公开(公告)号：WO03030885A2

公开(公告)日：2003-04-17

申请号：PCT/NL0200644

申请日：2002-10-10

Applicant: UNIV MEDISCH CENTRUM UTRECHT ,  UNIV UTRECHT ,  DE KLEIJN DOMINICUS PASCHALIS ,  PASTERKAMP GERARD

Inventor： DE KLEIJN DOMINICUS PASCHALIS ,  PASTERKAMP GERARD

IPC: A61K38/02 ,  A61K38/39 ,  A61P9/10 ,  A61P19/00 ,  C07K14/705 ,  A61K31/00

CPC classification number: A61K38/39 ,  A61K38/02 ,  C07K14/705

Abstract: The present invention relates to the field of molecular biology and medicine. It particularly relates to methods and means for interfering with the formation of a neointima/scar and/or a plaque. The invention provides a method for interfering with the formation of a neointima/scar and/or a plaque in a blood vessel comprising providing a ligand capable of modulating Toll-like receptor activity of adventitial cells.

Abstract translation: 本发明涉及分子生物学和医学领域。 它特别涉及用于干扰新内膜/瘢痕和/或斑块形成的方法和手段。 本发明提供了一种用于干扰血管中新内膜/瘢痕和/或斑块形成的方法，包括提供能调节外膜细胞的Toll样受体活性的配体。

公开(公告)号：WO2012110253A3

公开(公告)日：2013-02-07

申请号：PCT/EP2012000714

申请日：2012-02-17

Applicant: CAVADIS B V ,  DE KLEIJN DOMINIQUE ,  PASTERKAMP GERARD ,  TIMMERS LEONARDUS ,  SZE SIU KWAN

Inventor： DE KLEIJN DOMINIQUE ,  PASTERKAMP GERARD ,  TIMMERS LEONARDUS ,  SZE SIU KWAN

IPC: G01N33/68

CPC classification number: G01N33/6893 ,  G01N2333/78 ,  G01N2333/8121 ,  G01N2333/8139 ,  G01N2800/32

Abstract: The present invention relates to a method of predicting the risk of a subject developing a cardiovascular event, comprising determining the presence of a biomarker that is indicative of the risk of developing a cardiovascular event in an exosome sample from the subject. The exosomes are suitably isolated from a body fluid selected from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, saliva, in particular serum. Alternatively, the exosomes are present in a body fluid, in particular serum. The biomarker is selected- from the proteins Vitronectin, Serpin F2, CD14, Cystatin C, Plasminogen, Nidogen 2, Serpin Gl or any combination of two or more of these proteins. The invention further relates to a method of diagnosing the occurrence of acute coronary syndrome in a subject, comprising determining the presence of a biomarker that is indicative of the occurrence of acute coronary syndrome in an exosome sample from the subject. In this method the biomarker is selected from Serpin F2, CD14, Cystatin C or combinations thereof.

Abstract translation: 本发明涉及一种预测发展心血管事件的受试者的风险的方法，包括确定生物标志物的存在，所述生物标志物指示来自受试者的外来体样品中发生心血管事件的风险。 外来体合适地从选自血清，血浆，血液，尿液，羊水，恶性腹水，支气管肺泡灌洗液，滑液，母乳，唾液，特别是血清中的体液分离。 或者，外来体存在于体液中，特别是血清中。 生物标志物选自蛋白质Vitronectin，Serpin F2，CD14，半胱氨酸蛋白酶抑制剂C，纤溶酶原，Nidogen 2，Serpin Gl或两种或更多种这些蛋白质的任意组合。 本发明还涉及一种诊断受试者中急性冠状动脉综合征发生的方法，包括确定在来自受试者的外来体样品中指示急性冠状动脉综合征发生的生物标志物的存在。 在该方法中，生物标志物选自Serpin F2，CD14，半胱氨酸蛋白酶抑制剂C或其组合。

公开(公告)号：WO2012057613A1

公开(公告)日：2012-05-03

申请号：PCT/NL2011/050311

申请日：2011-05-06

Applicant: UMC UTRECHT HOLDING B.V. ,  ARSLAN, Fatih ,  PASTERKAMP, Gerard ,  DE KLEIJN, Dominicus Paschalis Victor

Inventor： ARSLAN, Fatih ,  PASTERKAMP, Gerard ,  DE KLEIJN, Dominicus Paschalis Victor

IPC: C07K16/18 ,  A61P9/10 ,  A61K39/395

CPC classification number: C07K16/18 ,  A61K2039/505 ,  C07K16/28 ,  C07K2317/21 ,  C07K2317/24

Abstract: The present invention is concerned with treatment, prevention, or prevention of progression of myocardial infarction or adverse cardiac remodeling related conditions such as heart failure, aneurysm formation and remote myocardial fibrosis by administering a binding member such as, for example, a neutralizing antibody, binding to fibronectin-EDA, in particular the EDA domain of fibronectin-EDA to a subject in need thereof.

