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41. 发明申请

WO1985000832A1 PRODUCTION OF STREPTOCOCAL M PROTEIN IMMUNOGENS AND MOLECULAR PROBES 审中-公开
标题翻译：生产角蛋白M蛋白质免疫调节因子和分子探针
公开(公告)号：WO1985000832A1
公开(公告)日：1985-02-28
申请号：PCT/US1984001261
申请日：1984-08-09
申请人： THE ROCKEFELLER UNIVERSITY , EMORY UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , EMORY UNIVERSITY , SCOTT, June, R. , FISCHETTI, Vincent, A.
IPC分类号： C12P21/00
CPC分类号： C07K14/315 , A61K39/00 , C12N15/70 , C12Q1/689 , Y10S530/806
摘要： Methods and compositions for the cloning and expression of Streptococcus pyogenes M protein genes, and, in particular, types 5, 6 and 24 gene in single-cell host organisms. The streptococcal M protein produced by the recombinant DNA techniques described herein may be formulated for use as immunogens in vaccines to protect against S. pyogenes infections. The gene for the M protein may further be employed as a molecular probe for the accurate identification of streptococci in infected body tissues and fluids.

42. 发明申请

WO1998029547A1 MODULATORS OF RADIAL GLIA-ASTROCYTE DIFFERENTIATION AND TRANSFORMATION, AND DIAGNOSTIC AND THERAPEUTIC USES THEREOF 审中-公开
标题翻译：径向玻璃体分化和转化的调节剂及其诊断和治疗用途
公开(公告)号：WO1998029547A1
公开(公告)日：1998-07-09
申请号：PCT/US1997023818
申请日：1997-12-31
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , HATTEN, Mary, E. , HUNTER, Kim, E.
IPC分类号： C12N15/12
CPC分类号： C07K14/4702 , A61K38/00
摘要： Modulators of radial glia-astrocyte differentiation and transformation comprising a secreted radial glial differentiation factor have been identified, isolated, purified and characterized. This radializing factor, herein called RF60, possesses an apparent molecular weight of approximately 60kD and functions as a radial glial maintenance signal, with the availability of the protein regulating the phenotype of cortical glia. RF60 can be utilized to reverse the glial scarring occurring during CNS trauma, and thus reverse the glia to their pre-event stage. RF60 can thus be utilized to induce cells to return to their embryonic form, and regenerate normally so as to provide treatment of brain or spinal cord injury or surgery, treatment of neurological disorders or diseases where there has been a diminution of the normal activity of the brain or central nervous system, such as dementia, Alzheimer's Disease, multiple sclerosis, and situations where regeneration of brain or central nervous system tissue is therapeutic, such as surgery, trauma, stroke due to ischemic or hemorrhagic occurrences, bacterial and viral infections, neoplasms, and the like.
摘要翻译：已经鉴定，分离，纯化和表征了包含分泌的径向胶质细胞分化因子的放射性神经胶质细胞分化和转化的调节剂。这种称为RF60的这种径向化因子具有约60kD的表观分子量，并且作为调节皮层神经胶质表型的蛋白质的可用性起到径向胶质维持信号的作用。 RF60可用于逆转CNS创伤期间发生的胶质瘢痕，从而将神经胶质反转到其事件前阶段。因此，RF60可以用于诱导细胞返回其胚胎形式，并且正常再生，以提供治疗脑或脊髓损伤或手术，治疗神经障碍或疾病，其中已经减少了正常的活动脑或中枢神经系统，例如痴呆，阿尔茨海默病，多发性硬化，以及脑或中枢神经系统组织再生治疗的情况，例如手术，创伤，由缺血性或出血性发作引起的中风，细菌和病毒感染，肿瘤，等等。

