公开(公告)号：WO1997047307A1

公开(公告)日：1997-12-18

申请号：PCT/US1997010262

申请日：1997-06-13

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  TOWNES, Tim, M. ,  CHEN, Wen, Yong ,  BAILEY, Evans, C.

IPC: A61K31/70

CPC classification number: A61K38/12 ,  A61K31/165 ,  A61K31/19

Abstract: The invention provides methods for activating transgene expression by administering histone deacetylase inhibitors, methods for identifying compounds that activate transgene expression, and cells that can be used in these screening methods.

Abstract translation: 本发明提供了通过施用组蛋白脱乙酰酶抑制剂来激活转基因表达的方法，用于鉴定激活转基因表达的化合物的方法，以及可用于这些筛选方法中的细胞。

公开(公告)号：WO1997016221A2

公开(公告)日：1997-05-09

申请号：PCT/IB1996001277

申请日：1996-10-30

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  BUCHSBAUM, Donald, J. ,  RABEN, David ,  KHAZAELI, Mohammad, B. ,  STACKHOUSE, Murray ,  CURIEL, David

IPC: A61N00/00

CPC classification number: A61K51/1036 ,  A61K38/00 ,  A61K38/105 ,  A61K38/1796 ,  A61K48/00 ,  A61K51/08 ,  A61K51/088 ,  A61K51/10 ,  A61K2123/00 ,  C07K14/70503 ,  C07K14/82 ,  C07K16/3007 ,  C07K2317/77

Abstract: The present invention provides a method to achieve radioisotopic localization at tumor sites, i.e., a method of enhancing radiolabeled ligand localization to a tumor in an individual in need of such treatment, comprising the steps of: transducing said tumor with a gene encoding a membrane expressed protein unique to said tumor; and administering to said individual a radiolabeled ligand which specifically binds to said protein. The use of gene therapy technology to induce expression of high affinity membrane molecules/receptors can enhance the specificity of radioisotope localization while the use of radioactive isotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency.

Abstract translation: 本发明提供了一种在肿瘤部位实现放射性同位素定位的方法，即在需要这种治疗的个体中增强放射性标记的配体定位于肿瘤的方法，包括以下步骤：用编码膜表达的基因转导所述肿瘤 所述肿瘤独特的蛋白质; 并向所述个体施用特异性结合所述蛋白质的放射性标记的配体。 使用基因治疗技术诱导高亲和力膜分子/受体的表达可以增强放射性同位素定位的特异性，而使用具有在几个细胞直径上传递辐射损伤的能力的放射性同位素将补偿不到完美的转导效率。

公开(公告)号：WO1995026412A1

公开(公告)日：1995-10-05

申请号：PCT/US1995003742

申请日：1995-03-28

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  CURIEL, David, T. ,  ENGLER, Jeffrey, A.

IPC: C12N15/86

CPC classification number: C12N15/86 ,  A61K48/00 ,  C07K14/005 ,  C07K2319/00 ,  C12N15/87 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2810/40

Abstract: The fiber protein of adenovirus has been genetically altered via attachment at the carboxyl end of a peptide linker, preferably up to 26 amino acids in length which forms a random coil, which can be used to attach a non-adenovirus ligand altering the binding specificity of the fiber protein. Examples of ligands include peptides which are selectively bound by a targeted cell so that the modified fiber protein is internalized by receptor-mediated endocytosis, and peptides which can act as an universal coupling agent, for example, biotin or streptavidin. The linker is designed to not interfere with normal trimerization of fiber protein, to avoid steric hindrance of binding of the fiber protein to a targeted cell, and to serve as a site to introduce new peptide sequence. The modified fiber protein is prepared by genetic engineering of the nucleotide sequence encoding the fiber protein, through the addtion of new sequence at the carboxyl tail-encoding region which encodes the linker and the ligand. The N-terminus of the fiber protein is not altered in the preferred embodiment, although in some embodiments it may be desirable to inhibit uptake by the nucleus of the fiber protein, by deletion of nuclear targeting signals. The modified fiber protein can be utilized as part of a recombinant adenovirus for use in gene therapy.