Abstract translation: 本发明涉及治疗，预防或预防心肌梗死或不良心脏重塑相关病症如心力衰竭，动脉瘤形成和远端心肌纤维化的进展，通过施用结合成员例如中和抗体，结合 纤连蛋白-EDA，特别是纤连蛋白EDA的EDA结构域与需要的受试者。

公开(公告)号：WO2009019260A2

公开(公告)日：2009-02-12

申请号：PCT/EP2008/060249

申请日：2008-08-04

Applicant: OPSONA THERAPEUTICS LIMITED ,  HEFFERNAN, Mark ,  O'NEILL, Luke ,  McGUIRK, Peter ,  KEOGH, Brian ,  LOCHER, Christopher ,  DE KLEIJN, Dominique ,  ARSLAN, Fatih ,  PASTERKAMP, Gerard

Inventor： HEFFERNAN, Mark ,  O'NEILL, Luke ,  McGUIRK, Peter ,  KEOGH, Brian ,  LOCHER, Christopher ,  DE KLEIJN, Dominique ,  ARSLAN, Fatih ,  PASTERKAMP, Gerard

IPC: C12N15/113

CPC classification number: A61K39/3955 ,  A61K31/00 ,  A61K31/7088 ,  A61K38/177 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2896 ,  C07K2317/76 ,  C12N15/1138 ,  G01N33/567 ,  G01N2500/00 ,  A61K2300/00

Abstract: The present invention provides compounds and methods for the treatment and prophylaxis of ischemia reperfusion injury. In particular the invention provides compounds which function to suppress Toll-like Receptor 2 biological function or expression.

Abstract translation: 本发明提供了治疗和预防缺血再灌注损伤的化合物和方法。 特别地，本发明提供了用于抑制Toll样受体2生物学功能或表达的化合物。

公开(公告)号：WO2012126531A1

公开(公告)日：2012-09-27

申请号：PCT/EP2011/054567

申请日：2011-03-24

Applicant: CAVADIS B.V. ,  DE KLEIJN, Dominique ,  PASTERKAMP, Gerard ,  TIMMERS, Leonardus ,  SZE, Siu Kwan

Inventor： DE KLEIJN, Dominique ,  PASTERKAMP, Gerard ,  TIMMERS, Leonardus ,  SZE, Siu Kwan

IPC: G01N33/68

CPC classification number: G01N33/6893 ,  G01N2800/324

Abstract: The invention relates to a method of diagnosing the occurrence of acute coronary syndrome in a subject, comprising determining the presence of a biomarker that is indicative of the occurrence of acute coronary syndrome in an exosome sample from the subject. The exosome sample consists of exosomes that are isolated from a body fluid, a body fluid that comprises exosomes selected from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, saliva, in particular serum.

Abstract translation: 本发明涉及一种诊断受试者中急性冠状动脉综合征发生的方法，包括确定在来自受试者的外来体样品中指示急性冠状动脉综合征发生的生物标志物的存在。 外来体样品由从体液分离的外来体组成，体液包含选自血清，血浆，血液，尿液，羊水，恶性腹水，支气管肺泡灌洗液，滑液，母乳，唾液中的外来体，特别是 血清。

公开(公告)号：WO2009019260A3

公开(公告)日：2010-02-04

申请号：PCT/EP2008060249

申请日：2008-08-04

Applicant: OPSONA THERAPEUTICS LTD ,  HEFFERNAN MARK ,  O'NEILL LUKE ,  MCGUIRK PETER ,  KEOGH BRIAN ,  LOCHER CHRISTOPHER ,  DE KLEIJN DOMINIQUE ,  ARSLAN FATIH ,  PASTERKAMP GERARD

Inventor： HEFFERNAN MARK ,  O'NEILL LUKE ,  MCGUIRK PETER ,  KEOGH BRIAN ,  LOCHER CHRISTOPHER ,  DE KLEIJN DOMINIQUE ,  ARSLAN FATIH ,  PASTERKAMP GERARD

IPC: A61K38/17 ,  A61K31/00 ,  A61K39/395 ,  A61P9/10 ,  A61P39/00 ,  A61P41/00 ,  C12N15/113 ,  C12Q1/00

CPC classification number: A61K39/3955 ,  A61K31/00 ,  A61K31/7088 ,  A61K38/177 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2896 ,  C07K2317/76 ,  C12N15/1138 ,  G01N33/567 ,  G01N2500/00 ,  A61K2300/00

Abstract: The present invention provides compounds and methods for the treatment and prophylaxis of ischemia reperfusion injury. In particular the invention provides compounds which function to suppress Toll-like Receptor 2 biological function or expression.