43. 发明申请

WO1997029182A1 METHOD AND COMPOSITIONS FOR OBTAINING MATURE DENDRITIC CELLS 审中-公开
标题翻译：用于获得成熟细胞的方法和组合物
公开(公告)号：WO1997029182A1
公开(公告)日：1997-08-14
申请号：PCT/US1997002110
申请日：1997-02-10
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , STEINMAN, Ralph, M. , BHARDWAJ, Nina , SCHULER, Gerald
IPC分类号： C12N05/08
CPC分类号： C12N5/0639 , A61K38/00 , A61K2039/5154 , C12N2501/22 , C12N2501/23 , C12N2502/11
摘要： We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or "priming" phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or "differentiation" phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derived from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.
摘要翻译：我们描述了一种用于从人血液中的非增殖祖细胞产生大量成熟树突状细胞的改进方法。第一步或“引发”阶段是补充有GM-CSF和IL-4的培养基中产生未成熟树突状细胞的T细胞耗尽的单核细胞的培养物。第二步或“分化”阶段需要暴露于树突状细胞成熟因子如单核细胞条件培养基。使用这种两步法，可以获得显着的产量。来自该方法的树突状细胞具有成熟细胞的所有特征。它们包括星状细胞形状，不粘附于塑料，以及非常强的T细胞刺激活性。根据本发明产生的成熟树突状细胞可用于激活T细胞。

44. 发明申请

WO1997012050A1 METHOD FOR TRANSFERRING GENES TO THE HEART USING AAV VECTORS 审中-公开
标题翻译：使用AAV矢量将基因转移到心脏的方法
公开(公告)号：WO1997012050A1
公开(公告)日：1997-04-03
申请号：PCT/US1996015446
申请日：1996-09-26
申请人： THE ROCKEFELLER UNIVERSITY , KAPLITT, Martin, J. , DIETHRICH, Edward, B.
发明人： THE ROCKEFELLER UNIVERSITY , KAPLITT, Michael, G.
IPC分类号： C12N15/86
CPC分类号： C12N15/86 , A61K48/00 , C12N2750/14143
摘要： The invention relates to the use of adeno-associated virus vectors for the transfer of genes to the heart and vasculature. The vector preferably contains a gene encoding a protein which improves heart and vascular function during heart failure. In a specific embodiment, the vector is introduced into the heart and vasculature via a catheter, with the aid of fluoroscopy. The method and vectors for use therein provide for safe and stable gene expression of the transferred genes.
摘要翻译：本发明涉及腺相关病毒载体用于将基因转移到心脏和脉管系统中的用途。载体优选含有编码在心力衰竭期间改善心脏和血管功能的蛋白质的基因。在一个具体实施方案中，借助于荧光透视，通过导管将载体引入心脏和脉管系统。其中使用的方法和载体提供了转移基因的安全和稳定的基因表达。

45. 发明申请

WO1996030038A1 PEPTIDE GROWTH FACTOR HAVING EPIDERMAL INDUCING ACTIVITY 审中-公开
标题翻译：具有皮膜诱导活性的肽生长因子
公开(公告)号：WO1996030038A1
公开(公告)日：1996-10-03
申请号：PCT/US1996004326
申请日：1996-03-29
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , HEMMATI-BRIVANLOU, Ali , WILSON, Paul
IPC分类号： A61K38/18
CPC分类号： A61K38/1875 , A61L27/60 , C07K14/51
摘要： The invention relates to a method for suppressing autoneuralization and inducing epidermis using a peptide growth factor which is a gene product of a member of the TGF- beta gene family. The method is useful in wound healing, skin culture technology, and treatment of tumors derived from neural tissue.
摘要翻译：本发明涉及一种使用作为TGF-β基因家族成员的基因产物的肽生长因子来抑制自发性和诱导表皮的方法。该方法可用于伤口愈合，皮肤培养技术和治疗由神经组织衍生的肿瘤。

