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    METHODS AND COMPOSITIONS FOR RADIOIMMUNOTHERAPY OF BRAIN AND CNS TUMORS
    1.
    发明申请
    METHODS AND COMPOSITIONS FOR RADIOIMMUNOTHERAPY OF BRAIN AND CNS TUMORS 审中-公开
    脑和CNS肿瘤放射免疫学的方法和组合

    公开(公告)号：WO2003101495A1

    公开(公告)日：2003-12-11

    申请号：PCT/GB2003/002334

    申请日：2003-05-28

    Applicant: IMMUNOMEDICS, INC. ,  MCCALL, John, Douglas ,  GRIFFITHS, Gary, L. ,  GOLDENBERG, David, M.

    Inventor： GRIFFITHS, Gary, L. ,  GOLDENBERG, David, M.

    IPC: A61K51/10

    CPC classification number: A61K51/109

    Abstract: A method for treating a brain tumor by administering to a patient (i) a multispecific antibody comprising at least one targeting arm that binds to a brain cancer antigen and at least one capture arm that binds to a radionuclide carrier; (ii) a therapeutic radionuclide carrier to which is bound a therapeutic radionuclide, wherein the multispecific antibody, radionuclide carrier and therapeutic radionuclide are administered in a substantially equimolar ratio.

    Abstract translation: 一种通过给予患者（i）包含至少一种与脑癌抗原结合的靶向臂的多特异性抗体和与放射性核素载体结合的至少一种捕获臂来治疗脑肿瘤的方法。 （ii）与治疗性放射性核素结合的治疗性放射性核素载体，其中所述多特异性抗体，放射性核素载体和治疗性放射性核素以基本上等摩尔比施用。

    IMPROVED DETECTION AND THERAPY OF LESIONS WITH BIOTIN-CHELATE CONJUGATES
    5.
    发明申请
    IMPROVED DETECTION AND THERAPY OF LESIONS WITH BIOTIN-CHELATE CONJUGATES 审中-公开
    改进的生物柴油凝胶的检测和治疗

    公开(公告)号：WO1998004293A1

    公开(公告)日：1998-02-05

    申请号：PCT/US1997013285

    申请日：1997-07-31

    Applicant: IMMUNOMEDICS, INC. ,  GRIFFITHS, Gary, L. ,  HANSEN, Hans, J. ,  KARACAY, Habibe

    Inventor： IMMUNOMEDICS, INC.

    IPC: A61K51/00

    CPC classification number: A61K49/10 ,  A61K49/085 ,  A61K49/14 ,  A61K51/0497 ,  B82Y5/00

    Abstract: An improved method of detecting and/or treating lesions in a patient in which a pre-targeting approach is used wherein the total amount of radionuclide delivered to a target cell, tissue, or pathogen is dramatically increased. In this method, the chelate conjugate may be purified by chromatography after chelate formation, may contain multiple chelates or a blood transit-modifying linker or added within the chelate conjugate, or both; or a combination of these. The improved chelate conjugates can be used as detection of therapeutic agents to detect or treat the targeted cell, tissue, or pathogen.

    Abstract translation: 一种用于检测和/或治疗患者中的损伤的改进方法，其中使用预靶向方法，其中递送至靶细胞，组织或病原体的放射性核素的总量显着增加。 在该方法中，螯合物形成后可以通过色谱法纯化螯合物缀合物，可以含有多个螯合物或血液转运修饰接头或加入到螯合缀合物内，或两者都可以。 或这些的组合。 改进的螯合物可用作检测或治疗靶细胞，组织或病原体的治疗剂的检测。

    THIOLATION OF PEPTIDES FOR RADIONUCLIDE-BASED RADIODETECTION AND RADIOTHERAPY
    6.
    发明申请
    THIOLATION OF PEPTIDES FOR RADIONUCLIDE-BASED RADIODETECTION AND RADIOTHERAPY 审中-公开
    基于放射性核素的放射治疗和放射治疗的肽的断裂

    公开(公告)号：WO1996040289A1

    公开(公告)日：1996-12-19

    申请号：PCT/US1996008693

    申请日：1996-06-07

    Applicant: IMMUNOMEDICS, INC. ,  GOVINDAN, Serengulam, V. ,  GRIFFITHS, Gary, L. ,  HANSEN, Hans, L.

    Inventor： IMMUNOMEDICS, INC.

