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    GERMLINE MUTATIONS IN THE MTS GENE AND METHOD FOR DETECTING PREDISPOSITION TO CANCER AT THE MTS GENE
    31.
    发明申请
    GERMLINE MUTATIONS IN THE MTS GENE AND METHOD FOR DETECTING PREDISPOSITION TO CANCER AT THE MTS GENE 审中-公开
    MTS基因中的GERMLINE突变体和用于检测MTS基因对癌症预测的方法

    公开(公告)号：WO1995025813A1

    公开(公告)日：1995-09-28

    申请号：PCT/US1995003537

    申请日：1995-03-17

    Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  MYRIAD GENETICS, INC. ,  SKOLNICK, Mark, H. ,  CANNON-ALBRIGHT, Lisa, A. ,  KAMB, Alexander

    Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  MYRIAD GENETICS, INC.

    IPC: C12Q01/68

    CPC classification number: C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  C12Q2600/172

    Abstract: The present invention relates to somatic mutations in the Multiple Tumor Suppressor (MTS) gene in human cancers and their use in the diagnosis and prognosis of human cancer. The invention further relates to germ line mutations in the MTS gene and their use in the diagnosis of predisposition to melanoma, leukemia, astrocytoma, glioblastoma, lymphoma, glioma, Hodgkin's lymphoma, CLL, and cancers of the pancreas, breast, thyroid, ovary, uterus, testis, kidney, stomach and rectum. The invention also relates to the therapy of human cancers which have a mutation in the MTS gene, including gene therapy, protein replacement therapy and protein mimetics. Finally, the invention relates to the screening of drugs for cancer therapy.

    Abstract translation: 本发明涉及人类癌症中多重肿瘤抑制因子（MTS）基因中的体细胞突变及其在人类癌症诊断和预后中的应用。 本发明还涉及MTS基因中的种系突变及其在诊断黑素瘤，白血病，星形细胞瘤，成胶质细胞瘤，淋巴瘤，胶质瘤，霍奇金淋巴瘤，CLL和胰腺，乳腺，甲状腺，卵巢癌， 子宫，睾丸，肾，胃和直肠。 本发明还涉及在MTS基因中具有突变的人类癌症的治疗，包括基因治疗，蛋白质替代疗法和蛋白质模拟物。 最后，本发明涉及用于癌症治疗的药物的筛选。

    APPARATUS AND METHODS FOR MULTIANALYTE HOMOGENEOUS FLUOROIMMUNOASSAYS
    32.
    发明申请
    APPARATUS AND METHODS FOR MULTIANALYTE HOMOGENEOUS FLUOROIMMUNOASSAYS 审中-公开
    多元共生荧光素酶的装置和方法

    公开(公告)号：WO1994027137A2

    公开(公告)日：1994-11-24

    申请号：PCT/US1994005567

    申请日：1994-05-18

    Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION

    Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  HERRON, James, N. ,  CHRISTENSEN, Douglas, A. ,  WANG, Hsu-Kun ,  CALDWELL, Karin, D. ,  JANATOVA', Vera ,  HUANG, Shao-Chie

    IPC: G01N21/64

    CPC classification number: G01N21/648 ,  G01N21/6428 ,  G01N21/6452 ,  G01N21/7703 ,  G01N33/54373 ,  G01N2021/7786

    Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide (124) with an integral semi-cylindrical lens (502), and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor (120) and assay method have patches (662) of capture molecules (720) each specific for a different analyte (210), disposed adjacent within a single reservoir (660). The capture molecules (720) are immobilized to the patches (662) on the waveguide surface by site-specific coupling of thiol groups on the capture molecules (720) to photo-affinity crosslinkers (706), which in turn are coupled to the waveguide surface (700) or to a non-specific-binding-resistant coating (702) on the surface (700). The patches (662, 664, 666) of different antibodies are produced by selectively irradiating a portion (714) of the waveguide surface (700) during the process of coupling the photo-affinity crosslinkers (706), the selective irradiation involving a mask (712), a laser light source, or the like.

