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1. 发明申请

WO2012098542A3 METHODS AND KITS FOR ASSESSING HEPARANASE PROCOAGULANT ACTIVITY, COMPOSITIONS COMPRISING HEPARANASE, AND METHODS FOR THE TREATMENT OF COAGULATION-RELATED DISORDERS 审中-公开
标题翻译：用于评估HEPARANASE PROCOAGULANT活性的方法和试剂盒，包含HEPARANASE的组合物和用于治疗凝血相关疾病的方法
公开(公告)号：WO2012098542A3
公开(公告)日：2012-12-06
申请号：PCT/IL2012000027
申请日：2012-01-18
申请人： HEALTH CORP RAMBAM , NADIR YONA , BRENNER BENJAMIN , VLODAVSKY ISRAEL
发明人： NADIR YONA , BRENNER BENJAMIN , VLODAVSKY ISRAEL
IPC分类号： A61K38/36
CPC分类号： G01N33/86 , A61K31/5377 , A61K31/727 , A61K38/08 , A61K38/10 , A61K38/36 , A61K38/47 , A61K38/51 , A61K38/55 , A61K45/06 , C07K14/745 , C07K14/8114 , C12Y302/01166 , G01N2333/924 , A61K2300/00
摘要： The present invention relates to methods and kits for determining heparanase procoagulant activity in a biological sample. The invention also relates to diagnostic methods for the detection and/or monitoring of a coagulation-related pathologic disorder in a mammalian subject. The invention further relates to compositions comprising heparanase and at least one tissue factor, uses and methods based thereon in the treatment, amelioration and prevention of coagulation-related pathologic conditions. The invention still further relates to methods for screening a coagulation modulatory compound, methods and uses based thereon in the treatment, amelioration and prevention of coagulation-related pathologic conditions.
摘要翻译：本发明涉及用于测定生物样品中乙酰肝素酶促凝血活性的方法和试剂盒。本发明还涉及用于在哺乳动物受试者中检测和/或监测凝血相关病理学病症的诊断方法。本发明还涉及包含乙酰肝素酶和至少一种组织因子的组合物，其在治疗，改善和预防凝血相关病理状况中的用途和方法。本发明还涉及凝血调节化合物的筛选方法，其基于治疗，改善和预防凝血相关病理状况的方法和用途。

2. 发明申请

WO2005071070A3 SUBSTANCES DIRECTED AGAINST SPECIFIC SEQUENCE ESSENTIAL FOR HEPARANASE CATALYTIC ACTIVITY END USES THEREOF AS HEPARANASE INHIBITORS 审中-公开
标题翻译：指导针对HEPARANASE催化活性的特异性序列的最终用途的化学物质作为HEPARANASE抑制剂的最终用途
公开(公告)号：WO2005071070A3
公开(公告)日：2006-01-05
申请号：PCT/IL2005000068
申请日：2005-01-20
申请人： HADASIT MED RES SERVICE , VLODAVSKY ISRAEL , ILAN NETA , LEVY-ADAM FLONIA
发明人： VLODAVSKY ISRAEL , ILAN NETA , LEVY-ADAM FLONIA
IPC分类号： A61K20060101 , A61K38/47 , C07K16/40 , C12N9/24
CPC分类号： A61K38/47 , A61K2039/505 , C07K16/40 , C07K2317/76 , C12N9/2402 , C12Y302/01166
摘要： Abstract The present invention relates to amino acid sequences derived from the 50 kDa subunit of heparanase, particularly in the regions between amino acid residues Lys158-Asp171, Gln270 to Lys280 and Lys411 to Arg432 of human heparanase and any functional fragments thereof. Heparin-bindng domains are comprised within said amino acid sequences. The invention further provides compositions for the inhibition of heparanase glycosidase catalytic activity, comprising as active ingredient peptides comprising said amino acid sequences. The invention also provides an antibody directed to said sequences, in particular to the region between Lys158-Asp171, and compositions and uses thereof as heparanase inhibitors. The invention further relates to a screening method for specific heparanase inhibitors and provides compositions comprising said heparanase inhibitors and methods for the treatment of heparanase related disorders.
摘要翻译：摘要本发明涉及衍生自乙酰肝素酶的50kDa亚基的氨基酸序列，特别是在人类肝素酶的Lys158-Asp171，Gln270至Lys280和Lys411至Arg432的氨基酸残基之间的区域及其任何功能片段。肝素结合域包含在所述氨基酸序列内。本发明还提供了用于抑制乙酰肝素酶糖苷酶催化活性的组合物，其包含作为活性成分的包含所述氨基酸序列的肽。本发明还提供了针对所述序列的抗体，特别是针对Lys158-Asp171之间的区域的抗体，以及作为肝素酶抑制剂的组合物及其用途。本发明还涉及特异性肝素酶抑制剂的筛选方法，并提供了包含所述乙酰肝素酶抑制剂的组合物和用于治疗乙酰肝素酶相关病症的方法。

