公开(公告)号：WO1998017682A1

公开(公告)日：1998-04-30

申请号：PCT/US1997019175

申请日：1997-10-17

Applicant: WASHINGTON UNIVERSITY ,  KORSMEYER, Stanley, J.

Inventor： WASHINGTON UNIVERSITY

IPC: C07K14/00

CPC classification number: C07K14/4747 ,  A61K38/00 ,  C07K2319/00

Abstract: Novel forms of mutant BAD polypeptides or fragments thereof having an amino acid substitution for serine-112 and/or serine-136 are provided along with their encoding polynucleotides. Also disclosed are methods for preparation of the mutant BAD polypeptides and methods for treating disease conditions involving decreased apoptosis.

Abstract translation: 提供具有丝氨酸-121和/或丝氨酸-136的氨基酸取代的突变体BAD多肽或其片段的新型形式及其编码多核苷酸。 还公开了用于制备突变体BAD多肽的方法和用于治疗涉及凋亡减少的疾病状况的方法。

公开(公告)号：WO1998009643A1

公开(公告)日：1998-03-12

申请号：PCT/US1997015871

申请日：1997-09-09

Applicant: WASHINGTON UNIVERSITY ,  KORSMEYER, Stanley, J.

Inventor： WASHINGTON UNIVERSITY

IPC: A61K38/16

CPC classification number: C07K16/18 ,  A61K38/00 ,  C07K14/4747

Abstract: Novel forms of BAD polypeptide phosphorylated at serine-112 and/or serine-136 are provided along with methods for detecting and modulating intracellular levels.

Abstract translation: 提供了在丝氨酸-121和/或丝氨酸-133磷酸化的BAD多肽的新形式以及用于检测和调节细胞内水平的方法。

公开(公告)号：WO1997038087A2

公开(公告)日：1997-10-16

申请号：PCT/US1997006010

申请日：1997-04-04

Applicant: CHIRON CORPORATION ,  WASHINGTON UNIVERSITY ,  DUBENSKY, Thomas, W., Jr. ,  POLO, John, M. ,  BELLI, Barbara, A. ,  SCHLESINGER, Sondra ,  DRYGA, Sergey A. ,  FROLOV, Ilya

Inventor： CHIRON CORPORATION ,  WASHINGTON UNIVERSITY

IPC: C12N00/00

CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K48/00 ,  C12N7/00 ,  C12N15/86 ,  C12N2770/36121 ,  C12N2770/36122 ,  C12N2770/36143 ,  C12N2770/36162 ,  C12N2830/003 ,  C12N2830/006 ,  C12N2830/15 ,  C12N2830/32 ,  C12N2830/42 ,  C12N2830/48 ,  C12N2840/203 ,  C12N2840/44

Abstract: Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.

Abstract translation: 公开了分离的核酸分子，其包含甲病毒非结构蛋白基因，当可操作地并入重组甲病毒颗粒中时，与野生型相比，真核分子载体启动系统或RNA载体复制子具有降低的载体特异性RNA合成水平 类型，以及与野生型重组甲病毒颗粒相比，从病毒连接区启动子转录的RNA编码的相同或更高水平的蛋白质。 还公开了RNA载体复制子，甲病毒载体构建体和含有上述核酸分子的真核分子载体启动系统。

公开(公告)号：WO1997033911A1

公开(公告)日：1997-09-18

申请号：PCT/US1997003461

申请日：1997-03-14

Applicant: WASHINGTON UNIVERSITY ,  JOHNSON, Eugene, M., Jr. ,  MILBRANDT, Jeffrey, D. ,  KOTZBAUER, Paul, T. ,  LAMPE, Patricia, A.

Inventor： WASHINGTON UNIVERSITY

IPC: C07K14/475

CPC classification number: C07K14/475 ,  A61K38/00 ,  C07K2319/00

Abstract: A novel growth factor, persephin, which belongs to the GDNF/neurturin family of growth factors, is disclosed. The mouse and rat amino acid sequences have been identified. Mouse and rat persephin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using persephin, methods for detecting persephin gene alterations and methods for detecting and monitoring patient levels of persephin are provided. Methods for identifying additional members of the persephin-neurturin-GDNF family of growth factors are also provided.

