公开(公告)号：US08048993B2

公开(公告)日：2011-11-01

申请号：US12003999

申请日：2008-01-04

申请人： Iris Pecker ,  Israel Vlodavsky ,  Yael Friedmann ,  Tuvia Peretz

发明人： Iris Pecker ,  Israel Vlodavsky ,  Yael Friedmann ,  Tuvia Peretz

IPC分类号： C07K16/00 ,  C07K16/40 ,  C07K14/00

CPC分类号： C12Y302/01166 ,  A61L27/34 ,  A61M15/009 ,  C07K16/40 ,  C12N9/2402 ,  G01N33/573 ,  G01N2333/988 ,  G01N2400/40

摘要： According to the present invention there is provided an antibody that specifically binds an epitope of a heparanase protein, the heparanase protein including an amino acid sequence as set forth in SEQ ID NO:2, provided that phenylalanine replaces tyrosine at position 246. The present invention also provides an antibody elicited by an epitope of a heparanase protein, the heparanase protein including an amino acid sequence as set forth in SEQ ID NO:2, provided that phenylalanine replaces tyrosine at position 246.

摘要翻译： 根据本发明，提供了一种特异性结合肝素酶蛋白的表位的抗体，乙酰肝素酶包括SEQ ID NO：2所示的氨基酸序列，条件是苯丙氨酸替代246位的酪氨酸。本发明 还提供了乙酰肝素酶蛋白的表位引起的抗体，乙酰肝素酶包括SEQ ID NO：2所示的氨基酸序列，条件是苯丙氨酸替代位置246处的酪氨酸。

公开(公告)号：US07666651B2

公开(公告)日：2010-02-23

申请号：US09776874

申请日：2001-02-06

申请人： Iris Pecker ,  Israel Vlodavsky ,  Elena Feinstein

发明人： Iris Pecker ,  Israel Vlodavsky ,  Elena Feinstein

IPC分类号： C12N9/00 ,  C12N9/14 ,  C12N9/24

CPC分类号： C12Y302/01166 ,  A61K38/00 ,  C12N9/2402

摘要： A polynucleotide (hpa) encoding a polypeptide having heparanase activity, vectors including same, genetically modified cells expressing heparanase, a recombinant protein having heparanase activity and antisense oligonucleotides and constructs for modulating heparanase expression.

摘要翻译： 编码具有乙酰肝素酶活性的多肽的多核苷酸（hpa），包含其的载体，表达乙酰肝素酶的遗传修饰的细胞，具有乙酰肝素酶活性的重组蛋白和反义寡核苷酸以及用于调节肝素酶表达的构建体。

公开(公告)号：US20060223108A1

公开(公告)日：2006-10-05

申请号：US11449775

申请日：2006-06-09

申请人： Iris Pecker ,  Israel Vlodavsky ,  Ben Katz ,  Amiram Eldor ,  Menachem Bitan ,  Aaron Polliack ,  Arnon Nagler ,  Zofia Eldor

发明人： Iris Pecker ,  Israel Vlodavsky ,  Ben Katz ,  Amiram Eldor ,  Menachem Bitan ,  Aaron Polliack ,  Arnon Nagler ,  Zofia Eldor

IPC分类号： C12Q1/68 ,  G01N33/574 ,  C12Q1/34

CPC分类号： G01N33/57426 ,  C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/158 ,  G01N2333/924

摘要： Methods and kits for distinguishing between heparanase expressing and heparanase non-expressing hematopoietic cells, particularly useful in distinguishing between different types of differentiated and/or undifferentiated lymphomas and leukemias. The methods and kits are designed to detect heparanase expression, or absence thereof, at the gene, protein and/or protein activity levels.

公开(公告)号：US06589782B1

公开(公告)日：2003-07-08

申请号：US09428909

申请日：1999-10-28

申请人： Gera Neufeld ,  Eli Keshet ,  Israel Vlodavsky ,  Zoya Poltorak

发明人： Gera Neufeld ,  Eli Keshet ,  Israel Vlodavsky ,  Zoya Poltorak

IPC分类号： C12N1563

CPC分类号： C07K14/52 ,  A61K38/00 ,  A61K48/00 ,  C12N2799/022

摘要： The present invention relates to a novel VEGF protein product, and nucleic acid encoding the novel protein product, comprising exons 1-6 and 8 of the VEGF gene, and its use thereof in treating the cardiovascular system and its diseases through effects on anatomy, conduit function, and permeability. VEGF145 has been found to be an active mitogen for vascular endothelial cells and to function as an angiogenic factor in-vivo. VEGF145 has novel properties compared with previously characterized VEGF species with respect to cellular distribution, susceptibility to oxidative damage, and extra-cellular matrix (ECM) binding ability. The present invention provides methods of treating the cardiovascular system, enhancing endothelialization of diseased vessels, and enhancing drug permeation by providing the novel VEGF protein product. The invention also provides expression vectors, compositions, and kits for use in the methods of the invention.

