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1. 发明申请

US20080090778A1 Telomerase reverse transcriptase fusion protein, nucleotides encoding it, and uses thereof 有权
标题翻译：端粒酶逆转录酶融合蛋白，编码它的核苷酸及其用途
公开(公告)号：US20080090778A1
公开(公告)日：2008-04-17
申请号：US11974067
申请日：2007-10-11
申请人： Elisa Scarselli , Carmela Mennuni , Nicola La Monica , Gennaro Ciliberto
发明人： Elisa Scarselli , Carmela Mennuni , Nicola La Monica , Gennaro Ciliberto
IPC分类号： A61K31/70 , C07H21/04 , C07K16/00 , C12N15/00 , C12N5/00
CPC分类号： C07K14/245 , C07K2319/00 , C07K2319/036 , C12N9/1241 , C12Y207/07049
摘要： Polynucleotides encoding telomerase reverse transcriptase (TERT) fusion proteins are provided, the TERT fusion proteins comprising a TERT protein, or functional variant thereof, fused to a substantial portion of the B subunit of heat labile enterotoxin (LTB). TERT variants useful in TERT-LTB fusion proteins of the invention comprise mutations that function to eliminate telomerase catalytic activity. The polynucleotides of the present invention can elicit an immune response in a mammal, which, in preferred embodiments, is stronger than the immune response elicited by a wild-type TERT. TERT expression is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the TERT tumor-associated antigen, wherein aberrant TERT expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying polynucleotides encoding TERT fusion proteins and TERT variants and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
摘要翻译：提供了编码端粒酶逆转录酶（TERT）融合蛋白的多核苷酸，包含与热不稳定肠毒素（LTB）的B亚基的大部分融合的TERT蛋白或其功能变体的TERT融合蛋白。在本发明的TERT-LTB融合蛋白中有用的TERT变体包含用于消除端粒酶催化活性的突变。本发明的多核苷酸可以在哺乳动物中引发免疫应答，在优选的实施方案中，其比由野生型TERT引起的免疫应答更强。 TERT表达通常与人类癌的发展有关。本发明提供了引发或增强对由TERT肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法，其中异常TERT表达与癌症或其发展相关。本发明具体提供了携带编码TERT融合蛋白和TERT变体的多核苷酸的腺病毒载体和质粒构建体，并公开了它们在预防和治疗癌症的疫苗和药物组合物中的用途。

2. 发明授权

US08017387B2 Telomerase reverse transcriptase fusion protein, nucleotides encoding it, and uses thereof 有权
标题翻译：端粒酶逆转录酶融合蛋白，编码它的核苷酸及其用途
公开(公告)号：US08017387B2
公开(公告)日：2011-09-13
申请号：US11974067
申请日：2007-10-11
申请人： Elisa Scarselli , Carmela Mennuni , Nicola La Monica , Gennaro Ciliberto
发明人： Elisa Scarselli , Carmela Mennuni , Nicola La Monica , Gennaro Ciliberto
IPC分类号： C12N15/00 , C12N5/10
CPC分类号： C07K14/245 , C07K2319/00 , C07K2319/036 , C12N9/1241 , C12Y207/07049
摘要： Polynucleotides encoding telomerase reverse transcriptase (TERT) fusion proteins are provided, the TERT fusion proteins comprising a TERT protein, or functional variant thereof, fused to a substantial portion of the B subunit of heat labile enterotoxin (LTB). TERT variants useful in TERT-LTB fusion proteins of the invention comprise mutations that function to eliminate telomerase catalytic activity. The polynucleotides of the present invention can elicit an immune response in a mammal, which, in preferred embodiments, is stronger than the immune response elicited by a wild-type TERT. TERT expression is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the TERT tumor-associated antigen, wherein aberrant TERT expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying polynucleotides encoding TERT fusion proteins and TERT variants and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
摘要翻译：提供了编码端粒酶逆转录酶（TERT）融合蛋白的多核苷酸，包含与热不稳定肠毒素（LTB）的B亚基的大部分融合的TERT蛋白或其功能变体的TERT融合蛋白。在本发明的TERT-LTB融合蛋白中有用的TERT变体包含用于消除端粒酶催化活性的突变。本发明的多核苷酸可以在哺乳动物中引发免疫应答，在优选的实施方案中，其比由野生型TERT引起的免疫应答更强。 TERT表达通常与人类癌的发展有关。本发明提供了引发或增强对由TERT肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法，其中异常TERT表达与癌症或其发展相关。本发明具体提供了携带编码TERT融合蛋白和TERT变体的多核苷酸的腺病毒载体和质粒构建体，并公开了它们在预防和治疗癌症的疫苗和药物组合物中的用途。

