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61. 发明申请

US20080241141A1 METHODS AND COMPOSITIONS FOR IMMUNOTHERAPY AND DETECTION OF INFLAMMATORY AND IMMUNE-DYSREGULATORY DISEASE, INFECTIOUS DISEASE, PATHOLOGIC ANGIOGENESIS AND CANCER 审中-公开
公开(公告)号：US20080241141A1
公开(公告)日：2008-10-02
申请号：US11929315
申请日：2007-10-30
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K38/02 , A61K39/395 , A61P37/00
CPC分类号： A61K39/3955 , A61K31/513 , A61K38/193 , A61K38/2013 , A61K38/4866 , A61K39/40 , A61K45/06 , A61K49/0002 , A61K2039/505 , A61K2039/507 , C07K16/1203 , C07K16/24 , C07K16/241 , C07K16/248 , C07K16/2803 , C07K16/2896 , C07K16/30 , C07K2317/24 , C07K2317/31 , C07K2317/734
摘要： Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.

62. 发明申请

US20080138333A1 INTERNALIZING ANTI-CD74 ANTIBODIES AND METHODS OF USE 有权
公开(公告)号：US20080138333A1
公开(公告)日：2008-06-12
申请号：US11754902
申请日：2007-05-29
申请人： Hans J. Hansen , Shui-on Leung , Zhengxing Qu , David M. Goldenberg
发明人： Hans J. Hansen , Shui-on Leung , Zhengxing Qu , David M. Goldenberg
IPC分类号： A61K39/395 , A61P17/00 , A61P21/00 , A61P31/00 , A61P35/00 , A61K39/00 , A61K38/46 , A61K51/00 , A61K31/70 , A61K45/00 , A61K38/21
CPC分类号： A61K45/06 , A61K38/00 , A61K47/6849 , A61K51/1027 , A61K2039/505 , C07K16/2833 , C07K16/2896 , C07K2317/24 , C07K2317/77
摘要： The present invention provides humanized, chimeric and human anti-CD74 antibodies, CD74 antibody fusion proteins, immunoconjugates, vaccines and bispecific that bind to CD74, the major histocompatibility complex (MHC) class-II invariant chain, Ii, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies, other malignancies in which the cells are reactive with CD74, and autoimmune diseases, and methods of treatment and diagnosis.

63. 发明授权

US07323168B2 Immunotherapy for chronic myelocytic leukemia 有权
标题翻译：免疫治疗慢性骨髓性白血病
公开(公告)号：US07323168B2
公开(公告)日：2008-01-29
申请号：US10853150
申请日：2004-05-26
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39/395
CPC分类号： C07K16/2803
摘要： Immunotherapy utilizing naked anti-granulocyte antibodies provides an effective means for treating chronic myelocytic leukemia (CML). Such antibodies can be administered alone or in combination with other therapies, such as immunoconjugates or chemotherapeutics. In either format, an effective therapy for treating CML is provided, which avoids the toxic side-effects typically associated with cancer therapy. The disclosed immunotherapy also is effective for treating acute myelocytic leukemia (AML) when co-administered with inducing agents which induce expression of antigens minimally displayed on the surface of myeloblasts.
摘要翻译：使用裸抗粒细胞抗体的免疫治疗提供治疗慢性骨髓性白血病（CML）的有效手段。这样的抗体可以单独施用或与其它疗法组合施用，例如免疫缀合物或化学治疗剂。以任一格式，提供治疗CML的有效治疗方法，其避免通常与癌症治疗相关的毒副作用。当与诱导表达共同施用时，所公开的免疫治疗也可有效治疗急性髓细胞性白血病（AML），所述诱导剂诱导表达最低限度地显示在原粒细胞表面上。

64. 发明授权

US07300655B2 Alpha-fetoprotein Immu31 antibodies and fusion proteins and methods of use thereof 有权
标题翻译：甲胎蛋白Immu31抗体和融合蛋白及其使用方法
公开(公告)号：US07300655B2
公开(公告)日：2007-11-27
申请号：US10631722
申请日：2003-08-01
申请人： Hans J. Hansen , Zhengxing Qu , David M. Goldenberg
发明人： Hans J. Hansen , Zhengxing Qu , David M. Goldenberg
IPC分类号： A61K39/395
CPC分类号： C07K16/30 , A61K41/0095 , A61K47/6843 , A61K49/0002 , A61K51/1018 , A61K2039/505 , C07K16/18 , C07K16/3076 , C07K2317/24 , C07K2317/56 , G01N33/57484 , G01N33/689
摘要： The present invention provides humanized, chimeric and human anti-alpha-fetoprotein antibodies, fusion proteins, and fragments thereof. The antibodies, fusion proteins, and fragments thereof, as well as combinations with other suitable antibodies, are useful for the treatment and diagnosis of hepatocellular carcinoma, hepatoblastoma, germ cell tumors carcinoma and other AFP-producing tumors.
摘要翻译：本发明提供人源化，嵌合和人抗甲胎蛋白抗体，融合蛋白及其片段。抗体，融合蛋白及其片段以及与其它合适抗体的组合可用于治疗和诊断肝细胞癌，肝母细胞瘤，生殖细胞肿瘤癌和其他产生AFP的肿瘤。

