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1. 发明申请

WO2004005348A1 SOLUBLE FORM OF CARBONIC ANHYDRASE IX (s-CA IX), ASSAYS TO DETECT s-CA IX AND CA IX's COEXPRESSION WITH HER-2/neu/c-erbB-2 审中-公开
标题翻译：碳水化合物IX（s-CA IX）的可溶形式，用于检测s-CA IX和CA IX与HER-2 / neu / c-erbB-2的共表达的测定
公开(公告)号：WO2004005348A1
公开(公告)日：2004-01-15
申请号：PCT/US2003/005137
申请日：2003-02-22
申请人： BAYER CORPORATION , INSTITUTE OF VIROLOGY , ZAVADA, Jan , PASTOREKOVA, Silvia , PASTOREK, Jaromir , ZAVADOVA, Zuzanna
发明人： ZAVADA, Jan , PASTOREKOVA, Silvia , PASTOREK, Jaromir , ZAVADOVA, Zuzanna
IPC分类号： C07K16/18
CPC分类号： C07K16/32 , C07K16/40 , C07K2317/14 , C07K2317/30 , C07K2317/56 , C07K2317/622 , C12N9/88 , G01N2333/82
摘要： Disclosed herein among other MN/CA IX-related inventions is the discovery of a soluble MN/CA IX (s-CA IX) in body fluids, such as, urine and serum. Said s-CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycanlike (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons (kd) upon Western blot. A smaller s-CA IX form of about 20 to about 30 kd comprising the CA domain or parts thereof, not linked to the PG domain, has also been found in body fluids. Also disclosed are diagnostic/prognostic methods for precancer and cancer that detect or detect and quantitate said s-CA IX in body fluids, particularly the CA IX extracellular domain comprising the PG and CA domains having a molecular weight of about 50/54 kd. Also disclosed herein is the coexpression of CA IX and HER-2/neu/c-erbB-2 that provides parallel, alternative and potentially synergistic diagnostic/prognostic and therapeutic strategies for pre-cancer and cancer.
摘要翻译：本文中披露的其他MN / CA IX相关发明是在体液（例如尿液和血清）中发现可溶性MN / CA IX（s-CA IX）。所述s-CA IX包含CA IX的胞外结构域或其部分。主要的s-CA IX物质是包含蛋白多糖样（PG）结构域和碳酸酐酶（CA）结构域的胞外结构域，并且在Western印迹时具有约50/54千道尔顿（kd）的分子量。还在体液中发现包含CA结构域或其部分的未连接到PG结构域的约20至约30kd的较小的s-CA IX形式。还公开了用于检测或检测和定量体液中的所述s-CA IX的预癌和癌症的诊断/预后方法，特别是包含分子量为约50/54kd的PG和CA结构域的CA IX细胞外结构域。本文还公开了CA IX和HER-2 / neu / c-erbB-2的共表达，其为前癌和癌症提供平行，替代和潜在的协同诊断/预后和治疗策略。