Abstract translation: 腺病毒的纤维蛋白已经通过在肽接头的羧基末端的连接被遗传改变，优选长达26个氨基酸长度，其形成无规卷曲，其可用于附着非腺病毒配体，其改变结合特异性 纤维蛋白。 配体的实例包括被靶细胞选择性结合以使经修饰的纤维蛋白质被受体介导的内吞作用内化的肽，以及可以作为通用偶联剂例如生物素或链霉亲和素的肽。 接头被设计成不干扰纤维蛋白质的正常三聚，以避免纤维蛋白质与靶细胞结合的空间位阻，并用作引入新肽序列的位点。 通过在编码接头和配体的羧基尾编码区添加新序列，通过编码纤维蛋白的核苷酸序列的遗传工程来制备修饰的纤维蛋白。 在优选的实施方案中，纤维蛋白质的N末端没有改变，尽管在一些实施方案中，可能需要抑制纤维蛋白质的细胞核的摄取，通过核靶向信号的缺失。 修饰的纤维蛋白可用作用于基因治疗的重组腺病毒的一部分。

公开(公告)号：WO1995012400A1

公开(公告)日：1995-05-11

申请号：PCT/US1994011173

申请日：1994-09-30

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  EL KOUNI, Mahmoud, H. ,  NAGUIB, Fardos, N., M. ,  SCHINAZI, Raymond, F.

IPC: A61K31/515

CPC classification number: C07D239/24 ,  C07D239/60

Abstract: Novel compounds are provided that are effective to inhibit the activity of DHUDase or UrdPase. Such compounds have general formula (I) or (II), where X is S or Se; Y is I, F, Cl, Br, methoxy, benzyl, selenenylphenyl, or thiophenyl, and R1 is an acyclo tail having general formula (III), where R2 is H, CH2OH or CH2NH2; R3 is OH, NH2, or OCOCH2CH2CO2H; and R4 is O, S, or CH2. The compounds can be used in pharmaceutical compositions, along with various chemotherapeutic agents to increase the efficacy of the treatment. These compounds can also be used in methods of treating patients by coadministering or sequentially administering the enzyme inhibiting compounds with a chemotherapeutic agent effective to treat cancers, or viral, fungal, bacterial, or parasitic infections. The compounds have further utility in enhancing imaging. Further, they can be administered alone to prevent and/or treat disorders of pyrimidine catabolism and other physiological disorders.

Abstract translation: 提供了有效抑制DHUDase或UrdPase活性的新型化合物。 这些化合物具有通式（I）或（II），其中X是S或Se; Y是I，F，Cl，Br，甲氧基，苄基，硒苯基苯基或噻吩基，R1是具有通式（III）的二环尾，其中R2是H，CH2OH或CH2NH2; R3是OH，NH2或OCOCH2CH2CO2H; R4是O，S或CH2。 该化合物可以与各种化学治疗剂一起用于药物组合物中以增加治疗的功效。 这些化合物也可以用于通过与有效治疗癌症或病毒，真菌，细菌或寄生虫感染的化学治疗剂共同给药或依次施用酶抑制化合物来治疗患者的方法。 这些化合物在增强成像方面具有进一步的实用价值。 此外，它们可以单独施用以预防和/或治疗嘧啶分解代谢紊乱和其他生理障碍。

公开(公告)号：WO1994021118A1

公开(公告)日：1994-09-29

申请号：PCT/US1994003197

申请日：1994-03-24

Applicant: THE UAB RESEARCH FOUNDATION ,  GARVER, Robert, I., Jr. ,  SORSCHER, Eric, J.

Inventor： THE UAB RESEARCH FOUNDATION

IPC: A01N25/26

CPC classification number: C12N15/85 ,  A61K48/00 ,  C12N2840/44

Abstract: A DNA construct for use in treating a human carcinoma is disclosed. The construct includes a cancer-therapeutic gene under the control of a promoter and a group of enhancer sequences which are conserved in 5' flanking regions of the human epithelial cell secretory leukoprotease inhibitor gene and the human epithelial cell cytokeratin gene 8. Also disclosed is a method employing the construct to selectively kill carcinoma cells which are characterized by expression of epithelial cell secretory leukoprotease inhibitor protein in a transformed state, and a method for confirming effective gene delivery to and transcriptional activity in target epithelial cells.

