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21.发明申请Combining Radioimmunotherapy and Antibody-Drug Conjugates for Improved Cancer Therapy 有权结合放射免疫治疗和抗体药物结合物改善癌症治疗公开(公告)号：US20110070156A1
公开(公告)日：2011-03-24
申请号：US12957655
申请日：2010-12-01
IPC分类号： A61K51/10 , A61K39/395 , A61K38/21 , A61P35/00 , C07K16/46
CPC分类号： A61K51/1057 , A61K31/4745 , A61K31/7068 , A61K39/39558 , A61K41/0038 , A61K45/06 , A61K47/643 , A61K47/6803 , A61K47/6857 , A61K47/6859 , A61K51/08 , A61K51/109 , A61K2039/505 , A61K2039/507 , B82Y5/00 , C07K16/30 , C07K16/303 , C07K16/3092 , C07K16/44 , C07K2317/24 , C07K2317/31 , C07K2317/54 , C07K2317/55 , C07K2317/565 , C07K2317/73 , C07K2317/77 , A61K2300/00
摘要： Described herein are compositions and methods of use of radionuclide-antibody conjugates (for RAIT) and drug-antibody conjugates (ADC). The combination of RAIT and ADC was more efficacious than either RAIT alone, ADC alone, or the sum of effects of RAIT and ADC. The unexpected synergy resulted in decreased tumor growth rate and increased survival, with a high incidence of tumor-free survival in Capan-1 human pancreatic cancer xenografts in nude mice.
摘要翻译： 本文描述了使用放射性核素 - 抗体缀合物（用于RAIT）和药物 - 抗体缀合物（ADC）的组合物和方法。 RAIT和ADC的组合比单独的RAIT，单独的ADC或RAIT和ADC的影响的总和更有效。 意外的协同作用导致肿瘤生长速度降低和存活率增加，裸鼠中Capan-1人胰腺癌异种移植物的无瘤生存率高。
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公开(公告)号：US08574575B2
公开(公告)日：2013-11-05
申请号：US13293608
申请日：2011-11-10
IPC分类号： A61K39/395
CPC分类号： A61K45/06 , A61K39/39558 , A61K51/1045 , A61K51/1051 , A61K2039/505 , C07K16/30 , C07K16/3015 , C07K2317/21 , C07K2317/24
摘要： This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.
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23.发明授权Camptothecin conjugates of anti-CD22 antibodies for treatment of B cell diseases 有权用于治疗B细胞疾病的抗CD22抗体的喜树碱缀合物公开(公告)号：US08420086B2
公开(公告)日：2013-04-16
申请号：US13213245
申请日：2011-08-19
CPC分类号： A61K51/1027 , A61K9/19 , A61K39/39558 , A61K47/26 , A61K47/48384 , A61K47/48561 , A61K47/4863 , A61K47/48715 , A61K47/6803 , A61K47/6809 , A61K47/6849 , A61K47/6851 , A61K47/6859 , A61K47/6867 , A61K47/6883 , A61K47/6889 , A61K51/1069 , A61K51/1096 , A61K2039/505 , A61K2039/507 , A61P35/02 , C07K16/1063 , C07K16/2803 , C07K16/2833 , C07K16/2863 , C07K16/2887 , C07K16/30 , C07K16/3061 , C07K2317/24 , C07K2317/31 , C07K2317/35 , C07K2317/51 , C07K2317/55 , C07K2317/565 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/77 , C07K2319/70
摘要： Disclosed herein are compositions and methods of use comprising combinations of anti-CD22 antibodies with a therapeutic agent. The therapeutic agent may be attached to the anti-CD22 antibody or may be separately administered, either before, simultaneously with or after the anti-CD22 antibody. In preferred embodiments, the therapeutic agent is an antibody or fragment thereof that binds to an antigen different from CD22, such as CD19, CD20, CD21, CD22, CD23, CD37, CD40, CD40L, CD52, CD80 and HLA-DR. However, the therapeutic agent may an immunomodulator, a cytokine, a toxin or other therapeutic agent known in the art. More preferably, the anti-CD22 antibody is part of a DNL complex, such as a hexavalent DNL complex. Most preferably, combination therapy with the anti-CD22 antibody or fragment and the therapeutic agent is more effective than the antibody alone, the therapeutic agent alone, or the combination of anti-CD22 antibody and therapeutic agent that are not conjugated to each other. Administration of the anti-CD22 antibody and therapeutic agent induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease.
