WO2000033878A3 - Stabilization of macrolides - Google Patents

Stabilization of macrolides Download PDF

Info

Publication number
WO2000033878A3
WO2000033878A3 PCT/EP1999/009521 EP9909521W WO0033878A3 WO 2000033878 A3 WO2000033878 A3 WO 2000033878A3 EP 9909521 W EP9909521 W EP 9909521W WO 0033878 A3 WO0033878 A3 WO 0033878A3
Authority
WO
WIPO (PCT)
Prior art keywords
stabilization
macrolides
poly
relates
crystalline form
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.)
Ceased
Application number
PCT/EP1999/009521
Other languages
French (fr)
Other versions
WO2000033878A2 (en
Inventor
Francois Navarro
Samuel Petit
Guy Stone
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis Pharma GmbH Austria
Novartis AG
Original Assignee
Novartis Erfindungen Verwaltungs GmbH
Novartis AG
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26314797&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2000033878(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to DK99959381.7T priority Critical patent/DK1137439T4/en
Priority to SI9930985T priority patent/SI1137439T2/en
Priority to CA2351580A priority patent/CA2351580C/en
Priority to ES99959381T priority patent/ES2288033T5/en
Priority to SK5032-2008A priority patent/SK287325B6/en
Priority to PL348333A priority patent/PL196627B1/en
Priority to DE69936352T priority patent/DE69936352T3/en
Priority to AU16573/00A priority patent/AU759219B2/en
Priority to EP99959381A priority patent/EP1137439B2/en
Priority to JP2000586368A priority patent/JP3805625B2/en
Priority to HK02100663.4A priority patent/HK1038889B/en
Priority to HU1300289A priority patent/HU230174B1/en
Priority to HU0104489A priority patent/HU228939B1/en
Application filed by Novartis Erfindungen Verwaltungs GmbH, Novartis AG filed Critical Novartis Erfindungen Verwaltungs GmbH
Priority to NZ511936A priority patent/NZ511936A/en
Priority to BR9915986-4A priority patent/BR9915986A/en
Priority to SK766-2001A priority patent/SK286688B6/en
Priority to IL14309299A priority patent/IL143092A0/en
Publication of WO2000033878A2 publication Critical patent/WO2000033878A2/en
Publication of WO2000033878A3 publication Critical patent/WO2000033878A3/en
Priority to NO20012424A priority patent/NO332698B1/en
Priority to US09/866,977 priority patent/US6605613B2/en
Anticipated expiration legal-status Critical
Priority to US10/393,795 priority patent/US6852729B2/en
Priority to US11/020,860 priority patent/US7297703B2/en
Priority to US11/973,927 priority patent/US7572804B2/en
Priority to US12/497,728 priority patent/US7741338B2/en
Priority to NO20121113A priority patent/NO334612B1/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention relates to the stabilization of poly-ene macrolides and to a particular macrolide obtained in crystalline form.
PCT/EP1999/009521 1998-12-07 1999-12-06 Stabilization of macrolides Ceased WO2000033878A2 (en)

Priority Applications (24)