    IPC: A61K51/00

    CPC classification number: A61K51/088 ,  A61K51/083

    Abstract: A method of radiolabeling a peptide, e.g., somatostatin or an analogue thereof or vasoactive intestinal peptide, with a radioisotope of technetium or rhenium, comprises the steps of: (a) reacting the peptide with an acetyl-protected t -thiol-containing, amine-reactive bifunctional chelating agent; (b) deprotecting the acetyl- t -thiol group to generate a free t -thiol group; and either (c) admixing the peptide- t -thiol-containing conjugate with a stannous salt; and (d) reacting the mixture of step (c) with pertechnetate or perrhenate, or (c') adding reduced pertechnetate or perrhenate to said peptide- t -thiol-containing conjugate, thereby forming a radiolabeled peptide. Kits for effecting the radiolabeling method, and methods of tumor detection/imaging or therapy are provided.

    Abstract translation: 将肽，例如生长抑素或其类似物或血管活性肠肽与锝或铼的放射性同位素放射标记的方法包括以下步骤：（a）使肽与乙酰基保护的u 含硫醇的胺反应性双功能螯合剂; （b）使乙酰基-t硫醇基脱保护以产生游离叔硫醇基团; 并且（c）将含有肽-TH-硫醇的缀合物与亚锡盐混合; 和（d）使步骤（c）的混合物与高锝酸盐或高铼酸盐反应，或（c'）向所述含有肽-TH-硫醇的缀合物加入减少的高锝酸盐或高铼酸盐，由此形成放射性标记的肽 。 提供了用于实现放射性标记方法的试剂盒，以及肿瘤检测/成像或治疗方法。

    METHODS OF TREATING CANCER AND OTHER DISEASES
    7.
    发明申请
    METHODS OF TREATING CANCER AND OTHER DISEASES 审中-公开
    治疗癌症及其他疾病的方法

    公开(公告)号：WO2012058269A2

    公开(公告)日：2012-05-03

    申请号：PCT/US2011/057820

    申请日：2011-10-26

    Applicant: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  GOLDSBOROUGH, Andrew S. ,  DULCEY, Andres ,  HANDLEY, Misty ,  HALL, Matthew D. ,  BRIMACOMBE, Kyle ,  GRIFFITHS, Gary L. ,  GOTTESMAN, Michael M.

    Inventor： GOLDSBOROUGH, Andrew S. ,  DULCEY, Andres ,  HANDLEY, Misty ,  HALL, Matthew D. ,  BRIMACOMBE, Kyle ,  GRIFFITHS, Gary L. ,  GOTTESMAN, Michael M.

    IPC: C07C321/14

    CPC classification number: C07C323/60

    Abstract: Disclosed are a method of treating cancer in a cell, a method of enhancing the chemotherapeutic treatment of a cancer treatment agent, a method of reducing resistance of a cancer cell to a chemotherapeutic agent, a method of reducing the amount or activity of an ABC-family mRNA and/or protein, a method of reducing the amount or activity of the ABCB1 mRNA and/or protein or the ABCC1 mRNA and/or protein in an animal cell undergoing cancer treatment, a method of reducing the amount or activity of glutathione and/or Bcl2 in the cancer cell, a method of treating other multidrug resistant diseases, and a method of treating a multidrug resistant cell such as a bacterial multidrug resistant Staphylococcus aureus (MRSA), tuberculosis, fungal infection, or MDR malaria, by administering a compound of the Formula (I): a diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 1 -R 4 are as described herein. Also disclosed are pharmaceutical compositions comprising a compound of formula (I), a diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

    Abstract translation: 公开了一种治疗细胞癌的方法，增强癌症治疗剂的化学治疗的方法，降低癌细胞对化学治疗剂的抗性的方法，降低ABC- 家族mRNA和/或蛋白质，在经历癌症治疗的动物细胞中减少ABCB1 mRNA和/或蛋白质或ABCC1 mRNA和/或蛋白质的量或活性的方法，减少谷胱甘肽的量或活性的方法和 /或Bcl2，治疗其他多药耐药性疾病的方法，以及治疗多药耐药性金黄色葡萄球菌（MRSA），结核病，真菌感染或MDR疟疾的多药耐药性细胞的方法，通过施用 式（I）化合物：其非对映异构体或其药学上可接受的盐，其中R 1 -R 4如本文所述。 还公开了包含式（I）化合物，其非对映异构体或其药学上可接受的盐和药学上可接受的载体的药物组合物。