3. 发明申请

WO2004048558A3 HEPARANASE MEDIATED CELL ADHESION AND USES THEREOF 审中-公开
标题翻译：肝素酶介导的细胞粘附及其用途
公开(公告)号：WO2004048558A3
公开(公告)日：2004-07-22
申请号：PCT/IL0300989
申请日：2003-11-24
申请人： HADASIT MED RES SERVICE , VLODAVSKY ISRAEL , ZECHARIA EYAL , GOLDSHMIDT ORIT , ILAN NETA
发明人： VLODAVSKY ISRAEL , ZECHARIA EYAL , GOLDSHMIDT ORIT , ILAN NETA
IPC分类号： A61K38/00 , A61L31/00 , C12N9/24 , C12N15/56 , C12Q1/34 , C12N9/26 , A61K38/47
CPC分类号： C12Y302/01166 , A61K38/00 , A61L31/005 , C12N9/2402 , C12Q1/34 , C12Y302/01031 , G01N2333/924 , G01N2500/10
摘要： The present invention relates to a nucleic acid construct comprising a polynucleotide sequence encoding a heparanase-derived polypeptide having cell-to-cell and cell-to-matrix adhesive properties and being devoid of heparanase catalytic activity. The invention further relates to expression vectors, and host cells expressing said adhesion promoting non-catalytic heparanase molecule and to the promotion of adhesion by using such non-catalytic heparanase. More particularly, the invention relates to the use of the adhesion promoting non-catalytic heparanase molecules for enhancing cell-to-cell and cell-to-matrix adhesion in a tissue sealant composition and in implantable medical devices. The invention further provides methods of treatment of adhesion-related pathologies.
摘要翻译：本发明涉及包含编码乙酰肝素酶衍生多肽的多核苷酸序列的核酸构建体，所述多肽具有细胞与细胞和细胞与基质的粘附特性并且不含乙酰肝素酶催化活性。本发明进一步涉及表达载体和表达所述粘附促进非催化乙酰肝素酶分子的宿主细胞，以及通过使用这种非催化乙酰肝素酶促进粘附。更具体地说，本发明涉及粘附促进非催化乙酰肝素酶分子用于增强组织密封剂组合物和植入式医疗装置中的细胞与细胞和细胞与基质的粘附。本发明进一步提供了治疗粘连相关病变的方法。

4. 发明申请

WO2004006949A1 METHODS AND COMPOSITIONS FOR REGULATION OF MAMMALIAN HAIR GROWTH 审中-公开
标题翻译：调控MAMMALIAN头发生长的方法和组合物
公开(公告)号：WO2004006949A1
公开(公告)日：2004-01-22
申请号：PCT/IL2003/000571
申请日：2003-07-10
申请人： HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD. , ZECHARIA, Eyal , METZGER, Shula , CHAJEK-SHAUL, Tova , VLODAVSKY, Israel , ELKIN, Michael
发明人： ZECHARIA, Eyal , METZGER, Shula , CHAJEK-SHAUL, Tova , VLODAVSKY, Israel , ELKIN, Michael
IPC分类号： A61K38/47
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/05 , A01K2227/10 , A01K2227/105 , A01K2267/02 , A01K2267/03 , A61K8/66 , A61K38/47 , A61K48/00 , A61Q7/00 , C12N9/2402 , C12Y302/01166
摘要： The invention relates to a method for regulating mammalian hair growth which is effected by regulating the differentiation and maturation of hair follicles and regulating the duration of active growth phase (anagen). The method of the invention comprises the step of modulating the levels, activity and/or expression of heparanase in cells of keratinocyte lineage and/or in cells of mesenchimal origin, so as to enhance or inhibit hair growth. The invention further provides for methods for the treatment of subjects suffering from primary or secondary alopecia and for compositions and uses of heparanase in the regulation of mammalian hair growth.
摘要翻译：本发明涉及调节哺乳动物毛发生长的方法，其通过调节毛囊的分化和成熟以及调节活性生长期（生长期）的持续时间来实现。本发明的方法包括调节角质形成细胞谱系细胞和/或间质起源的细胞中乙酰肝素酶的水平，活性和/或表达的步骤，以增强或抑制毛发生长。本发明还提供了治疗患有原发性或继发性脱发的受试者的方法以及用于调控哺乳动物毛发生长中的乙酰肝素酶的组合物和用途的方法。

