DK2350294T3 - Musemodeller af trombotisk trombocytpenisk purpura og fremgangsmåde til anvendelse deraf - Google Patents
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- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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Claims (8)
1. En musemodel afen blodkoagulationsforstyrrelse, hvor nævnte forstyrrelse karakteriseres ved tilstedeværelsen af koaguleret blod i blodårer i hele kroppen, hvor nævnte musemodel omfatter en manglende evne til at nedbryde rekombinant human von Willebrand faktor (VWF) polypeptid omfattende ultra-store multimerer, hvor nævnte forstyrrelse i nævnte musemodel er forårsaget efter intravenøs indgivelse af en dosis rekombinant human VWF omfattende ultra-store multimerer til en mus, hvor dosen af rekombinant human VWF er større eller lig med 500 RCoU/kg kropsvægt eller, hvis musen er mangelfuld for VWF polypeptid, da er dosen af rekombinant human VWF større eller lig med 1000 RCoU/kg kropsvægt, hvor musemodellen udviser histopatologiske ændringer, der indikerer dissemineret intravaskulær koagulopati og/eller trombotisk trombocytopenisk purpura, og hvor nævnte musemodel er egnet til testning af effekten af et terapeutisk stof i behandlingen af en blodkoagulationsforstyrrelse.
2. Modellen i krav 1, hvor forstyrrelsen er trombotisk trombocytopenisk purpura.
3. Modellen ifølge et hvilket som helst af de foregående krav, hvor musen er mangelfuld for disintegrin og metalloprotease med trombospondin type 1 domæner 13 (ADAMST13) polypeptid.
4. Modellen ifølge et hvilket som helst af de foregående krav, hvor musen er mangelfuld for VWF polypeptid.
5. Modellen ifølge et hvilket som helst af de foregående krav, hvor musen er af en C57BL/6J-stamme.
6. Modellen ifølge et hvilket som helst af de foregående krav, hvor rekombinant Faktor VIII (rFVIII) yderligere indgives til modellen.
7. Modellen ifølge et hvilket som helst af de foregående krav, hvor dosen er større eller lig med 2000 RColl/kg kropsvægt.
8. Modellen ifølge et hvilket som helst af de foregående krav, hvor dosen er større eller lig med 4000 RCoU/kg kropsvægt.
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EP (2) | EP3495488A1 (da) |
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EP3388529A1 (en) | 2008-12-05 | 2018-10-17 | Baxalta GmbH | Methods of measuring adamts13-mediated in vivo cleavage of von willebrand factor and uses thereof |
RU2570162C1 (ru) * | 2014-10-21 | 2015-12-10 | Общество с ограниченной ответственностью "АптаНова" | Способ моделирования тромбообразования у мышей для оценки действия препаратов антикоагулянта |
US11597778B2 (en) | 2015-04-07 | 2023-03-07 | The Trustees Of The University Of Pennsylvania | Human monoclonal autoantibodies to ADAMTS13 and uses thereof |
CN115413627B (zh) * | 2022-10-21 | 2023-03-24 | 首都医科大学附属北京儿童医院 | 腹型过敏性紫癜动物模型的构建方法及应用 |
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---|---|---|---|---|
US4757006A (en) * | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
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US5175384A (en) * | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
US6821287B1 (en) * | 1991-05-24 | 2004-11-23 | Advanced Cardiovascular Systems, Inc. | Multi-mode vascular catheter system |
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US5446143A (en) | 1993-09-14 | 1995-08-29 | Board Of Regents, The University Of Texas System | Adipose-specific promoter region of human aromatase cytochrome P450 gene |
US6447796B1 (en) * | 1994-05-16 | 2002-09-10 | The United States Of America As Represented By The Secretary Of The Army | Sustained release hydrophobic bioactive PLGA microspheres |