3. 发明申请

US20110182926A1 MINIGENE 审中-公开
公开(公告)号：US20110182926A1
公开(公告)日：2011-07-28
申请号：US13058304
申请日：2009-08-07
申请人： Nicola La Monica , Elisa Scarselli , Gennaro Ciliberto , Luigi Aurisicchio , Arthur Fridman , Ansuman Bagchi
发明人： Nicola La Monica , Elisa Scarselli , Gennaro Ciliberto , Luigi Aurisicchio , Arthur Fridman , Ansuman Bagchi
IPC分类号： A61K39/00 , C07K19/00 , A61P37/04 , A61P35/00 , A61P31/00
CPC分类号： C07K14/70503 , C07K2319/02 , C07K2319/50 , C07K2319/55 , C12N9/6459
摘要： The present invention provides minigenes suitable as a prophylactic or therapeutic vaccine against conditions such as cancer, infectious diseases or autoimmune diseases, and pharmaceutical compositions comprising the minigene. The minigenes of the present invention comprise (a) a human tissue plasminogen signal peptide; (b) at least one T-cell epitope; and (c) an E. coli heat labile enterotoxin B subunit; wherein the at least one T-cell epitope is linked to the rest of the minigene, and to any other epitopes, by furin sensitive linkers. In some embodiments of the invention, the minigene comprises T-cell epitopes from one or more of CEA, her-2/neu and hTERT. Also provided herein are immunogenic peptide epitopes of CEA, her-2/neu and hTERT, as well as immunogenic peptide analogs, and pharmaceutical compositions and vaccines comprising one or more of said peptides and analogs for prophylaxis and/or treatment of cancer or other disorder. Methods of inducing an immune response in a patient, in addition to methods of treatment using the minigenes, immunogenic peptides, and peptide analogs disclosed herein are also provided.
摘要翻译：本发明提供适合作为针对诸如癌症，感染性疾病或自身免疫性疾病的病症的预防或治疗性疫苗的微创，以及包含小基因的药物组合物。本发明的微生物包含（a）人组织纤溶酶原信号肽; （b）至少一个T细胞表位; 和（c）大肠杆菌热不稳定肠毒素B亚基; 其中所述至少一个T细胞表位与所述小基因的其余部分和通过弗林蛋白酶敏感性接头连接到任何其它表位。在本发明的一些实施方案中，小基因包含来自CEA，her-2 / neu和hTERT中的一种或多种的T细胞表位。本文还提供了CEA，her-2 / neu和hTERT的免疫原性肽表位以及免疫原性肽类似物，以及包含一种或多种所述肽和类似物用于预防和/或治疗癌症或其它疾病的药物组合物和疫苗。还提供了在使用本文公开的微生物，免疫原性肽和肽类似物的治疗方法之外，在患者体内诱导免疫应答的方法。