Abstract translation: 公开了属于GDNF / neurturin生长因子家族的新生长因子persephin。 已经鉴定了小鼠和大鼠的氨基酸序列。 已经克隆并测序了小鼠和大鼠persephin基因组DNA序列，并鉴定了各自的cDNA序列。 另外，提供了使用persephin治疗退行性病症的方法，用于检测persephin基因改变的方法以及用于检测和监测患者血浆含量的方法。 还提供了用于鉴定生长因子的persephin-neurturin-GDNF家族的额外成员的方法。

公开(公告)号：WO1997008310A1

公开(公告)日：1997-03-06

申请号：PCT/US1996014033

申请日：1996-08-28

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  RICE, Charles, III ,  KOLYKHALOV, Alexander, A.

IPC: C12N15/11

CPC classification number: C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  A61K2039/51 ,  C07K2319/00 ,  C12N2770/24222 ,  C12Q1/707

Abstract: The invention relates to the discovery of a novel RNA sequence at the 3' terminal sequence of hepatitis C virus (HCV) genome RNA. Included in the invention are the 3' sequence, its complement, and their use for nucleic-acid based diagnostics and for developing and evaluating novel anti-HCV therapies. This sequence element, which is conserved among HCV genotypes, is likely to be essential for viral replication, and required for construction of full-length HCV cDNA clones capable of yielding infectious RNA, progeny virus or replication-competent HCV replicons. Such functional clones are useful tools for evaluation of therapeutic approaches and as substrates for developing candidate attenuated or inactivated HCV derivatives for vaccination against HCV.

Abstract translation: 本发明涉及在丙型肝炎病毒（HCV）基因组RNA的3'末端序列上发现新的RNA序列。 本发明包括3'序列，其补体及其用于基于核酸的诊断和用于开发和评估新型抗HCV疗法的用途。 在HCV基因型之间保守的该序列元件可能对于病毒复制是必需的，并且是构建能够产生感染性RNA，后代病毒或复制能力的HCV复制子的全长HCV cDNA克隆所必需的。 这种功能性克隆是用于评价治疗方法的有用工具，以及用于开发用于针对HCV接种的候选减毒或灭活的HCV衍生物的底物。

公开(公告)号：WO1997008196A1

公开(公告)日：1997-03-06

申请号：PCT/US1996014065

申请日：1996-08-27

Applicant: WASHINGTON UNIVERSITY ,  JOHNSON, Eugene, M., Jr. ,  MILBRANDT, Jeffrey, D. ,  KOTZBAUER, Paul, T. ,  LAMPE, Patricia, A.

Inventor： WASHINGTON UNIVERSITY

IPC: C07K14/00

CPC classification number: C07K14/475 ,  A61K38/00 ,  A61K48/00

Abstract: A novel growth factor, neurturin, is disclosed and the human and mouse amino acid sequences are identified. Human and mouse neurturin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. The subcloning into vectors and the preparation of cells stably transformed with the vectors are also disclosed. In addition, methods for treating degenerative conditions, tumor cells and obesity; methods for detecting gene alterations and methods for detecting and monitoring patient levels of neurturin are provided. Methods for identifying additional members of the neurturin-GDNF family of growth factors are also provided.