CA2175720C (en) | 1996-05-03 | 2011-11-29 | Ian M. Penn | Bifurcated stent and method for the manufacture and delivery of same |
US6818014B2 (en) * | 1995-03-01 | 2004-11-16 | Scimed Life Systems, Inc. | Longitudinally flexible expandable stent |
US6824553B1 (en) * | 1995-04-28 | 2004-11-30 | Target Therapeutics, Inc. | High performance braided catheter |
DE19632532A1 (de) | 1996-08-13 | 1998-02-19 | Boehringer Ingelheim Int | Verfahren zur Herstellung von Säugetieren mit definierten genetischen Eigenschaften |
US6391032B2 (en) * | 1996-08-23 | 2002-05-21 | Scimed Life Systems, Inc. | Stent delivery system having stent securement means |
AT405485B (de) * | 1997-05-28 | 1999-08-25 | Immuno Ag | Eine das vwf-propeptid enthaltende pharmazeutische präparation |
US6818016B1 (en) | 1997-06-27 | 2004-11-16 | The Regents Of The University Of Michigan | Methods for coating stents with DNA and expression of recombinant genes from DNA coated stents in vivo |
US6827730B1 (en) | 1998-01-13 | 2004-12-07 | Endovascular Technologies, Inc. | Reduced diameter stent/graft deployment catheter |
US6206914B1 (en) * | 1998-04-30 | 2001-03-27 | Medtronic, Inc. | Implantable system with drug-eluting cells for on-demand local drug delivery |
JP4340339B2 (ja) | 1998-07-31 | 2009-10-07 | 財団法人化学及血清療法研究所 | 血液凝固因子もしくは血液凝固制御因子欠損モデル動物並びに該モデル動物の作製方法 |
JP2002537828A (ja) | 1999-03-10 | 2002-11-12 | フォゲン リミティド | 細胞への物質のデリバリー |
US6368315B1 (en) * | 1999-06-23 | 2002-04-09 | Durect Corporation | Composite drug delivery catheter |
US6829497B2 (en) | 1999-09-21 | 2004-12-07 | Jamil Mogul | Steerable diagnostic catheters |
US6254631B1 (en) * | 1999-09-23 | 2001-07-03 | Intratherapeutics, Inc. | Stent with enhanced friction |
DE19951477A1 (de) * | 1999-10-26 | 2001-05-03 | Biotronik Mess & Therapieg | Stent |
US6827703B1 (en) * | 1999-11-24 | 2004-12-07 | Coopersurgical, Inc. | Single lumen balloon catheter apparatus |
JP4263826B2 (ja) * | 1999-11-26 | 2009-05-13 | テルモ株式会社 | カテーテルの製造方法およびカテーテル |
US6254593B1 (en) | 1999-12-10 | 2001-07-03 | Advanced Cardiovascular Systems, Inc. | Bifurcated stent delivery system having retractable sheath |
US6537311B1 (en) | 1999-12-30 | 2003-03-25 | Advanced Cardiovascular Systems, Inc. | Stent designs for use in peripheral vessels |
CA2397980C (en) | 2000-03-03 | 2009-08-04 | Cook Incorporated | Endovascular device having a stent |
US6818247B1 (en) * | 2000-03-31 | 2004-11-16 | Advanced Cardiovascular Systems, Inc. | Ethylene vinyl alcohol-dimethyl acetamide composition and a method of coating a stent |
AU7528101A (en) * | 2000-06-05 | 2001-12-17 | Theragenics Corp | A device for delivering a therapeutic dosage |
US6805704B1 (en) * | 2000-06-26 | 2004-10-19 | C. R. Bard, Inc. | Intraluminal stents |
US6802857B1 (en) * | 2000-10-11 | 2004-10-12 | Uab Research Foundation | MRI stent |
US6565599B1 (en) | 2000-12-28 | 2003-05-20 | Advanced Cardiovascular Systems, Inc. | Hybrid stent |
US20020130430A1 (en) | 2000-12-29 | 2002-09-19 | Castor Trevor Percival | Methods for making polymer microspheres/nanospheres and encapsulating therapeutic proteins and other products |
US6821291B2 (en) | 2001-06-01 | 2004-11-23 | Ams Research Corporation | Retrievable stent and method of use thereof |
US6818013B2 (en) * | 2001-06-14 | 2004-11-16 | Cordis Corporation | Intravascular stent device |
US6517889B1 (en) * | 2001-11-26 | 2003-02-11 | Swaminathan Jayaraman | Process for coating a surface of a stent |