Abstract translation: 本发明提供了治疗和预防缺血再灌注损伤的化合物和方法。 特别地，本发明提供了用于抑制Toll样受体2生物学功能或表达的化合物。

公开(公告)号：WO2009017405A3

公开(公告)日：2009-07-23

申请号：PCT/NL2008050517

申请日：2008-07-25

Applicant: UNIV ERASMUS MEDICAL CT ,  UMC UTRECHT HOLDING BV ,  SWAGEMAKERS SIGRID MARIA ALICE ,  VAN DER SPEK PETRUS JOHANNES ,  PASTERKAMP GERARD ,  DE KLEIJN DOMINICUS PASCHALIS VICTOR ,  MOLL FRANCISCUS LAURENS

Inventor： SWAGEMAKERS SIGRID MARIA ALICE ,  VAN DER SPEK PETRUS JOHANNES ,  PASTERKAMP GERARD ,  DE KLEIJN DOMINICUS PASCHALIS VICTOR ,  MOLL FRANCISCUS LAURENS

IPC: G01N33/50 ,  G01N33/68

CPC classification number: G01N33/6893 ,  G01N2800/32 ,  Y10T436/143333

Abstract: The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m/II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

Abstract translation: 本发明涉及一种用于预测发展心血管事件的受试者的风险的方法，包括检测来自所述受试者的心血管系统的（样品）中的至少一种生物标志物，其中所述生物标志物包含至少一种选自以下的蛋白质： 的肿瘤坏死因子α前体; 溶酶体相关膜蛋白（1）; 白介素-5前体; 白细胞介素-6前体; C-C主题趋化因子（2）前体; C-C基序趋化因子（5）前体RANTES; 组织蛋白酶L1前体; 腺苷酸激酶（1）; 白三烯B4受体（1）; 补体因子D; 分泌磷蛋白（1）; 小诱导细胞因子A17前体; C-X-C主题趋化因子（10）前体; 肿瘤坏死因子配体超家族成员（11）（RANKL）; C-C主题趋化因子（18）前体; 72 kDa型IV型胶原酶前体; 嗜中性粒细胞胶原酶前体; 脂肪酸结合蛋白（4）; 钙蛋白酶（2），（m / II）大亚基; 巨噬细胞迁移抑制因子 组织蛋白酶S前体; 白介素（13）前体; 和可溶性ICAM-1。

公开(公告)号：WO2012110253A2

公开(公告)日：2012-08-23

申请号：PCT/EP2012/000714

申请日：2012-02-17

Applicant: CAVADIS B.V. ,  DE KLEIJN, Dominique ,  PASTERKAMP, Gerard ,  TIMMERS, Leonardus ,  SZE, Siu Kwan

Inventor： DE KLEIJN, Dominique ,  PASTERKAMP, Gerard ,  TIMMERS, Leonardus ,  SZE, Siu Kwan

IPC: G01N33/68

CPC classification number: G01N33/6893 ,  G01N2333/78 ,  G01N2333/8121 ,  G01N2333/8139 ,  G01N2800/32

Abstract: The present invention relates to a method of predicting the risk of a subject developing a cardiovascular event, comprising determining the presence of a biomarker that is indicative of the risk of developing a cardiovascular event in an exosome sample from the subject. The exosomes are suitably isolated from a body fluid selected from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, saliva, in particular serum. Alternatively, the exosomes are present in a body fluid, in particular serum. The biomarker is selected- from the proteins Vitronectin, Serpin F2, CD14, Cystatin C, Plasminogen, Nidogen 2, Serpin Gl or any combination of two or more of these proteins. The invention further relates to a method of diagnosing the occurrence of acute coronary syndrome in a subject, comprising determining the presence of a biomarker that is indicative of the occurrence of acute coronary syndrome in an exosome sample from the subject. In this method the biomarker is selected from Serpin F2, CD14, Cystatin C or combinations thereof.