5. 发明申请

WO2003059355A1 QUINAZOLINONE COMPOUNDS IN COMBINED MODALITIES FOR IMPROVED CANCER TREATMENT 审中-公开
标题翻译：用于改善癌症治疗的组合模式中的喹哪啶酮化合物
公开(公告)号：WO2003059355A1
公开(公告)日：2003-07-24
申请号：PCT/IL2002/001055
申请日：2002-12-30
申请人： HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD. , INSTITUTE OF ANIMAL SCIENCE, AGRICULTURAL RESEARCH ORG. , COLLGARD BIOPHARMACEUTICALS LTD. , PINES, Mark , VLODAVSKY, Israel , NAGLER, Arnon , YARKONI, Shai
发明人： VLODAVSKY, Israel , NAGLER, Arnon , YARKONI, Shai
IPC分类号： A61K31/517
CPC分类号： A61K45/06 , A61K31/517 , A61K2300/00
摘要： The present invention provides compositions and methods for improving the effectiveness of anti-tumor treatments. The compositions of the present invention comprise quinazolinones, specifically halofuginone. In currently preferred embodiments the compositions and methods of the present invention improve the effectiveness of radiation therapy and chemotherapy, and concomitantly alleviate or prevent the damage induced by radiation therapy.
摘要翻译：本发明提供了用于提高抗肿瘤治疗效果的组合物和方法。本发明的组合物包含喹唑啉酮，特别是卤夫酮。在目前优选的实施方案中，本发明的组合物和方法提高了放射治疗和化疗的有效性，并且同时缓解或预防了由放射治疗引起的损伤。

6. 发明申请

WO9823244A2 INTRACORONARY STENTS CONTAINING QUINAZOLINONE DERIVATIVES 审中-公开
标题翻译：含有喹唑啉酮衍生物的神经瘤
公开(公告)号：WO9823244A2
公开(公告)日：1998-06-04
申请号：PCT/US9715254
申请日：1997-08-14
申请人： AGRICULTURAL RES ORG , HADASIT MED RES SERVICE , DAVIDSON CLIFFORD M , NAGLER ARNON , SLAVIN SHIMON , HAZUM ELI , VLODAVSKY ISRAEL , GELLER EHUD , PINES MARK
发明人： DAVIDSON CLIFFORD M , NAGLER ARNON , SLAVIN SHIMON , HAZUM ELI , VLODAVSKY ISRAEL , GELLER EHUD , PINES MARK
IPC分类号： C07D401/06 , A61F2/06 , A61F2/82 , A61K31/506 , A61L27/00 , A61L31/10 , A61L31/16 , A61P9/00 , A61K
CPC分类号： A61L31/10 , A61F2/82 , A61K31/506 , A61L31/16 , A61L2300/216 , A61L2300/416 , A61L2300/606 , C08L31/04
摘要： The invention provides an intracoronary stent coated with a quinazolinone derivative of formula (I), wherein n is 1 or 2, R1 is a member 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, and physiologically acceptable salts thereof, for preventing restenosis after angioplasty.
摘要翻译：本发明提供涂覆有式（I）的喹唑啉酮衍生物的冠状动脉内支架，其中n为1或2，R 1为氢，卤素，硝基，苯并，低级烷基，苯基和低级烷氧基的成员; R2是由羟基，乙酰氧基和低级烷氧基组成的组的成员，R3是氢和低级烯氧基 - 羰基的成员及其生理上可接受的盐，用于防止血管成形术后的再狭窄。

7. 发明申请

WO2002024863A3 AVIAN AND REPTILE DERIVED POLYNUCLEOTIDE ENCODING A POLYPEPTIDE HAVING HEPARANASE ACTIVITY 审中-公开
公开(公告)号：WO2002024863A3
公开(公告)日：2002-03-28
申请号：PCT/IL2001/000864
申请日：2001-09-12
申请人： INSIGHT STRATEGY AND MARKETING LTD. , HADASIT MEDICAL RESEARCH SERVICES AND DEVELOPMENT LTD. , GOLDSHMIDT, Orit , PECKER, Iris , VLODAVSKY, Israel , MICHAL, Israel , ZCHARIA, Eyal
发明人： GOLDSHMIDT, Orit , PECKER, Iris , VLODAVSKY, Israel , MICHAL, Israel , ZCHARIA, Eyal
IPC分类号： C12N9/00
摘要： Avian and reptile derived heparanase and nucleic acids encoding same.

