ES2924830T3 - Moléculas de heparina reversibles - Google Patents
Moléculas de heparina reversibles Download PDFInfo
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- ES2924830T3 ES2924830T3 ES14812890T ES14812890T ES2924830T3 ES 2924830 T3 ES2924830 T3 ES 2924830T3 ES 14812890 T ES14812890 T ES 14812890T ES 14812890 T ES14812890 T ES 14812890T ES 2924830 T3 ES2924830 T3 ES 2924830T3
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- heparin
- ost
- sulfotransferase
- compound
- paps
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/10—Heparin; Derivatives thereof
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/04—Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/18—Preparation of compounds containing saccharide radicals produced by the action of a glycosyl transferase, e.g. alpha-, beta- or gamma-cyclodextrins
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
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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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Applications Claiming Priority (2)
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| US201361835875P | 2013-06-17 | 2013-06-17 | |
| PCT/US2014/042683 WO2014204929A2 (en) | 2013-06-17 | 2014-06-17 | Reversible heparin molecules and methods of making and using the same |
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| ES2924830T3 true ES2924830T3 (es) | 2022-10-11 |
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| EP (1) | EP3011043B1 (enExample) |
| JP (1) | JP6670235B2 (enExample) |
| CN (1) | CN105452479B (enExample) |
| ES (1) | ES2924830T3 (enExample) |
| WO (1) | WO2014204929A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US12397016B2 (en) | 2017-11-03 | 2025-08-26 | The University Of North Carolina At Chapel Hill | Sulfated oligosaccharides having anti-inflammatory activity |
Families Citing this family (18)
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| US11203772B2 (en) | 2010-12-23 | 2021-12-21 | The University Of North Carolina At Chapel Hill | Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins |
| EP3011043B1 (en) | 2013-06-17 | 2022-05-11 | The University of North Carolina At Chapel Hill | Reversible heparin molecules |
| EP3273239A1 (en) * | 2016-07-19 | 2018-01-24 | Laboratorios Farmacéuticos Rovi, S.A. | Procedure of analysis of glycosaminoglycans, heparins and their derivatives by nuclear magnetic resonance |
| TWI769176B (zh) * | 2016-09-07 | 2022-07-01 | 瑞瑟勒綜合技術協會 | 生合成肝素 |
| CN110446511B (zh) * | 2017-03-10 | 2024-04-02 | 北卡罗来纳大学查珀尔希尔分校 | 短效的基于肝素的抗凝血剂化合物和方法 |
| US10864227B2 (en) | 2017-03-20 | 2020-12-15 | Rensselaer Polytechnic Institute | Enzymatic preparation of increased anticoagulant bovine sourced heparin |
| US11993627B2 (en) | 2017-07-03 | 2024-05-28 | The University Of North Carolina At Chapel Hill | Enzymatic synthesis of homogeneous chondroitin sulfate oligosaccharides |
| EP3723862A4 (en) * | 2017-12-12 | 2021-08-25 | Academia Sinica | OCTASACCHARIDES AND THEIR USES |
| TW201937167A (zh) * | 2018-03-01 | 2019-09-16 | 中央研究院 | 用來偵測癌細胞的裝置及方法 |
| EP3810152A4 (en) | 2018-06-20 | 2022-04-27 | The University of North Carolina at Chapel Hill | CELL PROTECTION METHODS AND COMPOSITIONS |
| CN109321508B (zh) * | 2018-10-12 | 2022-12-27 | 北京化工大学 | 产heparosan的基因工程菌及其应用 |
| MX2021008479A (es) | 2019-01-15 | 2021-10-13 | Optimvia Llc | Enzimas dependientes de aril sulfato modificadas por ingenieria genetica. |
| WO2022015794A1 (en) | 2020-07-14 | 2022-01-20 | Optimvia, Llc | Methods for synthesizing non-anticoagulant heparan sulfate |
| CA3144968A1 (en) | 2019-07-09 | 2021-01-14 | Optimvia Llc | Methods for synthesizing anticoagulant polysaccharides |
| CN111154819B (zh) * | 2020-01-15 | 2022-08-30 | 山东大学 | 一种非动物源低分子量肝素及其制备方法与应用 |
| CN113583151B (zh) * | 2021-07-07 | 2023-06-20 | 山东大学 | 含at结合序列和连续2-o-葡糖醛酸残基的肝素分子及其制备方法与应用 |
| CN113564139B (zh) * | 2021-08-02 | 2023-03-10 | 山东大学 | 巴氏杆菌肝素骨架合酶BtHS1及其突变体与应用 |
| CN116120484B (zh) * | 2022-09-01 | 2024-11-08 | 山东大学 | 一种抗凝血肝素寡糖苯联二聚体及其制备方法与应用 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4554101A (en) | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
| US4865870A (en) | 1988-07-07 | 1989-09-12 | Becton, Dickinson And Company | Method for rendering a substrate surface antithrombogenic |
| PT93847A (pt) | 1989-04-24 | 1990-11-20 | Harvard College | Processo para a preparacao de oligossacaridos de baixo peso molecular derivados de heparina ou de sulfato de heparano despolimerizados e de composicoes farmaceuticas que os contem |
| US5378829A (en) | 1990-04-23 | 1995-01-03 | Akzo N.V. | Sulfated glycosaminoglycanoid derivatives of the heparin and heparan sulfate type |