2. 发明申请

WO2004048544A2 CA IX-SPECIFIC INHIBITORS 审中-公开
标题翻译： CA IX特异性抑制剂
公开(公告)号：WO2004048544A2
公开(公告)日：2004-06-10
申请号：PCT/US0337783
申请日：2003-11-26
申请人： BAYER HEALTHCARE , INST VIROLOGY , SUPURAN CLAUDIU , SCOZZAFAVA ANDREA , PASTOREKOVA SILVIA , PASTOREK JAROMIR
发明人： SUPURAN CLAUDIU , SCOZZAFAVA ANDREA , PASTOREKOVA SILVIA , PASTOREK JAROMIR
IPC分类号： A61K31/18 , A61K31/4155 , A61K31/428 , A61K31/47 , A61K31/505 , C07D417/12 , C12N9/88 , C12Q1/527 , C12N
CPC分类号： C07D417/12 , A61K31/18 , A61K31/4155 , A61K31/428 , A61K31/47 , A61K31/505 , C12N9/88 , C12Q1/527
摘要： Therapeutic methods for inhibiting the growth of preneoplastic/ neoplastic vertebrate cells that abnormally express MN protein are disclosed. Screening assays are provided for identifying compounds, preferably membraneimpermeant compounds, which inhibit the enzymatic activity of MN protein/ polypeptides and that are useful for treating patients with preneoplastic/neoplastic disease. Further methods are disclosed for the preparation of positively-charged, membrane-impermeant heterocyclic sulfonamide CA inhibitors with high affinity for the membrane-bound carbonic anhydrase CA IX. Preferred CA IX-specific inhibitors are aromatic and heterocylic sulfonamides, preferably that are membraneimpermeant. Particularly preferred CA IX-specific inhibitors are pyridinium derivatives of such aromatic and heterocyclic sulfonamides. The CA IX-specific inhibitors of the invention can also be used diagnostically/prognostically for preneoplastic/neoplastic disease, and for imaging use, for example, to detect precancerous cells, tumors and/or metastases. The CA IX-specific inhibitors can be labelled or conjugated to radioisotopes for radiotherapy. The CA IX-specific inhibitors may be combined with conventional therapeutic anticancer drugs, with other different inhibitors of cancer-related pathways, with bioreductive drugs, or with radiotherapy to enhance the efficiency of each treatment. The CA IX-specific inhibitors may also be combined with CA IX-specific antibodies, preferably monoclonal antibodies or biologically active antibody fragments, more preferably humanized or fully human CA IX monoclonal antibodies or biologically active fragments or such monoclonal antibodies. Still further, the CA IX-specific inhibitors can be used for gene therapy coupled to vectors for targeted delivery to preneoplastic/neoplastic cells expressing CA IX on their surfaces.
摘要翻译：公开了用于抑制异常表达MN蛋白的肿瘤前/新生脊椎动物细胞生长的治疗方法。筛选测定法用于鉴定抑制MN蛋白质/多肽的酶活性并可用于治疗癌前/肿瘤疾病的化合物，优选膜渗透性化合物。公开了另外的方法用于制备对膜结合的碳酸酐酶CA IX具有高亲和力的带正电的，膜不可渗透的杂环磺酰胺CA抑制剂。优选的CA IX-特异性抑制剂是芳香族和杂环磺酰胺，优选是膜渗透性的。特别优选的CA IX-特异性抑制剂是这种芳族和杂环磺酰胺的吡啶鎓衍生物。本发明的CA IX-特异性抑制剂还可用于诊断/预后用于肿瘤前/肿瘤疾病，以及用于成像用途，例如用于检测癌前细胞，肿瘤和/或转移灶。 CA IX特异性抑制剂可以被标记或与放射性同位素缀合用于放疗。 CA IX特异性抑制剂可与常规治疗性抗癌药物，其他不同的癌症相关途径抑制剂，生物还原药物或放射疗法联合使用以提高每种治疗的效率。 CA IX特异性抑制剂还可以与CA IX特异性抗体，优选单克隆抗体或生物活性抗体片段，更优选人源化或完全人源CA IX单克隆抗体或生物活性片段或此类单克隆抗体组合。此外，CA IX特异性抑制剂可用于与载体偶联的基因治疗，用于靶向递送至在其表面上表达CA IX的肿瘤前/肿瘤细胞。

