Helper Virus Is Present Patents (Class 435/457)
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Patent number: 6350575Abstract: Novel helper vectors are provided for complementing defective recombinant viral vectors, characterized in that they are provided with recombination sequences recognized by a recombinase. A complementation cell expressing the recombinase, and a method for preparing recombinant viral vectors as infectious viral particles for transferring and expressing genes of interest in a host organism or cell, are also provided. The invention is particularly suitable for use in gene therapy, especially in humans.Type: GrantFiled: May 2, 2000Date of Patent: February 26, 2002Assignee: Transgene S.A.Inventors: Monika Lusky, Majid Mehtali
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Publication number: 20020019051Abstract: The invention concerns adenoviral vectors having the characteristic of containing a region essential for heterologous packaging with respect to the adenoviral genome from which they are derived. The invention also concerns a method for making a viral preparation containing said adenoviral vectors, a cell, a pharmaceutical composition or material comprising them and their therapeutic or prophylactic use. Finally, the invention concerns an adenoviral genome of animal origin having attenuated packaging properties with respect to the native genome from which it is derived.Type: ApplicationFiled: May 31, 2001Publication date: February 14, 2002Inventors: Monika Lusky, Arend Jan Winter
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Patent number: 6346415Abstract: This invention provides transcriptionally-activated AAV ITRs (inverted terminal repeats) which are small and transcriptionally active and uses thereof to optimize the expression of relatively large transgenes packaged in recombinant AAV vectors.Type: GrantFiled: October 20, 1998Date of Patent: February 12, 2002Assignee: Targeted Genetics CorporationInventor: Andrew L. Feldhaus
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Patent number: 6340595Abstract: Novel means and methods for their use are provided to determine the function of the product(s) of one or more sample nucleic acids. The sample nucleic acids are synthetic oligonucleotides, DNA, or cDNA and encode polypeptides, antisense nucleic acids, or GSEs. The sample nucleic acids are expressed in a host by a vehicle to alter at least one phenotype of the host. The altered phenotype(s) is/are identified as a means to assign a biological function to the product(s) encoded by the sample nucleic acid(s).Type: GrantFiled: July 21, 1999Date of Patent: January 22, 2002Assignee: Galapagos Genomics N.V.Inventors: Ronald Vogels, Abraham Bout, Helmuth van Es, Govert Schouten
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Publication number: 20020001579Abstract: The invention relates to a nonhuman helper-dependent virus vector for transferring nucleic acid sequences. Areas of application are medicine, veterinary medicine, biotechnology and genetic engineering.Type: ApplicationFiled: February 16, 2001Publication date: January 3, 2002Inventors: Moritz Hillgenberg, Christian Hofmann, Peter Loser
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Patent number: 6333030Abstract: The present invention provides a chimeric viral vector system having a highly efficient in vivo gene delivery to cells after vascular administration and an intergrative capacity of heterologous gene sequences for stable genetic modification of cells after transduction. In this chimeric vector, an adenoviral vector is employed to deliver retroviral functions to a cell for local, in situ production of retroviral particles inside the cell by the construction of replication-defective adenoviral vectors which contain either retroviral “packaging” functions (retroviral genes gag, pol, env) and retroviral “vector” functions (retroviral LTR sequences flanking the “therapeutic” gene).Type: GrantFiled: November 19, 1997Date of Patent: December 25, 2001Assignee: UAB Research FoundationInventor: David T. Curiel
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Patent number: 6329181Abstract: The present invention provides methods and compositions for preparations of recombinant parvovirus virions with a reduced number of replication competent particles. The compositions of the present invention include nucleic acids encoding parvovirus helper functions which contain at least one non-native intron sequence. The present invention also includes helper function vectors, host cells transfected with the helper function vectors, methods of using the helper function vectors, and recombinant parvovirus virions produced by such methods.Type: GrantFiled: August 7, 2000Date of Patent: December 11, 2001Assignee: Neurologix, Inc.Inventors: Weidong Xiao, Matthew J. During, Lei Cao