Abstract translation: 公开了用于治疗人类癌症的DNA构建体。 该构建体包括在人上皮细胞分泌型白细胞蛋白酶抑制剂基因和人上皮细胞角蛋白基因8的5'侧翼区中保守的启动子和增强子序列控制下的癌症治疗基因8.还公开了 使用构建体选择性地杀死以转化状态表达上皮细胞分泌型白细胞蛋白酶抑制蛋白为特征的癌细胞的方法，以及确认靶上皮细胞中有效的基因递送和转录活性的方法。

公开(公告)号：WO1991017272A1

公开(公告)日：1991-11-14

申请号：PCT/US1991002798

申请日：1991-04-26

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  DeLUCAS, Lawrence, J. ,  VOLANAKIS, John, E.

IPC: C17N09/64

CPC classification number: C12N9/6424

Abstract: Disclosed are crystals of complement factor D and a method of making them involving diffusing water from an aqueous solution of complement factor D and PEG maintained at a pH of 5.2-7.0.

Abstract translation: 公开了补体因子D的晶体和使它们涉及从维持在pH为5.2-7.0的补体因子D和PEG的水溶液中扩散水的方法。

公开(公告)号：WO1997031124A1

公开(公告)日：1997-08-28

申请号：PCT/US1997002404

申请日：1997-02-18

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  ELGAVISH, Ada

IPC: C12Q01/02

CPC classification number: G01N33/6893 ,  G01N33/5091 ,  G01N2800/34 ,  G01N2800/348

Abstract: The invention provides a method of diagnosing interstitial cystitis comprising the steps of: obtaining primary cultures of urothelial cells from bladder biopsies; selecting urothelial cells of basal type and producing secondary cultures; measuring percentage of single cells and percentage of large colonies in the secondary cultures; determining proliferative ability by measuring percentage of large colonies incorporating bromodeoxyuridine in 1, 2, 3, 4, 5, 6 or more than 6 cells/colony; determining differentiation ability by observing percentages of cells exhibiting different specific characteristics; measuring the percentage of apoptotic cells; measuring the percentage of large colonies that contain 1, 2, 3, 4, 5, 6 or more than 6 apoptotic cells; and comparing the percentage of the colonies to baseline values of the same parameters determined in similarly cultured urothelial cells not suspected of having interstitial cystitis. The figure shows the distribution of colonies of varying size in cultures of bladder epithelial cells from interstitial cystitis patients (IC) and control subjects (control).

Abstract translation: 本发明提供了一种诊断间质性膀胱炎的方法，包括以下步骤：从膀胱活组织检查获得尿路上皮细胞的原代培养物; 选择基底型泌尿生殖细胞，产生二级培养; 测量单细胞的百分比和次要培养物中大菌落的百分比; 通过测量在1,2,3,4,5,6或多于6个细胞/菌落中掺入溴脱氧尿苷的大菌落的百分比来确定增殖能力; 通过观察表现出不同特征特征的细胞的百分比来确定分化能力; 测量凋亡细胞的百分比; 测量含有1,2,3,4,5,6或多于6个凋亡细胞的大菌落百分比; 并将不同怀疑患有间质性膀胱炎的类似培养的尿道上皮细胞中确定的相同参数的基线百分比与基线值进行比较。 该图显示来自间质性膀胱炎患者（IC）和对照受试者（对照）的膀胱上皮细胞培养物中不同大小的菌落的分布。

公开(公告)号：WO1995016787A1

公开(公告)日：1995-06-22

申请号：PCT/US1994013841

申请日：1994-11-16

Applicant: THE UAB RESEARCH FOUNDATION

Inventor： THE UAB RESEARCH FOUNDATION ,  SOLVASON, Nanette, W. ,  KELL, Sherron, H.

