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41. 发明申请

WO1994014471A1 METHODS AND COMPOSITIONS FOR INHIBITION OF HEPATIC CLEARANCE OF TISSUE-TYPE PLASMINOGEN ACTIVATOR 审中-公开
标题翻译：用于抑制组织型PLASMINOGEN激活剂的HEPATIC CLEARANCE的方法和组合物
公开(公告)号：WO1994014471A1
公开(公告)日：1994-07-07
申请号：PCT/US1993012380
申请日：1993-12-17
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , SCHWARTZ, Alan, L. , BU, Guojun
IPC分类号： A61K37/47
CPC分类号： C07K14/705 , A61K38/00 , C07K14/47
摘要： Methods and compositions for inhibiting the hepatic clearance of tissue-type plasminogen activator (t-PA) in vivo by administering a t-PA-hepatic clearance-inhibiting amount of 39kDa protein or a t-PA-hepatic clearance-inhibiting fragment thereof, or genetically or chemically modified forms of the 39kDa protein or fragments thereof are described. Compositions for treatment of thrombolytic diseases comprised of t-PA and a t-PA-hepatic clearance-inhibiting effective amount of 39kDa protein, a t-PA-hepatic clearance inhibiting fragment thereof, and genetically or chemically modified forms of the 39kDa protein or its fragments are described.
摘要翻译：通过施用t-PA-肝清除抑制量的39kDa蛋白质或其t-PA-肝脏清除抑制片段或在其中抑制组织型纤溶酶原激活物（t-PA）的肝脏清除的方法和组合物，或描述39kDa蛋白或其片段的遗传或化学修饰形式。用于治疗溶栓性疾病的组合物，其包含t-PA和t-PA-肝清除抑制有效量的39kDa蛋白质，其t-PA-肝脏清除抑制片段，以及遗传或化学修饰形式的39kDa蛋白或其描述片段。

42. 发明申请

WO1993017103A1 TIGHTLY REGULATED EXPRESSION SYSTEM FOR EUCARYOTIC CELLS 审中-公开
标题翻译：用于真核细胞的轻度调节表达系统
公开(公告)号：WO1993017103A1
公开(公告)日：1993-09-02
申请号：PCT/US1993002085
申请日：1993-02-24
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , THACH, Robert, E.
IPC分类号： C12N15/00
CPC分类号： C12N15/85 , C12N2830/002 , C12N2830/50 , C12N2830/85 , C12N2840/002 , C12N2840/105
摘要： The invention relates to an expression system which permits control of the levels of protein produced, and optionally provides production of the mature form of the protein directly. The expression systems of the invention include the desired gene downstream of a first DNA which comprises the reverse transcript of the iron-responsive element (IRE) and a second DNA which is the reverse transcript of a portion of the mRNA of an iron-responsive message corresponding to ferritin light chain-derived helping element. These reverse transcripts are operatively linked to a transcriptional promoter which may also be inducible. The expression system is useful, especially, for the production of toxic proteins since protein production can be delayed until desired.
摘要翻译：本发明涉及允许控制产生的蛋白质水平的表达系统，并且任选地直接提供成熟形式的蛋白质的产生。本发明的表达系统包括第一DNA下游所需的基因，其包含铁响应元件（IRE）的逆转录物和作为铁响应信息的mRNA的一部分的逆转录物的第二DNA 对应于铁蛋白轻链衍生的辅助元素。这些逆转录物可操作地连接到也可诱导的转录启动子。表达系统特别适用于生产毒性蛋白质，因为蛋白质生产可以延迟至所需。

43. 发明申请

WO1993004202A1 POLYNUCLEOTIDE PROBES FOR SALMONELLA 审中-公开
标题翻译：沙门氏菌的多核苷酸探针
公开(公告)号：WO1993004202A1
公开(公告)日：1993-03-04
申请号：PCT/US1992006984
申请日：1992-08-19
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , GALAN, Jorge , CURTISS, Roy, III
IPC分类号： C12Q01/68
CPC分类号： C12Q1/689
摘要： Polynucleotide probes and primers derived from the Salmonella typhimurium inv genes are described. These polynucleotides can be used as universal probes and primers to detect the presence or absence of Salmonella nucleotide sequences in a biological sample.
摘要翻译：描述了源自鼠伤寒沙门氏菌inv基因的多核苷酸探针和引物。这些多核苷酸可用作通用探针和引物以检测生物样品中沙门氏菌核苷酸序列的存在或不存在。