Application Number Priority Date Filing Date Title
HU1300289A HU230174B1 (en) 1998-12-07 1999-12-06 Molten mixture containing rapamycin derivate
NZ511936A NZ511936A (en) 1998-12-07 1999-12-06 Stabilization of macrolides
CA2351580A CA2351580C (en) 1998-12-07 1999-12-06 Stabilization of macrolides
ES99959381T ES2288033T5 (en) 1998-12-07 1999-12-06 Stabilization of rapamycins or derivatives of rapamycins
SK5032-2008A SK287325B6 (en) 1998-12-07 1999-12-06 Mixture comprising 40-O-(2-hydroxy)ethyl-rapamycin and antioxidant and pharmaceutical composition containing thereof
PL348333A PL196627B1 (en) 1998-12-07 1999-12-06 Macrolides
DE69936352T DE69936352T3 (en) 1998-12-07 1999-12-06 Stabilization of rapamycin or rapamycin derivatives
AU16573/00A AU759219B2 (en) 1998-12-07 1999-12-06 Stabilization of macrolides
EP99959381A EP1137439B2 (en) 1998-12-07 1999-12-06 Stabilization of rapamycins or derivatives of rapamycins
JP2000586368A JP3805625B2 (en) 1998-12-07 1999-12-06 Macrolide stabilization
HK02100663.4A HK1038889B (en) 1998-12-07 1999-12-06 Stabilization of rapamycins or derivatives of rapamycins
SI9930985T SI1137439T2 (en) 1998-12-07 1999-12-06 Stabilization of rapamycins or derivatives of rapamycins
HU0104489A HU228939B1 (en) 1998-12-07 1999-12-06 Stabilization of derivative of rapamicin
DK99959381.7T DK1137439T4 (en) 1998-12-07 1999-12-06 Stabilization of rapamycins or rapamycin derivatives
SK766-2001A SK286688B6 (en) 1998-12-07 1999-12-06 Process for stabilizing rapamycin or rapamycin derivative
IL14309299A IL143092A0 (en) 1998-12-07 1999-12-06 Stabilization of macrolides
BR9915986-4A BR9915986A (en) 1998-12-07 1999-12-06 Macro-stabilization
NO20012424A NO332698B1 (en) 1998-12-07 2001-05-16 Method for stabilizing rapamycin derivatives
US09/866,977 US6605613B2 (en) 1998-12-07 2001-05-29 Macrolides
US10/393,795 US6852729B2 (en) 1998-12-07 2003-03-21 Macrolides
US11/020,860 US7297703B2 (en) 1998-12-07 2004-12-23 Macrolides
US11/973,927 US7572804B2 (en) 1998-12-07 2007-10-11 Macrolides
US12/497,728 US7741338B2 (en) 1998-12-07 2009-07-06 Macrolides
NO20121113A NO334612B1 (en) 1998-12-07 2012-10-01 Stabilization of macrolides

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9826882.4A GB9826882D0 (en) 1998-12-07 1998-12-07 Organic compounds
GB9826882.4 1998-12-07
GB9904934.8 1999-03-04
GBGB9904934.8A GB9904934D0 (en) 1998-12-07 1999-03-04 Organic compounds

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09/866,997 Continuation US6544022B2 (en) 2000-03-20 2001-05-07 Heat staking head with radiant heat source
US09/866,977 Continuation US6605613B2 (en) 1998-12-07 2001-05-29 Macrolides

Publications (2)

Publication Number Publication Date
WO2000033878A2 WO2000033878A2 (en) 2000-06-15
WO2000033878A3 true WO2000033878A3 (en) 2000-11-02

Family

ID=26314797

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/009521 Ceased WO2000033878A2 (en) 1998-12-07 1999-12-06 Stabilization of macrolides

Country Status (38)

Country Link
US (5) US6605613B2 (en)
EP (4) EP2279751A3 (en)
JP (3) JP3805625B2 (en)
KR (2) KR100695834B1 (en)
CN (2) CN1261163C (en)
AR (3) AR026102A1 (en)
AT (1) ATE365051T1 (en)
AU (1) AU759219B2 (en)
BE (1) BE1012869A3 (en)
BR (1) BR9915986A (en)
CA (3) CA2351580C (en)
CO (1) CO4980847A1 (en)
CY (1) CY1106870T1 (en)
CZ (2) CZ303006B6 (en)
DE (1) DE69936352T3 (en)
DK (1) DK1137439T4 (en)
ES (1) ES2288033T5 (en)
FR (1) FR2786771B1 (en)
GB (2) GB9826882D0 (en)
HK (1) HK1038889B (en)
HU (2) HU228939B1 (en)
ID (1) ID29250A (en)
IL (1) IL143092A0 (en)
IT (1) IT1319701B1 (en)
MY (2) MY127579A (en)
NO (2) NO332698B1 (en)
NZ (2) NZ511936A (en)
PE (1) PE20001333A1 (en)
PL (2) PL208854B1 (en)
PT (1) PT1137439E (en)
RU (1) RU2243769C2 (en)
SG (1) SG151072A1 (en)
SI (1) SI1137439T2 (en)
SK (2) SK286688B6 (en)
TR (2) TR200101416T2 (en)
TW (2) TWI270550B (en)
WO (1) WO2000033878A2 (en)
ZA (1) ZA200104360B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8961588B2 (en) 2002-03-27 2015-02-24 Advanced Cardiovascular Systems, Inc. Method of coating a stent with a release polymer for 40-O-(2-hydroxy)ethyl-rapamycin
USRE45744E1 (en) 2003-12-01 2015-10-13 Abbott Cardiovascular Systems Inc. Temperature controlled crimping