摘要翻译： 本文公开了包含抗CD22抗体与治疗剂的组合的组合物和使用方法。 治疗剂可以在抗-CD22抗体之前，同时或之后与抗CD22抗体连接，或者可以分开施用。 在优选的实施方案中，治疗剂是与CD22，例如CD19，CD20，CD21，CD22，CD23，CD37，CD40，CD40L，CD52，CD80和HLA-DR不同的抗原结合的抗体或其片段。 然而，治疗剂可以是本领域已知的免疫调节剂，细胞因子，毒素或其它治疗剂。 更优选地，抗CD22抗体是DNL复合物的一部分，例如六价DNL复合物。 最优选地，与抗-CD22抗体或片段和治疗剂的组合治疗比单独的抗体，单独的治疗剂或者不相互结合的抗CD22抗体和治疗剂的组合更有效。 抗CD22抗体和治疗剂的施用在诸如B细胞淋巴瘤或白血病，自身免疫疾病或免疫功能障碍疾病的疾病中诱导靶细胞的凋亡和细胞死亡。
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公开(公告)号：US20120141372A1
公开(公告)日：2012-06-07
申请号：US13293608
申请日：2011-11-10
IPC分类号： A61K39/395 , A61P31/00 , A61P37/02 , A61K51/10 , A61P35/00
CPC分类号： A61K45/06 , A61K39/39558 , A61K51/1045 , A61K51/1051 , A61K2039/505 , C07K16/30 , C07K16/3015 , C07K2317/21 , C07K2317/24
摘要： This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.
摘要翻译： 本发明涉及单价和多价单特异性结合蛋白和多价多特异性结合蛋白。 这些结合蛋白的一个实施方案具有一个或多个结合位点，其中每个结合位点与靶抗原或靶抗原上的表位结合。 这些结合蛋白的另一个实施方案具有两个或多个结合位点，其中每个结合位点对靶抗原上的不同表位具有亲和力，或对靶抗原或半抗原具有亲和力。 本发明还涉及可用于在宿主中表达这些功能性结合蛋白的重组载体。 更具体地，本发明涉及称为RS7的肿瘤相关抗原结合蛋白和其它EGP-1结合蛋白。 本发明还涉及人源化，人和嵌合RS7抗原结合蛋白，以及这种结合蛋白在诊断和治疗中的用途。
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公开(公告)号：US20100221177A1
公开(公告)日：2010-09-02
申请号：US12389503
申请日：2009-02-20
CPC分类号： A61K45/06 , A61K39/39558 , A61K51/1045 , A61K51/1051 , A61K2039/505 , C07K16/30 , C07K16/3015 , C07K2317/21 , C07K2317/24
摘要： This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.
摘要翻译： 本发明涉及单价和多价单特异性结合蛋白和多价多特异性结合蛋白。 这些结合蛋白的一个实施方案具有一个或多个结合位点，其中每个结合位点与靶抗原或靶抗原上的表位结合。 这些结合蛋白的另一个实施方案具有两个或多个结合位点，其中每个结合位点对靶抗原上的不同表位具有亲和力，或对靶抗原或半抗原具有亲和力。 本发明还涉及可用于在宿主中表达这些功能性结合蛋白的重组载体。 更具体地，本发明涉及称为RS7的肿瘤相关抗原结合蛋白和其它EGP-1结合蛋白。 本发明还涉及人源化，人和嵌合RS7抗原结合蛋白，以及这种结合蛋白在诊断和治疗中的用途。
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公开(公告)号：US08877901B2
公开(公告)日：2014-11-04
申请号：US11388032
申请日：2006-03-23
CPC分类号： C07K16/2803 , A61K47/6803 , A61K47/6841 , A61K47/6849 , A61K47/6889 , A61K2039/505 , C07K16/1063 , C07K16/2833 , C07K16/2863 , C07K16/30 , C07K2317/76
摘要： The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.
摘要翻译： 本发明涉及具有改进的靶向各种患有靶向部分（例如抗体或抗体片段），接头和喜树碱作为治疗部分的病变细胞的能力的治疗性缀合物，还涉及制备和使用所述缀合物的方法 。
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公开(公告)号：US06818742B1
公开(公告)日：2004-11-16
申请号：US09696740
申请日：2000-10-26
IPC分类号： A61K3800
CPC分类号： A61K51/0491 , A61K51/088 , A61K51/10 , A61K51/1093 , C07H3/04 , C07K1/1077 , G01N33/543
摘要： Methods are described for conjugating radioiodinated non-metabolizable peptides to proteins and antibodies with improved yields and qualities of conjugates. Radioiodinated residualizing antibody conjugates comprising any aminopolycarboxylate-appended peptide, or any carbohydrate-appended peptide, are also provided. Additionally, methods are described for conjugating radioiodinated aminopolycarboxylates to proteins and antibodies, as well as for conjugating radioiodinated non-metabolizable carbohydrates to proteins and antibodies by a variety of chemical approaches. The instant radioiodinated residualizing antibody conjugates are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.