| IT1260137B (it) | 1992-04-17 | 1996-03-28 | Alfa Wassermann Spa | Glicosaminoglicani semisintetici a struttura eparinica od eparanica modificati nella posizione 2 dell'acido alfa-l-iduronico-2-0-solfato |
| JP3818676B2 (ja) | 1994-07-22 | 2006-09-06 | 生化学工業株式会社 | ヘパラン硫酸６−ｏ−硫酸基転移酵素 |
| IT1271057B (it) | 1994-11-04 | 1997-05-26 | Inalco Spa | Polisaccaridi aventi un elevato contenuto di acido iduronico |
| JP3672359B2 (ja) | 1995-07-24 | 2005-07-20 | 生化学工業株式会社 | ヘパラン硫酸 ２−ｏ−硫酸基転移酵素 |
| US5935824A (en) | 1996-01-31 | 1999-08-10 | Technologene, Inc. | Protein expression system |
| US6861254B1 (en) | 1997-10-24 | 2005-03-01 | Massachusetts Institute Of Technology | Heparan sulfate D-glucosaminyl 3-O-sulfotransferases, and uses therefor |
| US8088604B2 (en) | 1998-04-02 | 2012-01-03 | The Board Of Regents Of The University Of Oklahoma | Production of defined monodisperse heparosan polymers and unnatural polymers with polysaccharide synthases |
| US6624141B1 (en) | 1999-03-17 | 2003-09-23 | The Regents Of The University Of Michigan | Protamine fragment compositions and methods of use |
| US6255088B1 (en) | 1999-05-11 | 2001-07-03 | The Scripps Research Institute | Enzymatic sulfation of biomolecules |
| CA2441984A1 (en) | 2001-03-28 | 2002-10-10 | Massachusetts Institute Of Technology | Methods of 6-o-sulfating polysaccharides and 6-o-sulfated polysaccharide preparations |
| WO2002089742A2 (en) * | 2001-05-08 | 2002-11-14 | The Board Of Regents Of The University Of Oklahoma | Heparin/heparosan synthase and methods of making and using same |
| PT1401853E (pt) | 2001-05-25 | 2010-12-07 | Univ Duke | Modulador de oligonucleotídeos |
| WO2003018598A2 (en) * | 2001-08-30 | 2003-03-06 | University College Dublin | Monosaccharide derivatives |
| US7531338B2 (en) | 2002-07-05 | 2009-05-12 | The University Of North Carolina At Chapel Hill | Purified and isolated heparan sulfate 3-O-sulfotransferase isoform 5 nucleic acids and polypeptides and therapeutic and screening methods using same |
| GB0216861D0 (en) | 2002-07-19 | 2002-08-28 | Univ Birmingham | Saccharide libraries |
| WO2004017910A2 (en) * | 2002-08-23 | 2004-03-04 | Neose Technologies, Inc. | Total synthesis of heparin |
| WO2005014619A2 (en) * | 2003-03-28 | 2005-02-17 | Thomas Jefferson University | Heparin-binding peptides and uses thereof |
| US7655445B2 (en) | 2003-11-12 | 2010-02-02 | Massachusetts Institute Of Technology | Methods for synthesis of sulfated saccharides |
| US20090197308A1 (en) | 2005-05-12 | 2009-08-06 | Jian Liu | Enzymatic synthesis of sulfated polysaccharides |
| EP2447285A3 (en) | 2006-05-25 | 2013-01-16 | Momenta Pharmaceuticals, Inc. | Low molecular weight heparin composition and uses thereof |
| WO2009014715A2 (en) * | 2007-07-23 | 2009-01-29 | The University Of North Carolina At Chapel Hill | Enzymatic synthesis of sulfated polysaccharides without iduronic acid residues |
| US8455439B2 (en) | 2008-11-14 | 2013-06-04 | Portola Pharmaceuticals, Inc. | Antidotes for factor Xa inhibitors and methods of using the same in combination with blood coagulating agents |
| US20110054236A1 (en) * | 2009-08-25 | 2011-03-03 | The Regents Of The University Of Michigan | Compositions and methods for targeting tumors |
| WO2011038047A1 (en) | 2009-09-23 | 2011-03-31 | Momenta Pharmaceuticals, Inc. | Methods of treatment with a low molecular weight heparin composition |
| US11203772B2 (en) * | 2010-12-23 | 2021-12-21 | The University Of North Carolina At Chapel Hill | Chemoenzymatic synthesis of structurally homogeneous ultra-low molecular weight heparins |
| WO2012116048A1 (en) * | 2011-02-22 | 2012-08-30 | Rensselaer Polytechnic Institute | Single step heparosan n-deacetylation and depolymerization for making bioengineered heparin |
| US8519189B2 (en) | 2011-06-01 | 2013-08-27 | University Of British Columbia | Polymers for reversing heparin-based anticoagulation |
| EP3011043B1 (en) | 2013-06-17 | 2022-05-11 | The University of North Carolina At Chapel Hill | Reversible heparin molecules |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US12397016B2 (en) | 2017-11-03 | 2025-08-26 | The University Of North Carolina At Chapel Hill | Sulfated oligosaccharides having anti-inflammatory activity |
Also Published As
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| CN105452479B (zh) | 2021-05-18 |
| CN105452479A (zh) | 2016-03-30 |
| US9951149B2 (en) | 2018-04-24 |
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| US20160122446A1 (en) | 2016-05-05 |
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| EP3011043A4 (en) | 2017-01-18 |
| JP6670235B2 (ja) | 2020-03-18 |
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