    Abstract translation: 公开了消逝光荧光免疫测定法的方法和装置。 该装置采用具有整体半柱面透镜（502）的平面波导（124），并且具有多分析物特征和校准特征以及改善的渐逝场强度。 生物传感器（120）和测定方法的优选实施方案具有各自特定用于不同分析物（210）的捕获分子（720）的贴片（662），其邻近设置在单个储存器（660）内。 俘获分子（720）通过捕获分子（720）上的硫醇基团与光亲和交联剂（706）的位点特异性偶联固定在波导表面上的贴片（662）上，光亲和交联剂（706）又连接到波导 表面（700）或表面（700）上的非特异性结合抗性涂层（702）。 不同抗体的贴片（662,664,666）通过在耦合光亲和性交联剂（706）的过程中选择性地照射波导表面（700）的部分（714），涉及掩模的选择性照射 712），激光光源等。

    BIOCONJUGATES AND DELIVERY OF BIOACTIVE AGENTS
    34.
    发明申请
    BIOCONJUGATES AND DELIVERY OF BIOACTIVE AGENTS 审中-公开
    生物活性剂和生物活性剂的输送

    公开(公告)号：WO1998008859A1

    公开(公告)日：1998-03-05

    申请号：PCT/US1997014140

    申请日：1997-08-22

    Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  GRISSOM, Charles, B. ,  WEST, Frederick, G. ,  HOWARD, W., Allen, Jr.

    Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION

    IPC: C07H21/02

    CPC classification number: C07H21/00 ,  A61K41/0028 ,  A61K41/0042 ,  A61K47/54

    Abstract: The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise of bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the oragnocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the oragnocobalt complex. The cleavage may occur as a result of normal displacment by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively at a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis. Further, if the photolysis takes places in the presence of a magnetic field surrounding the release site, the release of the bioactive agent into surrounding healthy tissue is minimized.

    Abstract translation: 本发明涉及生物缀合物和递送生物活性剂，其优选靶向用于细胞，组织或器官中的位点特异性释放。 更具体地说，本发明涉及包含生物活性剂和有机钴复合物的生物缀合物。 生物活性剂直接或间接地共价结合到钴胺络合物的钴原子上。 生物活性剂通过在生物活性剂与钴酸盐络合物中的钴原子之间的共价键的切割从生物缀合物释放出来。 作为通过细胞亲核试剂的正常置换或酶促作用的结果可能发生切割，但优选通过施加外部信号在预定的释放位置选择性地发生。 外部信号可以是光或光激发，即光解，或者它可以是超声波，即分解。 此外，如果在存在释放位点周围的磁场的情况下进行光解，则将生物活性剂释放到周围的健康组织中被最小化。

    pH SENSITIVE HYDROGELS WITH ADJUSTABLE SWELLING KINETICS FOR COLON-SPECIFIC DELIVERY OF PEPTIDES AND PROTEINS
    35.
    发明申请
    pH SENSITIVE HYDROGELS WITH ADJUSTABLE SWELLING KINETICS FOR COLON-SPECIFIC DELIVERY OF PEPTIDES AND PROTEINS 审中-公开
    pH敏感水凝胶，具有可调节的动力学，用于特异性递送肽和蛋白质

    公开(公告)号：WO1998001421A1

    公开(公告)日：1998-01-15

    申请号：PCT/US1997012305

    申请日：1997-07-09

    Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  KOPECEK, Jindrich ,  KOPECKOVA, Pavla ,  AKALA, Emmanuel, O. ,  YEH, Ping-Yang ,  ULBRICH, Karel

    Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION

    IPC: C07C239/22

    CPC classification number: A61K9/4891 ,  A61K9/2027 ,  A61K9/2846 ,  A61K9/7007 ,  A61K47/32 ,  C07C239/22 ,  C08F220/54