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Patent number: 6303380Abstract: A combination of adenoviral and retroviral vectors used to construct second generation packaging cells that deliver marker genes to target cells is described. A vector based upon Moloney murine leukemia virus (MLV) was used to deliver marker genes, and an adenovirus-based delivery system was used to deliver MLV structural genes (gagpol and env) to cultured cells. The procedure transformed the cells into new retroviral producer cells, which generate replication-incompetent retroviral particles in the culture supernatant for transferring marker genes to target cells. The titer of the retroviral-containing supernatant generated from the second generation producer cells reached above 105 cfu/ml which is comparable to the MLV-based producer cell lines currently used in human gene therapy trials. The vector and procedures are adaptable for experimental human gene therapy in which the new producer cells are transplanted into patients for continuous gene transfer.Type: GrantFiled: April 29, 1999Date of Patent: October 16, 2001Assignee: Oklahoma Medical Research FoundationInventors: Xinli Lin, Jordan J. N. Tang
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Patent number: 6303331Abstract: The invention relates generally to compositions of and methods for obtaining and using a polypeptide other than BCL-2 that affects programmed vertebrate cell death. The invention relates as well to polynucleotides encoding those polypeptides, recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant polypeptides. The invention further provides methods for using the isolated, recombinant polypeptides in assays designed to select and improve substances capable of altering programmed cell death for use in diagnostic, drug design and therapeutic applications.Type: GrantFiled: June 5, 1995Date of Patent: October 16, 2001Assignees: Arch Development Corporation, The Regent of the University of MichiganInventors: Craig B. Thompson, Lawrence H. Boise, Gabriel Nuñez
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Patent number: 6303371Abstract: The invention is directed to novel systems for the high level production of purified recombinant adeno-associated virus (rAAV) vector stocks comprising producer cell lines and helper adenoviruses. These systems provide high level production of rAAV vector stocks that are not contaminated by helper viruses or have very minimal contamination with helper virus. The invention is also directed to methods for the production of high yield, purified rAAV vector stocks using the systems of the invention.Type: GrantFiled: July 25, 2000Date of Patent: October 16, 2001Assignee: Genzyme CorporationInventor: Samuel C. Wadsworth
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Patent number: 6277633Abstract: A recombinant lentiviral vector expression system comprises a first vector that comprises a nucleic acid sequence of at least part of the Equine Infectious Anemia Virus (EIAV) genome. The vector contains at least one defect in at least one gene encoding an EIAV structural protein, but is preferably a gaglpol expression vector. The expression system further comprises a second vector, also comprising a nucleic acid sequence of at least part of the Equine Infectious Anemia Virus (EIAV) genome, and additionally containing a multiple cloning site wherein a heterologous gene may be inserted. The expression system also comprises a third vector which expresses a viral envelope protein. The first and third vectors are packaging signal-defective. When the expression system is transfected into a lentivirus-permissive cell, replication-defective EIAV particles may be produced, which particles are useful in delivering heterologous genes to a broad range of both dividing and non-dividing cells.Type: GrantFiled: May 12, 1998Date of Patent: August 21, 2001Assignee: The University of North Carolina at Chapel HillInventor: John C. Olsen
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Patent number: 6274354Abstract: Methods for efficient production of recombinant AAV are described. In one aspect, three vectors are introduced into a host cell. A first vector directs expression of cre recombinase, a second vector contains a promoter, a spacer sequence flanked by loxP sites and rep/cap, and a third vector contains a minigene containing a transgene and regulatory sequences flanked by AAV ITRs. In another aspect, the host cell stably or inducibly expresses cre recombinase and two vectors carrying the other elements of the system are introduced into the host cell.Type: GrantFiled: February 22, 1999Date of Patent: August 14, 2001Assignee: The Trustees of the University of PennsylvaniaInventors: James M. Wilson, Daniel Phaneuf
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Patent number: 6270996Abstract: An adenovirus E1/E4 expressing packaging cell line is provided, which permits the generation of recombinant adenoviruses deleted in both gene regions. A method for enhancing the efficiency of transduction of a recombinant AAV into a target cell is provided by infecting a target cell with a recombinant AAV comprising a selected transgene under the control of regulatory sequences. The infected cell is contacted with an agent which facilitates the conversion of single stranded recombinant virus to its double stranded form.Type: GrantFiled: May 3, 2000Date of Patent: August 7, 2001Assignee: The Trustees of the University of PennsylvaniaInventors: James M. Wilson, Krishna J. Fisher, Guang-Ping Gao
