UA75064C2 - Modified porcine factor viii and its therapeutic use - Google Patents
Modified porcine factor viii and its therapeutic use Download PDFInfo
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- UA75064C2 UA75064C2 UA2002097145A UA2002097145A UA75064C2 UA 75064 C2 UA75064 C2 UA 75064C2 UA 2002097145 A UA2002097145 A UA 2002097145A UA 2002097145 A UA2002097145 A UA 2002097145A UA 75064 C2 UA75064 C2 UA 75064C2
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/10—Factor VIII, AHF; related peptides
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/523,656 US6458563B1 (en) | 1996-06-26 | 2000-03-10 | Modified factor VIII |
| PCT/US2001/005076 WO2001068109A1 (en) | 2000-03-10 | 2001-02-16 | Modified factor viii |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA75064C2 true UA75064C2 (en) | 2006-03-15 |
Family
ID=24085870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2002097145A UA75064C2 (en) | 2000-03-10 | 2001-02-16 | Modified porcine factor viii and its therapeutic use |
Country Status (36)
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|---|---|
| US (3) | US6458563B1 (es) |
| EP (1) | EP1280540B1 (es) |
| JP (1) | JP4044337B2 (es) |
| KR (1) | KR100485525B1 (es) |
| CN (1) | CN1191360C (es) |
| AT (1) | ATE391512T1 (es) |
| AU (2) | AU3841601A (es) |
| BE (1) | BE2016C024I2 (es) |
| BR (2) | BRPI0109131B8 (es) |
| CA (1) | CA2400295C (es) |
| CY (2) | CY1108179T1 (es) |
| CZ (1) | CZ298250B6 (es) |
| DE (1) | DE60133541T2 (es) |
| DK (1) | DK1280540T3 (es) |
| EE (1) | EE05075B1 (es) |
| ES (1) | ES2304379T3 (es) |
| FR (1) | FR16C0016I2 (es) |
| HK (1) | HK1051004A1 (es) |
| HU (2) | HU227804B1 (es) |
| IL (2) | IL151371A0 (es) |
| LT (1) | LTC1280540I2 (es) |
| LU (1) | LU93049I2 (es) |
| ME (1) | ME00601B (es) |
| MX (1) | MXPA02008798A (es) |
| NL (1) | NL300808I2 (es) |
| NO (2) | NO331935B1 (es) |
| NZ (1) | NZ520799A (es) |
| PL (1) | PL202936B1 (es) |
| PT (1) | PT1280540E (es) |
| RS (1) | RS50364B (es) |
| RU (1) | RU2285724C2 (es) |
| SI (1) | SI1280540T1 (es) |
| SK (1) | SK286205B6 (es) |
| UA (1) | UA75064C2 (es) |
| WO (1) | WO2001068109A1 (es) |
| ZA (1) | ZA200206810B (es) |
Families Citing this family (95)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7560107B2 (en) | 1996-06-26 | 2009-07-14 | Emory University | Modified factor VIII |
| CA2434097A1 (en) * | 2001-01-12 | 2002-08-08 | The American National Red Cross | Methods and compositions for reducing heparan sulfate proteoglycan-mediated clearance of factor viii |
| WO2003031598A2 (en) * | 2001-10-05 | 2003-04-17 | Emory University | Nucleic acid and amino acid sequences encoding high-level expressor factor viii polypeptides and methods of use |
| CN1630666A (zh) * | 2001-11-30 | 2005-06-22 | 埃默里大学 | 因子ⅷc2结构域变体 |
| GB0207092D0 (en) * | 2002-03-26 | 2002-05-08 | Sod Conseils Rech Applic | Stable pharmaceutical composition containing factor VIII |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| EP1636360A4 (en) * | 2003-06-03 | 2006-11-08 | Cell Genesys Inc | COMPOSITIONS AND METHODS FOR ENHANCED EXPRESSION OF RECOMBINANT POLYPEPTIDES FROM A SINGLE VECTOR USING A PEPTIDE CLEAVAGE SITE |
| US7485291B2 (en) * | 2003-06-03 | 2009-02-03 | Cell Genesys, Inc. | Compositions and methods for generating multiple polypeptides from a single vector using a virus derived peptide cleavage site, and uses thereof |