Families Citing this family (34)

* Cited by examiner, † Cited by third party
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US7452692B2 (en) 2002-02-13 2008-11-18 Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság Method for extracting a macrolide from biomatter
MXPA04007847A (en) 2002-02-13 2005-02-24 Biogal Gyogyszergyar Method for extracting a macrolide from biomatter.
NZ537829A (en) 2002-07-30 2006-09-29 Wyeth Corp Parenteral formulations containing a rapamycin hydroxyester
TR200500302T3 (en) * 2003-03-31 2005-04-21 Biogal Gyogyszergyar Rt. Crystallization and purification of macrolides.
TW200523266A (en) 2003-07-24 2005-07-16 Biogal Gyogyszergyar Method of purifying macrolides
CA2539324A1 (en) 2003-09-18 2005-03-31 Macusight, Inc. Transscleral delivery
US9114198B2 (en) * 2003-11-19 2015-08-25 Advanced Cardiovascular Systems, Inc. Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same
CN1889994A (en) * 2003-12-10 2007-01-03 艾克若克斯Dds有限公司 Methods of treatment with undesired effects of transdermal or topical drug delivery
US8551512B2 (en) 2004-03-22 2013-10-08 Advanced Cardiovascular Systems, Inc. Polyethylene glycol/poly(butylene terephthalate) copolymer coated devices including EVEROLIMUS
US20060094744A1 (en) * 2004-09-29 2006-05-04 Maryanoff Cynthia A Pharmaceutical dosage forms of stable amorphous rapamycin like compounds
JP4974903B2 (en) 2005-02-09 2012-07-11 参天製薬株式会社 Liquid formulations for treating diseases or conditions
BRPI0619592A2 (en) * 2005-12-07 2016-09-06 Wyeth Corp methods for measuring particle quality of a rapamycin compound, for determining the average particle size of a sample and the crystallinity of a rapamycin compound, and for rapamycin purification
US7700614B2 (en) * 2005-12-14 2010-04-20 Abbott Laboratories One pot synthesis of tetrazole derivatives of rapamycin
RU2008121713A (en) * 2005-12-20 2010-01-27 Вайет (Us) CONTROL OF STABILITY OF THE MEDICINAL FORM CCI-779 BY MEANS OF CONTROL OF THE IMPURITIES OF THE MEDICINE
WO2007092620A2 (en) * 2006-02-09 2007-08-16 Macusight, Inc. Stable formulations, and methods of their preparation and use
PL2001466T3 (en) 2006-03-23 2016-06-30 Santen Pharmaceutical Co Ltd Low-dose rapamycin for the treatment of vascular permeability-related diseases
WO2011151704A2 (en) 2010-06-02 2011-12-08 Fresenius Kabi Oncology Ltd. Stable pharmaceutical compositions of rapamycin esters
WO2011156025A1 (en) * 2010-06-07 2011-12-15 Telik, Inc. Crystalline Ezatiostat Hydrochloride Ansolvate
EP2601201B1 (en) * 2010-08-04 2014-09-24 Meril Life Sciences Pvt. Ltd. Process for preparation of novel 42-0-(heteroalkoxyalkyl) rapamycin compounds with anti-proliferative properties"
WO2012066502A1 (en) 2010-11-19 2012-05-24 Biocon Limited Processes for preparation of everolimus and intermediates thereof
JP2014516075A (en) 2011-06-06 2014-07-07 シェブロン フィリップス ケミカル カンパニー エルピー Use of metallocene compounds for the treatment of cancer
WO2013022201A1 (en) * 2011-08-11 2013-02-14 Dong-A Pharm. Co., Ltd. Process of preparing a stabilized and solubilized formulation of sirolimus derivatives
US9610385B2 (en) 2013-03-07 2017-04-04 Abbott Cardiovascular Systems Inc. Method of fabricating an implantable medical device comprising a rapamycin derivative
IN2013MU02532A (en) 2013-07-31 2015-06-26 Sahajanand Medical Technologies Pvt Ltd
CN104721158B (en) * 2013-12-24 2018-01-30 正大天晴药业集团股份有限公司 A kind of everolimus tablet of stabilization
CN104892632B (en) * 2015-06-03 2017-12-26 道中道（菏泽）制药有限公司 A kind of everolimus of crystal form and preparation method thereof
US10383860B2 (en) 2015-07-28 2019-08-20 Nippon Kayaku Kabushiki Kaisha Pharmaceutical composition comprising rapamycin or derivative thereof, and method for producing the same
JP6793651B2 (en) * 2015-08-28 2020-12-02 日本化薬株式会社 Pharmaceutical composition containing rapamycin or a derivative thereof
WO2017047618A1 (en) * 2015-09-18 2017-03-23 日本化薬株式会社 Medicinal composition comprising rapamycin or derivative thereof
WO2017129772A1 (en) 2016-01-29 2017-08-03 Xellia Phamaceuticals Aps Stable pharmaceutical compositions of temsirolimus
JP6855470B2 (en) 2016-05-27 2021-04-07 日本化薬株式会社 Pharmaceutical composition containing rapamycin or a derivative thereof
KR102051806B1 (en) * 2018-01-12 2019-12-04 주식회사 종근당 Stabilized pharmaceutical formulation comprising Everolimus
CN119431400A (en) * 2020-03-27 2025-02-14 波士顿科学国际有限公司 Method for crystallizing a drug
JP2023028473A (en) * 2021-08-19 2023-03-03 日本マイクロバイオファーマ株式会社 Method for producing everolimus

