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1. 发明申请

WO2014018117A1 AN MVA VACCINE FOR DELIVERY OF A UL128 COMPLEX AND PREVENTING CMV INFECTION 审中-公开
标题翻译：用于输送UL128复合物和预防CMV感染的MVA疫苗
公开(公告)号：WO2014018117A1
公开(公告)日：2014-01-30
申请号：PCT/US2013/032554
申请日：2013-03-15
申请人： DIAMOND, Don, J. , WUSSOW, Felix , BARRY, Peter, A.
发明人： DIAMOND, Don, J. , WUSSOW, Felix , BARRY, Peter, A.
IPC分类号： C12N15/38 , A61K39/245 , C07K14/045
CPC分类号： A61K39/245 , A61K39/12 , A61K2039/5254 , A61K2039/5256 , A61K2039/70 , C07K14/005 , C12N7/00 , C12N2710/16122 , C12N2710/16134 , C12N2710/24143 , C12N2799/023 , C12N2800/204
摘要： In one embodiment, an expression system for expressing a UL128 complex is provided herein. The expression system may include a bacterial artificial chromosome (BAC) construct, wherein the BAC construct comprises a viral vector inserted with a set of DNA sequences that encode a UL128 complex. In another embodiment, a vaccine composition for preventing HCMV infection is provided. The vaccine composition may include a viral or bacterial vector capable of expressing a UL128 complex and a pharmaceutically acceptable carrier, adjuvant, additive or combination thereof or additional vector expressing a protein adjuvant. The viral vector may be an MVA and the UL128 complex includes five HCMV proteins or antigenic fragments thereof: UL128, UL130, UL131A, gL, and gH. In some embodiments, the viral vector is further inserted with one or more additional DNA sequences that encode one or more additional HCMVHCMV proteins or antigenic fragments thereof such as pp65, gB or both, or such as gM/gN or gO.
摘要翻译：在一个实施方案中，本文提供了用于表达UL128复合物的表达系统。表达系统可以包括细菌人造染色体（BAC）构建体，其中BAC构建体包含插入一组编码UL128复合物的DNA序列的病毒载体。在另一个实施方案中，提供了用于预防HCMV感染的疫苗组合物。疫苗组合物可以包括能够表达UL128复合物和药学上可接受的载体，佐剂，添加剂或其组合或表达蛋白质佐剂的另外的载体的病毒或细菌载体。病毒载体可以是MVA，UL128复合物包括五种HCMV蛋白或其抗原片段：UL128，UL130，UL131A，gL和gH。在一些实施方案中，病毒载体进一步插入一个或多个另外的编码一种或多种另外的HCMVHCMV蛋白或其抗原性片段的DNA序列，例如pp65，gB或两者，或诸如gM / gN或gO。

2. 发明申请

WO2016154628A1 BI-SPECIFIC TARGETED CHIMERIC ANTIGEN RECEPTOR T CELLS 审中-公开
标题翻译：双特异性靶向的CHIMERIC抗原T细胞
公开(公告)号：WO2016154628A1
公开(公告)日：2016-09-29
申请号：PCT/US2016/024560
申请日：2016-03-28
申请人： WANG, Xiuli , FORMAN, Stephen J. , DIAMOND, Don J.
发明人： WANG, Xiuli , FORMAN, Stephen J. , DIAMOND, Don J.
IPC分类号： A61K39/00 , C12N5/0783 , A61K35/17 , C07K14/725 , C07K14/705 , C07K16/28 , A61K39/12 , A61K39/17
CPC分类号： A61K39/0011 , A61K35/17 , A61K39/12 , A61K39/17 , A61K2039/5156 , A61K2039/5158 , A61K2039/585 , C07K14/7051 , C07K16/2803 , C07K16/2833 , C07K2317/622 , C07K2317/73 , C07K2319/03 , C12N5/0638 , C12N2710/16134 , A61K2300/00
摘要： T cells expressing a chimeric antigen receptor and a T cell receptor specific for CMV (bi-specific T cells) are described as a methods for using such cells in immunotherapy. In the immunotherapy methods, the recipient can be exposed to a CMV vaccine in order to expand and/or stimulate the be-specific T cells.
摘要翻译：描述了表达嵌合抗原受体的T细胞和对CMV特异性的T细胞受体（双特异性T细胞）作为在免疫治疗中使用这种细胞的方法。在免疫治疗方法中，接受者可暴露于CMV疫苗以扩增和/或刺激be特异性T细胞。

