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    Blood treatment method
    1.
    发明授权
    Blood treatment method 失效
    血液处理方法

    公开(公告)号：US5418129A

    公开(公告)日：1995-05-23

    申请号：US803065

    申请日：1991-12-06

    申请人： Edward Nudelman ,  Anil Singhal ,  Henrik Clausen ,  Sen-itiroh Hakomori ,  Kazuo Muroi ,  Toshio Suda ,  Hisao Nojiri

    发明人： Edward Nudelman ,  Anil Singhal ,  Henrik Clausen ,  Sen-itiroh Hakomori ,  Kazuo Muroi ,  Toshio Suda ,  Hisao Nojiri

    IPC分类号： A61K38/00 ,  C07K16/30 ,  C12P21/08 ,  A01N1/02 ,  A61K39/395 ,  C07K15/28

    CPC分类号： C07K16/30 ,  A61K38/00

    摘要： A method of producing monoclonal antibodies that bind to tumor-associated gangliosides, the method comprising: (1) immunizing a host with tumor cells; (2) boosting the host with a suspension comprising a mixture of tumor cell membrane and at least one purified lactonized tumor-associated ganglioside; (3) boosting the host with an immunogen comprising a lactone of a tumor associated ganglioside adsorbed on or incorporated into a carrier; (4) fusing immunized cells from the host with myeloma cells to form hybridoma cells; (5) selecting hybridoma cells that produce antibody that binds to the ganglioside of step (3); (6) culturing the selected hybridoma cells; and (7) recovering the antibody.

    摘要翻译： 一种产生与肿瘤相关神经节苷脂结合的单克隆抗体的方法，所述方法包括：（1）用肿瘤细胞免疫宿主; （2）用包含肿瘤细胞膜和至少一种经内化的内源性肿瘤相关神经节苷脂的混合物的悬浮液加强宿主; （3）用包含吸附在载体上或结合到载体中的肿瘤相关神经节苷脂的内酯的免疫原来加强宿主; （4）将来自宿主的免疫细胞与骨髓瘤细胞融合以形成杂交瘤细胞; （5）选择产生与步骤（3）的神经节苷脂结合的抗体的杂交瘤细胞; （6）培养所选择的杂交瘤细胞; 和（7）回收抗体。

    Method for the production of monoclonal antibodies directed to tumor-associated gangliosides and fucogangliosides
    2.
    发明授权
    Method for the production of monoclonal antibodies directed to tumor-associated gangliosides and fucogangliosides 失效
    用于产生针对肿瘤相关神经节苷脂和神经节苷脂的单克隆抗体的方法

    公开(公告)号：US5240833A

    公开(公告)日：1993-08-31

    申请号：US787778

    申请日：1991-11-06

    申请人： Edward Nudelman ,  Anil Singhal ,  Henrik Clausen ,  Sen-itiroh Hakomori

    发明人： Edward Nudelman ,  Anil Singhal ,  Henrik Clausen ,  Sen-itiroh Hakomori

    IPC分类号： A61K38/00 ,  C07K16/30 ,  C12P21/08

    CPC分类号： C07K16/30 ,  A61K38/00

    摘要： A method of producing monoclonal antibodies that bind to tumor-associated gangliosides, the method comprising: (1) immunizing a host with tumor cells; (2) boosting the host with a suspension comprising a mixture of tumor cell membrane and at least one purified lactonized tumor-associated ganglioside; (3) boosting the host with an immunogen comprising a lactone of a tumor associated ganglioside adsorbed on or incorporated into a carrier; (4) fusing immunized cells from the host with myeloma cells to form hybridoma cells: (5) selecting hybridoma cells that produce antibody that binds to the ganglioside of step (3); (6) culturing the selected hybridoma cells; and (7) recovering the antibody. Hybridomas and monoclonal antibodies produced by the above-described method. A passive immunization method for treatment of tumors containing gangliosides comprising administering to a subject: (A) a pharmaceutically effective amount of an antibody produced by the above described method. A method for detecting tumors containing gangliosides comprising: (A) contacting a test sample with an antibody produced by the above described method; and (B) assaying for the specific binding of the antibody to antigen in the test sample.

