ES2799515T3 - ADN extracelular como una diana terapéutica en la neurodegeneración - Google Patents
ADN extracelular como una diana terapéutica en la neurodegeneración Download PDFInfo
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- ES2799515T3 ES2799515T3 ES16800375T ES16800375T ES2799515T3 ES 2799515 T3 ES2799515 T3 ES 2799515T3 ES 16800375 T ES16800375 T ES 16800375T ES 16800375 T ES16800375 T ES 16800375T ES 2799515 T3 ES2799515 T3 ES 2799515T3
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
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- C12Y301/02021—Dodecanoyl-[acyl-carrier-protein] hydrolase (3.1.2.21)
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- C12Y301/00—Hydrolases acting on ester bonds (3.1)
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| PCT/RU2016/000284 WO2016190780A1 (en) | 2015-05-22 | 2016-05-11 | Extracellular dna as a therapeutic target in neurodegeneration |
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| WO2016190780A1 (en) | 2015-05-22 | 2016-12-01 | Dmitry Dmitrievich Genkin | Extracellular dna as a therapeutic target in neurodegeneration |
| US20190083636A1 (en) * | 2017-04-25 | 2019-03-21 | Lipoxen Technologies Limited | Methods of treating diseases related to net formation with parenteral administration of polysialylated dnase i |
| US12274720B2 (en) | 2017-05-24 | 2025-04-15 | Viktor Veniaminovich Tets | Methods for treating and preventing diseases |
| ES2913665T3 (es) | 2017-09-18 | 2022-06-03 | Santersus Ag | Método y dispositivo para la purificación de sangre a partir de ADN celular libre en circulación |
| KR20200122320A (ko) | 2018-01-16 | 2020-10-27 | 씨엘에스 테라퓨틱스 리미티드 | 데옥시리보뉴클레아제 (dnase) 활성을 갖는 효소의 간 발현에 의한 질환의 치료 |
| CA3098444A1 (en) | 2018-04-30 | 2019-11-07 | Viktor Veniaminovich Tets | Tetz-proteins and prion-like proteins and associated methods |
| US12480150B2 (en) | 2018-06-29 | 2025-11-25 | Viktor Veniaminovich Tets and Georgy Viktorovich TETS | Compositions for modulating gut microbiota |
| WO2020006357A1 (en) | 2018-06-29 | 2020-01-02 | Tets Viktor Veniaminovich | Methods for diagnosis and treatment of type 1 diabetes |
| WO2020010214A1 (en) | 2018-07-03 | 2020-01-09 | Tets Viktor Veniaminovich | Method for assessing and inhibiting aging and means of determining biological age |
| CN110129245B (zh) * | 2019-07-08 | 2020-12-04 | 南京工业大学 | 一株敲除胞外核酸酶ExeP的谷氨酸棒杆菌及其构建方法与应用 |
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| EP4119149A1 (en) * | 2021-07-15 | 2023-01-18 | Foundation For Research And Technology Hellas | Extracellular vesicles comprising a therapeutic cargo |
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Family Cites Families (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3224942A (en) | 1962-01-15 | 1965-12-21 | Rorer Inc William H | Anti-inflammatory, anti-edema and anti-thrombi drug |
| US3324002A (en) | 1962-09-17 | 1967-06-06 | Armour Pharma | Anti-inflammatory preparations containing proteolytic enzymes and adrenal glucocorticoids |
| JPS5826822A (ja) | 1981-08-10 | 1983-02-17 | Kaken Pharmaceut Co Ltd | 慢性腎炎治療剤 |
| JPS61293927A (ja) | 1986-06-18 | 1986-12-24 | Kaken Pharmaceut Co Ltd | 肝臓疾患予防治療剤 |
| US4985243A (en) | 1988-01-20 | 1991-01-15 | Ml Technology Ventures, L.P. | Composition and method for protecting against diseases caused by microorganisms |
| ATE176924T1 (de) | 1988-12-23 | 1999-03-15 | Genentech Inc | Verfahren zur herstellung von menschlicher dnase |
| US5464817A (en) | 1990-04-11 | 1995-11-07 | Brigham And Women's Hospital | Method for reducing the viscosity of pathological mucoid airway contents in the respiratory tract comprising administering actin-binding compounds with or without DNASE I |