4. 发明申请

US20070104685A1 Synthetic gene encoding human carcinoembryonic antigen and uses thereof 审中-公开
标题翻译：编码人癌胚抗原的合成基因及其用途
公开(公告)号：US20070104685A1
公开(公告)日：2007-05-10
申请号：US10555744
申请日：2004-05-03
申请人： Nicola La Monica , Armin Lahm , Carmela Mennuni , Rocco Savino
发明人： Nicola La Monica , Armin Lahm , Carmela Mennuni , Rocco Savino
IPC分类号： A61K48/00 , C12Q1/68 , C07H21/04 , C12P21/06 , C12N15/861 , C07K14/82
CPC分类号： C07K14/4748 , A61K39/00 , A61K2039/53 , C07K14/70503 , C12N2799/022
摘要： Synthetic polynucleotides encoding human carcinoembryonic antigen (CEA) are provided, the synthetic polynucleotides being codon-optimized for expression in a human cellular environment. The gene encoding CEA is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the CEA tumor-associated antigen, wherein aberrant CEA expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying codon-optimed human CEA and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
摘要翻译：提供了编码人癌胚抗原（CEA）的合成多核苷酸，所述合成多核苷酸被密码子优化用于在人细胞环境中表达。编码CEA的基因通常与人类癌的发展有关。本发明提供了引发或增强由CEA肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法，其中异常CEA表达与癌症或其发展相关。本发明具体提供携带密码子优化的人CEA的腺病毒载体和质粒构建体，并公开了它们在预防和治疗癌症的疫苗和药物组合物中的用途。

5. 发明授权

US06641807B1 Adenoviral vectors encoding erythropoietin and their use in gene therapy 失效
标题翻译：编码促红细胞生成素的腺病毒载体及其在基因治疗中的应用
公开(公告)号：US06641807B1
公开(公告)日：2003-11-04
申请号：US09762668
申请日：2001-04-23
申请人： Rocco Savino , Gennaro Ciliberto , Nicola La Monica
发明人： Rocco Savino , Gennaro Ciliberto , Nicola La Monica
IPC分类号： A01N6300
CPC分类号： A61K38/1816 , A61K48/00 , C07K14/505 , C12N2799/022
摘要： Helper dependent adenoviral vectors encoding erythropoietin (epo) provide high levels of epo to achieve a long-term therapeutically effective dosage, and allow for repeat administration to patients with disorders such as anaemia of Chronic Renal Failure (CFR), anaemias due to beta-thalassaemia, and sickle cell anaemia (SCA).
摘要翻译：编码促红细胞生成素（epo）的辅助依赖性腺病毒载体提供高水平的epo以实现长期治疗有效剂量，并且允许对患有慢性肾功能衰竭（CFR）的贫血，由于β-地中海贫血造成的贫血的疾病患者重复施用，和镰状细胞性贫血（SCA）。

6. 发明申请

US20050004055A1 Increasing electro-gene transfer of nucleic acid molecules into host tissue 审中-公开
标题翻译：增加核酸分子进入宿主组织的电 - 基因转移
公开(公告)号：US20050004055A1
公开(公告)日：2005-01-06
申请号：US10495669
申请日：2002-11-21
申请人： Elena Fattori , Nicola La Monica , Carmela Mennuni
发明人： Elena Fattori , Nicola La Monica , Carmela Mennuni
IPC分类号： C12N15/09 , A61K31/7088 , A61K31/711 , A61K38/47 , A61K45/00 , A61K47/42 , A61M37/00 , A61P43/00 , C12N5/10 , A61K48/00
CPC分类号： A61K31/711 , A61K38/47 , A61K2300/00
摘要： A method of delivering a pharmaceutical agent, such as a nucleic acid molecule, to a vertebrate host is disclosed which comprises combining the synergistic steps of electrical stimulation with administration of a biologically active amount of hyaluronidase. Additionally, formulations which comprise hyaluronidase and a pharmaceutical agent, such as a nucleic acid molecule, are disclosed. The hyaluronidase preparation is preferably administered prior to or simultaneous with the pharmaceutical agent and in conjunction with an applied electrical stimulation, thus affecting increased transfer of the population of a pharmaceutical agent into the target tissue when compared to the affect of electrical stimulation alone. The combination of hyaluronidase administration and electrostimulation results in a substantial increase in the transfer of the pharmaceutical agent, such as a nucleic acid molecule, to the target vertebrate host tissue.
摘要翻译：公开了将药剂如核酸分子递送至脊椎动物宿主的方法，其包括将电刺激的协同步骤与施用生物活性量的透明质酸酶组合。此外，公开了包含透明质酸酶和药剂如核酸分子的制剂。透明质酸酶制剂优选在药物之前或与药剂同时施用，并与所施加的电刺激结合施用，因此与单独的电刺激的影响相比，影响药物剂群进入靶组织的增加的转移。透明质酸酶施用和电刺激的组合导致药剂如核酸分子转移到目标脊椎动物宿主组织的显着增加。

