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1. 发明申请

WO2005014618A2 BISPECIFIC ANTIBODIES FOR INDUCING APOPTOSIS OF TUMOR AND DISEASED CELLS 审中-公开
标题翻译：诱导肿瘤和疾病细胞凋亡的双重抗体
公开(公告)号：WO2005014618A2
公开(公告)日：2005-02-17
申请号：PCT/US2004/025840
申请日：2004-08-09
申请人： IMMUNOMEDICS, INC. , CHANG, Chien-Hsing , GOLDENBERG, David, M. , HANSEN, Hans, J. , HORAK, Eva , HORAK, Ivan
发明人： CHANG, Chien-Hsing , GOLDENBERG, David, M. , HANSEN, Hans, J. , HORAK, Eva , HORAK, Ivan
IPC分类号： C07K
CPC分类号： C07K16/2887 , C07K16/2803 , C07K2317/31 , C07K2317/55 , C07K2317/73 , C07K2317/75
摘要： The bispecific antibodies of the present invention are in the form of a heteroconjugate that inhibits growth and induces apoptosis of a diseased cell and that does not require the recruitment of effector cells. The heteroconjugate has at least two binding arms wherein each of the binding arms possesses a different specificity and need not have apoptotic activity when not conjugated to each other. Also provided are methods of treating and diagnosing a diseased cell using the bispecfic antibodies of the present invention.
摘要翻译：本发明的双特异性抗体是异源结合物的形式，其抑制生长并诱导病变细胞的凋亡，并且不需要募集效应细胞。杂合物具有至少两个结合臂，其中每个结合臂具有不同的特异性，并且当不彼此结合时不需要具有凋亡活性。还提供了使用本发明的双特异性抗体治疗和诊断患病细胞的方法。

2. 发明申请

WO2010017500A3 ANTI-PANCREATIC CANCER ANTIBODIES 审中-公开
公开(公告)号：WO2010017500A3
公开(公告)日：2010-02-11
申请号：PCT/US2009/053192
申请日：2009-08-07
申请人： IMMUNOMEDICS, INC. , GOLDENBERG, David, M. , HANSEN, Hans, J. , CHANG, Chien-Hsing , GOLD, David, V.
发明人： GOLDENBERG, David, M. , HANSEN, Hans, J. , CHANG, Chien-Hsing , GOLD, David, V.
IPC分类号： A61K39/395 , G01N33/53 , C07K16/00
摘要： Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful therapeutic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection, diagnosis and/or treatment of cancer, such as pancreatic cancer. The antibodies, such as PAM4 antibodies, bind to a PAM4 antigen that shows unique cell and tissue distributions compared with other known antibodies such as CA19.9, DUPAN2, SPAN1, Nd2, B72.3, and Leaª and Le(y) antibodies that bind to the Lewis antigens.

3. 发明申请

WO2005080586A1 FUSION PROTEINS CONTAINING RECOMBINANT CYTOTOXIC RNASES 审中-公开
标题翻译：含有重组细胞毒素RNA的融合蛋白
公开(公告)号：WO2005080586A1
公开(公告)日：2005-09-01
申请号：PCT/US2005/004860
申请日：2005-02-14
申请人： IMMUNOMEDICS, INC. , GOLDENBERG, David M. , HANSEN, Hans J. , CHANG, Chien-Hsing , VANAMA, Sailadja , ROSSI, Edmund A.
发明人： GOLDENBERG, David M. , HANSEN, Hans J. , CHANG, Chien-Hsing , VANAMA, Sailadja , ROSSI, Edmund A.
IPC分类号： C12P21/00
CPC分类号： C07K16/2803 , A61K47/6817 , A61K47/6877 , C07K16/2833 , C07K2317/24 , C07K2317/41 , C07K2319/00 , C07K2319/33 , C12N9/22 , C12N2510/02
摘要： Recombinant immunotoxins containing a cytotoxic RNAse fused to an antibody or antibody fragment may be produced in mammalian cell culture. Surprisingly, immunotoxins containing a cytotoxic RNAse fused to the N-terminus of one antibody variable domain can be prepared and retain the ability to specifically bind antigen. The immunotoxins may be used in a variety of therapeutic methods for treating diseases or syndromes associated with unwanted or inappropriate cell proliferation or activation.
摘要翻译：可以在哺乳动物细胞培养物中产生含有与抗体或抗体片段融合的细胞毒性RNA的重组免疫毒素。令人惊讶的是，可以制备含有与一个抗体可变结构域的N末端融合的细胞毒性RNA的免疫毒素，并保留特异性结合抗原的能力。免疫毒素可以用于治疗与不想要的或不适当的细胞增殖或活化相关的疾病或综合征的各种治疗方法。