| DE4024530A1 (de) | 1990-08-02 | 1992-02-06 | Klinger & Co Dr | Verfahren zur bekaempfung von viren |
| FR2666096B1 (fr) | 1990-08-21 | 1993-12-31 | Sfri Sa | Nouveau procede de dosage d'acide desoxyribonucleique present en position extracellulaire dans un milieu. |
| DE69207603T2 (de) | 1991-08-16 | 1996-09-12 | Vical Inc | Zusammensetzung und verfahren zur behandlung von zystischer fibrose |
| US5484589A (en) | 1992-04-20 | 1996-01-16 | Rufeld, Inc. | Anti-viral methods using RNAse and DNAse |
| NZ299257A (en) | 1992-06-08 | 2000-08-25 | Genentech Inc | Treating purulent material (eg pulmonary disease) accumulation in patients using deamidated DNase |
| WO1995000170A1 (en) | 1993-06-24 | 1995-01-05 | Rufeld, Inc. | Inhibition of human immunodeficiency virus reproduction by deoxyribonuclease i |
| CH686982A5 (fr) | 1993-12-16 | 1996-08-15 | Maurice Stroun | Méthode pour le diagnostic de cancers. |
| RU2099080C1 (ru) | 1994-02-11 | 1997-12-20 | Дмитрий Иванович Финько | Способ предотвращения развития рака |
| CA2184582C (en) | 1994-03-04 | 2001-12-25 | Hak-Kim Chan | Pharmaceutically acceptable dnase formulation |
| US5830744A (en) | 1995-06-06 | 1998-11-03 | Human Genome Sciences, Inc. | Gene encoding human Dnase |
| US5889153A (en) | 1994-05-20 | 1999-03-30 | Hisamitsu Pharmaceutical Co., Inc. | Protein or polypeptide, method for producing the same and intermediate compound therefor |
| JP4118334B2 (ja) | 1996-02-05 | 2008-07-16 | ジェネンテック・インコーポレーテッド | ヒトｄｎアーゼ |
| AU2324997A (en) | 1996-03-15 | 1997-10-01 | Penn State Research Foundation, The | Detection of extracellular tumor-associated nucleic acid in blood plasma or ser um using nucleic acid amplification assays |
| US6391607B1 (en) | 1996-06-14 | 2002-05-21 | Genentech, Inc. | Human DNase I hyperactive variants |
| US5855920A (en) | 1996-12-13 | 1999-01-05 | Chein; Edmund Y. M. | Total hormone replacement therapy |
| US6242426B1 (en) | 1997-07-25 | 2001-06-05 | Avigen, Inc. | Induction of immune response to antigens expressed by recombinant adeno-associated virus |
| US6455250B1 (en) | 1997-12-11 | 2002-09-24 | The Regents Of The University Of California | Endonuclease compositions and methods of use |
| WO2000003709A1 (en) | 1998-07-16 | 2000-01-27 | Research Development Foundation | Novel dna-cleaving antitumor agents |
| US6465177B1 (en) | 1998-10-26 | 2002-10-15 | John Wayne Cancer Institute | Detection of loss of heterozygosity in tumor and serum of melanoma patients |
| CA2352486A1 (en) | 1998-11-25 | 2000-06-02 | Genetica, Inc. | Methods and reagents for increasing proliferative capacity and preventing replicative senescence |
| JP2000229881A (ja) | 1999-02-10 | 2000-08-22 | Morinaga Milk Ind Co Ltd | 癌疾患の予後改善剤 |
| JP4522632B2 (ja) | 1999-08-17 | 2010-08-11 | 靖一 田沼 | 新規デオキシリボヌクレアーゼ、それをコードする遺伝子およびそれらの用途 |
| US6428785B1 (en) | 1999-10-28 | 2002-08-06 | Immunolytics Inc. | Method and composition for treating prostate cancer |
| UA78486C2 (uk) | 1999-12-10 | 2007-04-10 | Хемджен Корпорейшн | Композиція для перорального введення птахам та тваринам для лікування або зниження ризику інфекції травного тракту (варіанти), її застосування (варіанти) та спосіб лікування або зниження ризику інфекцій травного тракту (варіанти) |
| AU4430701A (en) | 2000-04-03 | 2001-10-15 | Antisoma Research Limited | Compounds for targeting |
| US6462017B1 (en) | 2000-05-01 | 2002-10-08 | Sciclone Pharmaceuticals, Inc. | Method of reducing side effects of chemotherapy in cancer patients |
