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1. 发明申请

WO1996007322A1 METHOD OF SENSITIZING TUMOR CELLS WITH ADENOVIRUS E1A 审中-公开
标题翻译：用ADENOVIRUS E1A致敏肿瘤细胞的方法
公开(公告)号：WO1996007322A1
公开(公告)日：1996-03-14
申请号：PCT/US1995011342
申请日：1995-09-05
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , FRISCH, Steven, M.
IPC分类号： A01N43/04
CPC分类号： C07K14/005 , A61K38/00 , A61K41/0038 , C12N2710/10322
摘要： The present invention is directed to methods of sensitizing a human tumor cell with adenovirus E1A. The methods involve treating a human tumor cell by, first, introducing into the tumor cell nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cell, and then either contacting the E1A expressing tumor cell with a chemotherapeutic agent or irradiating the E1A-expressing tumor cell. The invention also provides methods of enhancing a subject's response to chemotherapy or irradiation by introducing into a subject's tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cells and finally, administering either a chemotherapeutic agent or irradiation. The invention also provides a method of treating cancer.
摘要翻译：本发明涉及用腺病毒E1A敏化人肿瘤细胞的方法。所述方法包括通过首先将编码具有腺病毒E1A活性的多肽的肿瘤细胞核酸引入细胞中表达E1A活性多肽，然后将表达E1A的肿瘤细胞与化学治疗剂接触或照射表达E1A的肿瘤细胞。本发明还提供了通过将受试者的肿瘤细胞核酸编码为具有腺病毒E1A活性的多肽，在细胞中表达E1A活性多肽，最后施用化学治疗剂或照射，来提供受试者对化疗或照射的反应的方法。本发明还提供了一种治疗癌症的方法。

2. 发明申请

WO1995034661A1 FAS ASSOCIATED PROTEINS 审中-公开
标题翻译： FAS相关蛋白
公开(公告)号：WO1995034661A1
公开(公告)日：1995-12-21
申请号：PCT/US1995007583
申请日：1995-06-14
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , REED, John, C. , SATO, Takaaki
IPC分类号： C12N15/55
CPC分类号： C07K14/4747 , A61K38/00 , C12N9/16 , C12N15/1055 , C12Q1/6897
摘要： The present invention provides mammalian protein tyrosine phosphatases, human PTP-BAS type 4, human PTP-BAS type 5a and mouse PTP-BAS type 5b, each of which is a Fas-associated protein (FAP), nucleic acid molecules encoding a PTP-BAS type 4 or a PTP-BAS type 5 and antibodies specific for a PTP-BAS type 4 or for a PTP-BAS type 5. The invention also provides methods for identifying FAP's, which can associate with Fas and can modulate apoptosis. The invention also provides screening assays for identifying an agent that can effectively alter the association of a FAP with Fas and, therefore, can increase or decrease the level of apoptosis in a cell. The invention further provides methods of modulating apoptosis in a cell by introducing into the cell a nucleic acid molecule encoding a PTP-BAS or fragment of a PTP-BAS or an antisense nucleotide sequence, which is complementary to a portion of a nucleic acid molecule encoding a PTP-BAS. The invention also provides a method of using a reagent that can specifically bind to a FAP to diagnose a pathology that is characterized by an increased or decreased level of apoptosis in a cell. The invention also provides methods of modulating apoptosis in a cell by contacting the cell with an agent that effectively alters the association of a FAT and Fas in a cell or alters the activity of a FAP in a cell.
摘要翻译：本发明提供哺乳动物蛋白酪氨酸磷酸酶，人PTP-BAS型4，人PTP-BAS型5a和小鼠PTP-BAS型5b，其各自是Fas相关蛋白（FAP），编码PTP- BAS型4或PTP-BAS型5和PTP-BAS型4或PTP-BAS型5特异性抗体。本发明还提供鉴定FAP的方法，其可与Fas结合并可调节细胞凋亡。本发明还提供用于鉴定能够有效改变FAP与Fas的缔合的试剂的筛选测定，因此可以增加或降低细胞凋亡水平。本发明还提供了通过向细胞中引入编码PTP-BAS或PTP-BAS或反义核苷酸序列片段的核酸分子来调节细胞凋亡的方法，所述核酸分子与编码的核酸分子的一部分互补一个PTP-BAS。本发明还提供了使用能够特异性结合FAP的试剂来诊断细胞凋亡水平升高或降低的病理学的方法。本发明还提供了通过使细胞与有效改变细胞中FAT和Fas的缔合的试剂接触而改变细胞凋亡的方法或改变细胞中FAP的活性的方法。

