—Phosphotransferases in general with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
- G01N2333/91215—Phosphotransferases in general with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases with a definite EC number (2.7.1.-)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Analytical Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Food Science & Technology (AREA)
- Hospice & Palliative Care (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (41)
1. Способ лечения злокачественной опухоли, включающий введение пациенту ингибитора HER в количестве, эффективном для лечения злокачественной опухоли, где образец опухоли пациента экспрессирует два или более рецепторов HER и один или нескольких лигандов HER.
2. Способ по п.1, где рецепторы HER выбраны из группы, состоящей из EGFR, HER2 и HER3.
3. Способ по п.2, где рецепторы HER представляют собой EGFR и HER2.
4. Способ по п.2, где рецепторы HER представляют собой HER2 и HER3.
5. Способ по п.1, где лиганд HER выбран из группы, состоящей из бетацеллюлина, амфирегулина, эпирегулина и TGFα.
6. Способ по п.5, где лиганд HER представляет собой бетацеллюлин.
7. Способ по п.5, где лиганд HER представляет собой амфирегулин.
8. Способ по п.1, где образец опухоли экспрессирует HER2 и EGFR или HER3, а также бетацеллюлин или амфирегулин.
9. Способ по п.8, где образец опухоли экспрессирует HER2 и EGFR, а также бетацеллюлин.
10. Способ по п.1, где ингибитор HER представляет собой ингибитор димеризации HER.
11. Способ по п.1, где ингибитор HER представляет собой антитело к HER.
12. Способ по п.11, где антитело к HER представляет собой антитело к HER2.
13. Способ по п.12, где антитело к HER2 связывается с доменом II внеклеточного домена HER2.
14. Способ по п.13, где антитело к HER2 представляет собой пертузумаб.
15. Способ по любому из пп.11-14, где антитело к HER представляет собой свободное антитело.
16. Способ по любому из пп.11-14, где антитело к HER представляет собой интактное антитело.
17. Способ по любому из пп.11-14, где антитело к HER2 представляет собой фрагмент антитела, содержащий антигенсвязывающую область.
18. Способ по п.1, где экспрессию определяют посредством количественного анализа мРНК, кодирующей рецептор или лиганд HER.
19. Способ по п.18, где количество мРНК определяют с помощью полимеразной цепной реакции (ПЦР).
20. Способ по п.19, где ПЦР представляет собой количественную ПЦР с детекцией в реальном времени (кПЦР-РВ).
21. Способ по п.1, где образец опухоли представляет собой фиксированный образец опухоли.
22. Способ по п.21, где образец опухоли представляет собой фиксированный в формалине погруженный в парафин (FFPE) образец опухоли.
23. Способ по п.1, где образец опухоли представляет собой замороженный образец опухоли.
24. Способ по п.1, где экспрессия рецепторов HER и лиганда HER находится на среднем уровне или выше.
25. Способ по п.1, где злокачественная опухоль представляет собой рак яичников, перитонеальную злокачественную опухоль и злокачественную опухоль фаллопиевых труб.
26. Способ по п.1, где злокачественная опухоль представляет собой метастазирующий рак молочной железы (MBC).
27. Способ по п.1, где злокачественная опухоль представляет собой немелкоклеточный рак легких (NSCLC).
28. Способ по п.1, дополнительно включающий введение пациенту химиотерапевтического средства.
29. Способ по п.28, где химиотерапевтическое средство представляет собой антиметаболическое химиотерапевтическое средство.
30. Способ по п.29, где антиметаболическое химиотерапевтическое средство представляет собой гемцитабин.
31. Способ лечения злокачественной опухоли, включающий введение пациенту ингибитора HER в количестве, эффективном для лечения злокачественной опухоли, где образец опухоли пациента экспрессирует бетацеллюлин или амфирегулин.
32. Способ по п.31, где ингибитор HER ингибирует гетеродимеризацию HER2 с EGFR или HER3.
33. Способ лечения злокачественной опухоли, включающий введение пациенту антитела к HER2, связывающегося с доменом II HER2, в количестве, эффективном для лечения злокачественной опухоли, где образец опухоли пациента экспрессирует HER2 и EGFR или HER3, а также бетацеллюлин или амфирегулин.
34. Способ по п.33, где антитело HER2 связывается с местом соединения доменов I, II и III HER2.
35. Способ оценки фосфорилирования или активации HER в биологическом образце, включающий определение экспрессии двух или более рецепторов HER и одного или нескольких лигандов HER в образце, где экспрессия двух или более рецепторов HER и одного или нескольких лигандов HER служит признаком фосфорилирования или активации HER в образце.