Abstract translation: 公开了一种新的生长因子neurturin，并鉴定了人和小鼠的氨基酸序列。 已经克隆并测序了人和小鼠neurturin基因组DNA序列，并鉴定了各自的cDNA序列。 还公开了亚克隆入载体和用载体稳定转化的细胞的制备。 此外，治疗退行性疾病，肿瘤细胞和肥胖症的方法; 提供了检测基因改变的方法和用于检测和监测neurturin患者水平的方法。 还提供了用于鉴定生长因子的neurturin-GDNF家族的其他成员的方法。

公开(公告)号：WO1996040108A1

公开(公告)日：1996-12-19

申请号：PCT/US1996010079

申请日：1996-06-07

Applicant: WASHINGTON UNIVERSITY ,  PIWNICA-WORMS, David, R. ,  SHARMA, Vijay

Inventor： WASHINGTON UNIVERSITY

IPC: A61K31/33

CPC classification number: C07D273/00 ,  A61K31/555 ,  Y02A50/411

Abstract: The invention relates to multidentate metal complexes having formula (I) wherein M is Fe, In, Ga or Al; the dashed lines represent independently a sigle or a double bond; the hatched lines represent coordination to the metal cation (M); A and B are oxygen, or in the case where Ar is 2-pyridyl or 2-pyrrolyl, a shared pair of electrons on the nitrogen; Ar is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted 2-pyridyl or optionally substituted 2-pyrrolyl, with the proviso that at least one of the substituents comprises a boron atom; X is alternatively (i) (CHR )p[NR (CHR )q]r, wherein p and q are independently 1, 2, 3, 4, 5 or 6; r is 0, 1 or 2; and R , R and R are independently hydrogen, lower alkyl or phenyl, or two adjacent R or R groups represent a double bond or a fused benzene ring where p or q, respectively, is greater than 2; with the proviso that where r is 1 or 2, then there are 1 or two additional sites of coordination to the metal; or (ii) optionally substituted phenyl, wherein the phenyl, when substituted, has lower alkyl substituents, optionally with: proviso (A), wherein at least one of the substituents of Ar comprises boron, or with proviso (B), wherein at least one of substituents of Ar comprises a linkage to a pharmaceutically active substituent.

Abstract translation: 本发明涉及式（I）的多齿金属配合物，其中M为Fe，In，Ga或Al; 虚线独立地代表单峰或双键; 阴影线表示与金属阳离子（M）的配位; A和B是氧，或者在Ar是2-吡啶基或2-吡咯基的情况下，在氮上共享一对电子; Ar是任选取代的苯基，任选取代的萘基，任选取代的2-吡啶基或任选取代的2-吡咯基，条件是至少一个取代基包含硼原子; X可选地是（i）（CHR 2）p [NR 3（CHR 4）q] r，其中p和q独立地是1,2,3,4,5或6; r为0,1或2; 且R 2，R 3和R 4独立地为氢，低级烷基或苯基，或两个相邻的R 2或R 4基团表示双键或稠合苯环，其中p或q ，分别大于2; 条件是当r为1或2时，则存在与金属配位的1个或2个附加位点; 其中当被取代时，苯基具有低级烷基取代基，任选地具有：条件（A），其中至少一个Ar的取代基包含硼或条件（B），其中至少 Ar的取代基之一包含与药学活性取代基的连接。

公开(公告)号：WO1996031834A1

公开(公告)日：1996-10-10

申请号：PCT/US1996004286

申请日：1996-04-01

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  INDECK, Ronald, S. ,  MULLER, Marcel, W.

IPC: G06K07/00

CPC classification number: G06K1/125 ,  G06F21/79 ,  G06K19/06187 ,  G06K19/12 ,  G11B5/00813 ,  G11B5/02 ,  G11B5/035 ,  G11B5/488 ,  G11B5/54 ,  G11B5/58 ,  G11B20/10009 ,  G11B20/1816 ,  G11B20/24 ,  G11B33/10

Abstract: Data recorded on a magnetic medium (22) may be securely identified and manipulated for use in credit balance applications by determining a magnetic fingerprint benchmark (26) on the medium as well as a distance (d) between this benchmark and any pre-selected magnetic feature such as a magnetic transition (28) of a data bit of the data set. Verification of the data may be achieved by measuring this distance and comparing it with the distance recorded at the time that the data was originally placed on the medium. As there is a detectable difference in accuracy between reading this distance as contrasted with illegitimate attempts to write false data at a pre-selected distance from the benchmark, attempts at forgery are detectable.