3. 发明申请

WO1995014714A1 NOVEL INTEGRIN-BINDING PEPTIDES 审中-公开
标题翻译：新型整合胶原蛋白
公开(公告)号：WO1995014714A1
公开(公告)日：1995-06-01
申请号：PCT/US1994013542
申请日：1994-11-22
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , RUOSLAHTI, Erkki , KOIVUNEN, Erkki
IPC分类号： C07K14/75
CPC分类号： C07K14/70546 , A61K38/00 , A61L27/227 , C07K14/75 , C07K14/78
摘要： This invention is directed to novel integrin-binding peptides. These peptides bind to alpha v- or alpha 5-containing integrins and can exhibit high binding affinity. They contain one of the following sequence motifs: RX1ETX2WX3 [SEQ ID NO: 1] (especially RRETAWA [SEQ ID NO: 8]); RGDGX [SEQ ID NO: 2], in which X is an amino acid with a hydrophobic, aromatic side chain; the double cyclic CX1CRGDCX2C [SEQ ID NO: 15]; and RLD. The peptides generally exhibit their highest binding affinity when they assume a conformationally stabilized configuration. This invention also provides methods of using these peptides.
摘要翻译：本发明涉及新的整联蛋白结合肽。这些肽结合含α-β-或α5的整联蛋白并且可表现出高的结合亲和力。它们包含以下序列基序之一：RX1ETX2WX3 [SEQ ID NO：1]（特别是RRETAWA [SEQ ID NO：8]）; RGDGX [SEQ ID NO：2]，其中X是具有疏水性芳香族侧链的氨基酸; 双循环CX1CRGDCX2C [SEQ ID NO：15]; 和RLD。当肽呈现构象稳定的构型时，肽通常表现出最高的结合亲和力。本发明还提供了使用这些肽的方法。

4. 发明申请

WO1993018139A1 RECOMBINANT CALF INTESTINAL ALKALINE PHOSPHATASE 审中-公开
标题翻译：重组蛋白激酶碱性磷酸酶
公开(公告)号：WO1993018139A1
公开(公告)日：1993-09-16
申请号：PCT/US1993002172
申请日：1993-03-10
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , MILLAN, Jose, L.
IPC分类号： C12N09/16
CPC分类号： C12Q1/42 , C07K2319/00 , C12N9/16 , G01N33/535
摘要： The invention relates to isolated nucleic acids encoding recombinant calf intestinal alkaline phosphatase. Expression vectors and host cells transformed or transfected with such vectors are also provided. The invention further provides multifunctional polypeptides containing amino acid sequences encoding for calf intestinal alkaline phosphatase and a second amino acid sequence encoding a reagent having specific reactivity with a ligand. The recombinant calf intestinal alkaline phosphatase or its active fragments and the multifunctional polypeptides can be used in the methods for determining the presence or concentration of a ligand.
摘要翻译：本发明涉及编码重组小肠肠碱性磷酸酶的分离的核酸。还提供了用这种载体转化或转染的表达载体和宿主细胞。本发明还提供含有编码小肠肠碱性磷酸酶的氨基酸序列的多功能多肽和编码与配体具有特异性反应性的试剂的第二氨基酸序列。重组小牛肠碱性磷酸酶或其活性片段和多功能多肽可用于确定配体存在或浓度的方法中。

5. 发明申请

WO1991009874A1 NOVEL FIBRONECTIN RECEPTOR 审中-公开
标题翻译：新型纤维蛋白受体
公开(公告)号：WO1991009874A1
公开(公告)日：1991-07-11
申请号：PCT/US1991000048
申请日：1991-01-02
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , RUOSLAHTI, Erkki, I. , TARONE, Guido , GIANCOTTI, Filippo, G. , VOGEL, Bruce, E.
IPC分类号： C07K15/06
CPC分类号： C07K14/7055 , A61K38/00
摘要： The present invention provides a substantially pure integrin characterized in that it consists of an αv and a β1 subunit. The receptor binds to fibronectin and GRGDSPK but does not bind to vitronectin. The αvβ1 receptor can be used to determine the presence of fibronectin.

