JP2008531647A - 抗腫瘍作用を有する製剤 - Google Patents
抗腫瘍作用を有する製剤 Download PDFInfo
- Publication number
- JP2008531647A JP2008531647A JP2007557486A JP2007557486A JP2008531647A JP 2008531647 A JP2008531647 A JP 2008531647A JP 2007557486 A JP2007557486 A JP 2007557486A JP 2007557486 A JP2007557486 A JP 2007557486A JP 2008531647 A JP2008531647 A JP 2008531647A
- Authority
- JP
- Japan
- Prior art keywords
- angiogenesis
- antitumor activity
- defibrotide
- tumor
- preparation
- 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.)
- Pending
Links
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract 5
- 239000000203 mixture Substances 0.000 title claims description 4
- 238000009472 formulation Methods 0.000 title claims 3
- 238000000034 method Methods 0.000 claims abstract description 17
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 claims abstract description 7
- 238000000605 extraction Methods 0.000 claims abstract description 5
- 241001465754 Metazoa Species 0.000 claims abstract description 4
- 210000000056 organ Anatomy 0.000 claims abstract description 3
- 239000004480 active ingredient Substances 0.000 claims abstract 3
- JNWFIPVDEINBAI-UHFFFAOYSA-N [5-hydroxy-4-[4-(1-methylindol-5-yl)-5-oxo-1H-1,2,4-triazol-3-yl]-2-propan-2-ylphenyl] dihydrogen phosphate Chemical group C1=C(OP(O)(O)=O)C(C(C)C)=CC(C=2N(C(=O)NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O JNWFIPVDEINBAI-UHFFFAOYSA-N 0.000 claims description 16
- 229960004120 defibrotide Drugs 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 8
- 108091034117 Oligonucleotide Proteins 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 3
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 3
- 229960002930 sirolimus Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims 4
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 claims 1
- QPNKYNYIKKVVQB-UHFFFAOYSA-N crotaleschenine Natural products O1C(=O)C(C)C(C)C(C)(O)C(=O)OCC2=CCN3C2C1CC3 QPNKYNYIKKVVQB-UHFFFAOYSA-N 0.000 claims 1
- 229960004397 cyclophosphamide Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- QVCMHGGNRFRMAD-XFGHUUIASA-N monocrotaline Chemical compound C1OC(=O)[C@](C)(O)[C@@](O)(C)[C@@H](C)C(=O)O[C@@H]2CCN3[C@@H]2C1=CC3 QVCMHGGNRFRMAD-XFGHUUIASA-N 0.000 claims 1
- QVCMHGGNRFRMAD-UHFFFAOYSA-N monocrotaline Natural products C1OC(=O)C(C)(O)C(O)(C)C(C)C(=O)OC2CCN3C2C1=CC3 QVCMHGGNRFRMAD-UHFFFAOYSA-N 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
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- 230000004614 tumor growth Effects 0.000 description 3
- 108010047303 von Willebrand Factor Proteins 0.000 description 3
- 102100036537 von Willebrand factor Human genes 0.000 description 3
- 229960001134 von willebrand factor Drugs 0.000 description 3
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
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- 108010054218 Factor VIII Proteins 0.000 description 1
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- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
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- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- -1 alkali metal salts Chemical class 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
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- 230000002785 anti-thrombosis Effects 0.000 description 1
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- 238000002474 experimental method Methods 0.000 description 1
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- 230000003480 fibrinolytic effect Effects 0.000 description 1
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- 230000007954 hypoxia Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
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Images
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT000336A ITMI20050336A1 (it) | 2005-03-03 | 2005-03-03 | Formulazione ad attivita' anti-tumorale |
| US73140405P | 2005-10-28 | 2005-10-28 | |
| PCT/EP2006/060306 WO2006094917A2 (en) | 2005-03-03 | 2006-02-27 | Oligodeoxyribonucleotides of 4000-10000 dalton for treating tumors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008531647A true JP2008531647A (ja) | 2008-08-14 |
| JP2008531647A5 JP2008531647A5 (enExample) | 2009-04-02 |
Family
ID=36572331