4. 发明申请

WO2011034660A1 CLASS I ANTI-CEA ANTIBODIES AND USES THEREOF 审中-公开
标题翻译：一类抗体抗体及其用途
公开(公告)号：WO2011034660A1
公开(公告)日：2011-03-24
申请号：PCT/US2010/043663
申请日：2010-07-29
申请人： IMMUNOMEDICS, INC. , HANSEN, Hans J. , CHANG, Chien-Hsing , GOLDENBERG, David M.
发明人： HANSEN, Hans J. , CHANG, Chien-Hsing , GOLDENBERG, David M.
IPC分类号： C12P21/08
CPC分类号： C07K16/3007 , A61K39/39558 , A61K47/55 , A61K47/60 , A61K47/6801 , A61K47/6807 , A61K47/6813 , A61K47/6815 , A61K47/6817 , A61K47/6819 , A61K47/6829 , A61K47/6849 , A61K47/6851 , A61K47/6853 , A61K49/0058 , A61K49/221 , A61K51/088 , A61K51/1027 , A61K51/1093 , A61K51/1096 , A61K2039/505 , A61K2039/545 , C07K14/54 , C07K16/2803 , C07K16/3076 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/515 , C07K2317/53 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C07K2319/00 , C07K2319/30 , A61K2300/00
摘要： The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.
摘要翻译：本发明提供使用人源化，嵌合或人类I类抗CEA抗体或其片段的组合物和方法，优选包含轻链可变区CDR序列SASSRVSYIH（SEQ ID NO：1）; GTSTLAS（SEQ ID NO：2）; 和QQWSYNPPT（SEQ ID NO：3）; 和重链可变区CDR序列DYYMS（SEQ ID NO：4）; FIANKANGHTTDYSPSVKG（SEQ ID NO：5）; 和DMGIRWNFDV（SEQ ID NO：6）。 I类抗CEA抗体或片段可用于治疗诸如癌症的疾病，其中患病细胞表达CEACAM5和/或CEACAM6抗原。 I类抗CEA抗体或片段也可用于干扰特异性过程，例如癌细胞的转移，侵袭和/或粘附，或用于增强癌细胞对细胞毒性剂的敏感性，并对癌症患者

5. 发明申请

WO2010011697A1 STRUCTURAL VARIANTS OF ANTIBODIES FOR IMPROVED THERAPEUTIC CHARACTERISTICS 审中-公开
标题翻译：用于改善治疗特征的抗体的结构变体
公开(公告)号：WO2010011697A1
公开(公告)日：2010-01-28
申请号：PCT/US2009/051321
申请日：2009-07-21
申请人： IMMUNOMEDICS INC. , GOLDENBERG, David, M. , CHANG, Chien-Hsing , HANSEN, Hans, J.
发明人： GOLDENBERG, David, M. , CHANG, Chien-Hsing , HANSEN, Hans, J.
IPC分类号： A61K39/395 , C07K16/18
CPC分类号： C07K16/2887 , A61K2039/505 , A61K2039/545 , C07K2317/24 , C07K2317/565 , C07K2317/732 , C07K2317/734
摘要： The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 V H (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, more preferably 50 mg or less, most preferably 30 mg or less of naked antibody when administered i.v. or s.c.
摘要翻译：本发明提供取代的人源化，嵌合或人抗CD20抗体或其抗原结合片段和包含取代的抗体或其抗原结合片段的双特异性抗体或融合蛋白。抗体，融合蛋白或片段可用于治疗B细胞病变，如B细胞恶性肿瘤和自身免疫性疾病，以及GVHD，器官移植排斥，溶血性贫血和冷球蛋白血症。氨基酸取代，特别是取代CDR3 VH（CDRH3）Kabat 101位天冬氨酸残基导致改善的治疗性质，例如降低的解离速率，改善的CDC活性，改善的细胞凋亡，改善的B细胞消耗和改善的治疗功效非常低的剂量 Veltuzumab是与不同CDRH3序列的相似抗体相比具有改善的治疗效果的，具有这种序列变异性的人源化抗-CD20抗体，其能够以低至200mg或更低，更优选为100mg或更少，更优选为80mg mg或更少，更优选50mg或更少，最优选30mg或更少的裸抗体或s.c.