Citations (5)

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Publication number Priority date Publication date Assignee Title
EP0041795A2 (en) * 1980-06-02 1981-12-16 Ayerst, Mckenna And Harrison Inc. Injectable composition of rapamycin
EP0423714A2 (en) * 1989-10-16 1991-04-24 Fujisawa Pharmaceutical Co., Ltd. Hair revitalizing agent
WO1994009010A1 (en) * 1992-10-09 1994-04-28 Sandoz Ltd. O-alkylated rapamycin derivatives and their use, particularly as immunosuppressants
WO1997003654A2 (en) * 1995-07-14 1997-02-06 Novartis Ag Pharmaceutical compositions
WO1998004279A1 (en) * 1996-07-30 1998-02-05 Novartis Ag Pharmaceutical compositions for the treatment of transplant rejection, autoimmune or inflammatory conditions comprising cyclosporin a and 40-0-(2-hydroxiethyl)-rapamycin

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US3996355A (en) 1975-01-02 1976-12-07 American Home Products Corporation Permanent suspension pharmaceutical dosage form
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FI97472C (en) 1991-05-07 1996-12-27 American Home Prod Process for the preparation of therapeutically useful rapamycin derivatives as anti-inflammatory and antifungal agents
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Publication number Priority date Publication date Assignee Title
EP0041795A2 (en) * 1980-06-02 1981-12-16 Ayerst, Mckenna And Harrison Inc. Injectable composition of rapamycin
EP0423714A2 (en) * 1989-10-16 1991-04-24 Fujisawa Pharmaceutical Co., Ltd. Hair revitalizing agent
WO1994009010A1 (en) * 1992-10-09 1994-04-28 Sandoz Ltd. O-alkylated rapamycin derivatives and their use, particularly as immunosuppressants
WO1997003654A2 (en) * 1995-07-14 1997-02-06 Novartis Ag Pharmaceutical compositions
WO1998004279A1 (en) * 1996-07-30 1998-02-05 Novartis Ag Pharmaceutical compositions for the treatment of transplant rejection, autoimmune or inflammatory conditions comprising cyclosporin a and 40-0-(2-hydroxiethyl)-rapamycin