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007557486A Pending JP2008531647A (ja) | 2005-03-03 | 2006-02-27 | 抗腫瘍作用を有する製剤 |
| JP2007557485A Expired - Fee Related JP5714203B2 (ja) | 2005-03-03 | 2006-02-27 | 血管新生依存性腫瘍を治療するためのデフィブロチドおよび／またはオリゴデオキシリボヌクレオチド |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007557485A Expired - Fee Related JP5714203B2 (ja) | 2005-03-03 | 2006-02-27 | 血管新生依存性腫瘍を治療するためのデフィブロチドおよび／またはオリゴデオキシリボヌクレオチド |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US20080194507A1 (enExample) |
| EP (2) | EP1855697A2 (enExample) |
| JP (2) | JP2008531647A (enExample) |
| KR (3) | KR20070120953A (enExample) |
| AU (2) | AU2006222045B2 (enExample) |
| CA (2) | CA2598613A1 (enExample) |
| IL (3) | IL185182A0 (enExample) |
| MX (2) | MX2007010407A (enExample) |
| WO (2) | WO2006094916A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20031714A1 (it) | 2003-09-05 | 2005-03-06 | Gentium Spa | Formazioni ad azione antitumorale. |
| EP1982722A1 (en) * | 2007-04-16 | 2008-10-22 | Gentium S.p.A. | Use of oligotide for the treatment of renal diseases |
| EP2103689A1 (en) * | 2008-03-19 | 2009-09-23 | Gentium S.p.A. | Synthetic phosphodiester oligonucleotides and therapeutical uses thereof |
| US8187897B2 (en) | 2008-08-19 | 2012-05-29 | International Business Machines Corporation | Fabricating product chips and die with a feature pattern that contains information relating to the product chip |
| EP2637672B1 (en) | 2010-11-12 | 2018-08-22 | Gentium S.r.l. | Defibrotide for use in prophylaxis and/or treatment of graft versus host disease (gvhd). |
| KR102038357B1 (ko) | 2012-06-22 | 2019-10-31 | 젠티엄 에스알엘 | 디파이브로타이드의 생물학적 활성 측정을 위한 유우글로불린에 기초한 방법 |
| EP3026122A1 (en) | 2014-11-27 | 2016-06-01 | Gentium S.p.A. | Cellular-based method for determining the potency of defibrotide |
| EP3661484A1 (en) | 2017-08-03 | 2020-06-10 | Jazz Pharmaceuticals Ireland Limited | Formulations comprising a nucleic acid in a high concentration |
| WO2019200251A1 (en) | 2018-04-12 | 2019-10-17 | Jazz Pharmaceuticals, Inc. | Defibrotide for the prevention and treatment of cytokine release syndrome and neurotoxicity associated with immunodepletion |
| WO2020118165A1 (en) | 2018-12-07 | 2020-06-11 | Jazz Pharmaceuticals Ireland Limited | Subcutaneous delivery of high concentration formulations |
| US20230190783A1 (en) | 2020-02-28 | 2023-06-22 | Jazz Pharmaceuticals Ireland Limited | Delivery of low viscosity formulations |
| TW202308659A (zh) | 2021-05-06 | 2023-03-01 | 愛爾蘭商爵士製藥愛爾蘭有限責任公司 | 用於急性呼吸窘迫症候群之治療及預防的去纖維蛋白多核苷酸 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05247083A (ja) * | 1991-12-09 | 1993-09-24 | Crinos Ind Farmacobiolog Spa | 抗虚血活性を有する新規なオリゴデオキシリボヌクレオチド類およびその製造方法 |
| WO1998048843A1 (en) * | 1997-04-28 | 1998-11-05 | Arsinur Burcoglu | Method of treating hiv infection and related secondary infections thereof |
| DE19740384A1 (de) * | 1997-09-08 | 1999-03-11 | Max Delbrueck Centrum | Antisense Oligodesoxynukleotide (ODN) gegen Proteinkinase C (PKC)-Isoformen, ihre Verwendung und pharmazeutische Zubereitungen dieser ODN |
| US5919772A (en) * | 1993-12-01 | 1999-07-06 | Mcgill University | Antisense oligonucleotides having tumorigenicity-inhibiting activity |
| JP2002512508A (ja) * | 1997-05-30 | 2002-04-23 | マクギル・ユニヴァーシティ | Ｄｎａメチルトランスフェラーゼゲノミック配列およびアンチセンスオリゴヌクレオチド |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2154279A1 (de) * | 1970-11-03 | 1972-05-25 | Crinos Industria Farmaco | Medikamente für das fibrinolytische System |
| US3899481A (en) * | 1970-11-03 | 1975-08-12 | Crinos Industria Farmaco | Process for the controlled partial degradation of deoxyribonucleic acid extracted from animal organs |
| IT1043823B (it) * | 1970-11-03 | 1980-02-29 | Prephar | Procedimento per l estrazione di acidi nucleici da organi animali |
| IT1170214B (it) * | 1983-09-12 | 1987-06-03 | Crinos Industria Farmaco | Composizione farmaceutica per la cura delle arteriopatie periferiche |
| IT1206341B (it) * | 1984-02-16 | 1989-04-14 | Crinos Industria Farmaco | Composizione farmaceutica per il trattamento dell'ischemia acuta del miocardio. |
| US4694134A (en) * | 1985-05-28 | 1987-09-15 | Ajax Magnethermic Corporation | Apparatus for overheating edges of skelp for the production of compression welded pipe |
