DK2864496T3 - Euglobulin-baseret fremgangsmåde til bestemmelse af den biologiske aktivitet af defibrotid - Google Patents
Euglobulin-baseret fremgangsmåde til bestemmelse af den biologiske aktivitet af defibrotid Download PDFInfo
- Publication number
- DK2864496T3 DK2864496T3 DK12756826.9T DK12756826T DK2864496T3 DK 2864496 T3 DK2864496 T3 DK 2864496T3 DK 12756826 T DK12756826 T DK 12756826T DK 2864496 T3 DK2864496 T3 DK 2864496T3
- Authority
- DK
- Denmark
- Prior art keywords
- defibrotide
- euglobulin
- plasmin
- biological activity
- concentration
- Prior art date
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- 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 compound 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 title claims abstract description 103
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- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 claims description 3
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- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6435—Plasmin (3.4.21.7), i.e. fibrinolysin
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Claims (18)
1. Fremgangsmåde til bestemmelse af den biologiske aktivitet af defibrotid, der omfatter trinnene at: a) bringe defibrotid i kontakt med pattedyr-euglobulin og et substrat der er specifikt for plasmin, ved omsætning med plasmin, tilvejebringer et målbart produkt; og b) måle mængden af produkt dannet på hinanden følgende gange, for derved at bestemme den biologiske aktivitet af defibrotidet.
2. Fremgangsmåden ifølge krav 1, hvor euglobulinet er et pattedyr-euglobulin.
3. Fremgangsmåden ifølge krav 2, hvor euglobulinet er menneske-, kanin- eller bovin-euglobulin.
4. Fremgangsmåden ifølge krav 1, hvor plasminet der omsættes med substratet der er specifikt for plasminet frigives af plasminogenet indeholdt i euglobulin.
5. Fremgangsmåden ifølge krav 1, hvor substratet der er specifikt for plasminet er et chromogent substrat.
6. Fremgangsmåden ifølge krav 1, hvor substratet der er specifikt for plasminet er en forbindelse med formel A1-A2-A3-X hvor Ai og A2 er ikke-polære aminosyrer, A3 er lysin eller arginin og X er det målbare produkt.
7. Fremgangsmåden ifølge krav 6, hvor det målbare produkt X er valgt fra gruppen bestående af para-nitroanilin og 2-naphthylamin.
8. Fremgangsmåden ifølge krav 4, hvor substratet der er specifikt for plasminet er H-D-Valyl-L-Leucyl-L-Lysin-p-nitroanilin.
9. Fremgangsmåden ifølge krav 6, hvor det målbare produkt X måles ved spektrofotometri eller spekrofluoimetri.
10. Fremgangsmåden ifølge krav 2, hvor pattedyr-euglobulinet er rekonstitueret til det samme volumen af det oprindelige plasma eller fortyndet op til 1:10 med egnet buffer og det chromogene/fluorogene substrat har en koncentration på 2,5 til 3,5 mM, fortrinsvis 3 mM.
11. Fremgangsmåden ifølge krav 1, hvor fremgangsmåden udføres i et reaktionsmedium der er en vandig opløsning bufret til en pH på fra 7 til 8, fortrinsvis til en pH på 7,4.
12. Fremgangsmåden ifølge krav 1, hvor temperaturen opretholdes ved fra 35 to 39°C, fortrinsvis ved 37°C.
13. Fremgangsmåden ifølge krav 1, hvor koncentrationen af substratet der er specifikt for plasminet er fra 0,3 til 4 mM, fortrinsvis fra 2,5 til 3,5 mM, mere fortrinsvis 3 mM.
14. Fremgangsmåden ifølge krav 1, hvilken fremgangsmåde omfatter trinnene at: c) bestemme frigivelseshastigheden af det målbare produkt underforløbet af den enzymatiske omsætning af både en standardprøve og en testprøve; d) korrelere, matematisk og/eller grafisk, frigivelseshastigheden med den tilsvarende defibrotidkoncentration for at opnå den biologiske aktivitet af defibrotidtestprøven.
15. Fremgangsmåden ifølge et hvilket som helst af de foregående krav, hvor defibrotid er i form en flydende defibrotidformulering med en biologisk aktivitet på 25 til 35 IU/mg defibrotid, fortrinsvis fra 27,5 til 32,5 IU/mg, mere fortrinsvis, fra 28 til 32 IU/mg.