| EP1636261B1 (en) * | 2003-06-26 | 2007-08-01 | MERCK PATENT GmbH | Thrombopoietin proteins with improved properties |
| US20050059023A1 (en) * | 2003-09-16 | 2005-03-17 | Cantor Thomas L. | Methods and kits for monitoring resistance to therapeutic agents |
| US7211559B2 (en) * | 2003-10-31 | 2007-05-01 | University Of Maryland, Baltimore | Factor VIII compositions and methods |
| US7855274B2 (en) * | 2003-12-03 | 2010-12-21 | University Of Rochester | Recombinant factor VIII having increased specific activity |
| JP2007536230A (ja) * | 2004-05-03 | 2007-12-13 | エモリー ユニバーシティ | ブタＢドメイン欠損ｆＶＩＩＩの投与方法 |
| WO2005123928A1 (en) * | 2004-06-08 | 2005-12-29 | Battelle Memorial Institute | Production of human coagulation factor viii from plant cells and whole plants |
| SI3130601T1 (sl) * | 2004-11-12 | 2020-11-30 | Bayer Healthcare Llc | Usmerjena modifikacija FVIII |
| US20100256062A1 (en) | 2004-12-06 | 2010-10-07 | Howard Tommy E | Allelic Variants of Human Factor VIII |
| US7855279B2 (en) | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| JP2009518345A (ja) | 2005-12-07 | 2009-05-07 | テフニーシェ ウニヴェルジテート ミュンヘン | 因子ｖｉｉｉおよび因子ｖｉｉｉ様タンパク質に対する小型ペプチドおよびペプチド模倣物の親和性リガンド |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| DE602007007923D1 (de) * | 2006-04-11 | 2010-09-02 | Csl Behring Gmbh | Verfahren zur erhöhung der in-vivo-gewinnung therapeutischer polypeptide |
| US7939632B2 (en) * | 2006-06-14 | 2011-05-10 | Csl Behring Gmbh | Proteolytically cleavable fusion proteins with high molar specific activity |
| EP1935430A1 (en) * | 2006-12-22 | 2008-06-25 | CSL Behring GmbH | Modified coagulation factors with prolonged in vivo half-life |
| JP5448839B2 (ja) * | 2006-12-22 | 2014-03-19 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | インビボで長い半減期を有する修飾された凝固因子 |
| FR2913020B1 (fr) * | 2007-02-23 | 2012-11-23 | Biomethodes | Nouveaux facteurs viii pour le traitement des hemophiles de type a |
| EP1988101A1 (en) * | 2007-05-04 | 2008-11-05 | Novo Nordisk A/S | Improvement of factor VIII polypeptide titers in cell cultures |
| WO2009058446A1 (en) * | 2007-11-01 | 2009-05-07 | University Of Rochester | Recombinant factor viii having increased stability |
| EP2149603A1 (en) | 2008-07-28 | 2010-02-03 | DRK-Blutspendedienst Baden-Württemberg-Hessen gGmbH | Factor IX variants with clotting activity in absence of their cofactor and their use for treating bleeding disorders |
| BR122021021381B1 (pt) | 2009-02-03 | 2023-05-16 | Amunix Pharmaceuticals, Inc | Método de aprimoramento de uma propriedade de uma proteína biologicamente ativa |
| US8716448B2 (en) | 2009-02-03 | 2014-05-06 | Amunix Operating Inc. | Coagulation factor VII compositions and methods of making and using same |
| DK2440239T3 (en) | 2009-06-09 | 2017-10-16 | Prolong Pharmaceuticals Llc | HEMOGLOBIN FORMATIONS |
| EP2742949A1 (en) * | 2009-11-13 | 2014-06-18 | Puget Sound Blood Center | Factor VIII B cell epitope variants having reduced immunogenicity |
| NZ703153A (en) | 2009-12-06 | 2015-02-27 | Biogen Idec Hemophilia Inc | Factor viii-fc chimeric and hybrid polypeptides, and methods of use thereof |
| WO2011088391A2 (en) * | 2010-01-14 | 2011-07-21 | Haplomics, Inc. | Predicting and reducing alloimmunogenicity of protein therapeutics |