44. 发明申请

WO1993003137A1 HUMAN SUBSTANCE P RECEPTOR 审中-公开
标题翻译：人体物质受体
公开(公告)号：WO1993003137A1
公开(公告)日：1993-02-18
申请号：PCT/US1992006532
申请日：1992-08-05
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , KRAUSE, James, E.
IPC分类号： C12N01/20
CPC分类号： C07K14/70571
摘要： The disclosure describes the isolation, characterization and cDNA coding the human substance P receptor, the primary structure of the receptor protein, and a CHO cell line transformed with a DNA expression vector containing a cDNA encoding the human substance P receptor.
摘要翻译：本公开描述了人体物质P受体的分离，表征和cDNA编码，受体蛋白质的一级结构以及用含有编码人物质P受体的cDNA的DNA表达载体转化的CHO细胞系。

45. 发明申请

WO1992008486A1 AVIRULENT MICROBES AND USES THEREFOR: SALMONELLA TYPHI 审中-公开
标题翻译：微生物及其用途：SALMONELLA TYPHI
公开(公告)号：WO1992008486A1
公开(公告)日：1992-05-29
申请号：PCT/US1991008376
申请日：1991-11-08
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , CURTISS, Roy, III , KELLY, Sandra, M.
IPC分类号： A61K39/112
CPC分类号： C12R1/42 , A61K39/00 , A61K39/0275 , A61K2039/522 , C07K14/255 , C12N15/01 , Y02A50/407 , Y02A50/482 , Y02A50/484
摘要： This invention provides immunogenic compositions for the immunization of a vertebrate or invertebrate comprising an avirulent derivative of S. typhi. The derivatives having a mutation of the cya and/or crp and/or cdt genes. The invention also provides immunogenic compositions for the immunization of a vertebrate and invertebrate comprising an avirulent derivative of the above type which is capable of expressing a recombinant gene derived from a pathogen of said vertebrate or invertebrate individual to produce an antigen capable of inducing an immune response against said pathogen. Other embodiments of the invention include methods of preparing immunogenic compositions from these strains, and strains useful in the preparation of the immunogenic compositions, as well as methods of stimulating the immune system to respond to an immunogenic antigen of S. typhi by administration of the immunogenic composition.
摘要翻译：本发明提供了用于免疫含脊椎动物或无脊椎动物的免疫原性组合物，其包含伤寒沙利氏菌的无毒性衍生物。具有cya和/或crp和/或cdt基因突变的衍生物。本发明还提供用于免疫脊椎动物和无脊椎动物的免疫原性组合物，其包含上述类型的无毒力衍生物，其能够表达源自所述脊椎动物或无脊椎动物个体的病原体的重组基因以产生能够诱导免疫应答的抗原针对所述病原体。本发明的其它实施方案包括从这些菌株制备免疫原性组合物的方法，以及可用于制备免疫原性组合物的菌株，以及通过施用免疫原性刺激免疫系统对伤寒沙门氏菌的免疫原性抗原作出反应的方法组成。