6. 发明申请

WO1990011297A1 HYDROPHOBIC ATTACHMENT SITE FOR ADHESION PEPTIDES 审中-公开
标题翻译：粘合剂的疏水性附着物
公开(公告)号：WO1990011297A1
公开(公告)日：1990-10-04
申请号：PCT/US1990001486
申请日：1990-03-20
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , PIERSCHBACHER, Michael, D. , HONSIK, Cyril, J. , Dreisbach, Lisa, B.
IPC分类号： C07K07/10
CPC分类号： C12N5/0068 , C07K14/78 , C07K17/06 , C12N2533/50
摘要： The invention provides a method of attaching peptides containing a RGD adhesion peptides, to a solid surface through a hydrophobic domain, and peptides so attached. The hydrophobic domain can contain either hydrophobic amino acids, such as leucine, valine, isoleucine or phenylalanine, or fatty acids, such as, for example, myristic acid, palmitic acid, arachidic acid or other fatty acids. Additionally, spacers, such as amino acids, between the hydrophobic domain and the biologically active domain can improve the presentation of the biologically active site. Specific peptides of the invention include GRGDSPASSKG4SRL6RNH2; GRGDSPASSKS3RL6RNH2; AND GRGDSPASSKSSKRL6RNH2. Coupled to a solid surface, such peptides can be used to detect the presence of a ligand complementary to the biologically active site.

7. 发明申请

WO1990002556A1 METHODS FOR MODIFYING THE BINDING OF CELL ADHESION RECEPTORS 审中-公开
标题翻译：修饰细胞粘附受体结合的方法
公开(公告)号：WO1990002556A1
公开(公告)日：1990-03-22
申请号：PCT/US1989003979
申请日：1989-09-13
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , RUOSLAHTI, Erkki, I. , GAILIT, James, O. , GEHLSEN, Kurt, R. , HAUTANEN, Aarno , PIERSCHBACHER, Michael, D.
IPC分类号： A61K33/32
CPC分类号： C07K14/7055 , A61K33/06 , A61K33/24 , G01N33/5306 , G01N33/566
摘要： The present invention provides a method of increasing the binding avidity of integrin cell surface receptors for their ligands by providing the cations. Preferably, the receptor utilized in this method is the fibronectin, vitronectin, laminin, or a collagen receptor, although other integrins can also be used. Among the cations which result in an increase in binding avidity are the cations Mn , Co , Cd and Ni . Gd results in decreased avidity of the fibronectin and vitronectin receptors for their ligands. The method can be employed with a ligand matrix column in order to increase the yield of receptors purified therewith. The invention can also be used to increase the binding of receptors to a substrate, as in an ELISA or radioreceptor assay, and to increase the migration of cells.
摘要翻译：本发明提供了通过提供阳离子增加其配体的整联蛋白细胞表面受体的结合亲合力的方法。优选地，在该方法中使用的受体是纤连蛋白，玻连蛋白，层粘连蛋白或胶原受体，尽管也可以使用其它整联蛋白。导致结合亲和性增加的阳离子是阳离子Mn 2+，Co 2+，Cd 2+和Ni 2+。 Gd <3+>导致纤连蛋白和玻连蛋白受体对其配体的亲合力降低。该方法可以与配体基质柱一起使用，以增加用其纯化的受体的产率。本发明还可用于增加受体与底物的结合，如在ELISA或放射受体测定中，并增加细胞的迁移。