Abstract translation: 本发明涉及一种预测发展心血管事件的受试者的风险的方法，包括确定生物标志物的存在，所述生物标志物指示来自受试者的外来体样品中发生心血管事件的风险。 外来体合适地从选自血清，血浆，血液，尿液，羊水，恶性腹水，支气管肺泡灌洗液，滑液，母乳，唾液，特别是血清中的体液分离。 或者，外来体存在于体液中，特别是血清中。 生物标志物选自蛋白质Vitronectin，Serpin F2，CD14，半胱氨酸蛋白酶抑制剂C，纤溶酶原，Nidogen 2，Serpin Gl或两种或更多种这些蛋白质的任意组合。 本发明还涉及一种诊断受试者中急性冠状动脉综合征发生的方法，包括确定在来自受试者的外来体样品中指示急性冠状动脉综合征发生的生物标志物的存在。 在该方法中，生物标志物选自Serpin F2，CD14，半胱氨酸蛋白酶抑制剂C或其组合。

公开(公告)号：WO2012110099A1

公开(公告)日：2012-08-23

申请号：PCT/EP2011/052437

申请日：2011-02-18

Applicant: CAVADIS B.V. ,  DE KLEIJN, Dominique ,  PASTERKAMP, Gerard ,  TIMMERS, Leonardus ,  SZE, Siu, Kwan

Inventor： DE KLEIJN, Dominique ,  PASTERKAMP, Gerard ,  TIMMERS, Leonardus ,  SZE, Siu, Kwan

IPC: G01N33/68

CPC classification number: G01N33/6893 ,  G01N2333/78 ,  G01N2333/8121 ,  G01N2333/8139 ,  G01N2800/2871 ,  G01N2800/32 ,  G01N2800/324

Abstract: The present invention relates to a method of predicting the risk of a subject developing a cardiovascular event, comprising determining the presence of a biomarker that is indicative of the risk of developing a cardiovascular event in an exosome sample from the subject. The exosomes are suitably isolated from a body fluid selected from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, saliva, in particular serum. Alternatively, the exosomes are present in a body fluid, in particular serum. The biomarker is selected from the proteins Vitronectin, Serpin F2, CD14, Cystatin C, Plasminogen, Nidogen 2 or any combination of two or more of these proteins.

Abstract translation: 本发明涉及一种预测发展心血管事件的受试者的风险的方法，包括确定生物标志物的存在，所述生物标志物指示来自受试者的外来体样品中发生心血管事件的风险。 外来体合适地从选自血清，血浆，血液，尿液，羊水，恶性腹水，支气管肺泡灌洗液，滑液，母乳，唾液，特别是血清中的体液分离。 或者，外来体存在于体液中，特别是血清中。 生物标志物选自蛋白质Vitronectin，Serpin F2，CD14，半胱氨酸蛋白酶抑制剂C，纤溶酶原，Nidogen2或两种或更多种这些蛋白质的任何组合。

公开(公告)号：WO2009017405A2

公开(公告)日：2009-02-05

申请号：PCT/NL2008/050517

申请日：2008-07-25

Applicant: ERASMUS UNIVERSITY MEDICAL CENTER ROTTERDAM ,  UMC UTRECHT HOLDING B.V. ,  SWAGEMAKERS, Sigrid, Maria, Alice ,  VAN DER SPEK, Petrus, Johannes ,  PASTERKAMP, Gerard ,  DE KLEIJN, Dominicus, Paschalis, Victor ,  MOLL, Franciscus, Laurens

Inventor： SWAGEMAKERS, Sigrid, Maria, Alice ,  VAN DER SPEK, Petrus, Johannes ,  PASTERKAMP, Gerard ,  DE KLEIJN, Dominicus, Paschalis, Victor ,  MOLL, Franciscus, Laurens

IPC: G01N33/50 ,  G01N33/68

CPC classification number: G01N33/6893 ,  G01N2800/32 ,  Y10T436/143333

Abstract: The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m/II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

Abstract translation: 本发明涉及用于预测受试者发展心血管事件的风险的方法，其包括检测来自所述受试者的心血管系统（的样品）中的至少一种生物标志物，其中所述生物标志物包含在 至少一种选自肿瘤坏死因子α前体; 溶酶体相关膜蛋白（1）; 白细胞介素-5前体; 白细胞介素-6前体; C-C基序趋化因子（2）前体; C-C基元趋化因子（5）前体RANTES; 组织蛋白酶L1前体; 腺苷酸激酶（1）; 白三烯B4受体（1）; 补充因子D; 分泌型磷蛋白（1）; 小诱导性细胞因子A17前体; C-X-C基序趋化因子（10）前体; 肿瘤坏死因子配体超家族成员（11）（RANKL）; C-C基序趋化因子（18）前体; 72kDa IV型胶原酶前体; 嗜中性粒细胞胶原酶前体; 脂肪酸结合蛋白（4）; 钙蛋白酶（2），（m / II）大亚基; 巨噬细胞迁移抑制因子; 组织蛋白酶S前体; 白细胞介素（13）前体; 和可溶性ICAM-1。