46. 发明申请

WO1991006317A1 CROSS-PROTECTIVE SALMONELLA VACCINES 审中-公开
标题翻译：交叉保护性沙门氏菌疫苗
公开(公告)号：WO1991006317A1
公开(公告)日：1991-05-16
申请号：PCT/US1990006503
申请日：1990-11-02
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , CURTISS, Roy, III , MUNSON, MARYANN
IPC分类号： A61K39/112
CPC分类号： A61K39/0275 , A61K2039/522 , Y02A50/482
摘要： Vaccines are provided for treatment of individuals for infections by gram negative bacteria. The vaccines are comprised of live avirulent Salmonella which are able to induce immunity to homologous and to heterologous Salmonella serotypes, and to other gram-negative enteric bacteria. The Salmonella of which the vaccine is comprised possess at least one mutation in a gene which globally regulates other genes, and which also possess a mutation in at least one other of the following type: a mutation either in a gene encoding an enzyme in a lipopolysaccharide synthesis, which results in a reversibly rough phenotype; or in a gene which regulates the synthesis of iron-regulated OMPs, such that the mutation leads to constitutive expression of these proteins. Strains useful for the production of these vaccines are also provided.
摘要翻译：提供疫苗用于治疗革兰氏阴性细菌感染的个体。疫苗由无活力的沙门氏菌组成，能够诱导对同源和异源沙门氏菌血清型的免疫，以及其他革兰氏阴性肠细菌。包含疫苗的沙门氏菌在全球调节其他基因的基因中具有至少一个突变，并且还具有至少另一种以下类型的突变：编码脂多糖中的酶的基因中的突变合成，导致可逆的粗糙表型; 或在调节铁调节的OMP的合成的基因中，使得突变导致这些蛋白质的组成型表达。还提供了可用于生产这些疫苗的菌株。

47. 发明申请

WO1991002262A1 MAGNETIC RESONANCE RF PROBE WITH ELECTROMAGNETICALLY ISOLATED TRANSMITTER AND RECEIVER COILS 审中-公开
标题翻译：磁电谐振射频探头与电磁隔离发射器和接收器线圈
公开(公告)号：WO1991002262A1
公开(公告)日：1991-02-21
申请号：PCT/US1990004324
申请日：1990-08-07
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , ACKERMAN, Joseph, J., H. , CHEN, Wei
IPC分类号： G01R33/34
CPC分类号： G01R33/3657 , G01R33/341 , G01R33/3621
摘要： An RF probe (20) for use in magnetic resonance applications includes a transmitter coil (24) for transmitting RF energy to excite a specimen (34) and a receiver coil (28) for sensing the RF energy absorbed or emitted by the specimen (34) wherein the receiver coil (28) is electrically decoupled from the transmitter coil (24) through the geometrical shape and positioning of the receiver coil (28) with respect to the transmitter coil (24). The technique includes the concept of physically locating multiple elements of either a transmitter or receiver coil in a non-orthogonal manner such that the net current induced in the receiver coil (28) is equal to zero. In another embodiment, the receiver coil (28) has a primary coil loop (32) for placement immediately adjacent a specimen (34) and a secondary coil loop (30), said receiver coil loops (30, 32) being anti-phase and connected in series and wherein the secondary receiver coil loop (30) may be angularly rotated with respect to the transmit coil (24) in order to achieve a zero net induced current. In still another embodiment, the receiver coil (28) element has a pair of parallel connected anti-phase coil elements (30, 32) and the primary coil element (32) for placement immediately adjacent the specimen (34) has a reduced inductance.

48. 发明申请

WO1989003427A1 A METHOD OF MAINTAINING A DESIRED RECOMBINANT GENE IN A GENETIC POPULATION OF CELLS 审中-公开
标题翻译：维持细胞遗传群体中所需重组基因的方法
公开(公告)号：WO1989003427A1
公开(公告)日：1989-04-20
申请号：PCT/US1988003496
申请日：1988-10-06
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , CURTISS Ray, III
IPC分类号： C12N15/00
CPC分类号： C12N9/0008 , A61K39/04 , A61K2039/523 , C07K14/315 , C07K14/35 , C12N15/00 , C12N15/68 , C12R1/42 , C12Y102/01011 , Y02A50/484
摘要： The invention encompasses methods of maintaining desired recombinant genes in a genetic population of cells expressing the recombinant gene. The methods utilize mutant cells which are characterized by a lack of a functioning native gene encoding an enzyme which is essential for cell survival, wherein this enzyme catalyses a step in the biosynthesis of an essential cell wall structural component and the presence of a first recombinant gene encoding an enzyme which is a functional replacement for the native enzyme, wherein the first recombinant gene cannot replace the defective chromosomal gene. The first recombinant gene is structurally linked to a second recombinant gene encoding a desired product. Loss of the first recombinant gene causes the cells to lyse when the cells are in an environment where a product due to the expression of the first recombinant gene is absent. The invention also encompasses methods of creating and isolating mutant cells with the above characteristics. The cells of the invention are useful for commercial production of desired products, for components of vaccines for immunizing individuals, and for release into the environment.
摘要翻译：本发明包括在表达重组基因的细胞的遗传群体中维持所需重组基因的方法。该方法利用突变细胞，其特征在于缺乏编码细胞存活所必需的酶的功能性天然基因，其中该酶催化必需细胞壁结构组分的生物合成和第一重组基因的存在编码作为天然酶的功能性替代物的酶，其中第一重组基因不能代替有缺陷的染色体基因。第一重组基因在结构上与编码所需产物的第二重组基因连接。当细胞处于不存在第一重组基因表达的产物的环境中时，第一重组基因的损失导致细胞裂解。本发明还包括产生和分离具有上述特征的突变细胞的方法。本发明的细胞可用于商业生产所需产品，用于免疫个体的疫苗的组分和用于释放到环境中。