    摘要翻译： 一种产生与肿瘤相关神经节苷脂结合的单克隆抗体的方法，所述方法包括：（1）用肿瘤细胞免疫宿主; （2）用包含肿瘤细胞膜和至少一种经内化的内源性肿瘤相关神经节苷脂的混合物的悬浮液加强宿主; （3）用包含吸附在载体上或结合到载体中的肿瘤相关神经节苷脂的内酯的免疫原来加强宿主; （4）将来自宿主的免疫细胞与骨髓瘤细胞融合以形成杂交瘤细胞：（5）选择产生与步骤（3）的神经节苷脂结合的抗体的杂交瘤细胞; （6）培养所选择的杂交瘤细胞; 和（7）回收抗体。 通过上述方法制备的杂交瘤和单克隆抗体。 一种用于治疗含有神经节苷脂的肿瘤的被动免疫方法，包括对受试者施用：（A）药学有效量的由上述方法产生的抗体。 一种用于检测含有神经节苷脂的肿瘤的方法，包括：（A）使测试样品与通过上述方法产生的抗体接触; 和（B）在测试样品中测定抗体与抗原的特异性结合。

    Monoclonal antibodies and vaccine development directed to human cancer-associated antigens by immunization with carbohydrate-carrier conjugates
    3.
    发明授权
    Monoclonal antibodies and vaccine development directed to human cancer-associated antigens by immunization with carbohydrate-carrier conjugates 失效
    通过用碳水化合物 - 载体缀合物免疫，针对人类癌症相关抗原的单克隆抗体和疫苗开发

    公开(公告)号：US5660834A

    公开(公告)日：1997-08-26

    申请号：US400480

    申请日：1995-03-08

    申请人： Thomas J. Kjeldsen ,  Henrik Clausen ,  Anil Singhal ,  Tatsushi Toyokuni ,  Helio K. Takahashi ,  Sen-Itiroh Hakomori

    发明人： Thomas J. Kjeldsen ,  Henrik Clausen ,  Anil Singhal ,  Tatsushi Toyokuni ,  Helio K. Takahashi ,  Sen-Itiroh Hakomori

    IPC分类号： A61K39/00 ,  C07K14/47 ,  C07K16/30 ,  A61K38/14 ,  A61K39/39 ,  C07K14/82

    CPC分类号： C07K14/4727 ,  A61K39/0011 ,  C07K16/30 ,  A61K2039/55572 ,  A61K2039/6018 ,  A61K2039/6081 ,  A61K2039/645

    摘要： A vaccine and method to prevent growth and replication of cancer cells that express a core structure of a mucin-type glycoprotein is disclosed. The vaccine comprises: (a) a pharmaceutically effective amount of an antigen comprising a purified mucin-type glycoprotein or a chemically synthesized mucin-type glycoprotein carbohydrate determinant conjugated to a carrier peptide or macromolecule, wherein said mucin-type glycoprotein expresses or carries the core structure of a mucin-type glycoprotein expressed on said cancer cells; and (b) a pharmaceutically acceptable carrier including natural or synthetic adjuvants. The method comprises administering the above-described vaccine to a host. A medicament and method for treating cancer wherein the cancer cells express a core structure of a mucin-type glycoprotein is disclosed. The medicament comprises: (a) a pharmaceutically effective amount of an anti-cancer antibody or fragment comprising a binding site thereof, said anti-cancer antibody having been produced against a purified core structure of a mucin-type glycoprotein; and (b) a pharmaceutically acceptable carrier, diluent or excipient. The method comprises administering the above-described medicament to a host.

    摘要翻译： 公开了一种用于预防表达粘蛋白型糖蛋白的核心结构的癌细胞的生长和复制的疫苗和方法。 疫苗包含：（a）药学有效量的抗原，其包含与载体肽或大分子缀合的纯化的粘蛋白型糖蛋白或化学合成的粘蛋白型糖蛋白碳水化合物决定簇，其中所述粘蛋白型糖蛋白表达或携带核心 在所述癌细胞上表达的粘蛋白型糖蛋白的结构; 和（b）包括天然或合成佐剂的药学上可接受的载体。 该方法包括将上述疫苗给予宿主。 公开了一种治疗癌症的药物和方法，其中癌细胞表达粘蛋白型糖蛋白的核心结构。 药物包括：（a）药学有效量的抗癌抗体或包含其结合位点的片段，所述抗癌抗体是针对粘蛋白型糖蛋白的纯化核心结构产生的; 和（b）药学上可接受的载体，稀释剂或赋形剂。 该方法包括将上述药物施用于宿主。