16. Fremgangsmåden ifølge krav 15, hvor den flydende defibrotidformulering er en vandopløsning.
17. Fremgangsmåden ifølge krav 16, hvor defibrotidvandopløsningen er bufret.
18. Fremgangsmåden ifølge krav 17, hvor den bufrede defibrotidopløsning haren pH på fra 6,5 til 8,5, fortrinsvis fra 7 til 8.
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|---|---|---|---|
| PCT/IT2012/000193 WO2013190582A1 (en) | 2012-06-22 | 2012-06-22 | Euglobulin-based method for determining the biological activity of defibrotide |
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| DK2864496T4 DK2864496T4 (da) | 2021-01-04 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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). |
| ES2660969T5 (es) | 2012-06-22 | 2021-09-03 | Gentium S R L | Método basado en euglobulina para determinar la actividad biológica de defibrotida |
| EP3026122A1 (en) | 2014-11-27 | 2016-06-01 | Gentium S.p.A. | Cellular-based method for determining the potency of defibrotide |
| EP3574514B1 (en) * | 2017-01-25 | 2026-04-29 | Kemet Electronics Corporation | Self-damping mlcc array |
| TW201909904A (zh) * | 2017-08-03 | 2019-03-16 | 愛爾蘭商爵士製藥愛爾蘭有限責任公司 | 高濃度調配物 |
| CN112236149A (zh) | 2018-04-12 | 2021-01-15 | 贾兹制药公司 | 用于预防和治疗细胞因子释放综合征和与免疫耗竭相关的神经毒性的去纤苷 |
| US20220023533A1 (en) | 2018-12-07 | 2022-01-27 | Jazz Phrmaceticals Ireland Limited | Subcutaneous delivery of high concentration formulations |
| EP4110287A1 (en) | 2020-02-28 | 2023-01-04 | 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 |
Family Cites Families (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3899481A (en) | 1970-11-03 | 1975-08-12 | Crinos Industria Farmaco | Process for the controlled partial degradation of deoxyribonucleic acid extracted from animal organs |
| DE2154279A1 (de) | 1970-11-03 | 1972-05-25 | Crinos Industria Farmaco | Medikamente für das fibrinolytische System |
| IT1043823B (it) | 1970-11-03 | 1980-02-29 | Prephar | Procedimento per l estrazione di acidi nucleici da organi animali |
| DE2812943C3 (de) | 1978-03-23 | 1981-05-14 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verfahren und Reagens zur Bestimmung der biologischen Aktivität von Heparin im Plasma |
| US4853221A (en) | 1980-11-13 | 1989-08-01 | Warner-Lambert Company | Method for treating non-small cell lung cancer, head and neck cancers and breast cancer |
| IT1170215B (it) | 1983-09-12 | 1987-06-03 | Crinos Industria Farmaco | Composizione farmaceutica per il trattamento di stati di insufficienza renale acuta |
| 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 |
| US5231006A (en) | 1986-10-16 | 1993-07-27 | Behringwerke Aktiengesellschaft | Method for the determination of plasminogen |
| US4753221A (en) | 1986-10-22 | 1988-06-28 | Intravascular Surgical Instruments, Inc. | Blood pumping catheter and method of use |
| JP2907447B2 (ja) | 1988-08-24 | 1999-06-21 | 中外製薬株式会社 | 抗血栓剤 |
| IT1231509B (it) | 1989-09-07 | 1991-12-07 | Crinos Industria Farmaco | Composizione farmceutica ad uso topico per la terapia della fragilita' capillare. |
| JPH0539280A (ja) * | 1990-07-20 | 1993-02-19 | Takeda Chem Ind Ltd | サツカロアスコルビン酸誘導体および血栓症予防治療剤 |
| US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
| US5977083A (en) | 1991-08-21 | 1999-11-02 | Burcoglu; Arsinur | Method for using polynucleotides, oligonucleotides and derivatives thereof to treat various disease states |
| US6699985B2 (en) | 1991-08-21 | 2004-03-02 | Arsinur Burcoglu | Method of treating HIV infection and related secondary infections thereof |