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8961588B2 (en) 2002-03-27 2015-02-24 Advanced Cardiovascular Systems, Inc. Method of coating a stent with a release polymer for 40-O-(2-hydroxy)ethyl-rapamycin
USRE45744E1 (en) 2003-12-01 2015-10-13 Abbott Cardiovascular Systems Inc. Temperature controlled crimping

Also Published As

Publication number Publication date
ITMI992520A1 (en) 2001-06-02
BE1012869A3 (en) 2001-04-03
ES2288033T3 (en) 2007-12-16
US7572804B2 (en) 2009-08-11
SI1137439T2 (en) 2012-05-31
GB9904934D0 (en) 1999-04-28
ITMI992520A0 (en) 1999-12-02
AU1657300A (en) 2000-06-26
JP2006111637A (en) 2006-04-27
HUP0104489A3 (en) 2004-05-28
FR2786771A1 (en) 2000-06-09
PE20001333A1 (en) 2000-12-12
PT1137439E (en) 2007-09-25
CZ303006B6 (en) 2012-02-22
NO20012424D0 (en) 2001-05-16
WO2000033878A2 (en) 2000-06-15
CA2732620A1 (en) 2000-06-15
IL143092A0 (en) 2002-04-21
US7741338B2 (en) 2010-06-22
FR2786771B1 (en) 2002-12-27
AR048073A2 (en) 2006-03-29
EP2269651A2 (en) 2011-01-05
RU2243769C2 (en) 2005-01-10
TR200101416T2 (en) 2002-01-21
JP2002531527A (en) 2002-09-24
NO20012424L (en) 2001-05-16
CZ20012001A3 (en) 2001-09-12
ID29250A (en) 2001-08-16
NO20121113L (en) 2001-05-16
US20050107418A1 (en) 2005-05-19
CY1106870T1 (en) 2012-09-26
DK1137439T3 (en) 2007-09-10
US20030191148A1 (en) 2003-10-09
PL348333A1 (en) 2002-05-20
CN1876657B (en) 2013-01-09
EP2279751A3 (en) 2011-02-16
US6605613B2 (en) 2003-08-12
CA2351580C (en) 2012-03-20
TWI270550B (en) 2007-01-11
US20090270441A1 (en) 2009-10-29
EP1743657A3 (en) 2007-03-28
US6852729B2 (en) 2005-02-08
GB9826882D0 (en) 1999-01-27
TW200540179A (en) 2005-12-16
JP3805625B2 (en) 2006-08-02
SI1137439T1 (en) 2008-06-30
US20080161334A1 (en) 2008-07-03
EP2279751A2 (en) 2011-02-02
BR9915986A (en) 2001-09-04
EP1137439A2 (en) 2001-10-04
MY120594A (en) 2005-11-30
DE69936352T2 (en) 2008-02-14
ES2288033T5 (en) 2012-04-10
CO4980847A1 (en) 2000-11-27
PL196627B1 (en) 2008-01-31
HK1038889A1 (en) 2002-04-04
US7297703B2 (en) 2007-11-20
ZA200104360B (en) 2002-01-16
CZ302210B6 (en) 2010-12-22
EP1743657A2 (en) 2007-01-17
TWI248938B (en) 2006-02-11
HU228939B1 (en) 2013-07-29
EP1137439B1 (en) 2007-06-20
ATE365051T1 (en) 2007-07-15
TR200201428T2 (en) 2002-12-23
AR026102A1 (en) 2003-01-29
NO334612B1 (en) 2014-04-22
HU230174B1 (en) 2015-09-28
NZ527781A (en) 2004-11-26
KR20010101128A (en) 2001-11-14
CA2351580A1 (en) 2000-06-15
JP5043308B2 (en) 2012-10-10
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CN1876657A (en) 2006-12-13
JP2005200429A (en) 2005-07-28
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SK286688B6 (en) 2009-03-05
JP5165199B2 (en) 2013-03-21
EP1137439B2 (en) 2011-11-23
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US20020032213A1 (en) 2002-03-14
NZ511936A (en) 2003-10-31
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CA2732620C (en) 2013-08-06
EP2269651A3 (en) 2011-03-09
DE69936352T3 (en) 2012-05-03
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NO332698B1 (en) 2012-12-10

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