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1. 发明授权

US07217713B2 N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase 有权
标题翻译： HIV整合酶的N-取代羟基嘧啶酮羧酰胺抑制剂
公开(公告)号：US07217713B2
公开(公告)日：2007-05-15
申请号：US11491815
申请日：2006-07-24
申请人： Benedetta Crescenzi , Cristina Gardelli , Ester Muraglia , Emanuela Nizi , Federica Orvieto , Paola Pace , Giovanna Pescatore , Alessia Petrocchi , Marco Poma , Michael Rowley , Rita Scarpelli , Vincenzo Summa
发明人： Benedetta Crescenzi , Cristina Gardelli , Ester Muraglia , Emanuela Nizi , Federica Orvieto , Paola Pace , Giovanna Pescatore , Alessia Petrocchi , Marco Poma , Michael Rowley , Rita Scarpelli , Vincenzo Summa
IPC分类号： A61K31/515 , C07D239/54
CPC分类号： C07D239/557 , C07D401/04 , C07D401/06 , C07D401/10 , C07D401/12 , C07D401/14 , C07D403/04 , C07D403/06 , C07D403/10 , C07D403/12 , C07D403/14 , C07D413/04 , C07D413/10 , C07D413/12 , C07D417/04 , C07D513/04
摘要： N-substituted 5-hydroxypyrimidin-6-one-4-carboxamides of formula: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R1, R2, R3 and R4 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds-are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.
摘要翻译：描述了下式的N-取代的5-羟基嘧啶-6-酮-4-甲酰胺作为HIV整合酶的抑制剂和HIV复制抑制剂，其中R 1，R 2， R 3和R 4在本文中定义。这些化合物可用于预防和治疗艾滋病毒感染以及艾滋病的预防，延迟发作和治疗。化合物 - 作为化合物本身或以药学上可接受的盐的形式用于HIV感染和AIDS。化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。还描述了预防，治疗或延缓AIDS发病的方法以及预防或治疗HIV感染的方法。

2. 发明授权

US08354518B2 HCV replicons containing NS5B from genotype 2B 失效
标题翻译：含有来自基因型2B的NS5B的HCV复制子
公开(公告)号：US08354518B2
公开(公告)日：2013-01-15
申请号：US10577893
申请日：2004-11-03
申请人： Steven W. Ludmerer , Donald J. Graham , Robert L. LaFemina , Osvaldo A. Flores , Maura Pizzuti , Cinzia Traboni
发明人： Steven W. Ludmerer , Donald J. Graham , Robert L. LaFemina , Osvaldo A. Flores , Maura Pizzuti , Cinzia Traboni
IPC分类号： C07H21/04 , C12P21/00 , C12N15/00 , C12N7/00
CPC分类号： C12Q1/707 , C07K14/005 , C12N7/00 , C12N2770/24221 , C12N2770/24222
摘要： The present invention features methods for enhancing the ability of a genotype 2b NS5B sequence to function in a replicon, for producing replicons containing a functional genotype 2b NS5B, and for using replicons to measure the ability of a compound to affect HCV replication that is sustained with the genotype 2b polymerase. Also featured is a genotype 1b NS4B adaptive mutation. The ability to produce replicons containing a functional genotype 2b NS5B is illustrated by the production of chimeric replicons based on HCV genotype 1b where substantially all the NS5B sequence is replaced with a genotype 2b NS5B.
摘要翻译：本发明的特征在于增强基因型2b NS5B序列在复制子中起作用的能力的方法，用于产生含有功能性基因型2b NS5B的复制子，并且使用复制子来测量化合物影响HCV复制的能力基因型2b聚合酶。还有一个基因型1b NS4B自适应突变。通过产生基于HCV基因型1b的嵌合复制子来说明产生含有功能性基因型2b NS5B的复制子的能力，其中基本上所有NS5B序列被基因型2b NS5B替代。

3. 发明授权

US07629140B2 Assay for cytochrome P450 isoform 2C9 失效
标题翻译：细胞色素P450同工型2C9的测定
公开(公告)号：US07629140B2
公开(公告)日：2009-12-08
申请号：US11663587
申请日：2005-10-04
申请人： Ralph Laufer , Annalise Di Marco , Ashok Chaudhary
发明人： Ralph Laufer , Annalise Di Marco , Ashok Chaudhary
IPC分类号： C12Q1/26
CPC分类号： C12Q1/26 , G01N2333/90245 , G01N2500/02
摘要： A Rapid And Sensitive Radiometric Assay For Assessing The Activity Of Cytochrome P-450 (CYP) 2C9 And The Potential Of An Analyte To Inhibit CYP2C9 Activity Or Induce CYP2C9 Expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.
摘要翻译：描述了用于评估细胞色素P-450（CYP）2C9的活性的快速和敏感的辐射测定以及分析物抑制CYP2C9活性或诱导CYP2C9表达的潜力。测定的所有步骤，包括孵育，产物分离和放射性计数优选以可以自动化的多孔格式进行。