Abstract translation: 记录在磁性介质（22）上的数据可以通过确定介质上的磁性指纹基准（26）以及该基准与任何预先选定的磁性（26）之间的距离（d）被安全地识别和操纵用于信用平衡应用中 特征如数据组的数据位的磁转换（28）。 可以通过测量该距离并将其与在数据最初放置在介质上时记录的距离进行比较来实现数据的验证。 由于在读取此距离之间存在可检测的准确性差异，与非法尝试以基准预先选择的距离写入虚假数据相反，伪造的尝试可能被检测到。

公开(公告)号：WO1996029930A1

公开(公告)日：1996-10-03

申请号：PCT/US1996004384

申请日：1996-03-29

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  DIMAROGONAS, Andrew, D.

IPC: A61B05/05

CPC classification number: A61B5/4509 ,  A61B5/0051 ,  A61B9/00

Abstract: The density of a discrete piece of hard tissue such as a bone in a patient may be determined by either of two methods. In a first method, an impulse of energy is introduced into the tissue, and the resulting vibration in the hard tissue is sensed and analyzed to compute the modal damping factor of the tissue, the modal damping factor being directly related to the density of the tissue. In a second method, a continuous energy input is introduced into the hard tissue. The resulting vibration in the tissue is measured with a mechano-electrical vibration transducer (26) and a modal damping factor is calculated. The electro-mechanical vibration transducer (26) of the preferred embodiment measures the pressure with which the transducer (26) is pressed against the patient's flesh and only produces the continuous energy input when a predetermined pressure is achieved which is sufficient to prevent any significant vibration of the flesh surrounding the bone.

Abstract translation: 诸如患者体内的骨骼的分散的硬组织的密度可以通过两种方法中的任一种来确定。 在第一种方法中，将能量脉冲引入到组织中，并且感测和分析硬组织中产生的振动以计算组织的模态阻尼因子，模态阻尼因子与组织的密度直接相关 。 在第二种方法中，将连续的能量输入引入硬组织。 用机械电振动传感器（26）测量组织中产生的振动，并计算模态阻尼系数。 优选实施例的机电振动换能器（26）测量换能器（26）被压靠在患者肉上的压力，并且仅在达到预定压力时才产生连续能量输入，这足以防止任何明显的振动 的骨头周围的肉体。

公开(公告)号：WO1996029063A2

公开(公告)日：1996-09-26

申请号：PCT/IB1996000333

申请日：1996-03-15

Applicant: WASHINGTON UNIVERSITY

Inventor： WASHINGTON UNIVERSITY ,  OSTLUND, Richard, E. ,  SHERMAN, William, R.

IPC: A61K31/045

CPC classification number: A61K31/075 ,  Y10S514/866

Abstract: Pinitol and derivatives and metabolites thereof are useful in nutritional and medicinal compositions for lowering plasma free fatty acid levels and for treating conditions associated with insulin resistance, such as those which result from diabetes mellitus and its chronic complications; obesity; hyperlipidemias and dyslipidemias atherosclerosis; hypertension; cardiovascular disease; AIDS; cancer; wasting/cachexia; sepsis; trauma associated with burns, malnutrition, and stress; aging; lupus and other autoimmune diseases; endocrine disease; hyperuricemia, polycystic ovary syndrome and complications arising from athletic activity.

Abstract translation: Pinitol及其衍生物和代谢物可用于降低血浆游离脂肪酸水平的营养和药物组合物和用于治疗与胰岛素抵抗相关的病症，例如由糖尿病及其慢性并发症引起的疾病; 肥胖; 高脂血症和血脂异常动脉粥样硬化; 高血压; 心血管疾病; 艾滋病; 癌症; 浪费/恶病质; 败血症; 与烧伤，营养不良和压力相关的创伤; 老化; 狼疮等自身免疫性疾病; 内分泌疾病 高尿酸血症，多囊卵巢综合征和运动活动引起的并发症。