8. 发明申请

WO1996020002A1 IMMOBILIZATION OF PEPTIDES TO HYALURONATE 审中-公开
标题翻译：肽对海洛因的稳定化
公开(公告)号：WO1996020002A1
公开(公告)日：1996-07-04
申请号：PCT/US1995016959
申请日：1995-12-21
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , DICKERSON, Kenneth, T. , GLASS, James, R. , LIU, Lin-Shu , POLAREK, James, W. , CRAIG, William, S. , MULLEN, Daniel, G. , CHENG, Soan
IPC分类号： A61K38/03
CPC分类号： C07K1/1077 , A61K38/00 , C07K14/001 , C07K14/78
摘要： The present invention provides novel conjugates of a synthetic polypeptide containing RGD or (dR)GD and a biodegradable polymer, hyaluronate. The conjugates are prepared by any one of three different methods provided by the present invention: (1) an epoxide method, (2) a sodium periodate method, and (3) a tresyl chloride method. The conjugates prepared by these methods are useful to aid in wound healing and tissue regeneration by providing a temporary matrix for tissue repair. The invention also provides novel RGD-peptides.
摘要翻译：本发明提供了含有RGD或（dR）GD和可生物降解的聚合物透明质酸的合成多肽的新缀合物。通过本发明提供的三种不同方法中的任一种制备共轭物：（1）环氧化物法，（2）高碘酸钠法和（3）甲苯磺酸法。通过这些方法制备的缀合物可用于通过提供用于组织修复的临时基质来帮助伤口愈合和组织再生。本发明还提供新的RGD-肽。

9. 发明申请

WO1996006168A2 RETINOBLASTOMA PROTEIN-INTERACTING ZINC FINGER PROTEINS 审中-公开
标题翻译： RETINOBLASTOMA蛋白相互作用的锌指纹蛋白
公开(公告)号：WO1996006168A2
公开(公告)日：1996-02-29
申请号：PCT/US1995010574
申请日：1995-08-18
申请人： LA JOLLA CANCER RESEARCH FOUNDATION
发明人： LA JOLLA CANCER RESEARCH FOUNDATION , HUANG, Shi
IPC分类号： C12N15/12
CPC分类号： C07K14/4702 , A61K38/00
摘要： The present invention provides mammalian retinoblastoma (Rb)protein-interacting zinc finger (RIZ) proteins, nucleic acid molecules encoding the RIZ and antibodies specific for the RIZ. The invention also provides screening assays for identifying an agent that effectively alters the association of a RIZ with a second molecule, which can bind to the RIZ. The invention also provides active fragments of RIZ containing the PR domain, which can regulate transcription. In addition, the invention provides methods for introducing a nucleic acid molecule encoding a RIZ into a cell and for contacting a cell with an effective agent in order to modulate a function of a cell. Such methods are useful, for example, for inducing growth of a cardiac cell or a neuronal cell in a subject and for effecting normal growth control to a tumor cell or causing differentiation of tumor cells. The invention further provides methods for detecting a RIZ in a sample by detecting the RIZ or a nucleic acid molecule encoding the RIZ. Such methods are useful to diagnose a pathology that is characterized by an increased or decreased level of a RIZ in a cell or by expression of a mutant RIZ in a cell.
摘要翻译：本发明提供哺乳动物视网膜母细胞瘤（Rb）蛋白相互作用的锌指（RIZ）蛋白，编码RIZ的核酸分子和RIZ特异的抗体。本发明还提供用于鉴定有效改变RIZ与可与RIZ结合的第二分子的缔合的试剂的筛选试验。本发明还提供含有PR结构域的RIZ活性片段，其可以调节转录。此外，本发明提供了将编码RIZ的核酸分子引入细胞并使细胞与有效试剂接触以便调节细胞功能的方法。这样的方法可用于例如诱导受试者心脏细胞或神经元细胞的生长，以及对肿瘤细胞进行正常生长控制或引起肿瘤细胞分化。本发明还提供了通过检测RIZ或编码RIZ的核酸分子来检测样品中的RIZ的方法。这样的方法可用于诊断细胞中RIZ水平升高或降低或通过细胞中突变体RIZ的表达而特征化的病理学。

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