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Publication number: 20010009772Abstract: The present invention provides packaging cell lines and recombinant lentiviral or retroviral particles produced therefrom, particularly pseudotyped retroviral particles. The packaging cell lines of the invention are produced by inducibly expressing an envelope protein by methods described herein. Also described is a screening assay for compounds that affect integration of viral nucleic acid into target (e.g., host) nucleic acid. Such compounds are identified based on their effect on viral integrase.Type: ApplicationFiled: March 12, 2001Publication date: July 26, 2001Inventors: Inder M. Verma, Tal Kafri, Frederic Bushman, Mark Hansen
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Patent number: 6261551Abstract: An adenovirus E1/E4 expressing packaging cell line is provided, which permits the generation of recombinant adenoviruses deleted in both gene regions. A method for enhancing the efficiency of transduction of a recombinant AAV into a target cell is provided by infecting a target cell with a recombinant AAV comprising a selected transgene under the control of regulatory sequences. The infected cell is contacted with an agent which facilitates the conversion of single stranded recombinant virus to its double stranded form.Type: GrantFiled: December 5, 1997Date of Patent: July 17, 2001Assignee: The Trustees of the University of PennsylvaniaInventors: James M. Wilson, Krishna J. Fisher, Guang-Ping Gao
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Patent number: 6255104Abstract: The invention relates to a recombinant poliovirus vector and method of making the vector. The recombinant poliovirus vector comprises an RNA polymerase promoter operably linked to a poliovirus nucleic acid sequence which has been altered by removal of the CelII-SnaBI fragment and insertion of a heterologous nucleic acid sequence encoding a protein of interest. The heterologous nucleic acid sequence is flanked on both sides by internal ribosomal entry sites which allow for the expression of the encoded protein of interest and subsequent proteins encoded by the altered poliovirus nucleic acid sequence.Type: GrantFiled: May 12, 1998Date of Patent: July 3, 2001Inventor: Wolf Bertling
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Patent number: 6251677Abstract: The present invention provides a hybrid vector construct which comprises a portion of an adenovirus, 5′ and 3′ ITR sequences from an AAV, and a selected transgene. Also provided is a hybrid virus linked via a polycation conjugate to an AAV rep gene to form a single particle. These trans-infection particles are characterized by high titer transgene delivery to a host cell and the ability to stably integrate the transgene into the host cell chromosome. Also disclosed is the use of the hybrid vectors and viruses to produce large quantities of recombinant AAV.Type: GrantFiled: February 8, 1999Date of Patent: June 26, 2001Assignee: The Trustees of the University of PennsylvaniaInventors: James M. Wilson, William M. Kelley, Krishna J. Fisher
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Patent number: 6242259Abstract: Nucleic acid molecule are provided comprising a nucleic acid sequence which encodes, in order, an alphavirus capsid, a signal peptide, and an alphavirus E1 or E2 glycoprotein. Also provided are vectors encoding such nucleic acid molecules, and use of such vectors or expression cassettes to generate recombinant alphavirus particles and alphavirus packaging cell lines. In addition, modified alphavirus vector constructs are provided that permit reduced transgene expression during vector packaging, as well as methods of using such vector constructs for the production of alphavirus vector particles.Type: GrantFiled: December 30, 1999Date of Patent: June 5, 2001Assignee: Chiron CorporationInventors: John Polo, Barbara Beli, Thomas W. Dubensky, Jr., Stephen F. Hardy, Silvia Perri
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Patent number: 6232120Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.Type: GrantFiled: February 16, 1999Date of Patent: May 15, 2001Assignee: The Johns Hopkins University School of MedicineInventors: Boro Dropulić, Paula M. Pitha
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Patent number: 6228646Abstract: A method for producing in vivo packaged recombinant adenovirus vectors is provided. The recombinant Ad vectors do not contain any Adenovirus genes and are therefore useful for gene therapy. The recombinant Adenovirus vectors are packaged in vivo using a helper virus which is itself very inefficiently packaged, providing a recombinant viral preparation with very little or no contamination with helper virus. In particular, the method makes use of a helper virus in which the packaging site can be easily excised in vivo by recombination mediated by a recombinase. The helper virus is also useful for the in vivo construction of new recombinant adenovirus vectors containing substitutions in the E1 or other adenoviral region.Type: GrantFiled: March 7, 1997Date of Patent: May 8, 2001Assignee: The Regents of the University of CaliforniaInventor: Stephen F. Hardy