US7060498B1 (en) | 2001-11-28 | 2006-06-13 | Genta Salus Llc | Polycationic water soluble copolymer and method for transferring polyanionic macromolecules across biological barriers |
US7141540B2 (en) | 2001-11-30 | 2006-11-28 | Genta Salus Llc | Cyclodextrin grafted biocompatible amphilphilic polymer and methods of preparation and use thereof |
US6805707B1 (en) * | 2001-12-27 | 2004-10-19 | Advanced Cardiovascular Systems, Inc. | Stent with improved ring and link pattern |
US20050222064A1 (en) * | 2002-02-20 | 2005-10-06 | Sirna Therapeutics, Inc. | Polycationic compositions for cellular delivery of polynucleotides |
US6802859B1 (en) * | 2002-07-12 | 2004-10-12 | Endovascular Technologies, Inc. | Endovascular stent-graft with flexible bifurcation |
US6819951B2 (en) | 2002-09-24 | 2004-11-16 | Mayo Foundation For Medical Education And Research | Peripherally inserted central catheter with continuous central venous oximetry and proximal high flow port |
CA2506714A1 (en) * | 2002-11-26 | 2004-06-10 | University Of Massachusetts | Delivery of sirnas |
CA2549720C (en) | 2003-12-19 | 2013-10-15 | Chiron Corporation | Cell transfecting formulations of small interfering rna, related compositions and methods of making and use |
US20060014289A1 (en) * | 2004-04-20 | 2006-01-19 | Nastech Pharmaceutical Company Inc. | Methods and compositions for enhancing delivery of double-stranded RNA or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells |
US7514530B2 (en) * | 2004-04-26 | 2009-04-07 | Centre National De La Recherche Scientifique | Peptide carrier for delivering siRNA into mammalian cells |
PL1902141T3 (pl) * | 2005-06-17 | 2012-12-31 | Baxalta Inc | Kompozycje o działaniu trombolitycznym zawierające ADAMTS13 |
WO2008005290A2 (en) * | 2006-06-29 | 2008-01-10 | The Trustees Of Columbia University In The City Of New York | Methods for testing anti-thrombotic agents |
-
2009
- 2009-10-27 NZ NZ609908A patent/NZ609908A/en not_active IP Right Cessation
- 2009-10-27 NZ NZ601709A patent/NZ601709A/en not_active IP Right Cessation
- 2009-10-27 JP JP2011533425A patent/JP5749649B2/ja not_active Expired - Fee Related
- 2009-10-27 US US12/606,884 patent/US9587249B2/en not_active Expired - Fee Related
- 2009-10-27 CA CA2741634A patent/CA2741634A1/en not_active Abandoned
- 2009-10-27 WO PCT/US2009/062228 patent/WO2010062604A2/en active Application Filing
- 2009-10-27 DK DK09752581.0T patent/DK2350294T3/da active
- 2009-10-27 EP EP18202001.6A patent/EP3495488A1/en not_active Withdrawn
- 2009-10-27 EP EP09752581.0A patent/EP2350294B1/en not_active Not-in-force
- 2009-10-27 AU AU2009320088A patent/AU2009320088B2/en not_active Ceased
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- 2009-10-27 NZ NZ592905A patent/NZ592905A/xx not_active IP Right Cessation
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2017
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Also Published As
Publication number | Publication date |
---|---|
WO2010062604A2 (en) | 2010-06-03 |
KR20110089306A (ko) | 2011-08-05 |
JP5749649B2 (ja) | 2015-07-15 |
KR101785118B1 (ko) | 2017-10-12 |
EP2350294B1 (en) | 2018-12-05 |
US9587249B2 (en) | 2017-03-07 |
US20170196994A1 (en) | 2017-07-13 |
NZ601709A (en) | 2013-12-20 |
JP2012506707A (ja) | 2012-03-22 |
ES2713270T3 (es) | 2019-05-20 |
CA2741634A1 (en) | 2010-06-03 |
NZ609908A (en) | 2014-07-25 |
AU2009320088B2 (en) | 2015-03-19 |
EP2350294A2 (en) | 2011-08-03 |
NZ592905A (en) | 2012-11-30 |
WO2010062604A3 (en) | 2010-07-22 |
EP3495488A1 (en) | 2019-06-12 |
US20100115637A1 (en) | 2010-05-06 |
AU2009320088A1 (en) | 2010-06-03 |
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