3. 发明申请

WO2012149364A1 TUMOR ASSOCIATED VACCINES AND COMPOSITIONS FOR DISRUPTING TUMOR-DERIVED IMMUNOSUPPRESSION FOR USE IN COMBINATION CANCER IMMUNOTHERAPY 审中-公开
标题翻译：肿瘤相关疫苗和组合物，用于破坏肿瘤衍生的免疫抑制用于组合癌症免疫治疗
公开(公告)号：WO2012149364A1
公开(公告)日：2012-11-01
申请号：PCT/US2012/035512
申请日：2012-04-27
申请人： DIAMOND, Don, J. , MANUEL, Edwin , DECASTRO, Fernanda, V., V.
发明人： DIAMOND, Don, J. , MANUEL, Edwin , DECASTRO, Fernanda, V., V.
IPC分类号： A61K39/00 , A61K39/112 , A61P35/00 , C12N15/113
CPC分类号： C12N15/1138 , A61K39/0011 , A61K39/39 , C12N1/20 , C12N15/1136 , C12N15/1137 , C12N2310/14 , C12N2310/531 , C12N2320/32 , C12N2330/50 , C12Y113/11052 , C12Y305/03001 , Y02A50/484
摘要： In one embodiment, a single modality cancer immunotherapy regimen that includes a therapeutic composition is provided. Such a therapeutic composition may include a Salmonella strain comprising a plasmid that expresses an shRNA molecule that suppresses the expression of an immunosuppressive target and suppresses tumor growth. In some aspects, the Salmonella strain is an attenuated Salmonella typhimurium strain. In other aspects, the immunosuppressive target is STAT3, ID01, ID02, Arginase 1, iNOS, CTLA-4, TGF-β, IL-10, pGE2 or VEGF. In one embodiment, the immunosuppressive target is ID01 or Arg1 and the shRNA molecule is any one of SEQ ID NO:5-14.
摘要翻译：在一个实施方案中，提供了包括治疗组合物的单一模态癌症免疫治疗方案。这样的治疗组合物可以包括沙门氏菌菌株，其包含表达抑制免疫抑制性靶标的表达并抑制肿瘤生长的shRNA分子的质粒。在一些方面，沙门氏菌属菌株是减毒的鼠伤寒沙门氏菌菌株。在其他方面，免疫抑制靶标是STAT3，ID01，ID02，精氨酸酶1，iNOS，CTLA-4，TGF-β，IL-10，pGE2或VEGF。在一个实施方案中，免疫抑制靶标是ID01或Arg1，shRNA分子是SEQ ID NO：5-14中的任一个。

4. 发明申请

WO2004058801A3 MODIFIED VACCINIA ANKARA EXPRESSING P53 IN CANCER IMMUNOTHERAPY 审中-公开
标题翻译：表达P53的癌基因表达载体在癌症免疫治疗中的表达
公开(公告)号：WO2004058801A3
公开(公告)日：2004-11-11
申请号：PCT/US0341053
申请日：2003-12-22
申请人： HOPE CITY , ELLENHORN JOSHUA D I , DIAMOND DON J
发明人： ELLENHORN JOSHUA D I , DIAMOND DON J
IPC分类号： A61K39/12 , A61K48/00 , C07K20060101 , C07K14/47 , C12N7/00 , C12N15/00 , C12N15/86 , C12N15/863
CPC分类号： C12N15/86 , A61K2039/5156 , A61K2039/55516 , A61K2039/55561 , A61K2039/57 , C07K14/4746 , C12N2710/24143 , Y10S435/81
摘要： Mutations to the tumor suppressor protein p53 have been observed in 40-60% of all human cancers. These mutations are often associated with high nuclear and cytoplasmic concentrations of p53. Since many tumors exhibit highly elevated p53 levels, the protein is an attractive target for cancer immunotherapy. Unfortunately, p53 is an autoantigen that is likely to be tolerated as a self-protein by the immune system. The present invention is based on the discovery that this self-tolerance can be overcome by administration of recombinant modified vaccinia Ankara (MVA) containing a nucleic acid that encodes p53 (rMVAp53). The invention discloses a method of generating a p53-specific CTL response to tumor cells expressing mutated p53 by administering a composition comprising rMVAp53. Administration of rMVAp53 decreases tumor development, tumor growth, and mortality in a variety of malignant cell types. These effects are enhanced by administration of CTLA-4 blocker and/or CpG oligodeoxynucleotide immunomodulators.
摘要翻译：在所有人类癌症的40-60％中已观察到肿瘤抑制蛋白p53的突变。这些突变通常与p53的高核浓度和细胞质浓度有关。由于许多肿瘤表现出高水平的p53水平，该蛋白质是癌症免疫治疗的有吸引力的靶标。不幸的是，p53是一种自身抗原，可能被免疫系统作为自身蛋白质耐受。本发明基于这样的发现，即通过施用含有编码p53（rMVAp53）的核酸的重组修饰的安卡拉痘苗病毒（MVA）可以克服这种自身耐受性。本发明公开了通过施用包含rMVAp53的组合物产生对表达突变p53的肿瘤细胞的p53特异性CTL应答的方法。 rMVAp53的施用减少了多种恶性细胞类型中的肿瘤发展，肿瘤生长和死亡率。通过施用CTLA-4阻断剂和/或CpG寡脱氧核苷酸免疫调节剂可增强这些作用。