3. 发明申请

WO2005037083A2 MN/CA IX AND CANCER PROGNOSIS 审中-公开
标题翻译： MN / CA IX和癌症预测
公开(公告)号：WO2005037083A2
公开(公告)日：2005-04-28
申请号：PCT/US2004/034573
申请日：2004-10-18
申请人： BAYER HEALTHCARE , INSTITUTE OF VIROLOGY , EBERT, Matthias , ROCKEN, Christoph , PASTOREKOVA, Silvia , ZAVADA, Jan , PASTOREK, Jaromir
发明人： EBERT, Matthias , ROCKEN, Christoph , PASTOREKOVA, Silvia , ZAVADA, Jan , PASTOREK, Jaromir
IPC分类号： A61B
CPC分类号： G01N33/5748 , C07K14/82 , C12N9/88 , C12Q1/6886 , C12Q2600/118 , C12Q2600/154 , G01N33/57484 , G01N2333/82
摘要： Herein disclosed are methods that are prognostic for neoplastic/preneoplastic disease in a subject vertebrate, wherein said disease is associated with a tissue that normally expresses MN, but which MN expression is lost or diminished upon carcinogenesis. Exemplary of the types of preneoplastic/neoplastic diseases subject to the prognostic methods of this invention are those of gastric mucosa, gallbladder, biliary ducts, and ductal cells of duodenal glands. An exemplary prognostic method comprises comparing the level of MN gene expression product in a tissue sample from the affected subject, with the average MN gene expression product level found in analogous preneoplastic/neoplastic tissue samples; an above average MN gene expression product level indicates poorer prognosis for the subject. MN gene expression products useful in the prognostic methods include MN protein, MN polypeptide, and/or MN nucleic acids.
摘要翻译：本文公开的是对于受试脊椎动物中的肿瘤/肿瘤前疾病预后的方法，其中所述疾病与正常表达MN的组织相关，但是其在癌症发生时丧失或减少了MN表达。受本发明预后方法支配的肿瘤前/肿瘤疾病类型的实例是十二指肠腺的胃粘膜，胆囊，胆管和导管细胞的类型。示例性预后方法包括将来自受影响的受试者的组织样品中的MN基因表达产物的水平与类似的肿瘤前/新生物组织样品中发现的平均MN基因表达产物水平进行比较; 高于平均MN基因表达产物水平表明对象的预后较差。用于预后方法的MN基因表达产物包括MN蛋白，MN多肽和/或MN核酸。

4. 发明申请

WO2011098610A1 CARBONIC ANHYDRASE INHIBITORS 审中-公开
标题翻译：碳酸酐酶抑制剂
公开(公告)号：WO2011098610A1
公开(公告)日：2011-08-18
申请号：PCT/EP2011/052156
申请日：2011-02-14
申请人： UNIVERSITA DEGLI STUDI DI FIRENZE , UNIVERSITETET I OLSO , UNIVERSITY OF MANCHESTER , EBBESEN, Peter , SUPURAN, Claudiu T. , SCOZZAFAVA, Andrea , PETTERSEN, Erik Olai , WILLIAMS, Kaye , PASTOREKOVA, Silvia , DUBOIS, Ludwig , LAMBIN, Philippe
发明人： EBBESEN, Peter , SUPURAN, Claudiu T. , SCOZZAFAVA, Andrea , PETTERSEN, Erik Olai , WILLIAMS, Kaye , PASTOREKOVA, Silvia , DUBOIS, Ludwig , LAMBIN, Philippe
IPC分类号： A61K31/18 , A61P35/00 , C07C311/00
CPC分类号： A61K49/0021 , C07C307/02 , C07C307/10 , C07C335/18 , C07C2601/14
摘要： A carbonic anhydrase IX (CA IX) inhibitor which comprises a compound of general formula: R-NH-CX-NH-(CH 2 ) n -Ar-Q-SO 2 -NH 2 or a pharmaceutically-acceptable salt, derivative or prodrug thereof; wherein n = 0, 1 or 2; Q is O or NH; X is O or S; and R comprises an organic substituent group.
摘要翻译：包含通式为：R-NH-CX-NH-（CH2）n-Ar-Q-SO2-NH2的化合物或其药学上可接受的盐，衍生物或前药的碳酸酐酶IX（CA IX）抑制剂; 其中n = 0,1或2; Q是O或NH; X为O或S; R包含有机取代基。