36. Способ по п.35, где образец представляет собой погруженный в парафин, фиксированный в формалине образец опухоли.
37. Способ оценки фосфорилирования или активации HER в биологическом образце, включающий определение экспрессии бетацеллюлина или амфирегулина в образце, где экспрессия бетацеллюлина или амфирегулина служит признаком фосфорилирования или активации HER в образце.
38. Способ определения пациента для лечения ингибитором димеризации HER, включающий определение экспрессии двух или более рецепторов HER и одного или нескольких лигандов HER в образце пациента, где экспрессия рецепторов HER и лиганда HER служит признаком того, что пациент с большей вероятностью отвечает на лечение ингибитором димеризации HER.
39. Способ по п.38, где пациент представляет собой пациента со злокачественной опухолью.
40. Способ лечения рака яичников, включающий введение пациенту ингибитора HER в количестве, эффективном для лечения рака яичников, где образец опухоли пациента экспрессирует бетацеллюлин или амфирегулин.
41. Способ по п.40, где образец опухоли дополнительно экспрессирует два или более рецепторов HER.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63394104P | 2004-12-07 | 2004-12-07 | |
| US60/633,941 | 2004-12-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2007125644A true RU2007125644A (ru) | 2009-01-20 |
Family
ID=36177671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007125644/13A RU2007125644A (ru) | 2004-12-07 | 2005-12-06 | Отбор пациентов для терапии ингибитором her |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20060121044A1 (ru) |
| EP (1) | EP1825001A2 (ru) |
| JP (1) | JP2008523073A (ru) |
| KR (1) | KR20070085855A (ru) |
| CN (1) | CN101115849A (ru) |
| AR (1) | AR051524A1 (ru) |
| AU (1) | AU2005314127A1 (ru) |
| BR (1) | BRPI0518086A (ru) |
| CA (1) | CA2587519A1 (ru) |
| MX (1) | MX2007006529A (ru) |
| NO (1) | NO20073487L (ru) |
| RU (1) | RU2007125644A (ru) |
| WO (1) | WO2006063042A2 (ru) |
| ZA (1) | ZA200704796B (ru) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA9811162B (en) | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
| IL152656A0 (en) | 2000-05-19 | 2003-06-24 | Genentech Inc | Gene detection assay for improving the likelihood of an effective response to an erbb antagonist cancer therapy |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| PT1392359E (pt) | 2001-05-11 | 2010-01-27 | Ludwig Inst For Cancer Res Ltd | Proteínas de ligação específica e suas utilizações |
| US7767792B2 (en) * | 2004-02-20 | 2010-08-03 | Ludwig Institute For Cancer Research Ltd. | Antibodies to EGF receptor epitope peptides |
| SV2006002143A (es) * | 2004-06-16 | 2006-01-26 | Genentech Inc | Uso de un anticuerpo para el tratamiento del cancer resistente al platino |
| AU2005287404B2 (en) | 2004-07-22 | 2009-05-07 | Genentech, Inc. | HER2 antibody composition |
| JO3000B1 (ar) * | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| AU2005314127A1 (en) * | 2004-12-07 | 2006-06-15 | Genentech, Inc. | Selecting patients for therapy with a HER inhibitor |
| MX2007008768A (es) | 2005-01-21 | 2007-10-19 | Genentech Inc | Dosificacion fija de anticuerpos her. |
| CN103251946A (zh) * | 2005-02-23 | 2013-08-21 | 健泰科生物技术公司 | 使用her二聚化抑制剂在癌症患者中延长病情进展前时间或存活 |
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- 2005-12-06 BR BRPI0518086-4A patent/BRPI0518086A/pt not_active IP Right Cessation
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| CN101115849A (zh) | 2008-01-30 |
| WO2006063042A3 (en) | 2007-02-08 |
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| BRPI0518086A (pt) | 2008-10-28 |
| MX2007006529A (es) | 2007-06-22 |
| AR051524A1 (es) | 2007-01-17 |
| EP1825001A2 (en) | 2007-08-29 |
| JP2008523073A (ja) | 2008-07-03 |
| CA2587519A1 (en) | 2006-06-15 |
| US20060121044A1 (en) | 2006-06-08 |
| NO20073487L (no) | 2007-09-05 |
| US20080317753A1 (en) | 2008-12-25 |
| AU2005314127A1 (en) | 2006-06-15 |
| ZA200704796B (en) | 2008-11-26 |
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