| WO2012006633A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Chimeric clotting factors |
| EP2591101B1 (en) | 2010-07-09 | 2018-11-07 | Bioverativ Therapeutics Inc. | Systems for factor viii processing and methods thereof |
| EP2635297B1 (en) | 2010-11-05 | 2019-02-27 | Baxalta GmbH | A new variant of antihemophilic factor viii having increased specific activity |
| BR112013017281A2 (pt) * | 2011-01-05 | 2016-09-20 | Expression Therapeutics Llc | método e sistema para cultura de células em suspensão |
| WO2012170969A2 (en) | 2011-06-10 | 2012-12-13 | Biogen Idec Ma Inc. | Pro-coagulant compounds and methods of use thereof |
| LT3513804T (lt) | 2011-07-08 | 2022-05-25 | Bioverativ Therapeutics Inc. | Viii faktorius chimeriniai ir hibridiniai polipetidai bei jų panaudojimo būdai |
| EP2737311B1 (en) | 2011-07-25 | 2020-12-02 | Bioverativ Therapeutics Inc. | Assays to monitor bleeding disorders |
| CN102277379B (zh) * | 2011-08-18 | 2013-07-24 | 中国科学院遗传与发育生物学研究所 | 表达凝血因子viii的表达载体及其应用 |
| ES2700583T3 (es) | 2012-01-12 | 2019-02-18 | Bioverativ Therapeutics Inc | Procedimientos para reducir la inmunogenicidad contra el Factor VIII en individuos sometidos a terapia con Factor VIII |
| MY201293A (en) | 2012-01-12 | 2024-02-15 | Bioverativ Therapeutics Inc | Chimeric factor viii polypeptides and uses thereof |
| HUE060629T2 (hu) | 2012-02-15 | 2023-03-28 | Bioverativ Therapeutics Inc | VIII. faktor készítmények és eljárások elõállításukra és alkalmazásukra |
| AU2013204636B2 (en) | 2012-02-15 | 2016-04-14 | Bioverativ Therapeutics Inc. | Recombinant Factor VIII proteins |
| EP2666782A1 (en) * | 2012-05-22 | 2013-11-27 | Imnate Sarl | Coagulation factor VIII with reduced immunogenicity. |
| US10202595B2 (en) | 2012-06-08 | 2019-02-12 | Bioverativ Therapeutics Inc. | Chimeric clotting factors |
| CN104519897A (zh) | 2012-06-08 | 2015-04-15 | 比奥根艾迪克Ma公司 | 促凝血化合物 |
| EP2870250B2 (en) | 2012-07-06 | 2022-06-29 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor viii polypeptides and uses thereof |
| CA2878679A1 (en) | 2012-07-11 | 2014-01-16 | Amunix Operating Inc. | Factor viii complex with xten and von willebrand factor protein, and uses thereof |
| WO2014018777A2 (en) | 2012-07-25 | 2014-01-30 | Biogen Idec Ma Inc. | Blood factor monitoring assay and uses thereof |
| EP2908847B1 (en) | 2012-10-18 | 2022-03-30 | Bioverativ Therapeutics Inc. | Methods of using a fixed dose of a clotting factor |
| EP3943102A1 (en) | 2012-10-30 | 2022-01-26 | Bioverativ Therapeutics Inc. | Methods of using fviii polypeptide |
| EP2928303A4 (en) | 2012-12-07 | 2016-07-13 | Haplomics Inc | FACTOR VIII MUTATION REPAIR AND TOLERANCE INDUCTION |
| SI2956477T1 (sl) | 2013-02-15 | 2021-03-31 | Bioverativ Therapeutics Inc. | Optimiran gen dejavnika VIII |
| TWI788044B (zh) | 2013-03-15 | 2022-12-21 | 美商百歐維拉提夫治療公司 | 因子ｉｘ多肽調配物 |
| HUE047933T2 (hu) | 2013-03-15 | 2020-05-28 | Bioverativ Therapeutics Inc | Faktor VIII polipeptid készítmények |
| SG10201710616XA (en) | 2013-06-28 | 2018-02-27 | Biogen Ma Inc | Thrombin cleavable linker with xten and its uses thereof |
| US10947269B2 (en) | 2013-08-08 | 2021-03-16 | Bioverativ Therapeutics Inc. | Purification of chimeric FVIII molecules |
| US10548953B2 (en) | 2013-08-14 | 2020-02-04 | Bioverativ Therapeutics Inc. | Factor VIII-XTEN fusions and uses thereof |
