EA029023B1 - Применение молекул, связывающих семафорин-4d, для модуляции проницаемости гематоэнцефалического барьера - Google Patents
Применение молекул, связывающих семафорин-4d, для модуляции проницаемости гематоэнцефалического барьера Download PDFInfo
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| RU2753441C2 (ru) * | 2016-09-13 | 2021-08-16 | Ангиокрин Биосайенс, Инк. | Гематоэнцефалический барьер, содержащий сконструированные эндотелиальные клетки |
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| TWI859192B (zh) * | 2019-03-29 | 2024-10-21 | 日商中外製藥股份有限公司 | 包含抗il-6受體抗體之bbb功能低下之抑制劑 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020037851A1 (en) * | 1997-07-09 | 2002-03-28 | Bernhard Fleckenstein | Human semaphorin L (H-SemaL) and corresponding semaphorins in other species |
| US20100285036A1 (en) * | 2009-05-08 | 2010-11-11 | Vaccinex, Inc. | Anti-CD100 Neutralizing Antibodies and Methods of Using the Same |
Family Cites Families (64)
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|---|---|---|---|---|
| NZ201918A (en) | 1981-09-18 | 1987-04-30 | Genentech Inc | N-terminal methionyl analogues of bovine growth hormone |
| US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
| US5070192A (en) | 1988-03-23 | 1991-12-03 | The Johns Hopkins University | Cloned human topoisomerase i: cdna expression, and use for autoantibody detection |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| US6497872B1 (en) | 1991-07-08 | 2002-12-24 | Neurospheres Holdings Ltd. | Neural transplantation using proliferated multipotent neural stem cells and their progeny |
| FR2686087A1 (fr) | 1992-01-13 | 1993-07-16 | Inst Nat Sante Rech Med | Nouvel antigene lymphocytaire, anticorps correspondant et leurs applications. |
| US5639856A (en) | 1993-09-13 | 1997-06-17 | The Regents Of The University Of California | Semaphorin gene family |
| US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
| US6576754B2 (en) | 1995-11-09 | 2003-06-10 | Dana-Farber Cancer Institute | CD100 antigen and uses therefor |
| US20020032315A1 (en) | 1997-08-06 | 2002-03-14 | Manuel Baca | Anti-vegf antibodies |
| ES2236634T3 (es) | 1997-04-07 | 2005-07-16 | Genentech, Inc. | Anticuerpos anti-vegf. |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| WO1998046769A1 (en) | 1997-04-11 | 1998-10-22 | Dendreon Corporation | Composition and method for inducing an immune response against tumour-related antigens |
| US5968829A (en) | 1997-09-05 | 1999-10-19 | Cytotherapeutics, Inc. | Human CNS neural stem cells |
| US6638501B1 (en) | 1997-09-29 | 2003-10-28 | Neurospheres Holdings Ltd. | Use of multipotent neural stem cell progeny to augment non-neural tissues |
| US5958767A (en) | 1998-08-14 | 1999-09-28 | The Children's Medical Center Corp. | Engraftable human neural stem cells |
| AU776865B2 (en) | 1998-11-10 | 2004-09-23 | University Of Rochester | T cells specific for target antigens and methods and vaccines based thereon |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| JP3787473B2 (ja) | 1999-11-30 | 2006-06-21 | 独立行政法人科学技術振興機構 | セマフォリン受容体 |
| US6635742B1 (en) | 2000-01-25 | 2003-10-21 | Nuvelo, Inc. | Antibodies specific for semaphorin-like polypeptides |
| WO2001046384A2 (en) | 1999-12-23 | 2001-06-28 | Cornell Research Foundation, Inc. | A method for isolating and purifying multipotential neural progenitor cells and multipotential neural progenitor cells |