5. 发明申请

WO2004048544A3 CA IX-SPECIFIC INHIBITORS 审中-公开
公开(公告)号：WO2004048544A3
公开(公告)日：2004-06-10
申请号：PCT/US2003/037783
申请日：2003-11-26
申请人： BAYER HEALTHCARE , INSTITUTE OF VIROLOGY , SUPURAN, Claudiu , SCOZZAFAVA, Andrea , PASTOREKOVA, Silvia , PASTOREK, Jaromir
发明人： SUPURAN, Claudiu , SCOZZAFAVA, Andrea , PASTOREKOVA, Silvia , PASTOREK, Jaromir
IPC分类号： A61K31/18
摘要： Therapeutic methods for inhibiting the growth of preneoplastic/ neoplastic vertebrate cells that abnormally express MN protein are disclosed. Screening assays are provided for identifying compounds, preferably membraneimpermeant compounds, which inhibit the enzymatic activity of MN protein/ polypeptides and that are useful for treating patients with preneoplastic/neoplastic disease. Further methods are disclosed for the preparation of positively-charged, membrane-impermeant heterocyclic sulfonamide CA inhibitors with high affinity for the membrane-bound carbonic anhydrase CA IX. Preferred CA IX-specific inhibitors are aromatic and heterocylic sulfonamides, preferably that are membraneimpermeant. Particularly preferred CA IX-specific inhibitors are pyridinium derivatives of such aromatic and heterocyclic sulfonamides. The CA IX-specific inhibitors of the invention can also be used diagnostically/prognostically for preneoplastic/neoplastic disease, and for imaging use, for example, to detect precancerous cells, tumors and/or metastases. The CA IX-specific inhibitors can be labelled or conjugated to radioisotopes for radiotherapy. The CA IX-specific inhibitors may be combined with conventional therapeutic anticancer drugs, with other different inhibitors of cancer-related pathways, with bioreductive drugs, or with radiotherapy to enhance the efficiency of each treatment. The CA IX-specific inhibitors may also be combined with CA IX-specific antibodies, preferably monoclonal antibodies or biologically active antibody fragments, more preferably humanized or fully human CA IX monoclonal antibodies or biologically active fragments or such monoclonal antibodies. Still further, the CA IX-specific inhibitors can be used for gene therapy coupled to vectors for targeted delivery to preneoplastic/neoplastic cells expressing CA IX on their surfaces.

6. 发明申请

WO2003100029A3 MN/CA IX-SPECIFIC MONOCLONAL ANTIBODIES GENERATED FROM MN/CA IX-DEFICIENT MICE AND METHODS OF USE 审中-公开
公开(公告)号：WO2003100029A3
公开(公告)日：2003-12-04
申请号：PCT/US2003/005136
申请日：2003-02-22
申请人： BAYER HEALTHCARE , INSTITUTE OF VIROLOGY , PASTOREK, Jaromir , PASTOREKOVA, Silvia , ZATOVICOVA, Miriam , ZAVADA, Jan , ORTOVA GUT, Marta
发明人： PASTOREK, Jaromir , PASTOREKOVA, Silvia , ZATOVICOVA, Miriam , ZAVADA, Jan , ORTOVA GUT, Marta
IPC分类号： C12N5/20
摘要： Disclosed herein among other MN/CA IX-related inventions are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Subsets of the new antibodies are to either the proteoglycan-like (PG) domain or to the carbonic anhydrase (CA) domain of MN/CA IX, and methods are provided by which antibodies can be prepared to the other MN/CA IX domains. Such new MN/CA IX-specific antibodies, fragments and variants are useful diagnostically/prognostically and therapeutically for cancer and precancer. Particularly preferred are the new monoclonal antibodies, fragments and variants that are specific for the non-immunodominant epitopes of MN/CA IX, which antibodies are, among other uses, useful to detect soluble MN/CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.