摘要翻译： 本发明涉及一种新型的VEGF蛋白产物，以及编码新型蛋白质产物的核酸，其包含VEGF基因的外显子1-6和8及其在治疗心血管系统及其疾病中的用途，通过对解剖结构，导管 功能和渗透性。 已经发现VEGF145是血管内皮细胞的活性丝裂原并且在体内作为血管生成因子起作用。 VEGF145相对于细胞分布，对氧化损伤的敏感性和细胞外基质（ECM）结合能力与先前表征的VEGF物种相比具有新的特性。 本发明提供了治疗心血管系统，增强患病血管的内皮化，并通过提供新的VEGF蛋白产物增强药物渗透的方法。 本发明还提供用于本发明方法的表达载体，组合物和试剂盒。

公开(公告)号：US06420371B1

公开(公告)日：2002-07-16

申请号：US09479660

申请日：2000-01-10

申请人： Mark Pines ,  Israel Vlodavsky ,  Arnon Nagler

发明人： Mark Pines ,  Israel Vlodavsky ,  Arnon Nagler

IPC分类号： A61K31505

CPC分类号： A61K31/517

摘要： The invention provides a composition for attenuating neovascularization and treating malignancies, including a pharmaceutically effective amount of a compound having a formula: wherein: R1 is a number of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy, R2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy, and R3 is a member of the group consisting of hydrogen and lower alkenoxy carbonyl, as active ingredient therein, in combination with a pharmaceutically acceptable carrier.

摘要翻译： 本发明提供一种用于减毒新生血管形成和治疗恶性肿瘤的组合物，包括药学有效量的具有下式的化合物：其中：R1是氢，卤素，硝基，苯并，低级烷基，苯基和低级烷氧基 R2是羟基，乙酰氧基和低级烷氧基的成员，R 3是作为活性成分的氢和低级链烯氧基羰基的组成与药学上可接受的载体的组合。

公开(公告)号：US06190875B1

公开(公告)日：2001-02-20

申请号：US09113168

申请日：1998-07-10

申请人： Hanna Ben-Artzi ,  Maty Ayal-Hershkovitz ,  Israel Vlodavsky ,  Iris Pecker ,  Yoav Peleg ,  Daphna Miron

发明人： Hanna Ben-Artzi ,  Maty Ayal-Hershkovitz ,  Israel Vlodavsky ,  Iris Pecker ,  Yoav Peleg ,  Daphna Miron

IPC分类号： C12Q134

CPC分类号： C12Y302/01166 ,  A61K38/00 ,  A61L27/34 ,  C12N9/2402 ,  C12Q1/34 ,  C12Q1/527 ,  G01N2333/924 ,  G01N2333/988 ,  G01N2400/40 ,  G01N2500/20

摘要： Qualitative and quantitative methods of testing an agent for its potential at inhibiting glycosidase catalytic activity, the methods including the steps of interacting a glycosidase enzyme with a glycosidase substrate in a presence of the agent and qualitatively or quantitatively evaluating an effect of the agent on the catalytic activity of the glycosidase enzyme toward the glycosidase substrate. Preferably the glycosidase enzyme is a heparanase enzyme and the glycosidase substrate is, respectively, a heparanase substrate.

摘要翻译： 测定其抑制糖苷酶催化活性潜力的试剂的定性和定量方法，所述方法包括在试剂存在下将糖苷酶与糖苷酶底物相互作用的步骤，并定性或定量地评估试剂对催化剂的作用 糖苷酶对糖苷酶底物的活性。 优选地，糖苷酶是乙酰肝素酶，糖苷酶底物分别是乙酰肝素酶底物。

公开(公告)号：US6028075A

公开(公告)日：2000-02-22

申请号：US797703

申请日：1997-02-11

申请人： Mark Pines ,  Israel Vlodavsky ,  Arnon Nagler ,  Hua-Quan Miao

发明人： Mark Pines ,  Israel Vlodavsky ,  Arnon Nagler ,  Hua-Quan Miao

IPC分类号： C07D401/06 ,  A61K31/517 ,  A61P35/00 ,  A61P43/00 ,  A61K31/505

CPC分类号： A61K31/517

摘要： The invention provides a composition for attenuating neovascularization and treating malignancies, including a pharmaceutically effective amount of a compound having a formula: ##STR1## wherein: R.sub.1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;R.sub.2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy, andR.sub.3 is a member of the group consisting of hydrogen and lower alkenoxy carbonyl;as active ingredient therein, in combination with a pharmaceutically acceptable carrier.