| RU2202109C1 (ru) | 2001-08-03 | 2003-04-10 | Научно-исследовательский институт неврологии РАН | Способ выявления степени нарушения реологических свойств крови |
| RU2207876C1 (ru) | 2001-11-08 | 2003-07-10 | Ткаченко Виталий Васильевич | Способ комплексно-индивидуализированного воздействия на организм при медленной вирусной инфекции и способ подготовки лабораторного животного для испытания способа такого воздействия |
| US7402724B2 (en) | 2002-01-04 | 2008-07-22 | Mayo Foundation For Medical Education And Research | Longevity and PAPP-A |
| ES2527096T3 (es) * | 2002-02-18 | 2015-01-20 | Ockham Biotech Limited | Combinación de ADNasa I y glucosaminoglucanos para su uso en limpieza de ADN extracelular |
| DE10221194B4 (de) | 2002-05-13 | 2005-02-10 | Fryda, Waltraud, Dr.med. | Hyaluronidasehaltiges Hautpflegemittel |
| US20040001817A1 (en) | 2002-05-14 | 2004-01-01 | Giampapa Vincent C. | Anti-aging nutritional supplement |
| EP1431762B1 (en) | 2002-12-18 | 2007-04-25 | Coy, Johannes F., Dr. | Compounds and methods for detection of carcinomas and their precursor lesions |
| RU2239442C1 (ru) | 2003-05-05 | 2004-11-10 | Красноярская государственная медицинская академия | Способ профилактики внутриутробных инфекций у детей |
| US8431123B2 (en) | 2003-07-14 | 2013-04-30 | Cls Therapeutics Limited | Method for treating systemic bacterial, fungal and protozoan infection |
| RU2269356C2 (ru) | 2003-07-14 | 2006-02-10 | Дмитрий Дмитриевич Генкин | Способ лечения онкологических заболеваний |
| RU2269358C2 (ru) * | 2003-07-14 | 2006-02-10 | Дмитрий Дмитриевич Генкин | Способ лечения генерализованных инфекций, вызываемых бактериями, или заболеваний, вызываемых грибами и простейшими, или атеросклероза, или сахарного диабета, или заболеваний, связанных с реакцией гиперчувствительности замедленного типа, или заболеваний, обусловленных мутациями генов соматических клеток |
| EP1666055A4 (en) | 2003-07-14 | 2010-02-10 | Viktor Veniaminovich Tets | METHOD OF TREATMENT OF ONCOLOGICAL, INFECTIOUS, AND SOMATIC DISEASES, METHODS OF MONITORING THE EFFICACY OF TREATMENT, AGENTS AND PHARMACEUTICAL COMPOSITIONS THEREOF |
| US8388951B2 (en) | 2003-07-14 | 2013-03-05 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
| WO2005004904A1 (en) | 2003-07-14 | 2005-01-20 | Dmitry Dmitrievich Genkin | Method for treating diseases associated with modifications of qualitative and/ quantitative composition of blood extracellular dna (variants) |
| US8710012B2 (en) | 2003-07-14 | 2014-04-29 | Cls Therapeutics Limited | Method for treating oncological diseases |
| RU2269359C2 (ru) | 2004-03-12 | 2006-02-10 | Дмитрий Дмитриевич Генкин | Способ профилактики развития онкологических заболеваний или инфекций, вызываемых бактериями, грибами и простейшими, или атеросклероза, или сахарного диабета, или заболеваний, связанных с реакцией гиперчувствительности замедленного типа, или заболеваний, развивающихся вследствие мутации генов соматических клеток (варианты) |
| US8173618B2 (en) * | 2003-07-25 | 2012-05-08 | University Of Massachusetts | Formulations for reducing neuronal degeneration |
| RU2239404C1 (ru) | 2003-09-17 | 2004-11-10 | Бессонов Дмитрий Михайлович | Способ профилактики старения организма человека |
| RU2267329C2 (ru) | 2004-03-12 | 2006-01-10 | Дмитрий Дмитриевич Генкин | Способ лечения заболеваний, сопровождающихся изменениями качественного и/или количественного состава внеклеточной днк крови (варианты) |
| RU2269357C2 (ru) | 2004-03-12 | 2006-02-10 | Дмитрий Дмитриевич Генкин | Способ замедления наступления болезненных состояний, связанных с увеличением возраста человека |
