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PT1734049E - Peptídeos associados a tumores de ligação à molécula mhc - Google Patents

Peptídeos associados a tumores de ligação à molécula mhc Download PDF

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Publication number
PT1734049E
PT1734049E PT06015806T PT06015806T PT1734049E PT 1734049 E PT1734049 E PT 1734049E PT 06015806 T PT06015806 T PT 06015806T PT 06015806 T PT06015806 T PT 06015806T PT 1734049 E PT1734049 E PT 1734049E
Authority
PT
Portugal
Prior art keywords
cancer cells
cells
ile
val
incubated
Prior art date
Application number
PT06015806T
Other languages
English (en)
Inventor
Toni Weinschenk
Hans-Georg Rammensee
Stefan Stevanovic
Original Assignee
Immatics Biotechnologies Gmbh
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 Immatics Biotechnologies Gmbh filed Critical Immatics Biotechnologies Gmbh
Publication of PT1734049E publication Critical patent/PT1734049E/pt

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/10Cellular immunotherapy characterised by the cell type used
    • A61K40/11T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41Vertebrate antigens
    • A61K40/42Cancer antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41Vertebrate antigens
    • A61K40/42Cancer antigens
    • A61K40/4238Regulators of development
    • A61K40/424Apoptosis related proteins, e.g. survivin or livin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41Vertebrate antigens
    • A61K40/42Cancer antigens
    • A61K40/4242Transcription factors, e.g. SOX or c-MYC
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/46Viral antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/10Drugs for disorders of the urinary system of the bladder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/14Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4748Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047Cells of the immune system
    • G01N33/505Cells of the immune system involving T-cells
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966Animal cells
    • G01N33/56977HLA or MHC typing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48Blood cells, e.g. leukemia or lymphoma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/827Proteins from mammals or birds
    • Y10S530/828Cancer

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Reproductive Health (AREA)
  • Virology (AREA)
  • Endocrinology (AREA)
PT06015806T 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc PT1734049E (pt)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE10225144A DE10225144A1 (de) 2002-05-29 2002-05-29 An MHC-Moleküle bindende Tumor-assoziierte Peptide

Publications (1)

Publication Number Publication Date
PT1734049E true PT1734049E (pt) 2008-12-26

Family

ID=29557592

Family Applications (5)

Application Number Title Priority Date Filing Date
PT08014304T PT2006294E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT03720376T PT1507795E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT06015805T PT1734048E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT08014305T PT2014673E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT06015806T PT1734049E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc

Family Applications Before (4)

Application Number Title Priority Date Filing Date
PT08014304T PT2006294E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT03720376T PT1507795E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT06015805T PT1734048E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc
PT08014305T PT2014673E (pt) 2002-05-29 2003-03-27 Peptídeos associados a tumores de ligação à molécula mhc

Country Status (15)

Country Link
US (5) US7396904B2 (pt)
EP (5) EP1507795B1 (pt)
JP (5) JP4472520B2 (pt)
AT (5) ATE416188T1 (pt)
AU (2) AU2003224001B2 (pt)
CA (5) CA2736921C (pt)
CY (5) CY1108507T1 (pt)
DE (6) DE10225144A1 (pt)
DK (5) DK2006294T3 (pt)
ES (5) ES2317379T3 (pt)
HR (1) HRP20041108B1 (pt)
PL (5) PL206306B1 (pt)
PT (5) PT2006294E (pt)
SI (5) SI2006294T1 (pt)
WO (1) WO2003102023A1 (pt)

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CN101451975B (zh) * 2008-12-29 2012-01-25 浙江大学 一种检测胃癌预后与分期血清蛋白质的方法
US8075895B2 (en) * 2009-09-22 2011-12-13 Janssen Pharmaceutica N.V. Identification of antigenic peptides from multiple myeloma cells
GB201004575D0 (en) 2010-03-19 2010-05-05 Immatics Biotechnologies Gmbh Composition of tumor associated peptides and related anti cancer vaccine for the treatment of gastric cancer and other cancers
GB201009222D0 (en) * 2010-06-02 2010-07-21 Immatics Biotechnologies Gmbh Improved cancer therapy based on tumour associated antigens derived from cyclin D1
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JPWO2015050259A1 (ja) * 2013-10-03 2017-03-09 大日本住友製薬株式会社 腫瘍抗原ペプチド
AU2014348645B2 (en) 2013-11-13 2019-01-24 Regents Of The University Of Minnesota Annexin II variant compositions and methods
GB201505305D0 (en) 2015-03-27 2015-05-13 Immatics Biotechnologies Gmbh Novel Peptides and combination of peptides for use in immunotherapy against various tumors
ES2970246T3 (es) 2015-03-27 2024-05-27 Immatics Biotechnologies Gmbh Péptidos novedosos y combinación de péptidos para usarse en inmunoterapia contra diferentes tumores
NL2014935B1 (en) 2015-06-08 2017-02-03 Applied Immune Tech Ltd T cell receptor like antibodies having fine specificity.
GB201511546D0 (en) 2015-07-01 2015-08-12 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
IL308735A (en) 2015-07-01 2024-01-01 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers
GB201520550D0 (en) 2015-11-23 2016-01-06 Immunocore Ltd & Adaptimmune Ltd Peptides
GB201520558D0 (en) * 2015-11-23 2016-01-06 Immunocore Ltd & Adaptimmune Ltd Peptides
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GB201521746D0 (en) 2015-12-10 2016-01-27 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy against CLL and other cancers
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GB201609193D0 (en) 2016-05-25 2016-07-06 Immatics Biotechnologies Gmbh Novel peptides, combination of peptides as targets for use in immunotherapy against gallbladder cancer and cholangiocarcinoma and other cancers
JP7075125B2 (ja) 2016-05-25 2022-05-25 イマティクス バイオテクノロジーズ ゲーエムベーハー 標的としてのおよび胆嚢がんおよび胆管がんおよびその他のがんに対する免疫療法で使用するための新規ペプチド、ペプチド組み合わせ
KR102379955B1 (ko) 2016-12-08 2022-03-29 이매틱스 바이오테크놀로지스 게엠베하 짝짓기가 향상된 t 세포 수용체
DE102016123893A1 (de) 2016-12-08 2018-06-14 Immatics Biotechnologies Gmbh T-Zellrezeptoren mit verbesserter Bindung
KR102184377B1 (ko) 2018-02-19 2020-11-30 고려대학교 산학협력단 열충격단백질의 에피토프를 포함하는 백신 및 이의 용도
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Also Published As

