公开(公告)号：WO1996018419A1

公开(公告)日：1996-06-20

申请号：PCT/US1995016347

申请日：1995-12-14

Applicant: UNIVERSITY OF WASHINGTON ,  KAY, Mark, A. ,  LIEBER, Andre

Inventor： UNIVERSITY OF WASHINGTON

IPC: A61K48/00

CPC classification number: C12N15/1131 ,  A61K38/482 ,  A61K48/00 ,  C12N9/6456 ,  C12N9/6459 ,  C12N2310/121 ,  C12N2799/022 ,  C12N2799/027 ,  C12Y304/21069

Abstract: A combination of retroviral and adenoviral vectors are used for high efficiency gene transfer into hepatocytes, resulting in long term gene expression. Hepatocytes are transduced in vivo with a recombinant adenovirus vector that expresses a molecule capable of inducing hepatocyte regeneration, such as urokinase plasminogen activator (uPA) or tissue plasminogen activator (tPA), resulting in a high rate of liver regeneration. During the regenerative phase, ex vivo or in vivo retroviral-mediated gene transfer into hepatocytes results in greater transduction efficiencies. The compositions and methods thus provide new means for gene therapy, and transgenic non-human animals useful in developing new therapeutic and preventative agents. The vectors can be used for high efficiency transduction of ribozymes specific for hepatitis C virus RNA.

Abstract translation: 使用逆转录病毒和腺病毒载体的组合将高效率基因转移到肝细胞中，导致长期基因表达。 用表达能够诱导肝细胞再生的分子如尿激酶纤溶酶原激活物（uPA）或组织纤溶酶原激活物（tPA）的重组腺病毒载体在体内转导肝细胞，导致高的肝再生率。 在再生期，离体或体内逆转录病毒介导的基因转移到肝细胞中导致更大的转导效率。 因此，组合物和方法提供了用于基因治疗的新手段，以及可用于开发新的治疗和预防剂的转基因非人动物。 载体可用于丙型肝炎病毒RNA特异性核酶的高效转导。

公开(公告)号：WO1996017924A2

公开(公告)日：1996-06-13

申请号：PCT/US1995015463

申请日：1995-12-04

Applicant: THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE ,  UNIVERSITY OF WASHINGTON

Inventor： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE ,  UNIVERSITY OF WASHINGTON ,  BEACHY, Philip, A. ,  MOON, Randall, T. ,  PORTER, Jeffrey, A.

IPC: C12N00/00

CPC classification number: G01N33/5058 ,  A01K67/0339 ,  A01K2217/05 ,  A01K2227/40 ,  A01K2227/50 ,  A01K2227/706 ,  A01K2267/03 ,  A61K38/00 ,  C07K14/43581 ,  C07K2319/00 ,  C07K2319/21 ,  C07K2319/23 ,  C07K2319/50 ,  C12N15/62 ,  G01N33/5008 ,  G01N33/5017 ,  G01N33/502 ,  G01N33/5091 ,  G01N33/92 ,  G01N2500/10

Abstract: The present invention provides two novel polypeptides, referred to as the "N" and "C" fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G CF site recognized by the autoproteolytic domain in the native protein. Also provided are methods of use of the N and C fragments.

Abstract translation: 本发明涉及一种所谓的“刺猬”的片段称为“N”和“C”两个新的多肽或分别N-末端片段和C-末端这些多肽切割后在特定的所获得 在自然蛋白水平上其自溶蛋白结构域识别的G CF位点。 本发明还涉及使用N和C片段的方法。

公开(公告)号：WO1996012173A1

公开(公告)日：1996-04-25

申请号：PCT/US1995014624

申请日：1995-10-13

Applicant: UNIVERSITY OF WASHINGTON ,  VAN DEN ENGH, Ger ,  ESPOSITO, Richard, J.

Inventor： UNIVERSITY OF WASHINGTON

IPC: G01N15/14

CPC classification number: G01N15/1404 ,  G01N2015/149 ,  Y10T436/11 ,  Y10T436/115831

Abstract: A droplet flow cytometer system which includes a system to optimize the droplet formation time delay based on conditions actually experienced includes an automatic droplet sample (73) which rapidly moves a plurality of containers (75) stepwise through the droplet stream while simultaneously adjusting the droplet time delay. Through the system sampling of an actual substance to be processed can be used to minimize the effect of the substances variations or the determination of which time delay is optimal. Analysis such as cell counting and the like may be conducted manually or automatically and input to a time delay adjustement which may then act with analysis equipement to revise the time delay estimate actually applied during processing. The automatic sample (73) can be controlled through a microprocessor and approriate programming to bracket an inital droplet formation time delay estimate. When maximization counts through volume, weight, or other types of analysis exists in the containers, the increment may then be reduced for a more accurate ultimate setting. This may be accomplished while actually processing the sample without interruption.