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Patent number: 6218187Abstract: The invention provides a novel retroviral packaging system, in which retroviral packaging plasmids and packagable vector transcripts are produced from high expression plasmids after stable or transient transfection in mammalian cells. High titers of recombinant retrovirus are produced in these transfected mammalian cells and can then transduce a mammalian target cell by cocultivation or supernatant infection. The methods of the invention include the use of the novel retroviral packaging plasmids and vectors to transduce primary human cells, including T cells and human hematopoietic stem cells, with foreign genes by cocultivation or supernatant infection at high efficiencies. The invention is useful for the rapid production of high titer viral supernatants, and to transduce with high efficiency cells that are refractory to transduction by conventional means.Type: GrantFiled: March 11, 1999Date of Patent: April 17, 2001Assignee: Cell Genesys, Inc.Inventors: Mitchell H. Finer, Thomas J. Dull, Krisztina M. Zsebo, Keegan Cooke, Deborah A. Farson
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Patent number: 6207455Abstract: The present invention contemplates novel lentiviral vectors which exhibit strong promoter activity in human and other cells. Vectors are provided which are packaged efficiently in packaging cells and cell lines to generate high titer recombinant virus stocks. The present invention further relates to HIV vaccines and compositions for gene therapy. In particular, the present invention provides attenuated replication-competent HIV vaccines and replication-defective HIV vectors.Type: GrantFiled: September 22, 1997Date of Patent: March 27, 2001Inventor: Lung-Ji Chang
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Patent number: 6203975Abstract: A recombinant adenovirus and a method for producing the virus are provided which utilize a recombinant shuttle vector comprising adenovirus DNA sequence for the 5′ and 3′ cis-elements necessary for replication and virion encapsidation in the absence of sequence encoding viral genes and a selected minigene linked thereto, and a helper adenovirus comprising sufficient adenovirus gene sequences necessary for a productive viral infection. Desirably the helper gene is crippled by modifications to its 5′ packaging sequences, which facilitates purification of the viral particle from the helper virus.Type: GrantFiled: October 21, 1999Date of Patent: March 20, 2001Assignee: The Trustees of the University of PennsylvaniaInventors: James M. Wilson, Krishna J. Fisher, Shu-Jen Chen, Matthew Weitzman
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Patent number: 6168953Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.Type: GrantFiled: May 14, 1999Date of Patent: January 2, 2001Assignee: The Johns Hopkins University School of MedicineInventors: Boro Dropulic, Paula M. Pitha
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Patent number: 6156303Abstract: The present invention provides isolated adenovirus-associated viruses ("AAV"), including AAV isolates designated AAV3B and AAV6. The invention also provides nucleic acid molecules of AAV3B (SEQ ID NO: 1) or AAV6 (SEQ ID NO: 2), including DNA or RNA, and provides substantially purified polypeptides encoded by AAV3B or AAV6, as well as antibodies specific for such polypeptides. The invention also provides infectious AAV3B and AAV6 clones; AAV viral vectors, which can be hybrid AAV viral vectors; AAV vector plasmids; and AAV helper plasmids; each comprising at least a portion of an AAV3B (SEQ ID NO: 1) or AAV6 (SEQ ID NO: 2) nucleic acid molecule. The invention further provides host cells containing at least a portion of an AAV3B or AAV6 nucleic acid molecule and progeny cells derived therefrom, and provides non-human transgenic mammals having an AAV vector genome stably integrated in a chromosome.Type: GrantFiled: June 11, 1997Date of Patent: December 5, 2000Assignee: University of WashingtonInventors: David W. Russell, Elizabeth A. Rutledge
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Patent number: 6136538Abstract: A recombinant cell stably transformed with a cDNA of a silent, inducible replicon encoding a recombinant protein is disclosed. Transcription of the replicon cDNA is under the control of a silent promoter inducible by a DNA virus and expression of the recombinant protein is dependent upon the presence of the DNA virus in the cell. The cell can be engineered to package the replicon upon infection by the DNA virus, leading to intercellular amplification of expression of the recombinant protein. Where the recombinant protein is a reporter gene product, the recombinant cell may be used in an assay for detecting DNA viruses. A kit for performing such an assay is also provided.Type: GrantFiled: January 8, 1999Date of Patent: October 24, 2000Assignee: Washington UniversityInventors: Paul D. Olivo, Sondra Schlesinger