| IT1190313B (it) * | 1986-04-17 | 1988-02-16 | Crinos Industria Farmaco | Procedimento per l'ottenimento di polidesossiribonucleotidi chimicamente definiti e riproducibili e prodotto farmacologicamente attivo risultante |
| US5223609A (en) * | 1986-04-17 | 1993-06-29 | Crinos Industria Farmacobiologica S.P.A. | Process for obtaining chemically defined and reproducible polydeoxyribonucleotides |
| US6699985B2 (en) * | 1991-08-21 | 2004-03-02 | Arsinur Burcoglu | Method of treating HIV infection and related secondary infections thereof |
| US5977083A (en) * | 1991-08-21 | 1999-11-02 | Burcoglu; Arsinur | Method for using polynucleotides, oligonucleotides and derivatives thereof to treat various disease states |
| AU2002353783A1 (en) * | 2001-09-24 | 2003-04-07 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of | SUPPRESSORS OF CpG OLIGONUCLEOTIDES AND METHODS OF USE |
| ITMI20031714A1 (it) * | 2003-09-05 | 2005-03-06 | Gentium Spa | Formazioni ad azione antitumorale. |
-
2006
- 2006-02-27 EP EP06708537A patent/EP1855697A2/en not_active Withdrawn
- 2006-02-27 MX MX2007010407A patent/MX2007010407A/es not_active Application Discontinuation
- 2006-02-27 US US11/817,575 patent/US20080194507A1/en not_active Abandoned
- 2006-02-27 KR KR1020077021110A patent/KR20070120953A/ko not_active Withdrawn
- 2006-02-27 EP EP06708536A patent/EP1853277A1/en not_active Ceased
- 2006-02-27 KR KR1020077023861A patent/KR20070121001A/ko not_active Withdrawn
- 2006-02-27 CA CA002598613A patent/CA2598613A1/en not_active Abandoned
- 2006-02-27 JP JP2007557486A patent/JP2008531647A/ja active Pending
- 2006-02-27 WO PCT/EP2006/060304 patent/WO2006094916A1/en not_active Ceased
- 2006-02-27 JP JP2007557485A patent/JP5714203B2/ja not_active Expired - Fee Related
- 2006-02-27 WO PCT/EP2006/060306 patent/WO2006094917A2/en not_active Ceased
- 2006-02-27 CA CA2598072A patent/CA2598072C/en not_active Expired - Fee Related
- 2006-02-27 AU AU2006222045A patent/AU2006222045B2/en not_active Ceased
- 2006-02-27 AU AU2006222044A patent/AU2006222044A1/en not_active Abandoned
- 2006-02-27 US US11/817,572 patent/US20080194506A1/en not_active Abandoned
- 2006-02-27 MX MX2007010754A patent/MX2007010754A/es not_active Application Discontinuation
- 2006-02-27 KR KR1020077021114A patent/KR20070120954A/ko not_active Withdrawn
-
2007
- 2007-08-09 IL IL185182A patent/IL185182A0/en active IP Right Grant
- 2007-08-09 IL IL185181A patent/IL185181A0/en unknown
- 2007-08-14 IL IL185258A patent/IL185258A/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05247083A (ja) * | 1991-12-09 | 1993-09-24 | Crinos Ind Farmacobiolog Spa | 抗虚血活性を有する新規なオリゴデオキシリボヌクレオチド類およびその製造方法 |
| US5919772A (en) * | 1993-12-01 | 1999-07-06 | Mcgill University | Antisense oligonucleotides having tumorigenicity-inhibiting activity |
| WO1998048843A1 (en) * | 1997-04-28 | 1998-11-05 | Arsinur Burcoglu | Method of treating hiv infection and related secondary infections thereof |
| JP2002512508A (ja) * | 1997-05-30 | 2002-04-23 | マクギル・ユニヴァーシティ | Ｄｎａメチルトランスフェラーゼゲノミック配列およびアンチセンスオリゴヌクレオチド |
| DE19740384A1 (de) * | 1997-09-08 | 1999-03-11 | Max Delbrueck Centrum | Antisense Oligodesoxynukleotide (ODN) gegen Proteinkinase C (PKC)-Isoformen, ihre Verwendung und pharmazeutische Zubereitungen dieser ODN |
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| AU2006222044A1 (en) | 2006-09-14 |
| EP1853277A1 (en) | 2007-11-14 |
| AU2006222045A1 (en) | 2006-09-14 |
| MX2007010754A (es) | 2007-11-07 |
| KR20070121001A (ko) | 2007-12-26 |
| WO2006094917A2 (en) | 2006-09-14 |
| WO2006094917A3 (en) | 2006-12-14 |
| AU2006222045B2 (en) | 2011-10-20 |
| CA2598072C (en) | 2016-05-03 |
| US20080194507A1 (en) | 2008-08-14 |
| CA2598072A1 (en) | 2006-09-14 |
| KR20070120953A (ko) | 2007-12-26 |
| US20080194506A1 (en) | 2008-08-14 |
| CA2598613A1 (en) | 2006-09-14 |
| IL185181A0 (en) | 2008-01-20 |
| KR20070120954A (ko) | 2007-12-26 |
| WO2006094916A1 (en) | 2006-09-14 |
| WO2006094917A8 (en) | 2008-01-31 |
| IL185258A (en) | 2010-12-30 |
| JP5714203B2 (ja) | 2015-05-07 |
| IL185182A0 (en) | 2008-01-20 |
| EP1855697A2 (en) | 2007-11-21 |
| IL185258A0 (en) | 2008-02-09 |
| MX2007010407A (es) | 2007-10-17 |
| JP2008531646A (ja) | 2008-08-14 |
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