Abstract translation: 包括基于实际经历的条件来优化液滴形成时间延迟的系统的液滴流式细胞仪系统包括自动液滴样品（73），其将多个容器（75）逐步地快速移动通过液滴流，同时调节液滴时间 延迟。 通过对待处理的实际物质的系统采样可以用于最小化物质变化的影响或确定哪个时间延迟是最佳的。 可以手动或自动地进行诸如细胞计数等的分析，并输入到时间延迟调整部，然后可以与分析装置一起操作，以修改在处理期间实际应用的时间延迟估计。 自动样品（73）可以通过微处理器进行控制，并且适用于编程，以支配液滴形成时间估计。 当容器中存在通过体积，重量或其他类型的分析的最大化计数时，可以减小增量以获得更准确的最终设置。 这可以在不间断地实际处理样品的同时完成。

公开(公告)号：WO1996012171A3

公开(公告)日：1996-04-25

申请号：PCT/US1995013308

申请日：1995-10-13

Applicant: UNIVERSITY OF WASHINGTON ,  VAN DEN ENGH, Ger

Inventor： UNIVERSITY OF WASHINGTON

IPC: G01N15/14

公开(公告)号：WO1995029772A1

公开(公告)日：1995-11-09

申请号：PCT/US1995005528

申请日：1995-05-02

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  DASH, J., Gregory

IPC: B09B05/00

CPC classification number: E02D31/02 ,  B09C1/00 ,  B09C1/02 ,  B09C1/06 ,  B09C2101/00 ,  E02D3/115

Abstract: An advancing freeze front is established in a porous region (16) adjacent to or within contaminated earth (12). A flow of contaminated liquid phase water migrates toward the freeze front and a concentration of impurities is established in front of the advancing freeze front. When the freeze front reaches a collection zone, at least a portion is melted and the resultant water bearing concentrated impurities is collected and removed. This process may be repetitively performed.

Abstract translation: 在与污染的地球（12）相邻或内部的多孔区域（16）中建立一个前进的冷冻前沿。 受污染的液相水流向冷冻前部移动，并在前进的冷冻前部前面形成杂质浓度。 当冷冻前端到达收集区时，至少一部分熔化，并收集并除去所得到的含水浓缩杂质。 该过程可以重复执行。

公开(公告)号：WO1995025547A1

公开(公告)日：1995-09-28

申请号：PCT/US1995003735

申请日：1995-03-24

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  OSBORNE, William, R., A. ,  GEARY, Randolph, L. ,  LAU, Stella ,  CLOWES, Alexander, W. ,  DALE, David, C.

IPC: A61K48/00

CPC classification number: C12N9/1077 ,  A61K48/00 ,  C12N5/0691 ,  C12N2799/027

Abstract: Vascular grafts are used in gene therapy to implant autologous vascular smooth muscle cells that have been transduced with the gene of interest. The smooth muscle cells are immobilized within the pores and upon the interior surface of the wall of the graft, which is then coated with vascular endothelial cells and implanted into a patient's vascular system. The grafting device can be used in methods of treatment, such as supplying erythropoietin to a patient, and can be removed easily and replenished as necessary. The process is readily controlled and significantly reduces the risk of a viral gene vector spreading beyond a target cell population.

Abstract translation: 血管移植物用于基因治疗以植入已经用感兴趣的基因转导的自体血管平滑肌细胞。 平滑肌细胞被固定在孔内和移植物壁的内表面上，然后用血管内皮细胞涂覆并植入患者的血管系统。 接枝装置可用于治疗方法，例如向患者供应促红细胞生成素，并且可以根据需要容易地除去并补充。 该方法容易控制并显着降低病毒基因载体扩散超过靶细胞群的风险。

公开(公告)号：WO1995021920A1

公开(公告)日：1995-08-17

申请号：PCT/US1994008806

申请日：1994-08-05

Applicant: ZYMOGENETICS, INC. ,  UNIVERSITY OF WASHINGTON

Inventor： ZYMOGENETICS, INC. ,  UNIVERSITY OF WASHINGTON ,  HOLLY, Richard, D. ,  LOK, Si ,  FOSTER, Donald, C. ,  HAGEN, Frederick, S. ,  KAUSHANSKY, Kenneth ,  KUIJPER, Joseph, L. ,  LOFTON-DAY, Catherine ,  OORT, Pieter, J. ,  BURKHEAD, Steven, K.

IPC: C12N15/19

CPC classification number: G01N33/5055 ,  A61K38/196 ,  C07K14/705 ,  C07K14/715 ,  C12N5/0642 ,  C12N2501/145 ,  C12N2501/22 ,  G01N33/5005 ,  G01N33/5008 ,  G01N33/5088 ,  G01N33/5094

Abstract: Hematopoietic proteins and polypeptide fragments thereof are provided, including proteins and polypeptides from mice and humans. Also provided are DNA molecules encoding the proteins and polypeptides, as well as vectors and cells useful in their production. Antibodies that bind to an epitope on the proteins are also provided. The proteins and polypeptides are useful for in vivo and ex vivo therapy, and as reagents for cell culture and investigation of cell proliferation and development.

