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    SEMI-SYNTHETIC GLYCOPEPTIDES WITH ANTIBIOTIC ACTIVITY
    3.
    发明申请
    SEMI-SYNTHETIC GLYCOPEPTIDES WITH ANTIBIOTIC ACTIVITY 审中-公开
    具有抗生素活性的半合成糖蛋白

    公开(公告)号：WO2006093947A2

    公开(公告)日：2006-09-08

    申请号：PCT/US2006/007049

    申请日：2006-02-27

    Applicant: CHIRON CORPORATION ,  CHU, Daniel ,  PREOBRAZHENSKAYA, Maria ,  PRINTSEVSKAYA, Svetlana ,  OLSUFYEVA, Eugenia

    Inventor： CHU, Daniel ,  PREOBRAZHENSKAYA, Maria ,  PRINTSEVSKAYA, Svetlana ,  OLSUFYEVA, Eugenia

    CPC classification number: A61K38/14 ,  C07K9/008

    Abstract: Semi-synthetic glycopeptides having antibacterial activity are based on modifications of the eremomycin, A82846B, vancomycin, teicoplanin, and A-40,926 scaffolds, in particular, acylation of the sugar moieties on these scaffolds with certain acyl groups; and/or conversion of an acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides; or having a combination of an alkylation modification of the amino substituent on the amino-substituted sugar moiety on these scaffolds with certain alkyl groups or acylation modification of the amino substituent on the amino-substituted sugar moiety on this scaffold with certain alkyl groups, and conversion of the acid moiety on the macrocyclic ring of this scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.

    Abstract translation: 具有抗菌活性的半合成糖肽基于依依霉素，A82846B，万古霉素，替考拉宁和A-40,926支架的修饰，特别是在具有某些酰基的这些支架上糖部分的酰化; 和/或将这些支架的大环上的酸部分转化为某些取代的酰胺; 或具有这些支架上的氨基取代的糖部分上的氨基取代基的烷基化修饰与某些烷基的组合或在该支架上的某些烷基上的氨基取代的糖部分上的氨基取代基的酰化修饰和转化 的该支架的大环上的酸部分与某些取代的酰胺。 还提供了合成化合物的方法，含有该化合物的药物组合物，以及该化合物用于治疗和/或预防疾病，特别是细菌感染的方法。

    METHODS FOR TREATING RENAL CELL CARCINOMA
    4.
    发明申请
    METHODS FOR TREATING RENAL CELL CARCINOMA 审中-公开
    治疗肾细胞癌的方法

    公开(公告)号：WO2006081510A2

    公开(公告)日：2006-08-03

    申请号：PCT/US2006/003116

    申请日：2006-01-27

    Applicant: CHIRON CORPORATION ,  ELIAS, Laurence ,  WITHERELL, Gary

    Inventor： ELIAS, Laurence ,  WITHERELL, Gary

    CPC classification number: A61K38/2013 ,  A61K47/60

    Abstract: Methods for treating renal cell carcinoma using low doses of IL-2 are disclosed. In particular, the invention relates to methods of treating metastatic renal cell carcinoma in patients who are renally impaired and/or intolerant of high dose IL-2 therapy. The therapeutic regimen described herein significantly inhibits tumor growth with reduced toxicity and adverse side effects compared to high dose IL-2 therapy.

    Abstract translation: 公开了使用低剂量IL-2治疗肾细胞癌的方法。 特别地，本发明涉及在高剂量IL-2治疗的肾损伤和/或不耐受的患者中治疗转移性肾细胞癌的方法。 与高剂量IL-2治疗相比，本文所述的治疗方案显着抑制毒性降低和不良副作用的肿瘤生长。

    A METHOD FOR CHARACTERIZING THE EFFICACY OF AN AGENT TARGETING A PRIMARY CYSTIC FIBROSIS DEFECT
    5.
    发明申请
    A METHOD FOR CHARACTERIZING THE EFFICACY OF AN AGENT TARGETING A PRIMARY CYSTIC FIBROSIS DEFECT 审中-公开
    表征一种主要的CYSTIC FIBROSIS DEFECT的药物效能的方法

    公开(公告)号：WO2006081429A1

    公开(公告)日：2006-08-03

    申请号：PCT/US2006/002949

    申请日：2006-01-27

    Applicant: CHIRON CORPORATION ,  VADEVANTER, Donald

    Inventor： VADEVANTER, Donald

    IPC: G01N33/50

    CPC classification number: G01N33/5091 ,  G01N2333/31 ,  G01N2800/12 ,  G06F19/00 ,  G06Q50/24

    Abstract: Generally, the method for characterizing the efficacy of an agent targeting a primary cystic fibrosis defect comprises measuring a change in the status of lung infection in a sample population of subjects administered the agent in comparison to a control sample population of subjects; wherein the subjects in the sample population and the control sample population have the primary cystic fibrosis defect and are uninfected before the agent is administered; wherein a beneficial change in the presence of lung infection in the sample population in comparison to the control sample population is indicative of a treatment effect; and wherein the agent lacks intrinsic antibiotic activity.