| CN1329060A (zh) | 2000-06-19 | 2002-01-02 | 上海博德基因开发有限公司 | 一种新的多肽——人semaphorin蛋白9和编码这种多肽的多核苷酸 |
| IL159177A0 (en) | 2001-06-20 | 2004-06-01 | Prochon Biotech Ltd | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US20080219974A1 (en) | 2002-03-01 | 2008-09-11 | Bernett Matthew J | Optimized antibodies that target hm1.24 |
| EP1365018A1 (en) | 2002-05-23 | 2003-11-26 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | CD100 semaphorin in myelination |
| JP4524181B2 (ja) | 2002-05-30 | 2010-08-11 | マクロジェニクス,インコーポレーテッド | Cd16a結合タンパク質および免疫障害治療のための使用 |
| US9809654B2 (en) | 2002-09-27 | 2017-11-07 | Vaccinex, Inc. | Targeted CD1d molecules |
| EP1442749A1 (en) * | 2003-01-31 | 2004-08-04 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Use of anti-CD100 antibodies for the treatment and the diagnosis of inflammatory disorder affecting the central nervous system |
| CN1788017B (zh) * | 2003-02-10 | 2013-04-24 | to-BBB控股股份有限公司 | 炎症状态下在血脑屏障中差异表达的核酸 |
| RS20150135A1 (sr) | 2003-05-30 | 2015-08-31 | Genentech Inc. | Tretman sa anti-vegf antitelima |
| CA2882022A1 (en) | 2003-09-11 | 2005-03-24 | Walter Newman | Monoclonal antibodies against hmgb1 |
| JP5042631B2 (ja) | 2003-12-04 | 2012-10-03 | バクシネックス インコーポレーティッド | アポトーシス腫瘍細胞上に露出した細胞内抗原をターゲッティングすることによって腫瘍細胞を死滅させる方法 |
| RU2006124743A (ru) | 2003-12-11 | 2008-01-20 | Дженентек, Инк. (Us) | СПОСОБЫ И КОМПОЗИЦИИ ДЛЯ ИНГИБИРОВАНИЯ ДИМЕРИЗАЦИИ И АКТИВАЦИИ с-Мет |
| US7476724B2 (en) | 2004-08-05 | 2009-01-13 | Genentech, Inc. | Humanized anti-cmet antibodies |
| US20060147449A1 (en) | 2004-11-15 | 2006-07-06 | Brass Lawrence F | Method of using CD100 (or Sema4D) to mediate platelet activation and inflammatory responses |
| EP1871484A2 (en) | 2005-04-07 | 2008-01-02 | Chiron Corporation | Sema4d in cancer diagnosis, detection and treatment |
| WO2007057395A2 (en) | 2005-11-16 | 2007-05-24 | Novartis Ag | Biomarkers for anti-nogo-a antibody treatment in spinal cord injury |
| JP2007308465A (ja) | 2006-05-15 | 2007-11-29 | Boehringer Ingelheim Internatl Gmbh | 炎症性疾患、自己免疫疾患又は骨吸収異常の治療方法 |
| WO2008025020A2 (en) | 2006-08-25 | 2008-02-28 | Seattle Genetics, Inc. | Cd30 binding agents and uses thereof |
| US9382327B2 (en) | 2006-10-10 | 2016-07-05 | Vaccinex, Inc. | Anti-CD20 antibodies and methods of use |
| US8906367B2 (en) * | 2007-01-05 | 2014-12-09 | University Of Zurich | Method of providing disease-specific binding molecules and targets |
| EP2069404B1 (en) * | 2007-02-14 | 2011-01-05 | Vaccinex, Inc. | Humanized anti-cd100 antibodies |
| EP2112930B1 (en) | 2007-02-21 | 2017-01-11 | Vaccinex, Inc. | Modulation of nkt cell activity with antigen-loaded cdid molecules |
| EP2237792B1 (en) | 2007-12-26 | 2017-05-24 | Vaccinex, Inc. | Anti-c35 antibody combination therapies and methods |
| WO2009089461A1 (en) | 2008-01-10 | 2009-07-16 | Genentech, Inc. | Plexind1 agonists and their use |
| CA3017298C (en) | 2009-05-15 | 2021-09-28 | Irx Therapeutics, Inc. | Compositions comprising primary cell-derived biologics for enhancing immune responses in patients |
| JP5500944B2 (ja) | 2009-10-29 | 2014-05-21 | 三菱電機株式会社 | 加熱調理器 |
| US8834883B2 (en) | 2010-06-14 | 2014-09-16 | Vaccinex, Inc. | Anti-VEGF antibodies and uses thereof |
| AU2011295902B2 (en) | 2010-09-02 | 2014-12-04 | Vaccinex, Inc. | Anti-CXCL13 antibodies and methods of using the same |
