CA2450777C - Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia - Google Patents
Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia Download PDFInfo
- Publication number
- CA2450777C CA2450777C CA2450777A CA2450777A CA2450777C CA 2450777 C CA2450777 C CA 2450777C CA 2450777 A CA2450777 A CA 2450777A CA 2450777 A CA2450777 A CA 2450777A CA 2450777 C CA2450777 C CA 2450777C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- leukaemia
- tyrosine kinase
- kinase activity
- methyl
- 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.)
- Expired - Fee Related
Links
- 208000032839 leukemia Diseases 0.000 title claims abstract description 58
- 102000001332 SRC Human genes 0.000 title claims abstract description 53
- 108060006706 SRC Proteins 0.000 title claims abstract description 53
- 239000003112 inhibitor Substances 0.000 title claims description 6
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 title description 6
- 229960002411 imatinib Drugs 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 230000000694 effects Effects 0.000 claims abstract description 78
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 48
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 48
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 42
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 102000004441 bcr-abl Fusion Proteins Human genes 0.000 claims abstract description 6
- 108010056708 bcr-abl Fusion Proteins Proteins 0.000 claims abstract description 6
- 238000009097 single-agent therapy Methods 0.000 claims description 17
- 239000013543 active substance Substances 0.000 claims description 15
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- 102000038012 SFKs Human genes 0.000 abstract description 2
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- 102000051624 phosphatidylethanolamine binding protein Human genes 0.000 abstract description 2
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- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 4
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
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- 150000003230 pyrimidines Chemical class 0.000 description 4
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- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 2
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- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 2
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- 208000032800 BCR-ABL1 positive blast phase chronic myelogenous leukemia Diseases 0.000 description 1
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- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
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- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/02—Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2810339A CA2810339A1 (en) | 2001-08-10 | 2002-08-09 | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31169001P | 2001-08-10 | 2001-08-10 | |
| US60/311,690 | 2001-08-10 | ||
| PCT/EP2002/008941 WO2003013540A1 (en) | 2001-08-10 | 2002-08-09 | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2810339A Division CA2810339A1 (en) | 2001-08-10 | 2002-08-09 | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2450777A1 CA2450777A1 (en) | 2003-02-20 |
| CA2450777C true CA2450777C (en) | 2013-04-09 |
Family
ID=23208019
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2450777A Expired - Fee Related CA2450777C (en) | 2001-08-10 | 2002-08-09 | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
| CA2810339A Abandoned CA2810339A1 (en) | 2001-08-10 | 2002-08-09 | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2810339A Abandoned CA2810339A1 (en) | 2001-08-10 | 2002-08-09 | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
Country Status (6)
| Country | Link |
|---|---|
| US (5) | US20040248906A1 (enExample) |
| EP (2) | EP2258371A1 (enExample) |
| JP (1) | JP2005502643A (enExample) |
| CN (1) | CN1523991A (enExample) |
| CA (2) | CA2450777C (enExample) |
| WO (1) | WO2003013540A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| JP2005526008A (ja) * | 2001-12-04 | 2005-09-02 | オニックス ファーマシューティカルズ,インコーポレイティド | 癌を処置するためのraf−mek−erk経路インヒビター |