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Patent number: 6114111Abstract: The present invention is directed to compositions and methods for a genetic system of detecting protein--protein interactions in a mammalian host cell. Two fusion proteins are made in the host cell. The first fusion protein contains a DNA binding domain which is fused to a so-called bait protein. The second fusion protein consists of a transcriptional activation domain fused to a so-called test protein. The transcriptional activation domain is recruited to the promoter through the functional interaction between the bait protein and the test protein. Subsequently the transcriptional activation domain interacts with the basal transcription machinery to activate expression of one or more reporter genes which can be identified and characterized. The individual compositions are useful for analyzing protein--protein interactions between known proteins and to isolate, clone and characterize unknown proteins. The individual compositions can be used to express the fusion proteins either transiently or stably.Type: GrantFiled: March 30, 1998Date of Patent: September 5, 2000Assignee: Rigel Pharmaceuticals, Inc.Inventors: Ying Luo, Betty Huang, Donald Payan
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Patent number: 6114141Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.Type: GrantFiled: February 16, 1999Date of Patent: September 5, 2000Assignee: The Johns Hopkins University School of MedicineInventors: Boro Dropulic, Paula M. Pitha
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Patent number: 6106825Abstract: This invention provides recombinant entomopoxvirus as a novel vector and method of using such vector for delivery and expression of genes of biological significance to vertebrate cells, including human cells. This invention includes the use of an early entomopoxvirus or like gene promoter to drive the expression of an heterologous gene product in a vertebrate cell infected with the recombinant entomopoxvirus vector. We have discovered that, while the entomopoxvirus vector of this invention does not replicate in the vertebrate cell, it enters vertebrate cell cytoplasm and achieves expression of an heterologous gene inserted into the rEPV without causing cytopathic or cytotoxic effects. We further provide a method for expression of the heterologous gene under control of late, strong entomopoxvirus gene promoters, vertebrate gene or viral promoters, and for stable integration of the heterologous gene delivered by the rEPV into the vertebrate cell.Type: GrantFiled: May 7, 1997Date of Patent: August 22, 2000Assignee: University of FloridaInventors: Richard W. Moyer, Yi Li, Richard L. Hall
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Patent number: 6100086Abstract: The present invention relates to transgene expression systems, related pharmaceutical compositions, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA sequence encoding a transgene which codes for a desired product, expressibly contained within an adenovirus vector containing at least a portion of the E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or "E4 cassette") includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.Type: GrantFiled: April 14, 1997Date of Patent: August 8, 2000Assignee: Genzyme CorporationInventors: Johanne Kaplan, Donna Armentano, Richard J. Gregory
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Patent number: 6093570Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.Type: GrantFiled: June 7, 1995Date of Patent: July 25, 2000Assignee: The University of North Carolina at Chapel HillInventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
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Patent number: 6080569Abstract: The present invention provides an improved helper-dependent vector system for production of high capacity adenoviral cloning vectors. The invention makes use of the DNA size packaging constraints imposed on a pIX-defective Ad virion that prevent such virions from packaging DNA larger than approximately 35 kb. This constraint can be used to develop helper viruses that do not package their DNA. In one embodiment, the invention combines this methodology with the Cre-loxP helper-dependent system to decrease the quantity of contaminating helper virus in vector preparations. In another embodiment the invention is used for vector growth.Type: GrantFiled: September 25, 1996Date of Patent: June 27, 2000Assignee: Merck & Co., Inc.Inventors: Frank L. Graham, Robin Parks, Liane Chen
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Patent number: 6066478Abstract: Novel helper vectors are provided for complementing defective recombinant viral vectors, characterized in that they are provided with recombination sequences recognized by a recombinase. A complementation cell expressing the recombinase, and a method for preparing recombinant viral vectors as infectious viral particles for transferring and expressing genes of interest in a host organism or cell, are also provided. The invention is particularly suitable for use in gene therapy, especially in humans.Type: GrantFiled: March 9, 1998Date of Patent: May 23, 2000Assignee: Transgene S.A.Inventors: Monika Lusky, Majid Mehtali
