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    Blocked lectins, methods and affinity support for making same using affinity ligands, and method of killing selected cell populations having reduced nonselective cytotoxicity
    4.
    发明授权
    Blocked lectins, methods and affinity support for making same using affinity ligands, and method of killing selected cell populations having reduced nonselective cytotoxicity 失效
    阻断凝集素，方法和亲和力支持使用亲和配体进行相同的操作，以及杀死选择性细胞群降低非选择性细胞毒性的方法

    公开(公告)号：US5239062A

    公开(公告)日：1993-08-24

    申请号：US560948

    申请日：1990-07-31

    申请人： Walter A. Blattler ,  John M. Lambert ,  Victor S. Goldmacher ,  Ravi V. J. Chari ,  Charles F. Scott, Jr. ,  Linda J. Kostuba ,  Simon E. Moroney ,  Albert R. Collinson

    发明人： Walter A. Blattler ,  John M. Lambert ,  Victor S. Goldmacher ,  Ravi V. J. Chari ,  Charles F. Scott, Jr. ,  Linda J. Kostuba ,  Simon E. Moroney ,  Albert R. Collinson

    IPC分类号： A61K47/48 ,  C07H21/00

    CPC分类号： C07H21/00 ,  A61K47/48438

    摘要： An activated affinity ligand is described comprising: a ligand having (a) a region with affinity for binding sites of a lectin; and (b) a reactive group capable of covalently linking the ligand to the lectin to thereby block one or more of the binding sites of the lectin. A blocked lectin is described comprising one or more affinity ligands covalently linked by means of a reactive group present on each of the ligands to a lectin such that one or more binding sites of the lectin is blocked. A cell-binding agent-blocked lectin conjugate is described comprising the above-described blocked lectin and a cell-binding agent covalently linked to: (a) one of the covalently linked affinity ligands; or (b) the lectin. A method of preparing a blocked lectin is described. A method of preparing the cell-binding agent-blocked lectin conjugate is described. An affinity support capable of binding to a lectin to form a blocked lectin is described comprising an activated affinity ligand covalently linked to a solid support. A method of preparing the affinity support capable of binding to a lectin to form a blocked lectin is described. A method of killing selected cell populations having reduced cytotoxicity to non-selected cell populations is described comprising contacting a cell population or tissue suspected of containing cells from said selected cell population with the above-described cell-binding agent-blocked lectin conjugate, wherein the lectin is a cytotoxic lectin. Medicaments and methods of treatment using the above-described cell-binding agent-blocked lectin conjugate also are described.

    摘要翻译： 描述了活化的亲和配体，其包括：具有（a）对凝集素的结合位点具有亲和力的区域的配体; 和（b）能够将配体与凝集素共价连接从而阻断凝集素的一个或多个结合位点的反应性基团。 描述了封闭的凝集素，其包含通过存在于每个配体上的反应性基团与凝集素共价连接的一个或多个亲和配体，使得凝集素的一个或多个结合位点被阻断。 描述了包含上述封闭凝集素和共价连接的细胞结合剂的细胞结合剂阻断的凝集素缀合物：（a）共价连接的亲和配体之一; 或（b）凝集素。 描述了一种制备阻塞凝集素的方法。 描述了制备细胞粘附剂阻断的凝集素缀合物的方法。 描述了能够结合凝集素以形成封闭的凝集素的亲和载体，其包含与固体支持物共价连接的活化的亲和配体。 描述了制备能够结合凝集素形成封闭的凝集素的亲和载体的方法。 描述了杀死对未选择的细胞群体具有降低的细胞毒性的选定细胞群的方法，其包括使来自所述选择的细胞群的怀疑含有细胞的细胞群体或组织与上述细胞结合剂阻断的凝集素缀合物接触，其中 凝集素是一种细胞毒素凝集素。 还描述了使用上述细胞结合剂阻断的凝集素缀合物的药物和治疗方法。

    Blocked lectins; methods and affinity support for making the same using affinity ligands; and method of killing selected cell populations having reduced non-selective cytotoxicity
    5.
    发明授权
    Blocked lectins; methods and affinity support for making the same using affinity ligands; and method of killing selected cell populations having reduced non-selective cytotoxicity 失效
    阻断凝集素; 方法和亲和力支持使用亲和配体进行相同; 以及杀死所选择的具有降低的非选择性细胞毒性的细胞群的方法

