公开(公告)号：US06379918B1

公开(公告)日：2002-04-30

申请号：US09374560

申请日：1999-08-13

申请人： Philip T. Feldsine ,  David E. Kerr ,  Ping Zhu ,  Linda Mui

发明人： Philip T. Feldsine ,  David E. Kerr ,  Ping Zhu ,  Linda Mui

IPC分类号： C12Q104

CPC分类号： G01N33/56922 ,  C12Q1/04 ,  C12Q1/045 ,  G01N33/56916 ,  G01N2333/205 ,  G01N2333/245 ,  G01N2333/255

摘要： Compositions, formulae, devices and methods for the detection of target microorganisms, such as by visual immunoprecipitate assay, enzyme linked immunoassay, chemiluminescence, immunoblotting, or similar detection technology, wherein detection requires the discrimination among closely related genera, species and strains of antigenically related microorganisms based on immunological reactivity of a highly conserved antigen epitopes with a reagent system comprised of an antibody linked to a detecting reagent. The invention permits a detectable event to occur by exposing inaccessible but highly conserved and specific antigen epitopes to the detecting reagent. Exposure of such antigen epitopes without inactivating microbial metabolism allows for specific detection.

公开(公告)号：US4975278A

公开(公告)日：1990-12-04

申请号：US211301

申请日：1988-06-29

申请人： Peter D. Senter ,  Mark G. Saulnier ,  Joseph P. Brown ,  David E. Kerr

发明人： Peter D. Senter ,  Mark G. Saulnier ,  Joseph P. Brown ,  David E. Kerr

IPC分类号： A61K47/48

CPC分类号： B82Y5/00 ,  A61K47/48761

摘要： This invention relates to a novel method for the delivery of cytotoxic drugs to tumor cells by the administration of a tumor-specific antibody-enzyme conjugate that binds to the tumor cells, and the additional administration of a prodrug that is converted at the tumor site, in the presence of the antibody-bound enzyme, to an active cytotoxic drug. According to preferred embodiments of this invention, antibody-enzyme conjugates containing the enzyme, alkaline phosphatase ("AP"), have been used in conjunction with the novel prodrug, etoposide-4'-phosphate or 7-(2'-aminoethyl phosphate)mitomycin or a combination thereof, to effect killing of tumor cells. According to another embodiment of the invention, an antibody-enzyme conjugate containing the enzyme, penicillin V amidase ("PVA"), has been used in conjunction with a novel prodrug, N-(p-hydroxyphenoxyacetyl)adriamycin to effect killing of tumor cells. Still another embodiment of the invention relates to the use of an antibody-enzyme conjugate containing the enzyme, cytosine deaminase ("CD"), in combination with the prodrug, 5-fluorocytosine, to effect killing of tumor cells. The method, antibody-enzyme conjugates, prodrugs, pharmaceutical compositions and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.

摘要翻译： 本发明涉及通过施用与肿瘤细胞结合的肿瘤特异性抗体 - 酶结合物向肿瘤细胞递送细胞毒性药物的新方法，以及额外施用在肿瘤部位转化的前体药物， 在抗体结合酶存在下，与活性细胞毒性药物接触。 根据本发明的优选实施方案，含有酶碱性磷酸酶（“AP”）的抗体 - 酶缀合物已经与新的前药，依托泊苷-4'-磷酸或7-（2'-氨基乙基磷酸酯）结合使用， 丝裂霉素或其组合，以杀死肿瘤细胞。 根据本发明的另一个实施方案，含有酶青霉素V酰胺酶（“PVA”）的抗体 - 酶结合物已经与新的前体药物N-（对羟基苯氧基乙酰基）阿霉素结合使用，以杀死肿瘤细胞 。 本发明的另一个实施方案涉及含有酶，胞嘧啶脱氨酶（“CD”）与前体药物5-氟胞嘧啶组合的抗体 - 酶偶联物用于杀死肿瘤细胞的用途。 本发明的方法，抗体 - 酶缀合物，前药，药物组合物和组合提供增强的肿瘤细胞的选择性杀伤，因此可用于治疗癌症和其它肿瘤。