Publication number Publication date
PT2006294E (pt) 2010-11-12
DE10225144A1 (de) 2003-12-18
CY1108673T1 (el) 2014-04-09
CY1108680T1 (el) 2014-04-09
PT1507795E (pt) 2008-12-26
HRP20041108A2 (en) 2005-10-31
JP2010099079A (ja) 2010-05-06
HRP20041108B1 (hr) 2013-11-08
CA2736974C (en) 2014-09-02
CA2736972C (en) 2014-08-05
SI1507795T1 (sl) 2009-04-30
JP2010088449A (ja) 2010-04-22
US20100184211A1 (en) 2010-07-22
US20050222390A1 (en) 2005-10-06
US20080051347A1 (en) 2008-02-28
JP2010099080A (ja) 2010-05-06
CY1111174T1 (el) 2015-06-11
EP1734049A1 (de) 2006-12-20
EP2006294B1 (de) 2010-08-18
CA2736926A1 (en) 2003-12-11
SI1734049T1 (sl) 2009-02-28
JP4472520B2 (ja) 2010-06-02
CY1110723T1 (el) 2015-06-10
DE50313004D1 (de) 2010-09-30
EP1734049B1 (de) 2008-12-03
JP2010099078A (ja) 2010-05-06
EP1507795B1 (de) 2008-10-08
ATE466872T1 (de) 2010-05-15
DK2014673T3 (da) 2010-08-30
DE50310882D1 (de) 2009-01-15
DE50310613D1 (de) 2008-11-20
US7666984B2 (en) 2010-02-23
PL211158B1 (pl) 2012-04-30
CA2487137C (en) 2013-02-19
CA2736921C (en) 2013-09-03
AU2010200689A1 (en) 2010-03-18
PT1734048E (pt) 2009-01-02
US7763711B2 (en) 2010-07-27
ES2314196T3 (es) 2009-03-16
PL373700A1 (en) 2005-09-05
DK1507795T3 (da) 2008-12-08
ES2317378T3 (es) 2009-04-16
EP2014673A1 (de) 2009-01-14
JP2006511196A (ja) 2006-04-06
JP5042303B2 (ja) 2012-10-03
ATE416188T1 (de) 2008-12-15
AU2003224001A1 (en) 2003-12-19
CA2736972A1 (en) 2003-12-11
PL211157B1 (pl) 2012-04-30
DK1734048T3 (da) 2009-02-23
US8536304B2 (en) 2013-09-17
CA2736921A1 (en) 2003-12-11
ATE417859T1 (de) 2009-01-15
ATE410442T1 (de) 2008-10-15
ES2350461T3 (es) 2011-01-24
DK2006294T3 (da) 2010-12-13
US8399613B2 (en) 2013-03-19
WO2003102023A1 (de) 2003-12-11
SI2006294T1 (sl) 2010-11-30
ATE478088T1 (de) 2010-09-15
DE50312701D1 (de) 2010-06-17
SI1734048T1 (sl) 2009-02-28
CA2487137A1 (en) 2003-12-11
CA2736974A1 (en) 2003-12-11
AU2010200689B2 (en) 2012-07-12
JP5042302B2 (ja) 2012-10-03
CA2736926C (en) 2015-11-17
CY1108507T1 (el) 2014-04-09
US20080057077A1 (en) 2008-03-06
PL211159B1 (pl) 2012-04-30
SI2014673T1 (sl) 2010-09-30
ES2348468T3 (es) 2010-12-07
PL210356B1 (pl) 2012-01-31
DE50310952D1 (de) 2009-01-29
EP2006294A1 (de) 2008-12-24
PT2014673E (pt) 2010-08-04
JP5042300B2 (ja) 2012-10-03
DK1734049T3 (da) 2009-01-19
US7396904B2 (en) 2008-07-08
ES2317379T3 (es) 2009-04-16
US20100183644A1 (en) 2010-07-22
PL206306B1 (pl) 2010-07-30
EP1734048A1 (de) 2006-12-20
JP5042301B2 (ja) 2012-10-03
EP1734048B1 (de) 2008-12-17
AU2003224001B2 (en) 2010-03-11
EP2014673B1 (de) 2010-05-05
EP1507795A1 (de) 2005-02-23

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