| CL2003002287A1 (es) | 2002-11-25 | 2005-01-14 | Wyeth Corp | COMPUESTOS DERIVADOS DE TIENO[3,2-b]-PIRIDINA-6-CARBONITRILOS Y TIENEO[2,3-b]-PIRIDINA-5-CARBONITRILOS, COMPOSICION FARMACEUTICA, PROCEDIMIENTO DE PREPARACION Y COMPUESTOS INTERMEDIARIOS, Y SU USO EN EL TRATAMIENTO DEL CANCER, APOPLEJIA, OSTEOPOROSIS |
| US7276519B2 (en) | 2002-11-25 | 2007-10-02 | Wyeth | Thieno[3,2-b]pyridine-6-carbonitriles and thieno[2,3-b]pyridine-5-carbonitriles as protein kinase inhibitors |
| US20050009891A1 (en) | 2003-07-09 | 2005-01-13 | Lee Francis Y. | Combination of SRC Kinase inhibitors and chemotherapeutic agents for the treatment of proliferative diseases |
| US20050267182A1 (en) | 2003-11-13 | 2005-12-01 | Ambit Biosciences Corporation | Urea derivatives as FLT-3 modulators |
| JPWO2005063720A1 (ja) * | 2003-12-25 | 2007-07-19 | 日本新薬株式会社 | アミド誘導体及び医薬 |
| CN1918158B (zh) * | 2004-02-14 | 2011-03-02 | Irm责任有限公司 | 作为蛋白激酶抑制剂的化合物和组合物 |
| EP2298292A3 (en) | 2004-06-18 | 2011-08-10 | Agennix USA Inc. | Kinase inhibitors for treating cancers |
| JP2008520612A (ja) * | 2004-11-24 | 2008-06-19 | ノバルティス アクチエンゲゼルシャフト | JAK阻害剤およびBcr−Abl、Flt−3、FAKまたはRAFキナーゼ阻害剤のうち少なくとも1個の組合せ |
| WO2007059143A2 (en) * | 2005-11-15 | 2007-05-24 | Bristol-Myers Squibb Company | Methods of identifying and treating individuals exhibiting mdr-1 overexpression with protein tyrosine kinase inhibitors and combinations thereof |
| WO2007109527A1 (en) * | 2006-03-17 | 2007-09-27 | Bristol-Myers Squibb Company | Methods of identifying and treating individuals exhibiting mutant bcr/abl kinase polypeptides |
| EP2010182A2 (en) * | 2006-04-07 | 2009-01-07 | Novartis AG | Use of c-src inhibitors in combination with a pyrimidylaminobenzamide compound for the treatment of leukemia |
| SG166093A1 (en) | 2006-09-22 | 2010-11-29 | Pharmacyclics Inc | Inhibitors of brutonæs tyrosine kinase |
| WO2008077064A2 (en) * | 2006-12-19 | 2008-06-26 | Board Of Regents, The University Of Texas System | Biomarker identifying the reactivation of stat3 after src inhibition |
| US8809273B2 (en) | 2007-03-28 | 2014-08-19 | Pharmacyclics, Inc. | Inhibitors of Bruton's tyrosine kinase |
| CN101674834B (zh) * | 2007-03-28 | 2013-06-12 | 环状药物公司 | 布鲁顿氏酪氨酸激酶(Bruton's tyrosine kinase)抑制剂 |
| CA2705303A1 (en) * | 2007-11-07 | 2009-05-14 | Foldrx Pharmaceuticals, Inc. | Modulation of protein trafficking |
| CA2730930C (en) | 2008-07-16 | 2015-01-13 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors |
| NZ717373A (en) | 2010-06-03 | 2017-11-24 | Pharmacyclics Llc | The use of inhibitors of bruton’s tyrosine kinase (btk) |
| MX2014000518A (es) | 2011-07-13 | 2014-05-30 | Pharmacyclics Inc | Inhibidores de la tirosina quinasa de bruton. |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| JP6182593B2 (ja) * | 2012-04-20 | 2017-08-16 | アドヴィーナス セラピューティクス リミテッド | 置換ヘテロ二環化合物、組成物及び医薬並びにそれらの用途 |
| IN2014MN02338A (enExample) * | 2012-05-31 | 2015-08-14 | Pharmascience Inc | |
| TWI662963B (zh) | 2012-06-04 | 2019-06-21 | 美商製藥有限責任公司 | 布魯頓氏酪胺酸激酶抑制劑之結晶形式 |
| US10954567B2 (en) | 2012-07-24 | 2021-03-23 | Pharmacyclics Llc | Mutations associated with resistance to inhibitors of Bruton's Tyrosine Kinase (BTK) |
| MX2015006168A (es) | 2012-11-15 | 2015-08-10 | Pharmacyclics Inc | Compuestos de pirrolopirimidina como inhibidores de quinasas. |
| US10144828B2 (en) | 2012-11-21 | 2018-12-04 | Stratasys, Inc. | Semi-crystalline build materials |
| JP6800750B2 (ja) | 2013-08-02 | 2020-12-16 | ファーマサイクリックス エルエルシー | 固形腫瘍の処置方法 |
| ES2709509T3 (es) | 2013-08-12 | 2019-04-16 | Pharmacyclics Llc | Procedimientos para el tratamiento de cáncer amplificado por HER2 |
| MA38961A1 (fr) | 2013-09-30 | 2018-05-31 | Pharmacyclics Llc | Composés 3-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-ylamine substitués inhibiteurs de la tyrosine kinase de bruton utilisés pour traiter par exemple les maladies auto-immunes, respiratoires et inflammatoires, cancer, mastocytose et osteoporose |
| CA2942528A1 (en) | 2014-03-20 | 2015-09-24 | Pharmacyclics Inc. | Phospholipase c gamma 2 and resistance associated mutations |
| WO2015196072A2 (en) | 2014-06-19 | 2015-12-23 | Whitehead Institute For Biomedical Research | Uses of kinase inhibitors for inducing and maintaining pluripotency |
| US9533991B2 (en) | 2014-08-01 | 2017-01-03 | Pharmacyclics Llc | Inhibitors of Bruton's tyrosine kinase |