| AU2014339034A1 (en) | 2013-10-22 | 2016-05-19 | Dbv Technologies | Method of treating haemophilia by inducing tolerance to blood factors |
| EP3065769A4 (en) | 2013-11-08 | 2017-05-31 | Biogen MA Inc. | Procoagulant fusion compound |
| EP4332839A3 (en) | 2013-12-06 | 2024-06-05 | Bioverativ Therapeutics Inc. | Population pharmacokinetics tools and uses thereof |
| EP2881463A1 (en) | 2013-12-09 | 2015-06-10 | DRK-Blutspendedienst Baden-Württemberg-Hessen gGmbH | Factor IX variants with clotting activity in absence of their cofactor and/or with increased F.IX clotting activity and their use for treating bleeding disorders |
| SG11201605242YA (en) | 2014-01-10 | 2016-07-28 | Biogen Ma Inc | Factor viii chimeric proteins and uses thereof |
| AU2015214245B2 (en) | 2014-02-04 | 2020-09-10 | Biogen Ma Inc. | Use of cation-exchange chromatography in the flow-through mode to enrich post-translational modifications |
| US20170051041A1 (en) * | 2014-02-19 | 2017-02-23 | Kathleen Pratt | Factor viii b cell epitope variants having reduced immunogenicity |
| EP3114138B1 (en) | 2014-03-05 | 2021-11-17 | Pfizer Inc. | Improved muteins of clotting factor viii |
| MA40864A (fr) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | Hypotaurine, gaba, bêta-alanine et choline pour la régulation de l'accumulation de sous-produits résiduaires dans des procédés de culture de cellules mammifères |
| UA126016C2 (uk) | 2015-08-03 | 2022-08-03 | Біовератів Терапеутікс Інк. | Злитий білок фактора іх |
| PE20231949A1 (es) * | 2015-10-30 | 2023-12-05 | Spark Therapeutics Inc | VARIANTES DEL FACTOR VIII REDUCIDO CON CpG, COMPOSICIONES Y METODOS Y USOS PARA EL TRATAMIENTO DE TRASTORNOS DE LA HEMOSTASIA |
| TWI777175B (zh) | 2015-11-13 | 2022-09-11 | 日商武田藥品工業股份有限公司 | 用於ａ型血友病基因治療之編碼表現增加之重組ｆｖｉｉｉ變異體之病毒載體 |
| WO2017083764A1 (en) | 2015-11-13 | 2017-05-18 | Baxalta Incorporated | Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a |
| HUE059941T2 (hu) | 2016-02-01 | 2023-01-28 | Bioverativ Therapeutics Inc | Optimalizált VIII-as faktor gének |
| JP6877469B2 (ja) | 2016-06-24 | 2021-05-26 | モガム・インスティテュート・フォー・バイオメディカル・リサーチＭｏｇａｍ Ｉｎｓｔｉｔｕｔｅ Ｆｏｒ Ｂｉｏｍｅｄｉｃａｌ Ｒｅｓｅａｒｃｈ | Ｆｖｉｉｉおよびｖｗｆ因子を含むキメラタンパク質、ならびにそれらの使用 |
| IL266972B2 (en) | 2016-12-02 | 2024-04-01 | Bioverativ Therapeutics Inc | Methods for the treatment of hemophilic arthritis with the help of chimeric blood coagulation factors |
| CN110520149A (zh) | 2016-12-02 | 2019-11-29 | 比奥维拉迪维治疗股份有限公司 | 诱导对凝血因子的免疫耐受性的方法 |
| CN111108196A (zh) * | 2017-05-09 | 2020-05-05 | 爱莫里大学 | 凝血因子变体及其用途 |
| CA3072334A1 (en) | 2017-08-09 | 2019-02-14 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof |
| CA3090136A1 (en) | 2018-02-01 | 2019-08-08 | Bioverativ Therapeutics, Inc. | Use of lentiviral vectors expressing factor viii |
| UY38160A (es) | 2018-04-04 | 2019-11-29 | Sigilon Therapeutics Inc | Partículas implantables y métodos relacionados |
| AU2019270184A1 (en) | 2018-05-18 | 2020-11-26 | Bioverativ Therapeutics Inc. | Methods of treating hemophilia A |
| CN112449640A (zh) | 2018-07-16 | 2021-03-05 | 百深公司 | 使用编码具有增加的表达的重组fviii变体的病毒载体的a型血友病的基因疗法 |
| CN113227385A (zh) | 2018-08-09 | 2021-08-06 | 比奥维拉迪维治疗股份有限公司 | 核酸分子及其用于非病毒基因疗法的用途 |
| UY38389A (es) | 2018-09-27 | 2020-04-30 | Sigilon Therapeutics Inc | Dispositivos implantables para terapia celular y métodos relacionados |