| CA2604243C (en) | 2004-04-14 | 2015-11-24 | Avirid, Inc. | Compositions with modified nucleases targeted to viral nucleic acids and methods of use for prevention and treatment of viral diseases |
| ES2665422T3 (es) * | 2005-03-03 | 2018-04-25 | Immunomedics Inc. | Anticuerpos L243 humanizados |
| JP3989936B2 (ja) | 2005-04-07 | 2007-10-10 | 進 須永 | 抗腫瘍剤及び新規ｄｎアーゼ |
| US8916151B2 (en) | 2005-04-25 | 2014-12-23 | Cls Therapeutics Limited | Method for treating a reduction of fertility |
| BRPI0616012A2 (pt) | 2005-07-18 | 2011-05-31 | Protalix Ltd | administração via mucosa ou intestino de macromoléculas biologicamente ativas |
| RU2308968C2 (ru) | 2005-07-19 | 2007-10-27 | Дмитрий Дмитриевич Генкин | Способ лечения заболеваний человека, сопровождающихся повышенным содержанием дезоксирибонуклеиновой кислоты во внеклеточных пространствах тканей, и лекарственный препарат для его реализации |
| WO2008039989A2 (en) * | 2006-09-28 | 2008-04-03 | Transave, Inc. | Formulations of dnase and methods of use thereof |
| PT2086642E (pt) | 2006-10-18 | 2014-09-30 | Periness Ltd | Dnase para o tratamento de subfertilidade masculina |
| WO2008066403A1 (fr) | 2006-11-28 | 2008-06-05 | Dmitry Dmitrievich Genkin | Procédé de traitement de maladies humaines accompagnées d'une teneur plus élevée d'adn dans des espaces intercellulaires et préparation médicamenteuse destinée à sa mise en oeuvre |
| GB0922006D0 (en) | 2009-12-17 | 2010-02-03 | Genome Res Ltd | Diagnostic |
| AU2011336396B2 (en) * | 2010-12-02 | 2016-02-04 | Immunomedics, Inc. | In vivo copper-free click chemistry for delivery of therapeutic and/or diagnostic agents |
| US20130243794A1 (en) | 2010-12-03 | 2013-09-19 | Beth Israel Deaconess Medical Center, Inc. | Methods for predicting and treating infection-induced illnesses and predicting the severity of infection-induced illnesses |
| US9603907B2 (en) | 2012-02-01 | 2017-03-28 | Protalix Ltd. | Dry powder formulations of dNase I |
| AU2013221212B2 (en) | 2012-02-17 | 2018-08-09 | The Children's Hospital Of Philadelphia | AAV vector compositions and methods for gene transfer to cells, organs and tissues |
| JP6285436B2 (ja) | 2012-08-03 | 2018-02-28 | フェリング ベスローテン フェンノートシャップ | 雌性不妊症のための治療標的および診断マーカーとしての無細胞ｄｎａ |
| HUE052676T2 (hu) | 2013-10-11 | 2021-05-28 | Massachusetts Eye & Ear Infirmary | Eljárások õsi vírusszekvenciák elõrejelzésére és alkalmazásaik |
| CA2943296C (en) | 2014-03-21 | 2022-10-18 | The Sydney Children's Hospitals Network (Randwick And Westmead) (Incorporating The Royal Alexandra Hospital For Children) | Stable gene transfer to proliferating cells |
| WO2016081811A1 (en) | 2014-11-21 | 2016-05-26 | The University Of North Carolina At Chapel Hill | Aav vectors targeted to the central nervous system |
| WO2016190780A1 (en) | 2015-05-22 | 2016-12-01 | Dmitry Dmitrievich Genkin | Extracellular dna as a therapeutic target in neurodegeneration |
| RU2021102893A (ru) | 2015-11-05 | 2021-03-03 | Бамбу Терапьютикс, Инк. | Модифицированные гены атаксии фридрейха и векторы для генной терапии |
| CA3015353A1 (en) | 2016-02-25 | 2017-08-31 | Agenovir Corporation | Viral and oncoviral nuclease treatment |
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| EP3297657A1 (en) | 2018-03-28 |
| RU2726131C2 (ru) | 2020-07-09 |
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| JP6745873B2 (ja) | 2020-08-26 |
| RU2017145051A (ru) | 2019-06-24 |
| RU2017145051A3 (https=) | 2019-06-24 |
| WO2016190780A1 (en) | 2016-12-01 |
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| US11701410B2 (en) | 2023-07-18 |
| US20180360925A1 (en) | 2018-12-20 |
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