| US5624912A (en) | 1991-08-21 | 1997-04-29 | Burcoglu; Arsinur | Method of treating HIV infection and related secondary infections with defibrotide |
| IT1252174B (it) | 1991-12-09 | 1995-06-05 | Crinos Industria Farmaco | Oligodesossimibonucleotidi ad attivita' antiischemica e procedimenti per il loro ottenimento |
| US5578716A (en) | 1993-12-01 | 1996-11-26 | Mcgill University | DNA methyltransferase antisense oligonucleotides |
| US6335356B1 (en) | 1994-01-07 | 2002-01-01 | Sugen, Inc. | Method of treating a patient by parenteral administration of a lipophilic compound |
| JPH08127539A (ja) | 1994-10-31 | 1996-05-21 | Ajinomoto Co Inc | ヒトｉｌ−１１を含有する末梢血幹細胞増加剤 |
| CA2206496A1 (en) | 1994-11-30 | 1996-06-06 | Chugai Seiyaku Kabushiki Kaisha | Thrombocytotic factor |
| WO1998001151A1 (en) | 1996-07-10 | 1998-01-15 | Meiji Milk Products Co., Ltd. | Novel use of mk family as hematopoietic factor |
| AU754242B2 (en) | 1997-04-28 | 2002-11-07 | Arsinur Burcoglu | Method of treating HIV infection and related secondary infections thereof |
| WO1998054313A2 (en) | 1997-05-30 | 1998-12-03 | Mcgill University | Dna methyltransferase genomic sequences and antisense oligonucleotides |
| US6177545B1 (en) | 1997-09-02 | 2001-01-23 | Insight Strategy & Marketing Ltd. | Heparanase specific molecular probes and their use in research and medical applications |
| 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 |
| GB9719161D0 (en) * | 1997-09-09 | 1997-11-12 | Glaxo Group Ltd | New therapeutic method |
| US6573372B2 (en) | 1999-01-07 | 2003-06-03 | Heska Corporation | Feline immunoglobulin E molecules and compositions there of |
| WO2000074634A2 (en) | 1999-06-03 | 2000-12-14 | Au Jessie L S | Methods and compositions for modulating cell proliferation and cell death |
| ES2251134T3 (es) | 1999-06-08 | 2006-04-16 | Gentium S.P.A. | Uso de complejos entre liposomas cationicos y polidesoxirribonucleotidos como medicamentos. |
| US8771663B2 (en) | 2000-04-18 | 2014-07-08 | Gentium Spa | Formulation having mobilising activity |
| EP1147777A1 (en) | 2000-04-18 | 2001-10-24 | Crinos Industria Farmacobiologica S.p.A. | Combination of defibrotide and G-CSF and its use to activate haematopoietic progenitors |
| EP1334113A4 (en) | 2000-10-20 | 2007-08-08 | Expression Diagnostics Inc | EVALUATION OF LEUCOCYTAIRE EXPRESSION LEVEL |
| AU1788502A (en) | 2000-11-28 | 2002-06-11 | Univ Chicago | Genetically engineered herpes virus for the treatment of cardiovascular disease |
| EP1406930A4 (en) | 2000-12-29 | 2007-01-10 | Savient Pharmaceuticals Inc | "ISOLATED MOLECULES WITH SULFATED GROUPING CONTAINING EPITOPES, ANTIBODIES AGAINST SUCH EPITOPES AND USES THEREOF" |
| US7235358B2 (en) | 2001-06-08 | 2007-06-26 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| US6770753B2 (en) | 2001-07-05 | 2004-08-03 | The Trustees Of Columbia University In The City Of New York | Phosphorothioate antisense heparanase oligonucleotides |
| WO2003027313A2 (en) | 2001-09-24 | 2003-04-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SUPPRESSORS OF CpG OLIGONUCLEOTIDES AND METHODS OF USE |
| US6965025B2 (en) | 2001-12-10 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of connective tissue growth factor expression |
| EP1325962A1 (en) | 2001-12-17 | 2003-07-09 | Gentium S.p.A. | A method for determining the biological activity of defibrotide |
| CA2487171A1 (en) | 2002-05-31 | 2003-12-11 | Klinikum Der Universitat Regensburg | Method for the protection of endothelial and epithelial cells during chemotherapy |
| US20050215498A1 (en) | 2002-05-31 | 2005-09-29 | Guenther Eissner | Method for the protection of endothelial and epithclial cells during chemotherapy |