46. 发明申请

WO1996010086A1 GLYCOSYLTRANSFERASES FOR BIOSYNTHESIS OF OLIGOSACCHARIDES, AND GENES ENCODING THEM 审中-公开
标题翻译：用于生产低聚糖的糖苷酶及其编码基因
公开(公告)号：WO1996010086A1
公开(公告)日：1996-04-04
申请号：PCT/US1995012317
申请日：1995-09-25
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , GOTSCHLICH, Emil, C.
IPC分类号： C12N15/54
CPC分类号： C07K14/22 , C12N9/1048 , C12N9/1051 , C12P19/18
摘要： The present invention is directed to nucleic acids encoding glycosyltransferases, the proteins encoded thereby, and to methods for synthesizing oligosaccharides using the glycosyltransferases of the invention. In a specific embodiment, a glycosyltransferase locus of Neisseria gonorrhoeae containing five open reading frames for five different glycosyltransferases. The functionally active glycosyltransferases of the invention are characterized by catalyzing reactions such as adding Gal beta 1}4 to GlcNAc or Glc; adding Ga1NAc or GlcNAc beta 1}3 to Gal; and adding Gal alpha 1}4 to Gal. The glycosyltransferases of the invention are particularly suited to the syntheses of the oligosaccharides Gal beta 1}4G1cNAc beta 1}3Gal beta 1}4Glc (a mimic of lacto-N-neotetraose), GalNAc beta 1}3Gal beta 1}4GlcNAc beta 1}3Gal beta 1}4Glc beta 1}4 (a mimic ganglioside), and Gal alpha 1}4Gal beta 1}4Glc beta 1}4Hep}R (a mimic of the saccharide portion of globoglycolipids).
摘要翻译：本发明涉及编码糖基转移酶的核酸，由此编码的蛋白质，以及使用本发明的糖基转移酶合成寡糖的方法。在一个具体实施方案中，包含五个不同糖基转移酶的五个开放阅读框的淋病奈瑟氏球菌的糖基转移酶基因座。本发明的功能活性糖基转移酶的特征在于催化反应，例如向GlcNAc或Glc加入Galβ1} 4; 向Gal加入Ga1NAc或GlcNAcβ1} 3; 并加入Galα1} 4。本发明的糖基转移酶特别适用于低聚糖Galβ1} 4G1cNAcβ1}3Galβ1} 4Glc（乳糖N-新四糖的模拟物），GalNAcβ1}3Galβ1}4GlcNAcβ1} 3Gal beta 1} 4Glc beta 1} 4（模拟神经节苷脂）和Galα1} 4Gal beta 1} 4Glcβ1} 4Hep} R（模拟糖胶体的糖部分）。