65. 发明授权

US07282567B2 Monoclonal antibody hPAM4 有权
标题翻译：单克隆抗体hPAM4
公开(公告)号：US07282567B2
公开(公告)日：2007-10-16
申请号：US10461885
申请日：2003-06-16
申请人： David M. Goldenberg , Hans J. Hansen , Zhengxing Qu
发明人： David M. Goldenberg , Hans J. Hansen , Zhengxing Qu
IPC分类号： C07K16/00
CPC分类号： A61K49/0008 , A61K47/68 , A61K51/1057 , A61K2039/505 , C07K14/4748 , C07K16/2896 , C07K2317/24
摘要： This invention relates to monovalent and multivalent, monospecific antibodies and to multivalent, multispecific antibodies. One embodiment of these antibodies has one or more identical binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these antibodies has two or more binding sites where these binding sites have affinity towards different epitopes on a target antigen or different target antigens, or have affinity towards a target antigen and a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional antibodies in a host. More specifically, the present invention relates to the tumor-associated antibody designated PAM4. The invention further relates to humanized and human PAM4 antibodies, and the use of such antibodies in diagnosis and therapy.
摘要翻译：本发明涉及单价和多价单特异性抗体和多价多特异性抗体。这些抗体的一个实施方案具有一个或多个相同的结合位点，其中每个结合位点与靶抗原或靶抗原上的表位结合。这些抗体的另一个实施方案具有两个或多个结合位点，其中这些结合位点对靶抗原或不同靶抗原上的不同表位具有亲和力，或对靶抗原和半抗原具有亲和力。本发明还涉及可用于在宿主中表达这些功能性抗体的重组载体。更具体地说，本发明涉及称为PAM4的肿瘤相关抗体。本发明还涉及人源化和人类PAM4抗体，以及这些抗体在诊断和治疗中的用途。

66. 发明授权

US07138103B2 Use of bi-specific antibodies for pre-targeting diagnosis and therapy 有权
标题翻译：使用双特异性抗体进行预定位诊断和治疗
公开(公告)号：US07138103B2
公开(公告)日：2006-11-21
申请号：US10150654
申请日：2002-05-17
申请人： David M. Goldenberg , Hans J. Hansen , Shui-on Leung , William J. McBride , Zhengxing Qu
发明人： David M. Goldenberg , Hans J. Hansen , Shui-on Leung , William J. McBride , Zhengxing Qu
IPC分类号： A61K38/04 , A61K39/395 , A61K49/04 , A61K49/06 , A61K51/00
CPC分类号： A61K51/1048 , A61K47/665 , A61K47/6879 , A61K51/1063 , A61K2039/505 , B82Y5/00 , C07K5/0215 , C07K5/1016 , C07K5/1019 , C07K7/06 , C07K16/18 , C07K16/3007 , C07K16/3046 , C07K16/44 , C07K16/468 , C07K2317/12 , C07K2317/13 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2317/64 , C07K2319/00
摘要： The present invention relates to targetable constructs which may be bound by a bi-specific antibody or antibody fragment having at least one arm that specifically binds construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the targetable constructs and bi-specific antibodies or antibody fragments, as well as methods for using them.
摘要翻译：本发明涉及可由具有特异性结合构建体的至少一个臂的双特异性抗体或抗体片段结合的可靶向构建体。可靶向构建体包含载体部分，其包含或携带至少一个可被所述双特异性抗体或抗体片段的至少一个臂识别的表位。可靶向构建物还包含一种或多种治疗剂或诊断剂或酶。本发明提供用于产生可靶向构建体和双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法。

67. 发明授权

US07074403B1 Immunotherapy of autoimmune disorders using antibodies which target B-cells 有权
公开(公告)号：US07074403B1
公开(公告)日：2006-07-11
申请号：US09590284
申请日：2000-06-09
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39/395 , A61K38/17 , C07K16/00 , C07K16/28
CPC分类号： C07K16/2887 , A61K38/00 , A61K39/3955 , A61K45/06 , A61K47/6813 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K16/28 , C07K16/2803 , C07K16/2896 , C07K2317/24 , Y10S514/885 , Y10S514/903
摘要： Antibodies that bind with a B-cell antigen provide an effective means to treat autoimmune disorders. Antibodies and fragments, which may be conjugated or naked, are used alone or in multimodal therapies. The antibodies may be bispecific antibodies which may be produced recombinantly as fusion proteins, or as hybrid, polyspecific antibodies.