    公开(公告)号：US5395924A

    公开(公告)日：1995-03-07

    申请号：US19831

    申请日：1993-02-19

    申请人： Walter A. Blattler ,  John M. Lambert ,  Victor S. Goldmacher ,  Ravi V. J. Chari ,  Charles F. Scott, Jr. ,  Linda J. Kostuba ,  Simon E. Moroney ,  Albert R. Collison

    发明人： Walter A. Blattler ,  John M. Lambert ,  Victor S. Goldmacher ,  Ravi V. J. Chari ,  Charles F. Scott, Jr. ,  Linda J. Kostuba ,  Simon E. Moroney ,  Albert R. Collison

    IPC分类号： A61K47/48 ,  C07H21/00 ,  C07K3/00 ,  A61K39/00

    CPC分类号： C07H21/00 ,  A61K47/48438

    摘要： An activated affinity ligand is described comprising: a ligand having (a) a region with affinity for binding sites of a lectin; and (b) a reactive group capable of covalently linking the ligand to the lectin to thereby block one or more of the binding sites of the lectin. A blocked lectin is described comprising one or more affinity ligands covalently linked by means of a reactive group present on each of the ligands to a lectin such that one or more binding sites of the lectin is blocked. A cell-binding agent-blocked lectin conjugate is described comprising the above-described blocked lectin and a cell-binding agent covalently linked to: (a) one of the covalently linked affinity ligands; or (b) the lectin. A method of preparing the cell-binding agent-blocked lectin conjugate is described. An affinity support capable of binding to a lectin to form a blocked lectin is described comprising an activated affinity ligand covalently linked to a solid support. A method of preparing the affinity support capable of binding to a lectin to form a blocked lectin is described. A method of killing selected cell populations having reduced cytotoxicity to non-selected cell populations is described comprising contacting a cell population or tissue suspected of containing cells from said selected cell population with the above-described cell-binding agent-blocked lectin conjugate, wherein the lectin is a cytotoxic lectin. Medicaments and methods of treatment using the above-described cell-binding agent-blocked lectin conjugate also are described.

    摘要翻译： 描述了活化的亲和配体，其包括：具有（a）对凝集素的结合位点具有亲和力的区域的配体; 和（b）能够将配体与凝集素共价连接从而阻断凝集素的一个或多个结合位点的反应性基团。 描述了封闭的凝集素，其包含通过存在于每个配体上的反应性基团与凝集素共价连接的一个或多个亲和配体，使得凝集素的一个或多个结合位点被阻断。 描述了包含上述封闭凝集素和共价连接的细胞结合剂的细胞结合剂阻断的凝集素缀合物：（a）共价连接的亲和配体之一; 或（b）凝集素。 描述了制备细胞结合剂阻断的凝集素缀合物的方法。 描述了能够结合凝集素以形成封闭的凝集素的亲和载体，其包含与固体支持物共价连接的活化的亲和配体。 描述了制备能够结合凝集素形成封闭的凝集素的亲和载体的方法。 描述了杀死对未选择的细胞群体具有降低的细胞毒性的选定细胞群的方法，其包括使来自所述选择的细胞群的怀疑含有细胞的细胞群体或组织与上述细胞结合剂阻断的凝集素缀合物接触，其中 凝集素是一种细胞毒素凝集素。 还描述了使用上述细胞结合剂阻断的凝集素缀合物的药物和治疗方法。

    Cytotoxic agents comprising maytansinoids and their therapeutic use
    6.
    发明授权
    Cytotoxic agents comprising maytansinoids and their therapeutic use 失效
    含美登木素生物碱的细胞毒素及其治疗用途

    公开(公告)号：US5208020A

    公开(公告)日：1993-05-04

    申请号：US911380

    申请日：1992-07-13

    申请人： Ravi J. Chari ,  Victor S. Goldmacher ,  John M. Lambert ,  Walter A. Blattler

    发明人： Ravi J. Chari ,  Victor S. Goldmacher ,  John M. Lambert ,  Walter A. Blattler

    IPC分类号： A61K31/535 ,  A61K47/48

    CPC分类号： A61K47/48384 ,  A61K31/535

    摘要： A cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. A therapeutic agent for killing selected cell populations comprising: (a) a cytotoxic amount of one or more maytansinoids linked to a cell binding agent, and (b) a pharmaceutically acceptable carrier diluent or excipient. A method for killing selected cell populations comprising contacting a cell population or tissue suspected of containing cells from said selected cell population with a cytotoxic amount of a cytotoxic agent comprising one or more maytansinoids linked to a cell binding agent. An N-methyl-alanine-containing ester of maytansinol or an analogue of maytansinol, said N-methyl-alanine-containing ester comprising a linking group capable of linking an N-methyl-alanine-containing maytansinoid ester to a chemical moiety. N-methyl-cysteine-containing ester of maytansinol or an analogue of maytansinol.