IPC: C12Q01/00

CPC classification number: G01N33/56972 ,  G01N33/5091 ,  G01N33/564

Abstract: The present invention makes available diagnostic assays and reagents for facilitating accurate diagnosis and subsequent monitoring of Alzheimer's disease and its progression, as well as determination of stroke occurrence in a patient. As described herein, the percentage T-lymphocytes of a unique T-lymphocyte phenotype (IgM+ T cells) is statistically correlated with Alzheimer's disease as well as the recent occurrence of a stroke.

Abstract translation: 本发明提供用于促进准确诊断和随后监测阿尔茨海默氏病及其进展的诊断测定和试剂，以及确定患者的中风发生。 如本文所述，独特的T淋巴细胞表型（IgM + T细胞）的T淋巴细胞百分比与阿尔茨海默氏病以及最近发生的中风有统计学相关性。

公开(公告)号：WO1995007718A2

公开(公告)日：1995-03-23

申请号：PCT/US1994010130

申请日：1994-09-14

Applicant: THE UAB RESEARCH FOUNDATION ,  SOUTHERN RESEARCH INSTITUTE

Inventor： THE UAB RESEARCH FOUNDATION ,  SOUTHERN RESEARCH INSTITUTE ,  SORSCHER, Eric, J. ,  PARKER, William, B. ,  BENNETT, Leonard, L., Jr.

IPC: A61K48/00

CPC classification number: B82Y5/00 ,  A61K38/45 ,  A61K47/665 ,  A61K47/6899 ,  A61K48/00 ,  C12N9/1077

Abstract: Methods and compositions for killing replicating or non-replicating, targeted mammalian cells and bystander cells, comprising: (a) transfecting or transducing mammalian cells with a nucleic acid encoding a purine analog nucleoside cleavage enzyme, or providing the targeted cells directly with the enzyme; and (b) contacting the targeted cells with a purine analog nucleoside substrate for the enzyme to produce a toxic purine base analog thereby killing the targeted cells and bystander cells. In the present method of killing cells, the enzyme can be an E. coli purine analog nucleoside phosphorylase.

Abstract translation: 用于杀死复制或非复制的靶向哺乳动物细胞和旁观者细胞的方法和组合物，包括：（a）用编码嘌呤类似物核苷切割酶的核酸转染或转导哺乳动物细胞，或直接向酶提供靶细胞; 和（b）使目标细胞与酶的嘌呤类似物核苷底物接触以产生毒性嘌呤碱基类似物，从而杀死靶细胞和旁观者细胞。 在目前杀死细胞的方法中，酶可以是大肠杆菌嘌呤类似物核苷磷酸化酶。

公开(公告)号：WO1995007086A1

公开(公告)日：1995-03-16

申请号：PCT/US1994010208

申请日：1994-09-12

Applicant: EMORY UNIVERSITY ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  THE UAB RESEARCH FOUNDATION

Inventor： EMORY UNIVERSITY ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  THE UAB RESEARCH FOUNDATION ,  SCHINAZI, Raymond, F. ,  SOMMADOSSI, Jean-Pierre ,  IMBACH, Jean-Louis ,  GOSSELIN, Giles

IPC: A61K31/70

CPC classification number: A61K31/70 ,  A61K31/44 ,  A61K31/7068 ,  A61K31/7076 ,  A61K38/21 ,  A61K47/544 ,  A61K2300/00

Abstract: A method for the treatment of a host, and in particular, a human, infected with HBV is provided that includes administering an HBV-treatment amount of a nucleoside of formula (I), (II) or (III), wherein R is hydrogen, fluoro, bromo, chloro, iodo, methyl or ethyl; and R is OH, Cl, NH2, or H; or a pharmaceutically acceptable salt of the compound, optionally in a pharmaceutically acceptable carrier or diluent.

Abstract translation: 提供一种用于治疗感染HBV的宿主，特别是人的方法，其包括施用HBV治疗量的式（I），（II）或（III）的核苷，其中R 1 >是氢，氟，溴，氯，碘，甲基或乙基; 和R 2是OH，Cl，NH 2或H; 或化合物的药学上可接受的盐，任选地在药学上可接受的载体或稀释剂中。