49. 发明申请

WO1988009667A1 METHOD TO ISOLATE CELL CLUSTERS OF CELLS SUBTYPES FROM ORGANS 审中-公开
标题翻译：分离细胞细胞群的方法
公开(公告)号：WO1988009667A1
公开(公告)日：1988-12-15
申请号：PCT/US1988001933
申请日：1988-06-08
申请人： WASHINGTON UNIVERSITY
发明人： WASHINGTON UNIVERSITY , LACY, Paul, E. , SCHARP, David, W. , RICORDI, Camillo
IPC分类号： A61K37/00
CPC分类号： C12M45/09
摘要： A method to obtain purified, well defined cell populations from intact organs by digestion of the distended organ with suitable proteolytic enzymes in the main lower chamber (101) of the isolator and harvest of cell subpopulation by screening the effluent from treatment of the organ with physiologically compatible medium by a filtration screen (104) permitting the passage of desired cells into the conical upper chamber (105) converging to an outlet port (106), but preventing the passage of larger particles. In this manner, the physical/mechanical disruption of the cell population is unnecessary because of recircularization of the media by input ports (103) which is aided by agitation enhancers (102). The cells are eased out of their structural matrix and harvested directly. Application of this method to the preparation of purified islets of Langerhans from intact pancreas is described.

50. 发明申请

WO1998012309A2 METHOD OF CELL SURFACE ACTIVATION AND INHIBITION 审中-公开
标题翻译：细胞表面活化和抑制方法
公开(公告)号：WO1998012309A2
公开(公告)日：1998-03-26
申请号：PCT/US1997016216
申请日：1997-09-15
申请人： WASHINGTON UNIVERSITY , GOLDBERG, Gregory, I.
发明人： WASHINGTON UNIVERSITY
IPC分类号： C12N09/64
CPC分类号： C12N9/6491 , C12N9/6489
摘要： Disclosed are methods of cell surface activation and inhibition that involve the interaction of an inhibitor of matrix metalloprotease known as TIMP-2, with the enzyme, gelatinase-A (GelA). Critical to the methods of the invention is the discovery of a unique TIMP-2 binding site on the surface of the C-terminal domain (GelA-CTD) of the enzyme, which has been determined to be Asp , but which can also include other residues in the Ge1A-CTD domain with which Asp forms a contiguous surface, namely Gly , Phe , and Tyr . Identification of this binding site provides a useful target for the screening of MMP inhibitors and for prognosis and treatment of diseases in which MMPs are implicated. Compounds which are candidate MMP inhibitors can be structured to competitively inhibit cell surface activation.
摘要翻译：公开了涉及称为TIMP-2的基质金属蛋白酶抑制剂与酶，明胶酶-A（GelA）的相互作用的细胞表面活化和抑制的方法。本发明方法的关键在于已经确定为Asp <656>的酶的C末端结构域（GelA-CTD）的表面上发现了独特的TIMP-2结合位点，但是可以还包括其中Asp <656>形成邻接表面的Ge1A-CTD结构域中的其他残基，即Gly 651，Phe 650和Tyr 636。该结合位点的鉴定提供了用于筛选MMP抑制剂以及预后和治疗涉及MMP的疾病的有用靶标。作为候选MMP抑制剂的化合物可以结构化以竞争性地抑制细胞表面活化。

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