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.

公开(公告)号：EP1320621A2

公开(公告)日：2003-06-25

申请号：EP01975214.6

申请日：2001-09-14

申请人： Merck & Co., Inc.

发明人： EMINI, Emilio, A. ,  YOUIL, Rima ,  BETT, Andrew, J. ,  CHEN, Ling ,  KASLOW, David, C. ,  SHIVER, John, W. ,  TONER, Timothy, J. ,  CASIMIRO, Daniel, R.

IPC分类号： C12N15/86

CPC分类号： C12N7/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/57 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2740/16134 ,  C12N2740/16334 ,  C12N2830/42

摘要： First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1- Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

公开(公告)号：EP1611237A1

公开(公告)日：2006-01-04

申请号：EP03796304.8

申请日：2003-08-21

申请人： Merck & Co., Inc.

发明人： EMINI, Emilio, A. ,  SHIVER, John, W. ,  BETT, Andrew, J. ,  CASIMIRO, Danilo, R. ,  KASLOW, David, C. ,  CHASTAIN, Michael

IPC分类号： C12N15/00 ,  C12N15/01 ,  C12N15/33

CPC分类号： C12N15/86 ,  A61K48/00 ,  A61K2039/5256 ,  A61K2039/53 ,  C07K14/005 ,  C12N2710/10343 ,  C12N2710/10371 ,  C12N2740/16122 ,  C12N2740/16134

摘要： Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g., penton-base and hexon proteins), proteins responsible for cell binding (e.g, fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication-defective adenovirus of serotype 34, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for the delivery and expression of exogenous genes are provided.

公开(公告)号：EP1606397A1

公开(公告)日：2005-12-21

申请号：EP03816398.6

申请日：2003-08-21

申请人： Merck & Co., Inc.

发明人： EMINI, Emilio, A. ,  SHIVER, John, W. ,  BETT, Andrew, J. ,  CASIMIRO, Danilo, R. ,  CHASTAIN, Michael ,  KASLOW, David, C. ,  MORSY, Manal, A.

IPC分类号： C12N7/00

CPC分类号： C12N15/86 ,  A61K2039/5256 ,  C07K14/005 ,  C12N2710/10343 ,  C12N2710/10371 ,  C12N2740/16122 ,  C12N2740/16134

摘要： Adenoviral serotypes differ in their natural tropism. The various serotypes of adenovirus have been found to differ in at least their capsid proteins (e.g., penton-base and hexon proteins), proteins responsible for cell binding (e.g, fiber proteins), and proteins involved in adenovirus replication. This difference in tropism and capsid proteins among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins. The present invention bypasses such requirement for capsid protein modification as it presents a recombinant, replication-defective adenovirus of serotype 24, a rare adenoviral serotype, and methods for generating the alternative, recombinant adenovirus. Additionally, means of employing the recombinant adenovirus for the delivery and expression of exogenous genes are provided.

公开(公告)号：EP1539937A2

公开(公告)日：2005-06-15

申请号：EP03749094.3

申请日：2003-08-21

申请人： Merck & Co., Inc.

发明人： BETT, Andrew, J. ,  CHASTAIN, Michael ,  SANDIG, Volker ,  EMINI, Emilio, A. ,  SHIVER, John, W. ,  CASIMIRO, Danilo, R. ,  KASLOW, David, C. ,  MORSY, Manal

IPC分类号： C12N7/00

CPC分类号： C12N15/86 ,  A61K39/12 ,  A61K39/21 ,  A61K48/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/57 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234 ,  C12N2810/6018

摘要： Various methods for propagating and rescuing multiple serotypes of replication-defective adenovirus in a single adenoviral E1-complementing cell line are disclosed. Typically, replication-defective adenovirus vectors propagate only in cell lines which express E1 proteins of the same serotype or subgroup as the vector. The disclosed methods offer the ability to propagate vectors derived from multiple adenoviral serotypes in a single production cell line which expresses E1 proteins from a single serotype. Propagation in this manner is accomplished by providing all or a portion of an E4 region in cis within the genome of the replication-defective adenovirus. The added E4 region or portion thereof is cloned from a virus of the same or highly similar serotype as that of the E1 gene product(s) of the complementing cell line. Interaction between the expressed E1 of the cell line and the heterologous E4 of the replication-defective adenoviral vectors enables their propagation and rescue. The invention bypasses a need in the art to customize specific cell lines to the serotype or subgroup of the adenoviral vector being propagated and enables one to easily and rapidly develop alternative adenoviral serotypes as gene delivery vectors for use as vaccines or as a critical component in gene therapy.