9. 发明申请

WO1996001648A1 ATTENUATION OF WOUND HEALING PROCESSES 审中-公开
标题翻译：创伤治疗过程的衰退
公开(公告)号：WO1996001648A1
公开(公告)日：1996-01-25
申请号：PCT/US1995008608
申请日：1995-07-07
申请人： IBEX TECHNOLOGIES R AND D, INC. , ZIMMERMANN, Joseph , VLODAVSKY, Israel , BENNETT, D., Clark , DANAGHER, Pamela , BROUGHTON, Richard
发明人： IBEX TECHNOLOGIES R AND D, INC.
IPC分类号： A61K38/51
CPC分类号： A61K38/51 , Y10S530/825
摘要： Glycosaminoglycans, including heparinases 1, 2 and 3 as well as chondroitinases AC and B from the Gram negative bacteria Flavobacterium heparinum, can be used either separately or in combination to manipulate cell proliferation. In one embodiment, heparinases are administered to degrade heparan sulfate components of the extracellular matrix, thereby allowing the heparin binding growth factors which are stored in the extracellular matrix to migrate to adjacent cells. The mobility of chemoattractant agents, growth factors and cells also can be increased by treating tissues with glycosaminoglycan degrading enzymes, both chondroitinases and heparinases. The enzymatic removal of chondroitin sulfates from cell surfaces effectively increases the availability of growth factor receptors on the cell's surface. Selectively removing heparan sulfate from cell surfaces while leaving the extracellular matrix intact, conversely, inhibits cell proliferation by down regulating the cell's response to growth factors. This is achieved by targeting heparin or heparan sulfate degrading activites to the cell surface. Targeting the heparin degrading activity can be achieved by genetically engineering a ligand binding functionality into the heparinase proteins, or by physically controlling the localized enzyme concentration through the method of administration.
摘要翻译：糖胺聚糖，包括肝素酶1,2和3以及来自革兰氏阴性细菌肝炎黄杆菌的软骨素酶AC和B可以单独使用或组合使用以操纵细胞增殖。在一个实施方案中，施用肝素酶以降解细胞外基质的硫酸乙酰肝素成分，从而使存储在细胞外基质中的肝素结合生长因子迁移至相邻细胞。通过用糖胺聚糖降解酶（软骨素酶和肝素酶）处理组织，也可以增加化学引诱剂，生长因子和细胞的流动性。从细胞表面去除硫酸软骨素有效地增加细胞表面上生长因子受体的可用性。从细胞表面选择性地去除硫酸乙酰肝素，同时使细胞外基质保持完整，相反地，通过下调细胞对生长因子的反应来抑制细胞增殖。这是通过将肝素或硫酸乙酰肝素降解活性靶向细胞表面来实现的。靶向肝素降解活性可以通过将配体结合功能遗传工程化成肝素酶蛋白质，或通过通过施用方法物理控制局部酶浓度来实现。

10. 发明申请

WO9524907A3 PHARMACEUTICAL COMPOSITIONS CONTAINING LAMINARIN SULFATE 审中-公开
标题翻译：含有LAMINARIN SULFATE的药物组合物
公开(公告)号：WO9524907A3
公开(公告)日：1995-11-09
申请号：PCT/GB9500515
申请日：1995-03-10
申请人： HADASIT MED RES SERVICE , WHALLEY KEVIN , VLODAVSKY ISRAEL , MIAO HUA QUAN
发明人： VLODAVSKY ISRAEL , MIAO HUA-QUAN
IPC分类号： A61K20060101 , A61K31/725
CPC分类号： A61K31/715
摘要： The invention provides a pharmaceutical composition comprising sodium laminarin sulfate for mimicking heparin activity and for therapeutic use instead of heparin, in preventing restenosis by the inhibition of vascular smooth muscle cell proliferation; in accelerating wound healing by activating the release of active growth factors stored in the extra-cellular matrix; and for inhibiting tumor cell metastasis by inhibition of heparanase activity. The pharmaceutical composition includes a pharmaceutically effective amount of sodium laminarin sulfate, in combination with a pharmaceutically acceptable carrier, and wherein the molar ratio of sulfate groups to monosaccharide units in said laminarin sulfate is at least 1:1.

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