| TW202039546A (zh) | 2019-01-16 | 2020-11-01 | 美商巴克斯歐塔公司 | 用於a型血友病基因治療之編碼表現增加之重組fviii變異體的病毒載體 |
| TW202115127A (zh) | 2019-06-19 | 2021-04-16 | 美商百歐維拉提夫治療公司 | 治療血友病及低骨質密度之方法及組成物 |
| JP2022537555A (ja) | 2019-06-20 | 2022-08-26 | 武田薬品工業株式会社 | ウイルスベースの遺伝子療法による治療方法 |
| JP2023506171A (ja) | 2019-12-12 | 2023-02-15 | 武田薬品工業株式会社 | 発現が上昇した組換えｆｖｉｉｉバリアントをコードするウイルスベクターを使用する、血友病ａの遺伝子療法 |
| TW202246505A (zh) * | 2021-03-05 | 2022-12-01 | 俄羅斯聯邦商亞那拜恩有限公司 | 編碼凝血因子ｉｘ蛋白的密碼子優化的核酸及其用途 |
| JP2024514307A (ja) * | 2021-03-31 | 2024-04-01 | ヘモネティクス・コーポレーション | 血液凝固測定装置の品質管理配合物 |
| WO2022264040A1 (en) | 2021-06-14 | 2022-12-22 | Takeda Pharmaceutical Company Limited | Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression |
| AR126846A1 (es) | 2021-08-23 | 2023-11-22 | Bioverativ Therapeutics Inc | Genes del factor viii optimizados |
| AU2022355088A1 (en) | 2021-09-30 | 2024-05-16 | Bioverativ Therapeutics Inc. | Nucleic acids encoding factor viii polypeptides with reduced immunogenicity |
| WO2024081309A1 (en) | 2022-10-11 | 2024-04-18 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
| EP0182448A3 (en) | 1984-08-24 | 1987-10-28 | Genetics Institute, Inc. | Production of factor viii and related products |
| AU5772886A (en) * | 1985-04-12 | 1986-11-05 | Genetics Institute Inc. | Novel procoagulant proteins |
| JPH0387173A (ja) | 1987-09-10 | 1991-04-11 | Teijin Ltd | ヒト活性化天然型ファクター８ｃの製造方法及びそれに用いる形質転換体 |
| DK162233C (da) | 1989-11-09 | 1992-03-16 | Novo Nordisk As | Fremgangsmaade til isolering af faktor viii fra blodplasma og pharmaceutisk praeparat indeholdende den saaledes isolerede fator viii |
| US6180371B1 (en) * | 1996-06-26 | 2001-01-30 | Emory University | Modified factor VIII |
| US5364771A (en) | 1992-04-07 | 1994-11-15 | Emory University | Hybrid human/porcine factor VIII |
| US5663060A (en) | 1992-04-07 | 1997-09-02 | Emory University | Hybrid human/animal factor VIII |
| US5563045A (en) | 1992-11-13 | 1996-10-08 | Genetics Institute, Inc. | Chimeric procoagulant proteins |
| AU6291896A (en) | 1995-07-11 | 1997-02-10 | Chiron Corporation | Novel factor viii:c polypeptide analogs comprising factor v domains or subdomains |
| AU6455896A (en) | 1995-07-11 | 1997-02-10 | Chiron Corporation | Novel factor viii:c polypeptide analogs with altered metal-binding properties |
| EP1319016A4 (en) * | 2000-09-19 | 2006-05-10 | Univ Emory | MODIFIED FACTOR VIII |
| CN1630666A (zh) * | 2001-11-30 | 2005-06-22 | 埃默里大学 | 因子ⅷc2结构域变体 |
| US7105745B2 (en) * | 2002-12-31 | 2006-09-12 | Thomas & Betts International, Inc. | Water resistant electrical floor box cover assembly |
-
2000
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- 2001-02-16 CN CNB018063179A patent/CN1191360C/zh not_active Expired - Lifetime
- 2001-02-16 NZ NZ520799A patent/NZ520799A/en not_active IP Right Cessation
- 2001-02-16 IL IL15137101A patent/IL151371A0/xx unknown
- 2001-02-16 RS YUP-680/02A patent/RS50364B/sr unknown
- 2001-02-16 SI SI200130823T patent/SI1280540T1/sl unknown
- 2001-02-16 DK DK01910853T patent/DK1280540T3/da active
- 2001-02-16 CZ CZ20023346A patent/CZ298250B6/cs unknown
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- 2001-02-16 JP JP2001566673A patent/JP4044337B2/ja not_active Expired - Lifetime
- 2001-02-16 EE EEP200200510A patent/EE05075B1/xx active Protection Beyond IP Right Term
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