47. 发明申请

WO1995034289A1 COMPOSITIONS FOR NEUTRALIZATION OF LIPOPOLYSACCHARIDES 审中-公开
标题翻译：用于中性脂多糖的组合物
公开(公告)号：WO1995034289A1
公开(公告)日：1995-12-21
申请号：PCT/US1995007903
申请日：1995-06-07
申请人： THE ROCKEFELLER UNIVERSITY , WRIGHT, Samuel, D. , WURFEL, Mark, M. , HAILMAN, Peter, Eric
发明人： THE ROCKEFELLER UNIVERSITY
IPC分类号： A61K09/127
CPC分类号： C07K14/47 , A61K9/127 , A61K9/1275 , G01N33/92 , G01N2333/5412 , G01N2400/50 , Y10S436/811
摘要： The present invention relates to compositions and methods for neutralizing lipopolysaccharide, and treatment of gram-negative sepsis based thereon. Accordingly, the invention is directed to a composition of homogeneous particles comprising phospholipids and a lipid exchange protein, such as phospholipid transfer protein or LPS binding protein. The lipid exchange protein is characterized by being capable of faciliting an exchange of lipopolysaccharide into the particles. In a specific embodiment, exemplified herein, the lipid particles are high density lipoprotein particles comprising apolipoprotein A-I (apo A-I), a phospholipid, and cholesterol or a lipid bilayer binding derivative thereof. In a specific example, the phospholipid is phosphatidylcholine (PC). In a specific example, the ratio of phosphatidylcholine: cholesterol: apolipoprotein A-I is approximately 80:4:1. The level of LPS exchange protein activity in a sample from a patient provides a diagnostic, monitoring, or prognostic indicator for a subject with endotoxemia, gram-negative sepsis, or septic shock.
摘要翻译：本发明涉及中和脂多糖的组合物和方法，以及基于其的革兰氏阴性败血症的治疗。因此，本发明涉及包含磷脂和脂质交换蛋白如磷脂转移蛋白或LPS结合蛋白的均匀颗粒的组合物。脂质交换蛋白的特征在于能够促进脂多糖进入颗粒的交换。在本文示例的具体实施方案中，脂质颗粒是包含载脂蛋白A-1（载脂蛋白A-I），磷脂和胆固醇或其脂双层结合衍生物的高密度脂蛋白颗粒。在具体实例中，磷脂是磷脂酰胆碱（PC）。在一个具体实例中，磷脂酰胆碱：胆固醇：载脂蛋白A-I的比率为约80:4:1。来自患者的样品中LPS交换蛋白活性的水平为内毒素血症，革兰氏阴性脓毒症或败血性休克的受试者提供诊断，监测或预后指标。

48. 发明申请

WO1995028960A1 GROUP A STREPTOCOCCAL POLYSACCHARIDE IMMUNOGENIC COMPOSITIONS AND METHODS 审中-公开
标题翻译：组A多糖多糖免疫组化和方法
公开(公告)号：WO1995028960A1
公开(公告)日：1995-11-02
申请号：PCT/US1995004973
申请日：1995-04-20
申请人： THE ROCKEFELLER UNIVERSITY , NORTH AMERICAN VACCINE, INC.
发明人： THE ROCKEFELLER UNIVERSITY , NORTH AMERICAN VACCINE, INC. , BLAKE, Milan, S. , ZABRISKIE, John, B. , TAI, Joseph, Y. , MICHON, Francis
IPC分类号： A61K39/09
CPC分类号： A61K39/092 , A61K9/1271 , A61K2039/55505 , A61K2039/55555 , A61K2039/6037 , Y10S424/831
摘要： This invention provides a novel immunogenic composition and vaccine, processes for producing them and methods for immunization against infections and disease caused by group A Streptococci. The compositions include group A streptococcal polysaccharide covalently linked to protein or liposomes to form immunogenic conjugates. The method of immunization for this invention comprises administering to an individual an immunogenic amount of group A polysaccharide. The group A polysaccharide may be administered as a vaccine either on its own, conjugated to proteins or conjugated to liposomes. Additionally, the group A polysaccharides may be associated with an adjuvant. This invention is particularly useful for providing both active and passive immunogenic protection for those populations most at risk of contracting group A Streptococcal infections and disease namely adults, pregnant women and in particular infants and children.
摘要翻译：本发明提供了一种新型的免疫原性组合物和疫苗，其制备方法以及针对由A组链球菌引起的感染和疾病的免疫方法。组合物包括与蛋白质或脂质体共价连接以形成免疫原性缀合物的A组链球菌多糖。本发明的免疫方法包括向个体施用免疫原性量的A组多糖。 A组多糖可以单独作为疫苗施用，与蛋白缀合或与脂质体缀合。另外，A组多糖可以与佐剂结合。本发明特别可用于为那些最具有承担A型链球菌感染和疾病风险的群体，即成年人，孕妇，特别是婴儿和儿童提供主动和被动免疫原性保护。