4. 发明授权

US5739002A Method for reproducing in vitro the Proteolytic activity of the NS3 protease of hepatitis C virus (HCV) 失效
标题翻译：在体外再现丙型肝炎病毒（HCV）NS3蛋白酶的蛋白水解活性的方法
公开(公告)号：US5739002A
公开(公告)日：1998-04-14
申请号：US700356
申请日：1996-08-23
申请人： Raffaele De Francesco , Christina Failla , Licia Tomei
发明人： Raffaele De Francesco , Christina Failla , Licia Tomei
IPC分类号： A61K38/55 , A61P1/16 , A61P31/12 , C07K14/18 , C12N9/50 , C12N15/09 , C12Q1/37 , G01N33/573 , G01N33/576 , C07H21/04 , C12Q1/70
CPC分类号： C07K14/005 , G01N33/573 , G01N33/5767 , C12N2770/24222
摘要： This is a method for reproducing in vitro the serine protease activity associated with the HCV NS3 protein, that comprises using both of the sequences contained in NS3 and the sequences contained in NS4A. This method takes advantage of the ability of the HCV NS4A protein, or sequences contained therein, to act as a cofactor of the serine protease activity or more generally of the enzymatic activities associated with NS3. Optimal serine protease activity is obtained when NS4A is present in a molar ratio of at least 1:1 with NS3. NS3 and NS4A can also be incorporated in the reaction mixture as NS3-NS4A precursor, as this precursor will generate, by means of an autoproteolytic event, equimolar amounts of NS3 and NS4A. It is also possible to mutate the cleavage site between NS3 and NS4A in a procursor, so that NS4A remains covalently The sequences that do not influence the proteolytic activity of NS3 can subsequently be removed from protease activity.
摘要翻译： PCT No.PCT / IT95 / 00018 Sec。 371日期：1996年8月23日 102（e）日期1996年8月23日PCT提交1995年2月14日PCT公布。公开号WO95 / 22985 日期1995年8月31日这是一种再现体外与HCV NS3蛋白相关的丝氨酸蛋白酶活性的方法，其包括使用NS3中包含的两个序列和NS4A中包含的序列。该方法利用HCV NS4A蛋白或其中所含的序列的能力作为丝氨酸蛋白酶活性的辅因子或更一般地与NS3相关的酶活性。当NS4A与NS3以至少1:1的摩尔比存在时，获得最佳的丝氨酸蛋白酶活性。 NS3和NS4A也可以作为NS3-NS4A前体引入反应混合物中，因为该前体将通过自体蛋白水解事件产生等摩尔量的NS3和NS4A。也可能在前体中突变NS3和NS4A之间的切割位点，使得NS4A保持共价。随后可以从蛋白酶活性中除去不影响NS3的蛋白水解活性的序列。

5. 发明公开

EP2195326A1 NUCLEOSIDE DERIVATIVES AS INHIBITORS OF VIRAL POLYMERASES 有权
标题翻译：核苷作为抑制剂病毒性聚合酶
公开(公告)号：EP2195326A1
公开(公告)日：2010-06-16
申请号：EP08804247.8
申请日：2008-09-16
申请人： Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.
发明人： DI FRANCESCO, Maria, Emilia , SUMMA, Vincenzo , DESSOLE, Gabriella
IPC分类号： C07H19/23 , A61K31/7052
CPC分类号： C07H19/23
摘要： A class of nucleoside derivatives of formula (I), as defined herein, that are useful as inhibitors of RNA-dependent RNA viral replication and in particular HCV replication., are provided. Also provided are processes for the synthesis and use of such compounds for treating or preventing HCV infection. formula (I).

6. 发明公开

EP1436397A2 HEPATITIS C VIRUS VACCINE 有权
标题翻译：丙型肝炎病毒疫苗
公开(公告)号：EP1436397A2
公开(公告)日：2004-07-14
申请号：EP02773740.2
申请日：2002-10-10
申请人： Merck & Co., Inc. , Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.
发明人： EMINI, Emilio, A. , KASLOW, David, C. , BETT, Andrew, J. , SHIVER, John, W. , NICOSIA, Alfredo , LAHM, Armin , LUZZAGO, Alessandra , CORTESE, Riccardo , COLLOCA, Stefano
IPC分类号： C12N15/40 , C12N15/51 , C12N15/85 , C12N15/86 , C12N15/861 , A61K48/00
CPC分类号： C07K14/005 , A61K2039/5256 , A61K2039/53 , A61K2039/545 , A61K2039/57 , C12N15/86 , C12N2710/10343 , C12N2770/24222 , C12N2770/24234 , C12N2800/108 , C12N2810/6018 , C12N2830/003 , C12N2840/20 , C12N2840/203
摘要： The present invention features Ad6 vectors and a nucleic acid encoding a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide containing an inactive NS5B RNA-dependent RNA polymerase region. The nucleic acid is particularly useful as a component of an adenovector or DNA plasmid vaccine providing a broad range of antigens for generating an HCV specific cell mediated immune (CMI) response against HCV.