7. 发明申请

WO2003100029A2 MN/CA IX-SPECIFIC MONOCLONAL ANTIBODIES GENERATED FROM MN/CA IX-DEFICIENT MICE AND METHODS OF USE 审中-公开
标题翻译： MN / CA IX特异性单克隆抗体从MN / CA IX缺陷小鼠产生及其使用方法
公开(公告)号：WO2003100029A2
公开(公告)日：2003-12-04
申请号：PCT/US2003/005136
申请日：2003-02-22
申请人： BAYER CORPORATION , INSTITUTE OF VIROLOGY , PASTOREK, Jaromir , PASTOREKOVA, Silvia , ZATOVICOVA, Miriam , ZAVADA, Jan , ORTOVA GUT, Marta
发明人： PASTOREK, Jaromir , PASTOREKOVA, Silvia , ZATOVICOVA, Miriam , ZAVADA, Jan , ORTOVA GUT, Marta
IPC分类号： C12N
CPC分类号： A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , C07K16/32 , C07K16/40 , C12N9/88 , C12N15/8509
摘要： Disclosed herein among other MN/CA IX-related inventions are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, preferably monoclonal antibodies and immunoreactive fragments and engineered variants thereof. Subsets of the new antibodies are to either the proteoglycan-like (PG) domain or to the carbonic anhydrase (CA) domain of MN/CA IX, and methods are provided by which antibodies can be prepared to the other MN/CA IX domains. Such new MN/CA IX-specific antibodies, fragments and variants are useful diagnostically/prognostically and therapeutically for cancer and precancer. Particularly preferred are the new monoclonal antibodies, fragments and variants that are specific for the non-immunodominant epitopes of MN/CA IX, which antibodies are, among other uses, useful to detect soluble MN/CA IX (s-CA IX) in body fluids, alone but preferably in combination with antibodies specific to the immunodominant epitopes of MN/CA IX, for example, in a sandwich assay.
摘要翻译：本文中披露的其它MN / CA IX相关发明是由MN / CA IX缺陷型小鼠产生的新的MN / CA IX特异性抗体，优选单克隆抗体及其免疫反应性片段及其工程变体。新抗体的亚群是MN / CA IX的蛋白聚糖样（PG）结构域或碳酸酐酶（CA）结构域，并提供可以将抗体制备到其他MN / CA IX结构域的方法。这种新的MN / CA IX特异性抗体，片段和变体在癌症和癌前期在诊断/预后和治疗上是有用的。特别优选的是对于MN / CA IX的非免疫显性表位特异的新单克隆抗体，片段和变体，该抗体在其他用途中可用于检测体内可溶性MN / CA IX（s-CA IX）流体，但优选与MN / CA IX的免疫显性表位特异的抗体组合，例如在夹心测定中。

8. 发明申请

WO0024913A3 MN GENE AND PROTEIN 审中-公开
标题翻译： MN基因和蛋白质
公开(公告)号：WO0024913A3
公开(公告)日：2000-09-14
申请号：PCT/US9924879
申请日：1999-10-22
申请人： BAYER AG , INST VIROLOGY , ZAVADA JAN , PASTOREKOVA SILVIA , PASTOREK JAROMIR
发明人： ZAVADA JAN , PASTOREKOVA SILVIA , PASTOREK JAROMIR
IPC分类号： G01N33/566 , A61K38/00 , A61K39/395 , A61K48/00 , A61P35/00 , C07K7/06 , C07K14/47 , C07K14/82 , C12N9/88 , C12N15/09 , C12Q1/02 , C12R1/91 , C07K16/40
CPC分类号： C07K7/06 , C07K14/82 , C12N9/88
摘要： Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter, and which vectors preferably further encode a cytokine. The MN gene promoter is characterized, and the binding site for a repressor of MN transcription is disclosed.
摘要翻译：本文所确定的是MN蛋白结合位点的位置，以及用固定的MN蛋白竞争与脊椎动物细胞附着的MN蛋白质/多肽。这样的MN蛋白/多肽防止细胞粘附和细胞间接触的形成。 MN蛋白结合位点是可被有机或无机分子，优选有机分子，更优选特异性结合该位点的蛋白质/多肽阻断的治疗靶标。公开了抑制异常表达MN蛋白的肿瘤前/肿瘤脊椎动物细胞生长的治疗方法。提供编码MN-特异性抗体的可变结构域的载体和分离这些结构域的柔性接头多肽。公开了编码与MN基因启动子可操作地连接的细胞毒性蛋白/多肽的其它载体，并且哪些载体优选进一步编码细胞因子。表征MN基因启动子，并公开MN转录抑制子的结合位点。