| US9447191B2 (en) | 2011-05-13 | 2016-09-20 | National University Corporation Tokyo Medical And Dental University | Osteogenesis promoter |
| US8790652B2 (en) | 2011-12-06 | 2014-07-29 | Vaccinex, Inc. | Use of the combination of semaphorin-4D inhibitory molecules and VEGF inhibitory molecules to inhibit angiogenesis |
| IN2014DN08199A (enExample) | 2012-03-02 | 2015-05-01 | Vaccinex Inc | |
| US9090709B2 (en) | 2012-03-28 | 2015-07-28 | Vaccinex, Inc. | Anti-SEMA4D antibodies and epitopes |
| US9708601B2 (en) | 2012-04-26 | 2017-07-18 | Vaccinex, Inc. | Fusion proteins to facilitate selection of cells infected with specific immunoglobulin gene recombinant vaccinia virus |
| US10494440B2 (en) | 2012-05-11 | 2019-12-03 | Vaccinex, Inc. | Use of semaphorin-4D binding molecules to promote neurogenesis following stroke |
| EP2951204B1 (en) | 2013-01-31 | 2019-05-22 | Vaccinex, Inc. | Methods for increasing immunoglobulin a levels |
| US9371352B2 (en) | 2013-02-08 | 2016-06-21 | Vaccinex, Inc. | Modified glycolipids and methods of making and using the same |
| BR112015032690B1 (pt) | 2013-06-25 | 2020-03-10 | Vaccinex, Inc. | Uso de moléculas inibidoras de semaforina-4d em combinação com uma terapia imunomoduladora para inibir o crescimento tumoral e metástase |
| NZ630881A (en) | 2013-10-10 | 2016-03-31 | Vaccinex Inc | Use of semaphorin-4d binding molecules for treatment of atherosclerosis |
| NZ630892A (en) | 2013-10-21 | 2016-03-31 | Vaccinex Inc | Use of semaphorin-4d binding molecules for treating neurodegenerative disorders |
| BR112018071686A2 (pt) | 2016-04-22 | 2019-02-19 | Vaccinex, Inc. | exibição de proteínas integrais de membrana em vírions extracelulares envelopados de poxvírus |
| WO2018026715A1 (en) | 2016-08-02 | 2018-02-08 | Vaccinex, Inc. | Improved methods for producing polynucleotide libraries in vaccinia virus/eukaryotic cells |
| WO2018156509A1 (en) | 2017-02-22 | 2018-08-30 | Vaccinex, Inc. | Early detection of glial cell activation in neurodegenerative or neuroinflammatory diseases |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020037851A1 (en) * | 1997-07-09 | 2002-03-28 | Bernhard Fleckenstein | Human semaphorin L (H-SemaL) and corresponding semaphorins in other species |
| US20100285036A1 (en) * | 2009-05-08 | 2010-11-11 | Vaccinex, Inc. | Anti-CD100 Neutralizing Antibodies and Methods of Using the Same |
Non-Patent Citations (1)
| Title |
|---|
| OKUNO et al., Roles of Sema4D-Plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. Journal of Immunology, 1 February 2010, vol 184, no 3, pp 1499-1506; (page 1500, col 1, para 7) * |
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| CN110105452A (zh) | 2019-08-09 |
| CA2851805C (en) | 2021-12-28 |
| MX353550B (es) | 2018-01-18 |
| CN104168956A (zh) | 2014-11-26 |
| US20130095118A1 (en) | 2013-04-18 |
| EA201490768A1 (ru) | 2014-09-30 |
| EP2766093B1 (en) | 2018-02-21 |
| EP2766093A4 (en) | 2015-03-25 |
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| US20190358321A1 (en) | 2019-11-28 |
| JP2017193569A (ja) | 2017-10-26 |
| JP2014530239A (ja) | 2014-11-17 |
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| ES2669209T3 (es) | 2018-05-24 |
| SG11201401458UA (en) | 2014-07-30 |
| KR20140076616A (ko) | 2014-06-20 |
| JP6395606B2 (ja) | 2018-09-26 |
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