7. 发明公开

EP1768956A1 AMIDE DERIVATIVES AS INHIBITORS OF HISTONE DEACETYLASE 审中-公开
标题翻译：酰胺衍生物ALS组蛋白脱乙酰酶抑制剂
公开(公告)号：EP1768956A1
公开(公告)日：2007-04-04
申请号：EP05759859.1
申请日：2005-07-11
申请人： Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. , Merck and Co., Inc.
发明人： CHAKRAVARTY, Prasun K. , COLLETTI, Steven L. , INGENITO, Raffaele, IRBM , JONES, Philip , MEINKE, Peter T. , PETROCCHI, Alessia, IRBM , STEINKUHLER, Christian, IRBM
IPC分类号： C07D209/18 , C07D401/12 , C07D409/12 , A61K31/405 , A61P35/00
CPC分类号： C07D409/12 , C07D209/18 , C07D401/12
摘要： The present invention relates to carboxylic acid derivatives that are inhibitors of histone deacetylase (HDAC). The compounds of the present invention are useful for treating cellular proliferative diseases, including cancer. Further, the compounds of the present invention are useful for treating neurodegenerative diseases, schizophrenia and stroke among other diseases.

8. 发明授权

EP1441734B1 DIHYDROXYPYRIMIDINE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE 有权
标题翻译：二羟基嘧啶 - 碳青霉烯类抗体艾滋病毒整合剂
公开(公告)号：EP1441734B1
公开(公告)日：2007-02-28
申请号：EP02801949.5
申请日：2002-10-21
申请人： Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.
发明人： DI FRANCESCO, Maria Emilia, c/o IRBM , GARDELLI, Cristina, c/o IRBM , HARPER, Steven, c/o IRBM , MATASSA, Victor Giulio, c/o IRBM , MURAGLIA, Ester, c/o IRBM , NIZI, Emanuela, c/o IRBM , PACE, Paola, c/o IRBM , PACINI, Barbara, c/o IRBM , PETROCCHI, Alessia, c/o IRBM , POMA, Marco, c/o IRBM , SUMMA, Vincenzo, c/o IRBM
IPC分类号： A61K31/513 , A61K31/5377 , A61K31/541 , C07D239/52 , C07D239/557 , C07D401/04 , C07D401/06 , C07D401/12 , C07D401/14 , C07D403/04 , C07D403/12 , C07D403/14 , C07D405/04 , C07D413/04 , C07D409/04
CPC分类号： C07D239/557 , C07D401/04 , C07D401/06 , C07D401/12 , C07D401/14 , C07D403/04 , C07D403/06 , C07D403/12 , C07D403/14 , C07D405/04 , C07D405/06 , C07D405/12 , C07D405/14 , C07D409/04 , C07D409/06 , C07D409/14 , C07D413/04 , C07D413/06 , C07D413/12 , C07D413/14 , C07D417/04 , C07D417/14 , C07D471/04 , C07D487/08 , C07D491/10
摘要： 4,5-Dihydroxypyrimidine-6-carboxamides of formula (I); are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R?1, R2, R3 and R4¿ are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

9. 发明公开

EP1622937A2 SYNTHETIC GENE ENCODING HUMAN CARCINOEMBRYONIC ANTIGEN AND USES THEREOF 审中-公开
标题翻译：合成基因，对于HUMAES癌胚抗原编码及其用途
公开(公告)号：EP1622937A2
公开(公告)日：2006-02-08
申请号：EP04739137.0
申请日：2004-05-03
申请人： Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.
发明人： LA MONICA, Nicola, IRBM , LAHM, Armin, IRBM , MENNUNI, Carmela, IRBM , SAVINO, Rocco, IRBM
IPC分类号： C07K14/705 , C12N15/85 , C12N15/861 , A61P35/00 , A61K39/00
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.

10. 发明公开

EP2203463A2 ANTIVIRAL AGENTS 审中-公开
标题翻译： VIRUZIDE
公开(公告)号：EP2203463A2
公开(公告)日：2010-07-07
申请号：EP08750342.1
申请日：2008-05-19
申请人： Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.
发明人： ATTENNI, Barbara , DONGHI, Monica , GARDELLI, Cristina , MEPPEN, Malte , NARJES, Frank , PACINI, Barbara
IPC分类号： C07H19/10 , C07H19/20 , C07H19/04 , A61K31/706 , A61K31/7064 , A61K31/7076 , A61P31/14
CPC分类号： C07H19/10 , A61K31/706 , A61K31/7064 , A61K31/7076 , C07H19/04 , C07H19/20
摘要： A compound of formula (I) and pharmaceutically acceptable salts thereof; compositions containing it and its use in medicine, particularly for the treatment or inhibition of HCV infections, and processes for making it are disclosed.

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