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    Use of Specifically Engineered Enzymes to Enhance the Efficacy of Prodrugs
    55.
    发明申请
    Use of Specifically Engineered Enzymes to Enhance the Efficacy of Prodrugs 有权
    使用专门设计的酶来提高前药的功效

    公开(公告)号：US20070258968A1

    公开(公告)日：2007-11-08

    申请号：US11760399

    申请日：2007-06-08

    Applicant: Arnon Lavie ,  Manfred Konrad ,  Farhad Ravandi

    Inventor： Arnon Lavie ,  Manfred Konrad ,  Farhad Ravandi

    IPC: A61K38/00 ,  C07H21/00 ,  C12N15/00 ,  C12N5/06 ,  C12N9/12 ,  C12P1/00

    CPC classification number: B82Y5/00 ,  A61K47/6815 ,  A61K47/6899 ,  C07K16/2803 ,  C07K2319/30 ,  C12N9/1205

    Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with enhanced activity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activity. Furthermore, the invention provides antibody-conjugated enzymes that can be specifically delivered to leukemic blast cells in vivo or ex vivo.

    Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效率的方法，所述酶具有增强的对癌症化疗中使用的核苷类似物的活性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供可以在体内或体外特异性递送至白血病胚胎细胞的抗体缀合的酶。

    Nitrogen mustard compounds and prodrugs therefor
    58.
    发明授权
    Nitrogen mustard compounds and prodrugs therefor 有权
    氮芥化合物及其前药

    公开(公告)号：US06852755B1

    公开(公告)日：2005-02-08

    申请号：US09937714

    申请日：2000-03-29

    Applicant: Caroline J. Springer ,  Lawrence C. Davies

    Inventor： Caroline J. Springer ,  Lawrence C. Davies

    IPC: A61K48/00 ,  A61K31/606 ,  A61K31/609 ,  A61K38/46 ,  A61K47/48 ,  A61P35/00 ,  A61P43/00 ,  C07C229/60 ,  C07C237/36 ,  A61K31/235 ,  A61K31/255 ,  C07C229/14 ,  C07C303/00 ,  C07C313/00

    CPC classification number: B82Y5/00 ,  A61K47/6899 ,  A61K47/6957 ,  C07C229/60 ,  C07C237/36

    Abstract: This invention pertains to nitrogen mustard compounds (Formula (II)) and prodrugs therefor (Formula (I)), methods for their preparation, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in therapy and treatment, for example, of cancer, wherein: R1 and R2 are independently —Cl, —Br, —I, —OSO2CH3, or —OSO2Ph; R1a, R2a, R1b, and R2b are independently —H, a C1-4alkyl group, or a C1-4haloalkyl group; R3 is —F, —Cl, —Br, —I, —OCHF2, —C≡CH, —OCF3, —CH3, —CF3, —SF5, —SCF3, or —CF2CF3; R4 is —H or as defined for R3−, R5 is —H or —F; R7 is —H, —C(CH3)3, or —CH2—CH—CH2; Z is —CH2—T—W; T is —CH2—, —O—, —S—, —(S═O)—, or —(SO2)—; W is one of: (1) —COOH; (2)—(C═O)OR8; (3) —(C═O)NR9R9; (4) —SO2NHR10−, (5) SO2OR11; (6)—PO3R11R11; (7) a tetrazol-5-yl group; (8) —CONH—SO2R12; and, (9)-M-Het.

    Abstract translation: 本发明涉及氮芥化合物（式（II））及其前药（式（I）），其制备方法，包含这些化合物的药物组合物，以及这些化合物和组合物在体外和体内的用途， 在治疗和治疗中，例如癌症，其中：R 1和R 2独立地是-Cl，-Br，-I，-OSO 2 CH 3或-OSO 2 Ph; R 1a，R 2a，R 1b和R 2b独立地是-H，C 1-4烷基或C 1-4卤代烷基; R 3是-F，-Cl，-Br，-I，-OCHF 2，-C = CH，-OCF 3，-CH 3，-CF 3，-SF 5，-SCF 3或-CF 2 CF 3; R 4是-H或如对R 3-3所定义，R 5是-H或-F; R 7是-H，-C（CH 3）3或-CH 2 -CH-CH 2; Z是-CH 2 -T-W; T是-CH 2 - ， - O - ， - S - ， - （S = O） - 或 - （SO 2） - ; W是以下之一：（1）-COOH; （2） - （C = O）OR 8; （3） - （C = O）NR 9 R 9; （4）-SO 2 NHR 10，（5）SO 2 OR 11; （6）-PO 3 R 11 R 11; （7）四唑-5-基; （8）-CONH-SO 2 R 12; 和（9）-M-Het。

    Treatment and diagnosis of cancer
    60.
    发明授权
    Treatment and diagnosis of cancer 有权

    公开(公告)号：US06649163B1

    公开(公告)日：2003-11-18

    申请号：US09357707

    申请日：1999-07-20

    Applicant: Neil H. Bander

    Inventor： Neil H. Bander

    IPC: A61K39395

    CPC classification number: A61K47/48638 ,  A61K47/6869 ,  A61K47/6899 ,  A61K2039/505 ,  B82Y5/00 ,  C07K16/3069 ,  C07K2317/77 ,  G01N33/57434 ,  G01N2333/705

    Abstract: The present invention is directed to the use of antibodies or binding portions thereof, probes, ligands, or other biological agents which either recognize an extracellular domain of prostate specific membrane antigen or bind to and are internalized with prostate specific membrane antigen. These biological agents can be labeled and used for detection of cancerous tissues, particularly cancerous tissues proximate to or containing vascular endothelial cells, which express an extracellular domain of prostate specific membrane antigen. The labeled biological agents can also be used to detect normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate or other cancers. Also disclosed are four hybridoma cell lines, each of which produces a monoclonal antibody recognizing extracellular domains of prostate specific membrane antigens of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof.

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