6. 发明申请

WO2011072124A1 DELIVERY SYSTEM FOR CYTOTOXIC DRUGS BY BISPECIFIC ANTIBODY PRETARGETING 审中-公开
标题翻译：通过双向抗体预测的细胞毒素输送系统
公开(公告)号：WO2011072124A1
公开(公告)日：2011-06-16
申请号：PCT/US2010/059686
申请日：2010-12-09
申请人： IMMUNOMEDICS, INC. , MCBRIDE, William J. , D'SOUZA, Christopher A. , CHANG, Chien-Hsing , GOLDENBERG, David M.
发明人： MCBRIDE, William J. , D'SOUZA, Christopher A. , CHANG, Chien-Hsing , GOLDENBERG, David M.
IPC分类号： A61K39/395
CPC分类号： C07K16/303 , A61K47/6879 , A61K47/6897 , B82Y5/00 , C07K16/2803 , C07K16/2833 , C07K16/2863 , C07K16/2887 , C07K16/30 , C07K16/3007 , C07K16/3092 , C07K16/44 , C07K2317/31 , C07K2317/626 , C07K2317/73
摘要： The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.
摘要翻译：本发明涉及治疗剂预靶向递送的方法和组合物。在优选的实施方案中，预靶向方法包括：a）将双特异性抗体施用于疾病相关抗原的第一结合位点和可靶向构建体上的半抗原; b）施用包含至少一种治疗剂的可靶向构建体。在优选的实施方案中，双特异性抗体通过对接和锁定（DNL）技术制备。在更优选的实施方案中，可靶向构建体包含一个或多个SN-38部分。

7. 发明申请

WO2013043800A1 ANTI-HLA-DR ANTIBODIES SUPPRESS ALLOGENEIC AND XENOGENEIC IMMUNE RESPONSES TO ORGAN TRANSPLANTS 审中-公开
标题翻译：抗HLA-DR抗体抑制同种异体和对机器移植的XENOGENEIC免疫应答
公开(公告)号：WO2013043800A1
公开(公告)日：2013-03-28
申请号：PCT/US2012/056224
申请日：2012-09-20
申请人： IMMUNOMEDICS, INC. , SAWADA, Tokihiko , CHANG, Chien-Hsing , GOLDENBERG, David, M.
发明人： SAWADA, Tokihiko , CHANG, Chien-Hsing , GOLDENBERG, David, M.
IPC分类号： A61K39/395
CPC分类号： C07K16/2833 , A61K47/6849 , A61K47/6885 , A61K2039/505 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/73 , C07K2317/77 , C07K2319/00 , C12N15/111 , C12N2320/32
摘要： Disclosed herein are methods and compositions comprising anti-HLA-DR antibodies for treatment of allogeneic and xenogeneic immune responses occurring in organ transplant rejection and other immune dysfunction diseases. In preferred embodiments, the anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8 + memory T cells. The compositions and methods provide a novel therapeutic agent for suppressing or preventing allogeneic or xenogeneic immune responses, without altering preexisting anti-viral immunity.
摘要翻译：本文公开了包含用于治疗器官移植排斥和其他免疫功能障碍疾病中发生的同种异体和异种免疫应答的抗HLA-DR抗体的方法和组合物。在优选的实施方案中，抗HLA-DR抗体有效地消耗抗原呈递细胞，例如树突状细胞。最优选地，治疗组合物的给药消耗了APC的所有子集，包括mDC，pDC，B细胞和单核细胞，而不会明显消耗T细胞。在替代实施方案中，治疗组合物的施用抑制同种异体反应性T细胞的增殖，同时保留巨细胞病毒（CMV）特异性CD8 +记忆T细胞。组合物和方法提供了用于抑制或预防同种异体或异种免疫应答的新型治疗剂，而不改变预先存在的抗病毒免疫。