    IMPROVED METHOD FOR PREPARING CONJUGATES OF PROTEINS AND CHELATING AGENTS
    8.
    发明申请
    IMPROVED METHOD FOR PREPARING CONJUGATES OF PROTEINS AND CHELATING AGENTS 审中-公开
    制备蛋白质和螯合剂结合物的改进方法

    公开(公告)号：WO2005084179A3

    公开(公告)日：2006-03-16

    申请号：PCT/US2004040046

    申请日：2004-12-01

    Applicant: IMMUNOMEDICS INC ,  GRIFFITHS GARY L ,  GOVINDAN SERENGULAM V

    Inventor： GRIFFITHS GARY L ,  GOVINDAN SERENGULAM V

    IPC: A61K51/00 ,  A61K51/10 ,  C07K14/52 ,  C07K14/525 ,  C07K14/54 ,  C07K16/46 ,  A61K51/08

    CPC classification number: A61K51/1027 ,  A61K51/0482 ,  A61K51/1045

    Abstract: Improved synthesis methods are provided for preparing conjugates of proteins and chelating agents. In the synthesis methods, non-stable bonds are hydrolyzed after the conjugate is synthesized, for example by treating the conjugate with a quenching agent. The synthesis method provides conjugates that are substantially free of non-stable bonds between the protein and the chelating agent, such that the chelating agent is less likely to dissociate with the conjugate after the conjugate has been stored for extended periods. The conjugate may be useful for therapeutic or diagnostic methods.

    Abstract translation: 提供改进的合成方法用于制备蛋白质和螯合剂的缀合物。 在合成方法中，在合成共轭物后，例如通过用猝灭剂处理缀合物，非稳定键被水解。 合成方法提供基本上不含蛋白质和螯合剂之间非稳定键的缀合物，使得螯合剂在缀合物长时间储存​​后不太可能与缀合物解离。 缀合物可用于治疗或诊断方法。

    STABLE RADIOIODINE CONJUGATES AND METHODS FOR THEIR SYNTHESIS
    9.
    发明申请
    STABLE RADIOIODINE CONJUGATES AND METHODS FOR THEIR SYNTHESIS 审中-公开
    稳定的放射性素结合物及其合成方法

    公开(公告)号：WO1999011294A1

    公开(公告)日：1999-03-11

    申请号：PCT/US1997023711

    申请日：1997-12-19

    Applicant: IMMUNOMEDICS, INC. ,  GOVINDAN, Serengulam, V. ,  GRIFFITHS, Gary, L.

    Inventor： IMMUNOMEDICS, INC.

    IPC: A61K51/04

    CPC classification number: A61K51/0491 ,  A61K51/088 ,  A61K51/10 ,  A61K51/1093 ,  C07H3/04 ,  C07K1/1077 ,  G01N33/543

    Abstract: Methods are described for conjugating radioiodinated peptides or carbohydrate structures to proteins with improved yields and qualities of conjugates. In one method, specially designed radioiodinated bifunctional peptides containing nonmetabolizable bonds such as amide bonds are coupled to cell targeting protein. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to protein. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to protein. In a fourth method, a hydrazide-appended protein is coupled to a radioiodinated carbohydrate or a thiolated protein is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated protein. Radioiodinated residualizing protein conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

    Abstract translation: 描述了将放射性碘化肽或碳水化合物结构与缀合物的产率和质量提高的蛋白质缀合的方法。 在一种方法中，特异设计的含有非代谢性键如酰胺键的放射性碘化双功能肽与细胞靶向蛋白偶联。 在第二种方法中，也含有氨基多羧酸盐的放射性碘化的不可代谢的双功能肽与蛋白质偶联。 在第三种方法中，放射性碘化双官能氨基多羧酸盐与蛋白质偶联。 在第四种方法中，酰肼附着的蛋白质与放射性碘化碳水化合物偶联，或硫醇化蛋白质与酰肼附着和放射性碘化碳水化合物偶联。 在第五种方法中，使用monoderivatized氰尿酰氯来缀合硫醇化蛋白质。 通过这些方法制备的放射性碘化残留蛋白质缀合物在体内特别稳定，适用于放射免疫检测和放射免疫治疗。

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