49. 发明申请

WO1995028409A1 PROCESS, APPARATUS AND REAGENTS FOR ISOLATING CELLULAR COMPONENTS 审中-公开
标题翻译：用于分离细胞成分的方法，装置和试剂
公开(公告)号：WO1995028409A1
公开(公告)日：1995-10-26
申请号：PCT/US1995004586
申请日：1995-04-13
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , FISCHETTI, Vincent, A. , CHEUNG, Ambrose
IPC分类号： C07H01/08
CPC分类号： C12N1/06 , C12N15/1003 , C12N15/1006
摘要： A reagent, method and container for the isolation of cellular components such as ribonucleic acid (RNA) from cells in a liquid solution. The container includes a cover assembly and a holder which is normally closed by the cover assembly and contains an RNA extractant solvent, micron-sized particles and at least one larger particle suitably of millimeter size. The container contains the reagent, which is an extractant solvent which contains phenol and guanidinium thiocyanate or guanidinium chloride and has a pH of about 4. The container also includes a friable sealing layer which separates the extractant solvent from the liquid medium containing the cells until the container is reciprocally shaken. The method includes the reciprocal shaking of the container, wherein the larger particle breaks the friable layer to permit mixing of the liquid medium with the extractant solvent resulting in the breaking of the cell walls by the micron-sized beads and the release of the RNA.
摘要翻译：用于从液体溶液中的细胞中分离细胞成分如核糖核酸（RNA）的试剂，方法和容器。容器包括盖组件和保持器，其通常由盖组件封闭，并且包含RNA提取剂溶剂，微米级颗粒和适合于毫米尺寸的至少一个较大颗粒。该容器含有试剂，其为含有苯酚和硫氰酸胍或氯化胍的萃取剂溶剂，其pH约为4.该容器还包括易碎的密封层，其将萃取剂溶剂与含有该细胞的液体介质分离直至容器相互摇动。该方法包括容器的相互摇动，其中较大的颗粒破坏易碎层，以允许液体介质与萃取剂溶剂混合，导致细胞壁破碎由微米级珠粒和RNA的释放。

50. 发明申请

WO1995008629A1 RECEPTOR RECOGNITION FACTORS, PROTEIN SEQUENCES AND METHODS OF USE THEREOF 审中-公开
标题翻译：受体识别因子，蛋白质序列及其使用方法
公开(公告)号：WO1995008629A1
公开(公告)日：1995-03-30
申请号：PCT/US1994010849
申请日：1994-09-26
申请人： THE ROCKEFELLER UNIVERSITY
发明人： THE ROCKEFELLER UNIVERSITY , DARNELL, James, E., Jr. , SCHINDLER, Christian, W. , SHUAI, Ke , WEN, Zilong , ZHONG, Zhong
IPC分类号： C12N15/12
CPC分类号： C07K14/4705 , A61K38/00
摘要： Receptor recognition factors exist that recognize the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN alpha and IFN gamma . Specific DNA and amino acid sequences for various human and murine receptor recognition factors are provided, as are polypeptide fragments of two of the ISGF-3 genes, and antibodies have also been prepared and tested. The polypeptides confirm direct involvement of tyrosine kinase in intracellular message transmission. Numerous diagnostic and therapeutic materials and utilities are also disclosed.
摘要翻译：存在识别特异性配体已被结合的特异性细胞受体的受体识别因子，从而可以信号和/或启动转录因子与DNA位点的结合。受体识别因子在一个例子中是转录因子的一部分，并且还可以与其他转录因子相互作用，以使其激活并前往细胞核进行DNA结合。受体识别因子似乎在其活动中是与第二信使无关的，因为第二信使浓度的明显的扰动是无效的。通过用干扰素（IFN）刺激的基因转录进行的研究结果，特别是由IFNα和IFNγ引起的活化来说明本发明的概念。提供了各种人和鼠受体识别因子的特异性DNA和氨基酸序列，两种ISGF-3基因的多肽片段也已经被制备和测试。这些多肽证实了酪氨酸激酶在细胞内消息传播中的直接参与。还公开了许多诊断和治疗材料和效用。

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