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公开(公告)号：US5846741A
公开(公告)日：1998-12-08
申请号：US687626
申请日：1996-07-26
IPC分类号： A61K33/22 , A61K39/395 , A61K41/00 , A61K47/48 , A61K51/10 , A61P35/00 , G01N33/534 , G01N33/574 , G01N33/53
CPC分类号： B82Y5/00 , A61K41/0095 , A61K47/48353 , A61K47/48753 , A61K51/1078 , G01N33/534 , G01N33/574
摘要： The present invention provides a method for targeting boron atoms to tumor cells in a patient. The method comprises the steps of: (A) administering a targeting composition comprising a conjugate of a first member of a binding pair and an antibody, wherein the antibody selectively binds to antigens produced by or associated with the tumor cells, and allowing the conjugate to localize at said tumor cells; (B) optionally, administering a clearing composition, and allowing the clearing composition to clear non-localized conjugate from circulation; (C) administering a boron-containing compound comprising a conjugate comprising a complementary member of said binding pair and boron atoms, and allowing the compound to localize at the tumor cells. The method may further comprise the step of irradiating the boron atoms of the boron compound, thereby effecting BNCT of the tumor cells. Compositions and kits for carrying out the method also are provided.
摘要翻译： 本发明提供了一种将硼原子靶向患者肿瘤细胞的方法。 该方法包括以下步骤：（A）施用包含结合对的第一个成员和抗体的缀合物的靶向组合物，其中所述抗体选择性地结合由肿瘤细胞产生或与肿瘤细胞相关的抗原，并且允许缀合物 在所述肿瘤细胞上定位; （B）任选地，施用清除组合物，并使清除组合物从循环中清除非局部缀合物; （C）施用含有包含所述结合对的互补成员和硼原子的缀合物的含硼化合物，并使化合物定位于肿瘤细胞。 该方法还可以包括照射硼化合物的硼原子，从而实现肿瘤细胞的BNCT的步骤。 还提供了用于实施该方法的组合物和试剂盒。
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公开(公告)号：US06558669B1
公开(公告)日：2003-05-06
申请号：US08919477
申请日：1997-08-28
IPC分类号： C07K506
CPC分类号： A61K51/0491 , A61K51/088 , A61K51/10 , A61K51/1093 , C07H3/04 , C07K1/1077 , G01N33/543
摘要： 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 amide bonds are coupled to antibodies. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to antibodies. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to antibodies. In a fourth method, a hydrazide-appended antibody is coupled to a radioiodinated carbohydrate or a thiolated antibody is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated antibody. Radioiodinated residualizing antibody conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.
摘要翻译： 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，将特异设计的含有非代谢性酰胺键的放射性碘化双功能肽与抗体偶联。 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抗体偶联。 在第三种方法中，放射性碘化双官能氨基多羧酸盐与抗体偶联。 在第四种方法中，将酰肼附着的抗体与放射性碘化碳水化合物偶联，或硫醇化抗体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抗体。 通过这些方法制备的放射性碘化残留抗体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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公开(公告)号：US5965131A
公开(公告)日：1999-10-12
申请号：US731107
申请日：1996-10-09
IPC分类号： A61K38/22 , A61K39/395 , A61K41/00 , A61K45/08 , A61K47/48 , A61K49/00 , A61K51/00 , A61K51/10 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/68 , A01N37/18 , G01N33/53
CPC分类号： B82Y5/00 , A61K41/0095 , A61K47/48353 , A61K47/4873 , A61K47/48746 , A61K47/48753 , A61K49/0017 , A61K51/1078 , A61K51/1093 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/686 , A61K2121/00 , A61K2123/00 , Y10S424/90
摘要： An improvement in in vivo pretargeting methods for delivering diagnostic or therapeutic agents to a target site in a mammal uses a clearing agent that binds to the target-binding site of the targeting species, whereby non-bound primary targeting species is cleared from circulation but the clearing agent does not remove the bound primary targeting species. Anti-idiotype antibodies and antibody fragments are preferred clearing agents. Fast clearance is achieved by glycosylating the clearing agent with sugar residues that bind to the hepatic asialoglycoprotein receptor.
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