5. 发明申请

WO2004093905A1 HUMAN CYTOMEGALOVIRUS ANTIGENS EXPRESSED IN MVA AND METHODS OF USE 审中-公开
标题翻译：在MVA中表达的人体细胞病毒抗原及其使用方法
公开(公告)号：WO2004093905A1
公开(公告)日：2004-11-04
申请号：PCT/US2004/011891
申请日：2004-04-16
申请人： CITY OF HOPE , DIAMOND, Don, J.
发明人： DIAMOND, Don, J.
IPC分类号： A61K39/12
CPC分类号： C12N15/86 , A61K39/12 , A61K39/245 , A61K39/275 , A61K2039/5256 , A61K2039/545 , C07K14/005 , C12N2710/16122 , C12N2710/16134 , C12N2710/24143
摘要： ABSTRACT OF THE DISCLOSURE DNA and protein constructs useful in producing vaccines against human cytomegalovirus contain optionally N-end modified and N-terminal ubiquitinated human cytomegalovirus antigenic proteins, including pp65, pp150, IE1, gB and antigenic fragments thereof. Vaccine viruses, in particular poxviruses such as vaccinia and Modified Vaccinia Ankara, that express the constructs may be used as vaccines to augment the immune response to human cytomegalovirus, both prophylatically and in patients already carrying human cytomegalovirus, as well as to create and expand cytomegalovirus-reactive T cells for transfer of adoptive immunity.
摘要翻译：公开内容的摘要可用于生产针对人巨细胞病毒的疫苗的DNA和蛋白质构建体包含任选N末端修饰和N-末端泛素化的人巨细胞病毒抗原蛋白，包括pp65，pp150，IE1，gB及其抗原性片段。表达构建体的疫苗病毒，特别是痘苗病毒例如痘苗病毒和修饰牛痘安卡拉可以用作疫苗，以增强对人巨细胞病毒的免疫应答，预防和已经携带人巨细胞病毒的患者，以及创建和扩大巨细胞病毒 - 反应性T细胞用于转移过继免疫。

6. 发明申请

WO2004058801A2 MODIFIED VACCINIA ANKARA EXPRESSING P53 IN CANCER IMMUNOTHERAPY 审中-公开
标题翻译：癌症免疫组织化学显示P53修饰的疫苗
公开(公告)号：WO2004058801A2
公开(公告)日：2004-07-15
申请号：PCT/US2003/041053
申请日：2003-12-22
申请人： CITY OF HOPE , ELLENHORN, Joshua, D., I. , DIAMOND, Don, J.
发明人： ELLENHORN, Joshua, D., I. , DIAMOND, Don, J.
IPC分类号： C07K
CPC分类号： C12N15/86 , A61K2039/5156 , A61K2039/55516 , A61K2039/55561 , A61K2039/57 , C07K14/4746 , C12N2710/24143 , Y10S435/81
摘要： Mutations to the tumor suppressor protein p53 have been observed in 40-60% of all human cancers. These mutations are often associated with high nuclear and cytoplasmic concentrations of p53. Since many tumors exhibit highly elevated p53 levels, the protein is an attractive target for cancer immunotherapy. Unfortunately, p53 is an autoantigen that is likely to be tolerated as a self-protein by the immune system. The present invention is based on the discovery that this self-tolerance can be overcome by administration of recombinant modified vaccinia Ankara (MVA) containing a nucleic acid that encodes p53 (rMVAp53). The invention discloses a method of generating a p53-specific CTL response to tumor cells expressing mutated p53 by administering a composition comprising rMVAp53. Administration of rMVAp53 decreases tumor development, tumor growth, and mortality in a variety of malignant cell types. These effects are enhanced by administration of CTLA-4 blocker and/or CpG oligodeoxynucleotide immunomodulators.
摘要翻译：已经在40-60％的人类癌症中观察到肿瘤抑制蛋白p53的突变。这些突变通常与p53的高核和细胞质浓度相关。由于许多肿瘤表现出高度升高的p53水平，蛋白质是癌症免疫治疗的有吸引力的靶标。不幸的是，p53是一种自身抗原，可能被免疫系统的自身蛋白所耐受。本发明基于这样的发现：通过施用含有编码p53（rMVAp53）的核酸的重组修饰的痘苗安卡拉（MVA）可以克服这种自身耐受性。本发明公开了通过施用包含rMVAp53的组合物来产生对表达突变的p53的肿瘤细胞的p53特异性CTL应答的方法。 rMVAp53的给药减少了各种恶性细胞类型的肿瘤发展，肿瘤生长和死亡率。通过施用CTLA-4阻断剂和/或CpG寡脱氧核苷酸免疫调节剂来增强这些作用。

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