    Synthesis of Le.sup.x ; dimeric Le.sup.x (difucosyl Y.sub.2 ; III.sup.3 FucV.sup.3 FucnLc.sub.6 Cer); sialylated forms thereof; and analogues thereof
    6.
    发明授权
    Synthesis of Le.sup.x ; dimeric Le.sup.x (difucosyl Y.sub.2 ; III.sup.3 FucV.sup.3 FucnLc.sub.6 Cer); sialylated forms thereof; and analogues thereof 失效
    合成Lex; 二聚Lex（二氟代基Y2; III3FucV3FucnLc6Cer）; 唾液酸化形式; 及其类似物

    公开(公告)号：US5421733A

    公开(公告)日：1995-06-06

    申请号：US705671

    申请日：1991-05-24

    申请人： Edward Nudelman ,  Khalid K. Sadozai ,  Henrik Clausen ,  Sen-itiroh Hakomori ,  Mark Stroud

    发明人： Edward Nudelman ,  Khalid K. Sadozai ,  Henrik Clausen ,  Sen-itiroh Hakomori ,  Mark Stroud

    IPC分类号： C12P19/26 ,  A61K39/00 ,  C12P19/04 ,  C12R1/91 ,  G01N33/574 ,  G01N33/577 ,  C12P19/02

    CPC分类号： C12P19/04

    摘要： A process for preparing difucosyl Y.sub.2 antigen (dimeric Le.sup.x) , said process comprising: (1) preparing a lactonorhexaosylceramide backbone or a lactonorhexaosylsaccharide backbone linked to a carrier molecule; and (2) enzymatically fucosylating said backbone at the III.sup.3 and V.sup.3 positions through an .alpha.1.fwdarw.3 linkage. A process for preparing Le.sup.y antigen analogues, said process comprising: (1) preparing a lactonorhexaosyl-ceramide backbone or a lactonorhexaosylsaccharide backbone linked to a carrier molecule; and (2) enzymatically fucosylating said backbone at the terminal .beta.-Gal through an .alpha.1.fwdarw.2 linkage; and (3) enzymatically fucosylating said backbone at one or more positions through an .alpha.1.fwdarw.3 linkage, provided that steps (2) and (3) can be conducted simultaneously or in any order. A process for preparing a fucosylated lactonorhexaosylceramide, lactonorhexaosylsaccharide linked to a carrier molecule or higher analogues thereof, said process comprising: (1) preparing a lactonorhexaosylceramide backbone, a lactonorhexaosylsaccharide backbone linked to a carrier molecule or backbones of higher analogues thereof; and (2) enzymatically fucosylating one or more residues of said backbone. A process for preparing sialyl Le.sup.x and sialyl dimeric Le.sup.x.

    摘要翻译： 一种制备二氟吗啉Y2抗原（二聚Lex）的方法，所述方法包括：（1）制备与载体分子连接的乳糖六烯酰基神经酰胺主链或乳糖六糖糖主链; 和（2）通过α1-> 3键在III3和V3位置酶解岩藻糖基化所述骨架。 一种制备Ley抗原类似物的方法，所述方法包括：（1）制备与载体分子连接的乳酰六烯酰基 - 神经酰胺主链或乳糖六糖糖主链; 和（2）通过α1-> 2键在末端β-Gal处对所述骨架进行酶促岩藻糖化; 和（3）通过α1-> 3键在一个或多个位置对所述主链进行酶促岩藻糖化，条件是步骤（2）和（3）可以同时或以任何顺序进行。 一种制备岩藻糖基化的乳酰六烯酰基神经酰胺，与载体分子或其更高类似物连接的内酯六糖基糖的方法，所述方法包括：（1）制备乳糖六烯酰基神经酰胺主链，连接于载体分子或其较高类似物的骨架的乳糖六糖糖主链; 和（2）酶促岩藻糖化所述骨架的一个或多个残基。 唾液酸Lex和唾液酸二聚体Lex的制备方法。

    Methods for glyco-engineering plant cells for controlled human O-glycosylation
    10.
    发明授权
    Methods for glyco-engineering plant cells for controlled human O-glycosylation 有权
    糖酵解植物细胞用于受控人O-糖基化的方法