7. 发明授权

US08188244B2 Carcinoembryonic antigen fusions and uses thereof 有权
标题翻译：癌胚抗原融合物及其用途
公开(公告)号：US08188244B2
公开(公告)日：2012-05-29
申请号：US10589180
申请日：2005-02-03
申请人： Nicola La Monica , Andrea Facciabene , Luigi Aurisicchio , Gennaro Ciliberto
发明人： Nicola La Monica , Andrea Facciabene , Luigi Aurisicchio , Gennaro Ciliberto
IPC分类号： C12N15/11 , C12N15/63
CPC分类号： C07K14/70503 , A61K2039/53 , C07K2319/30 , C07K2319/55 , Y02A50/472
摘要： Polynucleotides encoding carcinoembryonic antigen (CEA) fusion proteins are provided, the CEA fusion proteins comprising a CEA protein, or functional variant thereof, fused to a substantial portion of an immunoenhancing element. The polynucleotides of the present invention can elicit an immune response in a mammal, which, in preferred embodiments, is stronger than the immune response elicited by a wild-type CEA. The gene encoding CEA is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the CEA tumor-associated antigen, wherein aberrant CEA expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying polynucleotides encoding CEA fusion proteins and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
摘要翻译：提供了编码癌胚抗原（CEA）融合蛋白的多核苷酸，包含CEA蛋白或其功能变体的CEA融合蛋白与免疫增强元件的大部分融合。本发明的多核苷酸可以在哺乳动物中引发免疫应答，在优选的实施方案中，它们比由野生型CEA引起的免疫应答更强。编码CEA的基因通常与人类癌的发展有关。本发明提供了引发或增强由CEA肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法，其中异常CEA表达与癌症或其发展相关。本发明具体提供携带编码CEA融合蛋白的多核苷酸的腺病毒载体和质粒构建体，并公开了其用于预防和治疗癌症的疫苗和药物组合物中。

8. 发明授权

US08106176B2 Matrix metalloproteinase 11 vaccine 有权
标题翻译：基质金属蛋白酶11疫苗
公开(公告)号：US08106176B2
公开(公告)日：2012-01-31
申请号：US12083031
申请日：2006-10-03
申请人： Luigi Aurisicchio , Daniela Peruzzi , Nicola La Monica , Gennaro Ciliberto , Domenico Lazzaro , Federica Mori
发明人： Luigi Aurisicchio , Daniela Peruzzi , Nicola La Monica , Gennaro Ciliberto , Domenico Lazzaro , Federica Mori
IPC分类号： C07H1/00 , C07H5/04 , C07H5/06 , C07H19/00 , C07H21/00 , C07H21/04 , C08B37/00 , C12P21/06 , C12N5/00 , C12N5/02
CPC分类号： C12N9/6416 , A61K39/00 , C07K2319/00 , Y02A50/472
摘要： Compositions comprising matrix metalloproteinase 11 (MMP-11) or stromelysin-3 (ST-3) or the nucleic acid encoding the MMP-11 for use in vaccines for treating tumors and cancers, which overexpress MMP-11, are described. In particular embodiments, the compositions comprise a nucleic acid encoding a fusion polypeptide that includes the catalytically inactivated MMP-11 linked at the C-terminus to an immunoenhancing element wherein the codons encoding the MMP-11 and the immunoenhancing element have been optimized for enhanced expression of the fusion polypeptide in human cells. In other embodiments, the compositions comprise the catalytically inactivated MMP-11 linked at the C-terminus to an immunoenhancing element. The compositions can be used alone or in synergy with vaccines against other tumor associated antigens as well as with conventional therapies such as radiation therapy and chemotherapy.
摘要翻译：描述了包含基质金属蛋白酶11（MMP-11）或基质溶素-3（ST-3）的组合物或编码用于治疗过表达MMP-11的肿瘤和癌症的疫苗中的MMP-11的核酸。在具体实施方案中，组合物包含编码融合多肽的核酸，其包含在C-末端连接至免疫增强元件的催化失活的MMP-11，其中编码MMP-11和免疫增强元件的密码子已被优化以增强表达的人类细胞中的融合多肽。在其它实施方案中，组合物包含在C末端与免疫增强元件连接的催化失活的MMP-11。组合物可以单独使用或与抗其他肿瘤相关抗原的疫苗以及常规疗法如放射治疗和化学疗法协同使用。