| KR20170033358A (ko) | 2014-08-07 | 2017-03-24 | 파마싸이클릭스 엘엘씨 | 브루톤 티로신 키나아제 저해제의 신규한 제제 |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| WO2017156350A1 (en) | 2016-03-09 | 2017-09-14 | K-Gen, Inc. | Methods of cancer treatment |
| CN108101905A (zh) * | 2016-11-24 | 2018-06-01 | 中国科学院上海药物研究所 | 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途 |
| CN111432833A (zh) | 2017-11-29 | 2020-07-17 | 自适应噬菌体治疗公司 | 使用二十面体噬菌体的疫苗接种方法 |
| HUE071715T2 (hu) | 2018-09-10 | 2025-09-28 | Mirati Therapeutics Inc | Dasatinib és adagrasib kombinációja felhasználásra nem-kissejtes tüdõrák kezelésében |
| AU2020348947B2 (en) | 2019-09-16 | 2025-11-27 | Amgen Inc. | Method for external sterilization of drug delivery device |
| AR122159A1 (es) * | 2020-05-28 | 2022-08-17 | Novartis Ag | Inhibidores de mll1 y agentes antineoplásicos |
| WO2021252450A1 (en) | 2020-06-08 | 2021-12-16 | Adaptive Phage Therapeutics, Inc. | Phage display vaccine for covid-19 using a novel peptide sequence |
| US12371667B2 (en) | 2021-05-13 | 2025-07-29 | Washington University | Enhanced methods for inducing and maintaining naive human pluripotent stem cells |
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|---|---|---|---|---|
| ATE159257T1 (de) * | 1994-05-03 | 1997-11-15 | Ciba Geigy Ag | Pyrrolopyrimidinderivate mit antiproliferativer wirkung |
| US5869485A (en) * | 1994-09-29 | 1999-02-09 | Novartis Finance Corp. | Pyrrolo 2,3-d!pyrimidines and their use |
| GB9517060D0 (en) | 1995-08-17 | 1995-10-25 | Ciba Geigy Ag | Acylated oligopeptide derivatives |
| GB9516842D0 (en) | 1995-08-17 | 1995-10-18 | Ciba Geigy Ag | Various acylated oligopeptides |
| AU7296896A (en) * | 1995-11-01 | 1997-05-22 | Novartis Ag | Purine derivatives and processes for their preparation |
| CH690773A5 (de) | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| WO1997032879A1 (de) | 1996-03-06 | 1997-09-12 | Novartis Ag | 7-ALKYL-PYRROLO[2,3-d]PYRIMIDINE |
| AU3176297A (en) | 1996-06-25 | 1998-01-14 | Novartis Ag | Substituted 7-amino-pyrrolo{3,2-d}pyrimidines and the use thereof |
| CO4940418A1 (es) | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| US6100254A (en) * | 1997-10-10 | 2000-08-08 | Board Of Regents, The University Of Texas System | Inhibitors of protein tyrosine kinases |
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| EP2308833A3 (en) | 1999-04-15 | 2011-09-28 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| TWI338004B (en) | 2004-02-06 | 2011-03-01 | Bristol Myers Squibb Co | Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors |
| US20050215795A1 (en) | 2004-02-06 | 2005-09-29 | Bang-Chi Chen | Process for preparing 2-aminothiazole-5-aromatic carboxamides as kinase inhibitors |
-
2002
- 2002-08-09 EP EP10175362A patent/EP2258371A1/en not_active Withdrawn
- 2002-08-09 CA CA2450777A patent/CA2450777C/en not_active Expired - Fee Related
- 2002-08-09 EP EP02794592A patent/EP1418917A1/en not_active Withdrawn
- 2002-08-09 CA CA2810339A patent/CA2810339A1/en not_active Abandoned
- 2002-08-09 JP JP2003518549A patent/JP2005502643A/ja not_active Withdrawn
- 2002-08-09 US US10/485,803 patent/US20040248906A1/en not_active Abandoned
- 2002-08-09 CN CNA028136969A patent/CN1523991A/zh active Pending
- 2002-08-09 WO PCT/EP2002/008941 patent/WO2003013540A1/en not_active Ceased
-
2005
- 2005-11-22 US US11/285,664 patent/US8268837B2/en not_active Expired - Fee Related
-
2006
- 2006-09-05 US US11/515,981 patent/US20070027167A1/en not_active Abandoned
-
2007
- 2007-02-28 US US11/679,901 patent/US20070149539A1/en not_active Abandoned
-
2009
- 2009-05-14 US US12/466,186 patent/US8119649B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20070027167A1 (en) | 2007-02-01 |
| WO2003013540A1 (en) | 2003-02-20 |
| US20070149539A1 (en) | 2007-06-28 |
| CN1523991A (zh) | 2004-08-25 |
| US20060074094A1 (en) | 2006-04-06 |
| US8119649B2 (en) | 2012-02-21 |
| CA2450777A1 (en) | 2003-02-20 |
| EP2258371A1 (en) | 2010-12-08 |
| CA2810339A1 (en) | 2003-02-20 |
| JP2005502643A (ja) | 2005-01-27 |
| US8268837B2 (en) | 2012-09-18 |
| EP1418917A1 (en) | 2004-05-19 |
| US20040248906A1 (en) | 2004-12-09 |
| US20090227608A1 (en) | 2009-09-10 |
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| EEER | Examination request | ||
| MKLA | Lapsed |
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