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Patent number: 6040172Abstract: A replication defective DNA viral vector that comprises a gene of interest encoding a protein having a demonstrated therapeutic effect on a host cell is disclosed. The vector comprises the gene in operable linkage with a neural tissue-specific promoter, which is a promoter derived from a gene normally produced in the host cell. In particular an HSV-1 vector is used. A preferred DNA defective vector is the dvHBENK which includes a promoter prepared from the rat preproenkephalin gene, the promoter being in operable linkage with the lacZ gene. The disclosed DNA viral vector is useful for achieving stable in vivo long-term expression, in particular in mammalian brain cells.Type: GrantFiled: February 14, 1995Date of Patent: March 21, 2000Assignee: The Rockefeller UniversityInventor: Michael G. Kaplitt
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Patent number: 6040183Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.Type: GrantFiled: June 7, 1995Date of Patent: March 21, 2000Assignee: University of North Carloina at Chapel HillInventors: Forrest K. Ferrari, Xiao Xiao, Richard Jude Samulski
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Patent number: 6004803Abstract: A recombinant vector comprising a gene encoding a Herpes Simplex Virus Type 1 thymidine kinase (HSV1-TK) comprising a deletion in the 5' sequence upstream of the second ATG initiation codon of the complete HSV1-TK sufficient to inhibit transcription initiation from a cryptic promoter site contained within the 5' sequence, wherein the gene is under the control of a promoter is disclosed for use as a suicide gene both in vitro and in vivo. The HSV1-TK produced by the strong expression of the modified gene is toxic to cells in the presence of nucleoside analogs, whereas weak expression of the gene is not toxic to cells. The deletion can comprise all or part of the first initiation codon and the vector can be a retrovirus. As also disclosed are cells transduced with the vector.Type: GrantFiled: April 11, 1997Date of Patent: December 21, 1999Assignee: Universite Pierre et Marie Curie (Paris VI)Inventors: David Klatzmann, Benoit Salomon
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Patent number: 5980885Abstract: A method is described for inducing in vivo proliferation of precursor cells located in mammalian neural tissue by administering to the mammal a fibroblast growth factor and at least one additional growth factor selected from the group consisting of epidermal growth factor, transforming growth factor alpha, and amphiregulin. The method can be used to replace damaged or missing neurons and/or glia. Another method is described for transplanting multipotent neural stem cell progeny into a mammal. The method comprises the steps of administering growth factors to a mammal to induce in vivo proliferation of neural precursor cells, removing the precursor cell progeny from the mammal, culturing the removed cells in vitro in the presence of one or more growth factors that induces multipotent neural stem cell proliferation, and implanting the multipotent neural stem cell progeny into the mammal.Type: GrantFiled: June 7, 1995Date of Patent: November 9, 1999Assignee: NeuroSpheres Holdings Ltd.Inventors: Samuel Weiss, Brent Reynolds
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Patent number: 5981225Abstract: A gene transfer vector comprising adenovirus inverted terminal repeats, at least one adenovirus packaging signal, and an adenoviral VAI gene and/or VAII gene; recombinant adenovirus particles containing the same; a method for producing the same and a method of use of the same to introduce and express a foreign gene in adenovirus target cells, is disclosed.Type: GrantFiled: April 16, 1998Date of Patent: November 9, 1999Assignee: Baylor College of MedicineInventors: Stefan Kochanek, Gudrun Schiedner
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Patent number: 5965441Abstract: The present invention relates to a hybrid vector system which incorporates elements of herpesvirus and adeno-associated virus and which is capable of expressing a gene product in eukaryotic cells. The vector system of the present invention provides a means of packaging plasmid DNA into highly infectious virions which can efficiently and safely deliver large transgenes to both mitotic and postmitotic cells in a state which can be maintained for extended periods. The invention pertains to the use of this vector system in introducing and expressing gene sequences in mitotic and postmitotic cells.Type: GrantFiled: November 12, 1997Date of Patent: October 12, 1999Assignee: The General Hospital CoporationInventors: Xandra O. Breakefield, David R. Jacoby, Frances I. Smith
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Patent number: 5882877Abstract: Adenoviral vectors which contain deletions of the early regions and/or late genes provide efficient delivery and expression of foreign nucleic acids of interest to patients. These vectors have a particular use in the treatment of cystic fibrosis patients. Furthermore, PAV vectors provide for a second generation of adenoviral vectors that contain the 5' ITR's, the packaging signal and the E1A enhancer. Other adenoviral vectors contain a deletion of the E1 region or a deletion of E4 but retain orf3 or orf6, and can either retain or delete the E3 region.Type: GrantFiled: July 16, 1997Date of Patent: March 16, 1999Assignee: Genzyme CorporationInventors: Richard J. Gregory, Donna Armentano, Larry A. Couture, Alan E. Smith