摘要翻译： 本发明提供用于减毒新生血管形成和治疗恶性肿瘤的组合物，包括药学有效量的具有下式的化合物：其中：R 1是氢，卤素，硝基，苯并，低级烷基，苯基和低级烷氧基 ; R2是由羟基，乙酰氧基和低级烷氧基组成的组的成员，R3是由氢和低级链烯氧基羰基组成的组的成员; 作为其中的活性成分，与药学上可接受的载体组合。

公开(公告)号：US5206223A

公开(公告)日：1993-04-27

申请号：US583851

申请日：1990-09-17

申请人： Israel Vlodavsky ,  Amiram Eldor ,  Yaakov Naparstek ,  Irun Cohen

发明人： Israel Vlodavsky ,  Amiram Eldor ,  Yaakov Naparstek ,  Irun Cohen

IPC分类号： C08B37/10

CPC分类号： A61K31/715 ,  Y10S514/825 ,  Y10S514/885

摘要： Heparanase activity in a patient may be inhibited by administering an effective heparanase-inhibiting amount of heparin or an effective chemically modified derivative of heparin which inhibits heparanase activity. Such derivatives are preferably N-desulfated, N-acetylated heparin or O-desulfated, N-acetylated heparin. By means of this invention, allograft rejection may be prevented or delayed and autoimmune diseases such as arthritis may be alleviated and treated.

摘要翻译： 可以通过施用抑制肝素酶活性的有效的乙酰肝素酶抑制量的肝素或有效的化学修饰的肝素衍生物来抑制患者中的肝素酶活性。 此类衍生物优选为N-脱硫酸，N-乙酰化肝素或O-脱硫酸，N-乙酰化肝素。 通过本发明，可以预防或延迟同种异体移植排斥反应，并且可以减轻和治疗自身免疫性疾病如关节炎。

公开(公告)号：US20120232263A1

公开(公告)日：2012-09-13

申请号：US13056085

申请日：2009-07-09

申请人： Giangiacomo Torri ,  Elena Vismara ,  Israel Vlodavsky ,  Annamaria Naggi

发明人： Giangiacomo Torri ,  Elena Vismara ,  Israel Vlodavsky ,  Annamaria Naggi

IPC分类号： C07H5/10

CPC分类号： C07H11/00 ,  C07H17/04

摘要： The present invention is directed to sulfated oligosaccharides having 4, 5 or 6 saccharidic units and wherein a glycosidic bond between two saccharide units is substituted by a C—C bond, and wherein the sulfation degree expressed as percentage of OH groups substituted by a OSO3− group is comprised between 50 and 100%. The sulfated oligosaccharides according to the invention are useful as a drug, in particular in the treatment of angiogenesis, metastasis, and inflammation.

摘要翻译： 本发明涉及具有4,5或6个糖苷单元的硫酸化低聚糖，并且其中两个糖单元之间的糖苷键被C-C键取代，并且其中所述硫酸化度表示为被OSO 3 - 组为50〜100％。 根据本发明的硫酸化寡糖可用作药物，特别是用于治疗血管生成，转移和炎症。

公开(公告)号：US07772187B2

公开(公告)日：2010-08-10

申请号：US10901943

申请日：2004-07-28

申请人： Israel Vlodavsky ,  Neta Ilan ,  Flonia Levy-Adam

发明人： Israel Vlodavsky ,  Neta Ilan ,  Flonia Levy-Adam

IPC分类号： A61K38/10 ,  C12N9/24 ,  C07K7/08

CPC分类号： A61K38/47 ,  A61K2039/505 ,  C07K16/40 ,  C07K2317/76 ,  C12N9/2402 ,  C12Y302/01166

摘要： An amino acid sequence derived from the N′ terminus region of the 50 Kd subunit of heparanase, preferably, the sequence including amino acid residues Lys158-Asn171 of human heparanase and any functional fragments thereof. Compositions for the inhibition of heparanase glycosidase catalytic activity, having as an active ingredient an isolated and purified peptide as the amino acid sequence. An antibody directed to the sequence and compositions and uses thereof as heparanase inhibitor. The use of the amino acid sequence in a screening method for specific heparanase inhibitors. Compositions including the heparanase inhibitors and methods for the treatment of heparanase related disorders.

摘要翻译： 衍生自乙酰肝素酶的50Kd亚基的N'末端区域的氨基酸序列，优选包括人肝素酶的氨基酸残基Lys158-Asn171及其任何功能片段的序列。 用于抑制乙酰肝素酶糖苷酶催化活性的组合物，其作为活性成分是分离和纯化的肽作为氨基酸序列。 针对该序列及其组合物的抗体作为乙酰肝素酶抑制剂的用途。 在特异性肝素酶抑制剂的筛选方法中使用氨基酸序列。 组合物，包括乙酰肝素酶抑制剂和治疗乙酰肝素酶相关疾病的方法。