9. 发明申请

US20060239969A1 Rhesus her2/neu, nucleotides encoding same, and uses thereof 失效
标题翻译：恒河猴her2 / neu，编码相同的核苷酸及其用途
公开(公告)号：US20060239969A1
公开(公告)日：2006-10-26
申请号：US10541270
申请日：2003-12-29
申请人： Paolo Monaci , Maurizio Nuzzo , Nicola La Monica , Gennaro Ciliberto , Armin Lahm
发明人： Paolo Monaci , Maurizio Nuzzo , Nicola La Monica , Gennaro Ciliberto , Armin Lahm
IPC分类号： A61K48/00 , C07H21/04 , C12P21/06 , C12N5/06 , C12N15/861 , C07K14/82
CPC分类号： A61K38/1709 , A61K2039/5256 , A61K2039/53 , A61K2039/545 , C07K14/71 , C12N15/86 , C12N2710/10343 , C12N2799/022
摘要： Polynucleotides encoding rhesus monkey HER2/neu have been isolated, cloned and sequenced. The gene encoding the HER2/neu is commonly associated with the development of epithelial-derived human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the HER2/neu tumor-associated antigen, wherein aberrant HER2/neu expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector constructs carrying rhHER2/neu and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.
摘要翻译：编码恒河猴HER2 / neu的多核苷酸已被分离，克隆和测序。编码HER2 / neu的基因通常与上皮衍生的人类癌的发展有关。本发明提供了引发或增强对由HER2 / neu肿瘤相关抗原表达的蛋白质产物的免疫的组合物和方法，其中异常HER2 / neu表达与癌或其发展相关。本发明具体提供携带rhHER2 / neu的腺病毒载体构建体，并公开了它们在预防和治疗癌症的疫苗和药物组合物中的用途。

10. 发明授权

US06521426B1 Preparation of recombinant adenovirus carrying a rep gene of adeno-associated virus 失效
标题翻译：携带腺相关病毒代谢基因的重组腺病毒的制备
公开(公告)号：US06521426B1
公开(公告)日：2003-02-18
申请号：US09647795
申请日：2000-12-08
申请人： Gennaro Ciliberto , Stefano Colloca , Nicola La Monica
发明人： Gennaro Ciliberto , Stefano Colloca , Nicola La Monica
IPC分类号： C12P2104
CPC分类号： C12N15/86 , C12N2710/10344 , C12N2750/14143
摘要： Adenoviral particles are produced by incubating cells containing a helper adenovirus vector and a helper-dependent adenoviral vector including an Adeno-Associated Virus (AAV) rep gene, such as rep 78. Cells are provided containing a helper adenovirus vector. A helper-dependent adenoviral vector including an AAV rep gene is introduced into the cells, for instance by infection with infective viral particles. The cells are incubated to produce adenoviral particles containing nucleic acid including the AAV rep gene. Advantageously, cells containing helper adenovirus vector are pre-incubated for 0.5-12 hours, preferably about 4 hours, to allow expression of viral proteins required for adenoviral genome replication before introducing the helper-dependent adenovirus vector including an AAV rep gene.
摘要翻译：腺病毒颗粒通过温育含有辅助性腺病毒载体和辅助性依赖性腺病毒载体的细胞产生，所述腺病毒载体包括腺相关病毒（AAV）rep基因，例如rep 78.提供含有辅助性腺病毒载体的细胞。将包括AAV rep基因的辅助依赖性腺病毒载体引入细胞中，例如通过感染性病毒颗粒感染。将细胞孵育以产生含有包含AAV rep基因的核酸的腺病毒颗粒。有利地，含有辅助腺病毒载体的细胞预先孵育0.5-12小时，优选约4小时，以允许在引入包括AAV rep基因的辅助性依赖性腺病毒载体之前表达腺病毒基因组复制所需的病毒蛋白。

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