    摘要翻译： 包含与细胞结合剂连接的一种或多种美登木素生物碱的细胞毒性剂。 一种用于杀死所选细胞群的治疗剂，包括：（a）细胞毒性量的与细胞结合剂连接的一种或多种美登木素生物碱，和（b）药学上可接受的载体稀释剂或赋形剂。 一种用于杀死所选择的细胞群的方法，包括使来自所述选择的细胞群的怀疑含有细胞的细胞群体或组织与细胞毒性量的细胞毒性剂接触，所述细胞毒性剂包含与细胞结合剂连接的一种或多种美登木素生物碱。 含有N-甲基 - 丙氨酸的美登素的酯或美登素的类似物，所述含有N-甲基 - 丙氨酸的酯包含能够将含有N-甲基 - 丙氨酸的美登木素生物酯与化学部分连接的连接基团。 美登素的N-甲基 - 半胱氨酸酯或美登醇的类似物。

    Gelonin immunotoxin
    8.
    发明授权
    Gelonin immunotoxin 失效
    葛根素免疫毒素

    公开(公告)号：US4888415A

    公开(公告)日：1989-12-19

    申请号：US166777

    申请日：1988-03-07

    申请人： John M. Lambert ,  Walter A. Blattler ,  Peter D. Senter

    发明人： John M. Lambert ,  Walter A. Blattler ,  Peter D. Senter

    IPC分类号： A61K47/48

    CPC分类号： A61K47/48461 ,  Y10S530/828

    摘要： Immunotoxins having improved toxic activity have the composition ##STR1## wherein Toxin-NH is a ribosome-inactivating protein containing no accessible sulfhydryl groups, n is an integer from 1 to 5, m is an integer from 1 to 5, and NH-Antibody is a monoclonal antibody specific to eucaryotic cells or antigens associated therewith. The immunotoxins are made by reacting the Toxin-NH with an iminothiolester salt to form a first conjugate, reacting the NH-Antibody with N-succinimidyl-3-(2-pyridyldithio) propionate to form a second conjugate, and reacting the two conjugates to form the immunotoxin.

    摘要翻译： 具有改善的毒性活性的免疫毒素具有组成，其中毒素-NN是不含可接受巯基的核糖体失活蛋白，n为1至5的整数，m为1至5的整数，NH-抗体为 对真核细胞或与其相关的抗原特异的单克隆抗体。 通过使毒素-NN与亚氨基硫酸酯盐反应以形成第一缀合物，使NH抗体与N-琥珀酰亚胺基-3-（2-吡啶基二硫代）丙酸酯反应形成第二缀合物，并使两个缀合物与 形成免疫毒素。

    Cell-delivery agent
    10.
    发明授权
    Cell-delivery agent 失效
    细胞递送剂

    公开(公告)号：US4625014A

    公开(公告)日：1986-11-25

    申请号：US629363

    申请日：1984-07-10

    申请人： Peter D. Senter ,  John M. Lambert ,  Walter A. Blattler

    发明人： Peter D. Senter ,  John M. Lambert ,  Walter A. Blattler

    IPC分类号： C07K14/415 ,  A61K36/00 ,  A61K36/18 ,  A61K38/00 ,  A61K38/36 ,  A61K39/00 ,  A61K39/395 ,  A61K41/00 ,  A61K45/00 ,  C07K1/107 ,  C07K14/00 ,  C07K16/00 ,  C07K7/00 ,  A61K37/02

    CPC分类号： A61K41/0042 ,  Y10S530/808 ,  Y10S530/81

    摘要： A photo-cleavable compound for delivery and release of a biologically active substance to selected target cells; the compound includes a binding partner for a specific cell-surface receptor of those target cells, the biologically active substance to be delivered, and a photo-cleavable bridge between the binding partner and the biologically active substance. When the compound is exposed to a heterogeneous population of target and non-target cells, it binds selectively to the receptors on the surface of the target cells. Exposing the compound to light of selected wave length cleaves it, yielding the active substance.

    摘要翻译： 用于将选择的靶细胞递送和释放生物活性物质的光可切割化合物; 该化合物包括用于这些靶细胞的特定细胞表面受体的结合配偶体，待递送的生物活性物质和结合配偶体与生物活性物质之间的可光切割的桥。 当化合物暴露于靶和非靶细胞的异质群体时，其选择性结合靶细胞表面上的受体。 将化合物暴露于所选择的波长的光下，从而产生活性物质。