68. 发明授权

US06440416B1 Vaccines against cancer and infectious diseases 失效
公开(公告)号：US06440416B1
公开(公告)日：2002-08-27
申请号：US08183381
申请日：1992-01-02
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39395
CPC分类号： A61K39/39566 , Y02A50/403 , A61K2300/00
摘要： A method of stimulating an immune response in a human against malignant cells or an infectious agent comprises the step of administering to the human an immunogenic amount of a primate anti-idiotype antibody or antibody fragment that acts as an immunogenic functional mimic of an antigen produced by or associated with a malignant cell or an infectious agent. Sub-human primate anti-idiotype antisera, especially from baboons, are preferred. Such anti-idiotype antibodies are used to make vaccines for inducing preventive immunity or a therapeutic immune response against tumors, viruses, bacteria, rickettsia, mycoplasma, protozoa, fungi and multicellular parasites.

69. 发明授权

US5677427A Chimeric antibody for detection and therapy of infectious and inflammatory lesions 失效
公开(公告)号：US5677427A
公开(公告)日：1997-10-14
申请号：US457138
申请日：1995-06-01
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39/395 , A61K45/00 , A61K47/48 , A61K49/00 , A61K49/16 , A61K51/00 , A61K51/10 , A61P29/00 , A61P31/04 , A61K49/02
CPC分类号： A61K51/109 , A61K47/48369 , A61K47/48546 , A61K47/48669 , A61K47/48676 , A61K49/16 , A61K51/1087 , A61K51/1093 , A61K2121/00 , A61K2123/00
摘要： A chimeric antibody-agent conjugate for targeting foci of leukocyte accretion comprises a recombinant chimera having an antigen-binding hypervariable region which binds specifically to granulocytes, and a constant region of a human immunoglobulin having an Fc portion with high affinity for receptors on human mononuclear lymphoid cells, said chimera being conjugated to at least one diagnostic agent or therapeutic agent. A method for targeting an imaging or therapy agent to an inflammatory or infectious lesion comprises injecting a mammal parenterally with an effective amount for targeting of the above chimeric anti-leukocyte conjugate.

70. 发明授权

US08722047B2 Humanized anti-HLA-DR antibodies 有权
标题翻译：人源化抗HLA-DR抗体
公开(公告)号：US08722047B2
公开(公告)日：2014-05-13
申请号：US12754140
申请日：2010-04-05
申请人： David M. Goldenberg , Hans J. Hansen , Chien-Hsing Chang
发明人： David M. Goldenberg , Hans J. Hansen , Chien-Hsing Chang
IPC分类号： C07K16/28 , C07K16/46 , A61K39/395 , C07H21/04
CPC分类号： C07K16/2833 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K47/6849 , A61K47/6867 , A61K51/1027 , A61K51/1093 , A61K2039/505 , A61K2039/507 , C07K16/28 , C07K16/2887 , C07K16/4241 , C07K19/00 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/71 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/75 , C07K2317/92
摘要： The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.
摘要翻译：本发明涉及使用人源化抗HLA-DR抗体的组合物和方法。在优选的实施方案中，抗体诱导凋亡并抑制淋巴瘤细胞的增殖而不诱导CDC或ADCC。在更优选的实施方案中，人源化抗HLA-DR抗体与鼠L243抗体结合HLA-DR相同的表位或与鼠L243抗体竞争结合HLA-DR。最优选地，人源化抗HLA-DR抗体对亲本鼠抗体的HLA-DR表现出更高的亲和力。人源化HLA-DR抗体可用于治疗各种疾病如癌症，自身免疫疾病或免疫调节功能，并且特别用于治疗B细胞淋巴瘤和白血病。在最优选的实施方案中，人源化抗HLA-DR抗体能够诱导对其它B细胞抗体如利妥昔单抗有抗性的淋巴瘤的至少部分缓解。

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