RU2726131C2 - Внеклеточная днк в качестве терапевтической мишени при нейродегенерации - Google Patents
Внеклеточная днк в качестве терапевтической мишени при нейродегенерации Download PDFInfo
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100061971A1 (en) * | 2006-11-28 | 2010-03-11 | Dmitry Dmitrievich Genkin | Method for Treating Human Diseases Associated With an Increased Deoxyribonucleic Acid Content in Extracellular Spaces of Tissues and a Medicinal Preparation for Carrying Out Said Method |
| US20120252750A1 (en) * | 2003-07-25 | 2012-10-04 | University Of Massachusetts | Formulations for reducing neuronal degeneration |
Family Cites Families (73)
| 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 |
| WO1990007572A1 (en) | 1988-12-23 | 1990-07-12 | Genentech, Inc. | HUMAN 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. |
| ATE132742T1 (de) | 1991-08-16 | 1996-01-15 | 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 |
| WO1995023613A1 (en) | 1994-03-04 | 1995-09-08 | Genentech, Inc. | 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 |
| NZ331063A (en) | 1996-02-05 | 2000-03-27 | Inc Genentech | Isolated nucleotide sequences encoding for mature LS- DNase which is resistant to actin inhibition |
| US6156504A (en) | 1996-03-15 | 2000-12-05 | The Penn State Research Foundation | Detection of extracellular tumor-associated nucleic acid in blood plasma or serum 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 |
| IL143328A0 (en) | 1998-11-25 | 2002-04-21 | 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 |
| ATE369419T1 (de) | 1999-08-17 | 2007-08-15 | Sei-Ichi Tanuma | Deoxyribonuklease, dafür kodierendes gen und verfahren |
| 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 |
| WO2003068254A1 (en) | 2002-02-18 | 2003-08-21 | University Of Southampton | Glycosaminoglycan-dnase combination therapy |
| 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 |
| ATE360817T1 (de) | 2002-12-18 | 2007-05-15 | Coy Johannes F Dr | Verbindungen und verfahren zur nachweiss von karzinomen und deren vorstufen |
| RU2239442C1 (ru) | 2003-05-05 | 2004-11-10 | Красноярская государственная медицинская академия | Способ профилактики внутриутробных инфекций у детей |
| 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 |
| 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 |
| US8388951B2 (en) | 2003-07-14 | 2013-03-05 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
| US9248166B2 (en) | 2003-07-14 | 2016-02-02 | Cls Therapeutics Limited | Method for treating oncological diseases |
| 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 |
| 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) |
| 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 |
| RU2239404C1 (ru) | 2003-09-17 | 2004-11-10 | Бессонов Дмитрий Михайлович | Способ профилактики старения организма человека |
| RU2269357C2 (ru) | 2004-03-12 | 2006-02-10 | Дмитрий Дмитриевич Генкин | Способ замедления наступления болезненных состояний, связанных с увеличением возраста 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) |
| US9592277B2 (en) | 2004-04-14 | 2017-03-14 | Avirid, Inc. | Compositions with modified nucleases targeted to viral nucleic acids and methods of use for prevention and treatment of viral diseases |
| ES2829566T3 (es) * | 2005-03-03 | 2021-06-01 | 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 |
| EP1880733A4 (en) | 2005-04-25 | 2009-08-12 | Genkin Dmitry Dmitrievich | Method for increasing longevity of a human being and animals |
| JP2009501784A (ja) | 2005-07-18 | 2009-01-22 | プロタリクス リミテッド | 生物学的に活性な高分子の粘膜投与または経腸投与 |
| 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 |
| AU2007311444B2 (en) | 2006-10-18 | 2012-11-29 | Periness Ltd. | Method and pharmacological composition for the diagnosis and treatment of male sub-fertility |
| GB0922006D0 (en) | 2009-12-17 | 2010-02-03 | Genome Res Ltd | Diagnostic |
| CN103221072A (zh) * | 2010-12-02 | 2013-07-24 | 免疫医疗公司 | 用于递送治疗剂和/或诊断剂的体内无铜催化的点击化学 |
| WO2012075506A2 (en) | 2010-12-03 | 2012-06-07 | Beth Israel Deaconess Medical Center, Inc. | Methods for predicting and treating infection-induced illnesses and predicting the severity of infection-induced illnesses |
| US9603906B2 (en) | 2012-02-01 | 2017-03-28 | Protalix Ltd. | Inhalable liquid formulations of DNase I |
| KR102057540B1 (ko) | 2012-02-17 | 2019-12-19 | 더 칠드런스 호스피탈 오브 필라델피아 | 세포, 기관 및 조직으로의 유전자 전이를 위한 ａａｖ 벡터 조성물 및 방법 |
| ES2588387T3 (es) | 2012-08-03 | 2016-11-02 | Ferring Bv | ADN libre de células como diana terapéutica para esterilidad femenina y marcador de diagnóstico |
| NZ718926A (en) | 2013-10-11 | 2021-12-24 | Massachusetts Eye & Ear Infirmary | Methods of predicting ancestral virus sequences and uses thereof |
| AU2015234242B2 (en) | 2014-03-21 | 2020-09-24 | Children's Medical Research Institute | Stable gene transfer to proliferating cells |
| EP4344741A3 (en) | 2014-11-21 | 2024-08-28 | The University of North Carolina at Chapel Hill | Aav vectors targeted to the central nervous system |
| RU2726131C2 (ru) | 2015-05-22 | 2020-07-09 | Дмитрий Дмитриевич Генкин | Внеклеточная днк в качестве терапевтической мишени при нейродегенерации |
| PE20181156A1 (es) | 2015-11-05 | 2018-07-19 | Bamboo Therapeutics Inc | Genes de ataxia de friedreich modificados y vectores para terapia genica |
| WO2017147446A1 (en) | 2016-02-25 | 2017-08-31 | Agenovir Corporation | Viral and oncoviral nuclease treatment |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120252750A1 (en) * | 2003-07-25 | 2012-10-04 | University Of Massachusetts | Formulations for reducing neuronal degeneration |
| US20100061971A1 (en) * | 2006-11-28 | 2010-03-11 | Dmitry Dmitrievich Genkin | Method for Treating Human Diseases Associated With an Increased Deoxyribonucleic Acid Content in Extracellular Spaces of Tissues and a Medicinal Preparation for Carrying Out Said Method |
Non-Patent Citations (2)
| Title |
|---|
| GLEBOVA KV., et al., Properties of extracellular DNA from the cerebrospinal fluid and blood plasma during Parkinson's disease.Bull Exp Biol Med. 2014 Apr;156(6):826-8. doi: 10.1007/s10517-014-2461-9. Epub 2014 May 3. * |
| MIGLIORE L., et al., Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients. Neurobiol Aging. 2005 May;26(5):567-73. * |
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| RU2017145051A (ru) | 2019-06-24 |
| US20180360925A1 (en) | 2018-12-20 |
| EP3297657B1 (en) | 2020-03-25 |
| RU2017145051A3 (enExample) | 2019-06-24 |
| EP3297657A4 (en) | 2018-11-14 |
| US11701410B2 (en) | 2023-07-18 |
| ES2799515T3 (es) | 2020-12-18 |
| CN108289932A (zh) | 2018-07-17 |
| WO2016190780A1 (en) | 2016-12-01 |
| EP3297657A1 (en) | 2018-03-28 |
| JP6745873B2 (ja) | 2020-08-26 |
| JP2018520208A (ja) | 2018-07-26 |
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