8. 发明申请

WO2011026026A1 COMPOSITIONS AND METHODS OF USE OF IMMUNOTOXINS COMPRISING RANPIRNASE (RAP) SHOW POTENT CYTOTOXIC ACTIVITY 审中-公开
标题翻译：包含RANPIRNASE（RAP）显示细胞因子活性的免疫毒素的组合物和使用方法
公开(公告)号：WO2011026026A1
公开(公告)日：2011-03-03
申请号：PCT/US2010/047132
申请日：2010-08-30
申请人： IMMUNOMEDICS, INC. , IBC PHARMACEUTICALS, INC. , CHANG, Chien-Hsing , GOLDENBERG, David, M. , ROSSI, Edmund, A.
发明人： CHANG, Chien-Hsing , GOLDENBERG, David, M. , ROSSI, Edmund, A.
IPC分类号： A61K39/00
CPC分类号： C07K16/30 , A61K38/00 , A61K47/6815 , A61K47/6849 , A61K47/6851 , C07K16/2803 , C07K16/2887 , C07K2317/24 , C07K2317/35 , C07K2317/77 , C07K2317/92
摘要： The present invention concerns methods and compositions for forming immunotoxin complexes having a high efficacy and low systemic toxicity. In preferred embodiments, the toxin moiety is a ranpirnase (Rap), such as Rap(Q). In more preferred embodiments, the immunotoxin is made using dock-and-lock (DNL) technology. The immunotoxin exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to toxin alone, antibody alone, unconjugated toxin plus antibody or even other types of toxin-antibody constructs. In a most preferred embodiment the construct comprises an anti-Trop-2 antibody conjugated to Rap, although other combinations of antibodies, antibody fragments and toxins may be used to form the subject immunotoxins. The immunotoxins are of use to treat a variety of diseases, such as cancer, autoimmune disease or immune dysfunction.
摘要翻译：本发明涉及用于形成具有高效力和低全身毒性的免疫毒素复合物的方法和组合物。在优选的实施方案中，毒素部分是兰普瑞酶（Rap），例如Rap（Q）。在更优选的实施方案中，免疫毒素使用对接 - 锁（DNL）技术制备。与单独的毒素，单独的抗体，未缀合的毒素加抗体或甚至其它类型的毒素 - 抗体构建体相比，免疫毒素表现出改进的药代动力学，具有较长的血清半衰期和显着更高的功效。在最优选的实施方案中，构建体包含与Rap结合的抗Trop-2抗体，尽管抗体，抗体片段和毒素的其它组合可用于形成受试者免疫毒素。免疫毒素可用于治疗各种疾病，例如癌症，自身免疫性疾病或免疫功能障碍。