Abstract translation: 提供了造血蛋白及其多肽片段，包括来自小鼠和人的蛋白质和多肽。 还提供了编码蛋白质和多肽的DNA分子，以及可用于其生产的载体和细胞。 还提供了与蛋白质上的表位结合的抗体。 蛋白质和多肽可用于体内和离体治疗，以及作为细胞培养和细胞增殖和发育调查的试剂。

公开(公告)号：WO1995018227A1

公开(公告)日：1995-07-06

申请号：PCT/US1994014298

申请日：1994-12-14

Applicant: ZYMOGENETICS, INC. ,  UNIVERSITY OF WASHINGTON

Inventor： ZYMOGENETICS, INC. ,  UNIVERSITY OF WASHINGTON ,  DAY, Joseph, R. ,  ALBERS, John, J. ,  LOFTON-DAY, Catherine, E. ,  ADOLPHSON, Janet, L.

IPC: C12N15/12

CPC classification number: C07K14/47 ,  A61K38/00

Abstract: Isolated polynucleotide molecules encoding mammalian phospholipid transfer proteins (PLTP) and phospholipid transfer protein polypeptides are disclosed. The DNA molecules are transformed or transfected into host cells and the cells cultured to produce recombinant PLTP and PLTP polypeptides. PLTP and PLTP polypeptides may be combined with a pharmaceutically acceptable vehicle and administered to patients to regulate phospholipid transfer activity and thereby obtain a more favorable lipoprotein profile in the blood. The proteins and polypeptides may also be used within methods to measure phospholipid transfer activity or identify inhibitors of phospholipid transfer activity.

Abstract translation: 公开了编码哺乳动物磷脂转移蛋白（PLTP）和磷脂转移蛋白多肽的分离的多核苷酸分子。 将DNA分子转化或转染到宿主细胞中，培养细胞以产生重组PLTP和PLTP多肽。 PLTP和PLTP多肽可以与药学上可接受的载体组合并施用于患者以调节磷脂转移活性，从而在血液中获得更有利的脂蛋白特征。 蛋白质和多肽也可用于测量磷脂转移活性的方法中，或鉴定磷脂转移活性的抑制剂。

公开(公告)号：WO1995018152A1

公开(公告)日：1995-07-06

申请号：PCT/US1994014303

申请日：1994-12-14

Applicant: ZYMOGENETICS, INC. ,  UNIVERSITY OF WASHINGTON

Inventor： ZYMOGENETICS, INC. ,  UNIVERSITY OF WASHINGTON ,  LABROO, Virender, M. ,  SASAKI, Tomikazu

IPC: C07K14/585

CPC classification number: C07K14/57527 ,  A61K38/00 ,  C07K14/585

Abstract: Derivatized calcitonin molecules, pharmaceutical compositions comprising derivatized calcitonins, and methods of reducing serum calcium in a patient using the derivatized calcitonins are disclosed. The molecules are characterized by a derivatized amino terminus formed by combining a calcitonin with a cyclic, polycyclic or heterocyclic moiety. Multimeric forms of the molecules are also disclosed.

Abstract translation: 公开了衍生降钙素分子，包含衍生的降钙素的药物组合物，以及使用衍生的降钙素降低患者血清钙的方法。 分子的特征在于通过将降钙素与环状，多环或杂环部分组合形成的衍生化氨基末端。 还公开了分子的多聚体形式。

公开(公告)号：WO1995014788A1

公开(公告)日：1995-06-01

申请号：PCT/US1994013537

申请日：1994-11-23

Applicant: UNIVERSITY OF WASHINGTON

Inventor： UNIVERSITY OF WASHINGTON ,  LYON, Martha, E. ,  HENDERSON, Paul ,  MALIK, Sohail ,  KENNY, Margaret, A. ,  LYON, Andrew, W.

IPC: C12Q01/56

CPC classification number: G01N33/86 ,  C12Q1/56

Abstract: The invention provides methods of using anticoagulants to retard the coagulation of blood, so that properties and functions of blood, plasma, and blood cells may be determined analytically. The methods do not interfere with electrochemichal techniques use to detect divalent cations and permit accurate analysis of many analytes within a single blood sample, which currently require separately anticoagulated blood samples. The serine protease inhibitors used may be combined with each other or blood cell activation, aggregation, and adhesion inhibitors in mixtures that provide anticoagulant activity. The methods permit, for the first time, the possibility of using a single blood sample to perform a full range of blood, plasma, and blood cell analyses.

Abstract translation: 本发明提供了使用抗凝剂来延缓血液凝固的方法，从而可以分析地确定血液，血浆和血细胞的性质和功能。 这些方法不会干扰电化学技术用于检测二价阳离子并允许准确分析单个血液样品中的许多分析物，目前需要单独的抗凝血液样品。 使用的丝氨酸蛋白酶抑制剂可以在提供抗凝血活性的混合物中彼此组合或血细胞活化，聚集和粘附抑制剂。 该方法首次允许使用单个血液样品进行全面血液，血浆和血细胞分析的可能性。