    Abstract: A hydrogel polymeric system for the site specific delivery of peptide and protein drugs to the colon is prepared. The hydrogel protects the drug through the acid environment of the stomach, swells at a chemically controlled rate in the higher pH environment of the small intestine and is enzymatically degraded by azoreductases in the colon. pH sensitive hydrogels are formulated from monomers of N-substituted (meth)acrylamides, acrylic or methacrylic acid, a cross-linking agent containing an aromatic azo bond and an N,O-diacylhydroxylamine. Chemical control of swelling is attained by initially providing labile N,O-diacylhydroxylamine moieties in the hydrogel that are stable in the acidic medium of the stomach but that are susceptible to hydrolysis at the intestinal pH, i.e. above about pH 6.5. Upon hydrolysis, ionized -COOH groups attached to the polymer network are generated and swelling is maximized as the hydrogel reaches the colon where degradation occurs by the azoreductase cleavage of the aromatic azo cross-linking agent.

    Abstract translation: 制备用于向结肠进行肽和蛋白质药物的特异性递送的水凝胶聚合体系。 水凝胶保护药物通过胃的酸性环境，以小肠较高pH环境中的化学控制速率膨胀，并通过结肠中的亚光折射酶进行酶促降解。 pH敏感性水凝胶由N-取代的（甲基）丙烯酰胺，丙烯酸或甲基丙烯酸的单体，含有芳香族偶氮键的交联剂和N，O-二酰基羟胺配制而成。 通过最初在水凝胶中提供不稳定的N，O-二酰基羟胺部分，其在胃的酸性介质中是稳定的，但是在肠pH（即高于约pH6.5）时易于水解，可获得化学控制。 在水解时，产生连接到聚合物网络上的电离的-COOH基团，随着水凝胶到达结肠，溶胀最大化，其中通过芳族偶氮交联剂的亚芳基还原酶裂解发生降解。

    RAPID, ACCURATE IDENTIFICATION OF DNA SEQUENCE VARIANTS BY ELECTROSPRAY MASS SPECTROMETRY
    36.
    发明申请
    RAPID, ACCURATE IDENTIFICATION OF DNA SEQUENCE VARIANTS BY ELECTROSPRAY MASS SPECTROMETRY 审中-公开
    快速鉴定DNA序列变异体通过电喷雾质谱分析

    公开(公告)号：WO1997047766A1

    公开(公告)日：1997-12-18

    申请号：PCT/US1997008518

    申请日：1997-06-10

    Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  HOPKINS, Chris, E. ,  GESTELAND, Raymond, F. ,  PEIFFER, Andy ,  STAUFFER, Dora ,  LEPPERT, Mark ,  CRAIN, Pamela, F. ,  MCCLOSKEY, James, A.

    Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION

    IPC: C12Q01/68

    CPC classification number: C12Q1/6827 ,  C12Q2563/167

    Abstract: A method of detecting a polymorphism at a polymorphic site in the genome of an individual is described. The method involves amplifying a portion of a genomic DNA sample by polymerase chain reaction to produce an amplified segment that contains the polymorphic site, desalting the amplified segment, and determining the mass of the amplified segment by electrospray ionization mass spectrometry. Comparison of the mass of the amplified segment to a reference mass permits detection of the presence or absence of the polymorphism. Methods for heterozygosity and disease inheritance by mass spectrometry are also described. The figure shows the molecular weight transform spectrum obtained from the mass-to-charge spectrum of a 53-base oligonucleotide.

    Abstract translation: 描述了检测个体基因组中多态性位点多态性的方法。 该方法包括通过聚合酶链反应扩增基因组DNA样品的一部分以产生含有多态性位点的扩增区段，对扩增区段脱盐，并通过电喷雾离子化质谱法测定扩增区段的质量。 将扩增片段的质量与参考质量的比较允许检测多态性的存在或不存在。 还描述了通过质谱法进行杂合性和疾病遗传的方法。 该图示出了从53碱基寡核苷酸的质量 - 电荷光谱获得的分子量变换光谱。

    CONOTOXIN PEPTIDE PVIIA
    38.
    发明申请
    CONOTOXIN PEPTIDE PVIIA 审中-公开

    公开(公告)号：WO1997034925A1

    公开(公告)日：1997-09-25

    申请号：PCT/US1997003483

    申请日：1997-03-14

    Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDATION

    Inventor： UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  TERLAU, Heinrich ,  SHON, Ki-Joon ,  GRILLEY, Michelle, M. ,  OLIVERA, Baldomero, M.