9. 发明申请

WO2013052484A1 DYE CONJUGATED PEPTIDES FOR FLUORESCENT IMAGING 审中-公开
标题翻译：用于荧光成像的DYE结合肽
公开(公告)号：WO2013052484A1
公开(公告)日：2013-04-11
申请号：PCT/US2012/058462
申请日：2012-10-02
申请人： IMMUNOMEDICS, INC. , REGINO, Celeste Aida S. , MCBRIDE, William J. , CHANG, Chien-Hsing , GOLDENBERG, David M.
发明人： REGINO, Celeste Aida S. , MCBRIDE, William J. , CHANG, Chien-Hsing , GOLDENBERG, David M.
IPC分类号： G01N33/533 , G01N21/76
CPC分类号： A61K51/088 , A61K51/1045 , A61K51/1078 , G01N21/6428 , G01N21/6456 , G01N33/542 , G01N33/57407 , G01N33/57484 , G01N33/582 , G01N33/6854 , G01N33/6872 , G01N2333/912 , Y02A50/57
摘要： The present application discloses compositions and methods of use of dye conjugated peptides for fluorescent detection, diagnosis and/or imaging. In preferred embodiments, the compositions comprise a DNL complex comprising an anti-hapten antibody or antigen-binding fragment thereof conjugated to an AD moiety and a DDD moiety conjugated to an antibody or antigen-binding fragment thereof that binds to the target antigen, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the DNL complex. More preferably, the compositions comprise a targetable construct comprising at least one hapten and a fluorescent probe. Binding of the DNL complex to the target antigen and of the hapten on the targetable construct to the DNL complex results in fluorescent labeling of the target antigen. Most preferably, fluorescent imaging is of use in intraoperative, intraperitoneal, laparoscopic, endoscopic or intravascular procedures for detection of diseased tissues.
摘要翻译：本申请公开了用于荧光检测，诊断和/或成像的染料缀合肽的组合物和方法。在优选的实施方案中，组合物包含DNL复合物，其包含与AD部分缀合的抗半抗原抗体或其抗原结合片段和与靶抗原结合的抗体或其抗原结合片段缀合的DDD部分，其中两个 DDD部分的拷贝形成与AD部分结合形成DNL复合物的二聚体。更优选地，组合物包含包含至少一个半抗原和荧光探针的可靶向构建体。将DNL复合物与目标抗原和可靶向构建体上的半抗原结合到DNL复合物上导致靶抗原的荧光标记。最优选地，荧光成像在术中，腹膜内，腹腔镜，内窥镜或血管内程序中用于检测患病组织。

10. 发明申请

WO2011123428A1 ANTIBODY-BASED DEPLETION OF ANTIGEN-PRESENTING CELLS AND DENDRITIC CELLS 审中-公开
标题翻译：抗原呈递细胞和感染细胞的基于抗体的方法
公开(公告)号：WO2011123428A1
公开(公告)日：2011-10-06
申请号：PCT/US2011/030294
申请日：2011-03-29
申请人： IMMUNOMEDICS, INC. , CHANG, Chien-Hsing , GOLDENBERG, David, M.
发明人： CHANG, Chien-Hsing , GOLDENBERG, David, M.
IPC分类号： A61K39/395
CPC分类号： C07K16/2833 , A61K31/4965 , A61K47/484 , A61K47/48423 , A61K47/4843 , A61K47/6807 , A61K47/6813 , A61K47/6815 , A61K47/6849 , A61K47/6881 , A61K47/6885 , C07K16/18 , C07K16/2803 , C07K16/2851 , C07K16/2863 , C07K16/2887 , C07K16/30 , C07K16/3007 , C07K16/3092 , C07K16/44 , C07K2317/24 , C07K2317/31 , C07K2317/35 , C07K2317/51 , C07K2317/52 , C07K2317/522 , C07K2317/55 , C07K2317/73 , C07K2317/734 , C07K2317/75 , C07K2317/77 , C07K2319/70 , C12N15/113 , C12N2310/14 , C12N2310/3513 , C12N2320/32 , Y02A50/403
摘要： Disclosed herein are methods and compositions comprising anti-CD74 and/or anti-HLA-DR antibodies for treatment of GVHD and other immune dysfunction diseases. In preferred embodiments, the anti-CD74 and/or anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8 + memory T cells. The compositions and methods provide a novel conditioning regimen for preventing aGVHD and/or treating chronic GVHD, without altering preexisting anti-viral immunity.
摘要翻译：本文公开了包含用于治疗GVHD和其他免疫功能障碍疾病的抗CD74和/或抗HLA-DR抗体的方法和组合物。在优选的实施方案中，抗CD74和/或抗HLA-DR抗体有效地消耗抗原呈递细胞，例如树突状细胞。最优选地，治疗组合物的施用消耗了APC的所有子集，包括mDC，pDC，B细胞和单核细胞，而没有T细胞的显着消耗。在替代实施方案中，施用治疗组合物抑制同种异体反应性T细胞的增殖，同时保留巨细胞病毒（CMV）特异性CD8 +记忆T细胞。组合物和方法提供了用于预防aGVHD和/或治疗慢性GVHD的新型调节方案，而不改变预先存在的抗病毒免疫。

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