    公开(公告)号：US09024110B2

    公开(公告)日：2015-05-05

    申请号：US13070248

    申请日：2011-03-23

    申请人： Zhang Yang ,  Damian Paul Drew ,  Emma Adhiambo Arigi ,  Peter Ulvskov ,  Steven B. Levery ,  Eric Bennett ,  Henrik Clausen ,  Brent Larsen Petersen

    发明人： Zhang Yang ,  Damian Paul Drew ,  Emma Adhiambo Arigi ,  Peter Ulvskov ,  Steven B. Levery ,  Eric Bennett ,  Henrik Clausen ,  Brent Larsen Petersen

    IPC分类号： C12N15/82 ,  C12N15/12 ,  C12N15/30 ,  C12N15/31 ,  C12N9/10 ,  C12N9/90 ,  C12P19/00 ,  C12P19/44 ,  A61K38/47 ,  C12N1/13 ,  C07K14/47 ,  C12P21/00

    CPC分类号： C12N15/8257 ,  C07K14/4727 ,  C12N15/8245 ,  C12P21/005

    摘要： This invention discloses the development of a novel platform for recombinant production of bioactive glycoproteins and cancer specific vaccines in plants. Plants and plant cell cultures have been humanized with respect to human mucin-type protein O-glycosylation. A panel of plant cell factories for production of recombinant glycoproteins with designed human O-glycosylation, including an improved cancer vaccine candidate, has been developed. The platform provides basis for i) production of an essentially unlimited array of O-glycosylated human glycoprotein therapeutics, such as human interferon α2B and podoplanin, and ii) for further engineering of additional cancer specific O-glycans on glycoproteins of therapeutical value. Currently, mammalian cells are required for human O-glycosylation, but plants offer a unique cell platform for engineering O-glycosylation since they do not perform human type O-glycosylation. Introduction of O-glycosylation into plant cells requires i) that wild-type plant cells do not modify the target peptide substrates and ii) that the appropriate enzymes and substrates are introduced into of plant cells such that O-glycosylation in the secretory pathway proceed and the glycosylated peptide substrates are preferentially exported to the exterior of the cell or accumulated in the cell. In this invention i) the integrity of transiently and stably expressed ‘mucin’ type target peptides in plants cells has been determined and ii) mucin-type O-glycosylation has been established in plants by transient and stable introduction of a Pseudomonas aeruginosa C4-epimerase, the human polypeptide GalNAc-transferases T2 and T4 (GalNAc-T2 and T4) and various human target peptides or proteins. In the present invention GalNAc-T2 and -T4 have been used to produce a Tn cancer glycoform of MUC1.

    摘要翻译： 本发明公开了在植物中重组生物活性糖蛋白和癌特异性疫苗重组生产的新平台的开发。 植物和植物细胞培养物相对于人粘蛋白型蛋白O-糖基化已被人源化。 已经开发了一组用于生产具有设计的人O-糖基化的重组糖蛋白的植物细胞工厂，包括改进的癌症疫苗候选物。 该平台为i）生产基本上无限量的O-糖基化的人类糖蛋白治疗剂例如人干扰素α2B和podoplanin的基础，以及ii）用于在治疗价值的糖蛋白上进一步工程化另外的癌症特异性O-聚糖。 目前，哺乳动物细胞是人O-糖基化所必需的，但由于它们不进行人类O-糖基化，植物提供了独特的用于工程化O-糖基化的细胞平台。 将O-糖基化引入到植物细胞中需要i）野生型植物细胞不修饰靶肽底物，和ii）将合适的酶和底物引入植物细胞，使分泌途径中的O-糖基化进行， 糖基化肽底物优选地输出到细胞的外部或者积聚在细胞中。 在本发明中，i）已经确定了植物细胞中瞬时稳定表达的“粘蛋白”型靶肽的完整性，并且ii）通过暂时稳定地引入铜绿假单胞菌C4差向异构酶，在植物中建立了粘蛋白型O-糖基化 ，人多肽GalNAc-转移酶T2和T4（GalNAc-T2和T4）和各种人靶肽或蛋白质。 在本发明中，已经使用GalNAc-T2和-T4来产生MUC1的Tn癌糖蛋白。