    IPC: C07K14/00

    CPC classification number: C07K14/43504 ,  A61K38/00

    Abstract: A new peptide, λ-conotoxin PVIIA, is disclosed. This peptide is found naturally in the cone snail Conus purpurascens and has the amino acid sequence Cys-Arg-Ile-Xaa-Asn-Gln-Lys-Cys-Phe-Gln-His-Leu-Asp-Asp-Cys-Cys-Ser-Arg-Lys-Cys-Asn-Arg-Phe-Asn-Lys-Cys-Val (SEQ ID NO:1) where Xaa represents 4-trans-hydroxyproline, hydroxyproline or proline. This peptide together with a previously disclosed peptide, δ-conotoxin PVIA, act synergistically to rapidly immobilize fish which are injected with the two peptides. Injection of λ-conotoxin PVIIA alone results in different symptoms with an injected fish becoming hyperactive and then contracting and suddenly extending all major fins. This 'fin-popping' occurs repeatedly resulting in a series of jerky movements, but injection of only λ-conotoxin PVIIA does not immobilize or kill the fish.

    TARGETING MACROMOLECULAR PRODRUGS TO T LYMPHOCYTES
    39.
    发明申请
    TARGETING MACROMOLECULAR PRODRUGS TO T LYMPHOCYTES 审中-公开
    将大分子产品定向到淋巴细胞

    公开(公告)号：WO1997033618A1

    公开(公告)日：1997-09-18

    申请号：PCT/US1997003832

    申请日：1997-03-12

    Applicant: THERATECH, INC. ,  UNIVERSITY OF UTAH RESEARCH FOUNDATION

    Inventor： THERATECH, INC. ,  UNIVERSITY OF UTAH RESEARCH FOUNDATION ,  PRAKASH, Ramesh, K. ,  KOPECEK, Jindrich ,  KOPECKOVA, Pavla ,  OMELYANENKO, Vladimir

    IPC: A61K39/395

    CPC classification number: C07K16/2896 ,  A61K47/6425 ,  C07K14/70596

    Abstract: A composition for intracellular delivery of a chemical agent into a T cell comprises a receptor-binding and endocytosis-inducing ligand and a chemical agent coupled to a water soluble polymer. The ligand binds to a receptor on T lymphocytes and elicits endocytosis of the composition. The composition also includes a spacer for coupling the chemical agent and the ligand to the polymer. Chemical agents can include cytotoxins, transforming nucleic acids, gene regulators, labels, antigens, drugs, and the like. A preferred water soluble polymer is a copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA). The composition can further comprise a carrier such as a water soluble polymer, liposome, or particulate. Methods of using these compositions for delivering a chemical agent in vivo or in vitro are also disclosed.

    Abstract translation: 用于细胞内递送化学试剂到T细胞中的组合物包含受体结合和内吞作用诱导配体和与水溶性聚合物偶联的化学试剂。 该配体与T淋巴细胞上的受体结合并引起组合物的内吞作用。 该组合物还包括用于将化学试剂和配体偶联到聚合物上的间隔物。 化学试剂可以包括细胞毒素，转化核酸，基因调节剂，标记，抗原，药物等。 优选的水溶性聚合物是N-（2-羟丙基）甲基丙烯酰胺（HPMA）的共聚物。 组合物还可以包含载体，例如水溶性聚合物，脂质体或颗粒。 还公开了使用这些组合物在体内或体外递送化学试剂的方法。

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