9. 发明申请

WO2012093340A3 VIRAL DIAGNOSTICS 审中-公开
标题翻译：病毒诊断
公开(公告)号：WO2012093340A3
公开(公告)日：2012-12-13
申请号：PCT/IB2012000293
申请日：2012-01-06
申请人： BIOSCIENCE SLOVAKIA , TOMASKOVA JANA , KOPACEK JURAJ , PASTOREK JAROMIR , PASTOREKOVA SILVIA
发明人： TOMASKOVA JANA , KOPACEK JURAJ , PASTOREK JAROMIR , PASTOREKOVA SILVIA
IPC分类号： C12Q1/70 , G01N33/569
CPC分类号： C12Q1/701 , C07K16/10 , G01N33/56983
摘要： The present disclosure provides methods for determining whether a subject is infected with lymphocytic choriomeningitis virus (LCMV). These methods include obtaining a sample from a subject with increased susceptibility to LCMV infection, contacting the sample with one or more compositions for detecting LCMV, and determining whether the one or more compositions for detecting LCMV is associated with a marker of LCMV from the sample, wherein detection of an association indicates that that the subject is infected with LCMV.
摘要翻译：本公开提供了用于确定受试者是否感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）的方法。这些方法包括从具有增加的LCMV感染易感性的受试者获得样品，使样品与用于检测LCMV的一种或多种组合物接触，以及确定用于检测LCMV的一种或多种组合物是否与来自样品的LCMV标记物相关联，其中关联的检测表明受试者被LCMV感染。

10. 发明申请

WO2012093340A2 VIRAL DIAGNOSTICS 审中-公开
标题翻译：病毒诊断
公开(公告)号：WO2012093340A2
公开(公告)日：2012-07-12
申请号：PCT/IB2012/000293
申请日：2012-01-06
申请人： BIOSCIENCE SLOVAKIA , TOMASKOVA, Jana , KOPACEK, Juraj , PASTOREK, Jaromir , PASTOREKOVA, Silvia
发明人： TOMASKOVA, Jana , KOPACEK, Juraj , PASTOREK, Jaromir , PASTOREKOVA, Silvia
IPC分类号： C12Q1/70 , C12Q1/68
CPC分类号： C12Q1/701 , C07K16/10 , G01N33/56983
摘要： The present disclosure provides methods for determining whether a subject is infected with lymphocytic choriomeningitis virus (LCMV). These methods include obtaining a sample from a subject with increased susceptibility to LCMV infection, contacting the sample with one or more compositions for detecting LCMV, and determining whether the one or more compositions for detecting LCMV is associated with a marker of LCMV from the sample, wherein detection of an association indicates that that the subject is infected with LCMV.
摘要翻译：本公开提供了用于确定受试者是否感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）的方法。这些方法包括从具有增加的LCMV感染易感性的受试者获得样品，使样品与用于检测LCMV的一种或多种组合物接触，以及确定用于检测LCMV的一种或多种组合物是否与来自样品的LCMV标记物相关联，其中关联的检测表明受试者被LCMV感染。

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