| WO2004003166A2 (en) | 2002-07-01 | 2004-01-08 | Savient Pharmaceuticals, Inc. | Antibodies and uses thereof |
| CA2501719C (en) | 2002-08-06 | 2013-02-05 | Toray Industries, Inc. | Remedy or preventive for kidney disease and method of diagnosing kidney disease |
| US20050196382A1 (en) | 2002-09-13 | 2005-09-08 | Replicor, Inc. | Antiviral oligonucleotides targeting viral families |
| DE10244453A1 (de) | 2002-09-24 | 2004-04-01 | Phenomiques Gmbh | Hemmung der Proteinkinase C-alpha zur Behandlung von Krankheiten |
| US7803781B2 (en) | 2003-02-28 | 2010-09-28 | Isis Pharmaceuticals, Inc. | Modulation of growth hormone receptor expression and insulin-like growth factor expression |
| ITMI20031714A1 (it) | 2003-09-05 | 2005-03-06 | Gentium Spa | Formazioni ad azione antitumorale. |
| WO2005089503A2 (en) | 2004-03-19 | 2005-09-29 | Progenics Pharmaceuticals, Inc. | Cd4-igg2 formulations |
| CA2623142C (en) * | 2004-09-22 | 2016-01-19 | The Regents Of The University Of Colorado, A Body Corporate | Methods for a global assay of coagulation and fibrinolysis |
| US7723127B2 (en) | 2005-03-03 | 2010-05-25 | Novx Systems Inc. | Immunoassay with extended dynamic range |
| AU2006222045B2 (en) | 2005-03-03 | 2011-10-20 | Gentium Spa | Oligodeoxyribonucleotides of 4000-10000 Dalton for treating tumors |
| WO2006119619A1 (en) | 2005-05-06 | 2006-11-16 | Replicor Inc. | Oligonucleotides inhibiting cell proliferation |
| EP1872787A1 (en) | 2006-06-27 | 2008-01-02 | Gentium S.p.A. | Use of defibrotide for the inhibition of heparanase |
| EP1982722A1 (en) | 2007-04-16 | 2008-10-22 | Gentium S.p.A. | Use of oligotide for the treatment of renal diseases |
| FR2917172B1 (fr) * | 2007-06-07 | 2014-01-03 | Inst Nat Sante Rech Med | Methode de mesure de l'activite plasmine des microparticules presentes dans un echantillon de fluide biologique et utilisation |
| CA2692604A1 (en) | 2007-07-13 | 2009-01-22 | Elan Pharmaceuticals, Inc. | Compositions and methods for identifying substrate specificity of inhibitors of gamma secretase |
| EP2103689A1 (en) | 2008-03-19 | 2009-09-23 | Gentium S.p.A. | Synthetic phosphodiester oligonucleotides and therapeutical uses thereof |
| EP2274617A4 (en) | 2008-04-10 | 2011-11-09 | Massachusetts Inst Technology | METHOD OF DETECTING AND USING MEDIUM-TREATMENT AID ON CANCER STEM CELLS |
| CN101301306A (zh) | 2008-06-30 | 2008-11-12 | 广东天普生化医药股份有限公司 | Dft在制备治疗和预防休克药物中的应用 |
| PT2403865E (pt) | 2009-03-03 | 2015-11-18 | Grifols Therapeutics Inc | Métodos de preparação de plasminogénio |
| SG175390A1 (en) | 2009-04-29 | 2011-12-29 | Amarin Corp Plc | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| US20130065260A1 (en) * | 2009-11-06 | 2013-03-14 | The Regents Of The University Of Colorado, A Body Corporate | Compositions, Methods and Uses for Simultaneous Assay of Thrombin and Plasmin Generation |
| 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). |
| ES2660969T5 (es) | 2012-06-22 | 2021-09-03 | Gentium S R L | Método basado en euglobulina para determinar la actividad biológica de defibrotida |
| EP3026122A1 (en) | 2014-11-27 | 2016-06-01 | Gentium S.p.A. | Cellular-based method for determining the potency of defibrotide |
| TW201909904A (zh) | 2017-08-03 | 2019-03-16 | 愛爾蘭商爵士製藥愛爾蘭有限責任公司 | 高濃度調配物 |
| US20220023533A1 (en) | 2018-12-07 | 2022-01-27 | Jazz Phrmaceticals Ireland Limited | Subcutaneous delivery of high concentration formulations |
| EP4110287A1 (en) | 2020-02-28 | 2023-01-04 | Jazz Pharmaceuticals Ireland Limited | Delivery of low viscosity formulations |
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