    Abstract translation: 通常，用于表征靶向原发性囊性纤维化缺陷的药剂的功效的方法包括测量与受试者的对照样品群体相比施用该试剂的受试者样本群体中肺部感染状态的变化; 其中样品群体中的受试者和对照样本群体具有原发性囊性纤维化缺陷，并且在施用该药剂之前未感染; 其中与对照样本群体相比，样品群体中肺部感染存在的有益变化指示治疗效果; 并且其中所述试剂缺乏内在的抗生素活性。

    DEAMIDATED INTERFERON-BETA
    6.
    发明申请
    DEAMIDATED INTERFERON-BETA 审中-公开

    公开(公告)号：WO2006053134A2

    公开(公告)日：2006-05-18

    申请号：PCT/US2005/040758

    申请日：2005-11-10

    Applicant: CHIRON CORPORATION ,  FURUYA, Kenji ,  JOHNSON-JACKSON, Deborah ,  RUSCIO, Diana, Tierra

    Inventor： FURUYA, Kenji ,  JOHNSON-JACKSON, Deborah ,  RUSCIO, Diana, Tierra

    CPC classification number: C07K14/565 ,  A61K38/00

    Abstract: Interferon-β protein analogs in which the asparagine at position 25, numbered in accordance with native interferon-β, is deamidated exhibit a biological activity of native human interferon-β at an increased level and do not require HA for protein stabilization. The deamidated product is suitable for large scale manufacturing for incorporation in HA-containing or HA-free therapeutics for treatment of diseases including multiple sclerosis. An endoproteinase-C peptide map technique that produces a fingerprint profile for proteins using an enzymatic digest followed by RP-HPLC is also useful in quality control as an ID and/or quantitative test for the deamidated products.

    Abstract translation: 干扰素-β蛋白类似物，其中根据天然干扰素-β编号的位置25处的天冬酰胺脱酰胺化表现出天然人干扰素-β的生物活性在增加的水平，并且不需要 HA用于蛋白质稳定。 脱酰胺产物适合于大规模生产以掺入含有HA或HA的治疗剂中，用于治疗包括多发性硬化症的疾病。 使用酶消化产生蛋白质指纹图谱然后进行RP-HPLC的内蛋白酶-C肽图谱技术在质量控制中也可用作脱酰胺产物的ID和/或定量测试。

    TRIVALENT METAL MEDIATED HOMOGENEOUS LUMINESCENT PROXIMITY ASSAY
    7.
    发明申请
    TRIVALENT METAL MEDIATED HOMOGENEOUS LUMINESCENT PROXIMITY ASSAY 审中-公开
    多金属介质均质光致亲和性测定

    公开(公告)号：WO2006034417A2

    公开(公告)日：2006-03-30

    申请号：PCT/US2005/034026

    申请日：2005-09-19

    Applicant: CHIRON CORPORATION ,  KUO, Richard, C. ,  DAWES, Timothy, D. ,  MACHAJEWSKI, Timothy, D.

    Inventor： KUO, Richard, C. ,  DAWES, Timothy, D. ,  MACHAJEWSKI, Timothy, D.

    IPC: C12Q1/48 ,  C12Q1/42 ,  C09K11/06 ,  C09K11/07 ,  G01N33/58 ,  G01N33/50

    CPC classification number: G01N33/542 ,  C12Q1/42 ,  C12Q1/44 ,  C12Q1/485

    Abstract: An in vitro protein kinase assay technology that (1) exhibits a high assay signal to background ratio (S/B) and range (S-B); (2) is homogenous; (3) is non-radioactive; and (4) does not require a phospho-specific antibody involves complexing a trivalent metal ion (e.g. Ga 3+ , Fe 3+ , Al 3+ , In 3+ , Ru 3+ , Sc 3+ , Y 3+ ) to the surface of amplified luminescent proximity assay acceptor or donor beads, e.g., via a suitable linker such as nitrilotriacetic acid (NTA; also referred to as carboxymethyl-lysine), iminodiacetic acid (IDA), or an appropriately substituted N-containing heterocycle, for example a triazoheterocycle, for example a triazocyclononaneononane, such as 1-propylamino-4-acetato-1,4,7-triazacyclononane. A protein (or constituent part) or other kinase substrate is bound to the surface of the other of an amplified luminescent proximity assay acceptor or donor bead and, if phosphorylated, brought into proximity with the trivalent metal ion-complexed acceptor bead to generate a luminescent signal. Presence of a kinase inhibitor inhibits phosphorylation and therefore signal generation and, in this way, is detectable. As the invention described herein recognizes the presence or absence of phosphate groups on a protein, (or constituent part), or other biological macromolecule (e.g., mono, di, or trinucleotides, cyclic nucleotides or phosphate substituted inositols), it is broadly applicable to any phosphorlylation or dephosphorylation reaction enzymes and provides a highly robust and flexible assay format for protein kinases and other enzyme classes, including lipid kinases, phosphatases, phosphodiesterases and others.

    Abstract translation: （1）表现出高测定信号与背景比（S / B）和范围（S-B）的体外蛋白激酶测定技术; （2）是均匀的; （3）是非放射性的; 和（4）不需要磷酸特异性抗体涉及使三价金属离子（例如，Ga 3+，Fe 3+，N 3+， SUP>，In 3+，R 3+，S 3+，Y 3+ +）与表面 例如通过合适的接头，例如次氮基三乙酸（NTA;也称为羧甲基赖氨酸），亚氨基二乙酸（IDA）或适当取代的含N的杂环，例如 三唑杂环，例如三氮杂环壬烷，例如1-丙基氨基-4-乙酰-1,4,7-三氮杂环壬烷。 蛋白质（或组成部分）或其他激酶底物与扩增的发光亲和测定受体或供体小珠的另一个的表面结合，并且如果磷酸化，则与三价金属离子络合的受体珠接近以产生发光 信号。 激酶抑制剂的存在抑制磷酸化并因此产生信号，并且以这种方式可检测。 如本文所述的发明认识到蛋白质（或组成部分）或其他生物大分子（例如单，二或三核苷酸，环状核苷酸或磷酸酯取代的肌醇）上磷酸基团的存在或不存在，广泛适用于 任何磷酸化或去磷酸化反应酶，并为蛋白激酶和其他酶类提供了强大而灵活的测定形式，包括脂质激酶，磷酸酶，磷酸二酯酶等。

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