Genvec, Inc.

Cornell Research Foundation Inc.

USA As Represented by Secretary of the Navy

Other

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

Hospital for Special Surgery

Vectorlogics, Inc.

Imre Kovesdi

Douglas E Brough

Duncan L McVey

Thomas J Wickham

Joseph T Bruder

Petrus W Roelvink

Alena Lizonova

C Richter King

Erik S Falck-Pedersen

Jason Gall

Ronald G Crystal

Jason G D Gall

Denise Louise Doolan

Marilyn Menger

Daniel John Carucci

Martha Sedegah

Miguel E Carri&oacute;n

Keith Limbach

Miguel E Carrion

Mohammed Zuber

Joao Carlos Aguair

Walter R Weiss

Stephen C Ransom

Damodar R Ettyreddy

Lisa Wei

Tibor Bakács

Miklós Szabó

Joseph T Brader

Chisa Hidaka

Oheneba Boachie-Adjei

Bernard A Rawlins

Miguel E Carrión

Jasper J Schaible

The invention provides a method of identifying an antigen from a pathogen or a disease antigen comprising the use of an adenoviral vector array comprising two or more different adenoviral vectors, wherein each adenoviral vector comprises a nucleic acid sequence encoding a different antigen of a pathogen. The adenoviral vectors are administered to antigen presenting cells (APCs) in vitro or to an animal in vivo. The immunogenicity of the antigen is measured by screening for an immune response from effector T lymphocytes in vitro and by screening for the absence of pathogen-induced disease onset in vivo.

Malaria antigen screening method

The invention provides a method of targeting T-cells to tumor cells using a tumor-associated antigen (TAA) specific antibody and a T-cell specific antibody, wherein the two antibodies can bind to each other through a high affinity avidin/biotin or streptavidin/biotin connection. The invention further provides methods to target activated T-cells to different tumor types by using a T-cell specific antibody that is specific to an activated T-cell surface molecule like CTLA-4.

Methods of targeting T-cells to tumors

The invention provides adenoviral vectors comprising an adenoviral genome comprising heterologous antigen-encoding nucleic acid sequences, such asnucleic acid sequences, operably linked to promoters. The invention further provides a method of inducing an immune response against malaria in a mammal comprising administering the adenoviral vectors to the mammal.

Adenoviral vector-based malaria vaccines

The present invention provides multiply deficient adenoviral vectors and complementing cell lines. Also provided are recombinants of the multiply deficient adenoviral vectors and a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such recombinants.

Complementary adenoviral vector systems and cell lines

A method of enriching a solution for an adenovirus comprising contacting a solution containing an adenovirus with an anion exchange chromatography resin comprising an acrylate or sulphonamide linker such that the adenovirus binds to the chromatography resin and eluting the adenovirus from the resin with an eluant to obtain an enriched solution of adenovirus.

Efficient purification of adenovirus

The present invention provides an improved method of making eukaryotic gene transfer vectors comprising homologous recombining lambdid vectors with a second DNA in a bacterium to generate novel recombinant eukaryotic viral gene transfer vectors as well as a novel lambdid vector used in the inventive method and an inventive system comprising the novel lambdid vector.

Chimeric vectors comprising a phage packaging site and a portion derived from the genome of a eukaryotic virus

The present invention provides a library of viral vectors, wherein each member comprises a first heterologous DNA encoding a first gene product and a second heterologous DNA encoding a second gene product. The first heterologous DNA is common to each member of the library, while the second heterologous DNA varies between members of the library. The present invention additionally provides a method of constructing a library of viral vectors. The method comprises carrying out homologous recombination between a first DNA molecule and a second DNA molecule to form a pool of intermediate viral vector genomes. One or more linear third DNA molecules are ligated into the pool of intermediate viral genomes to produce a library of viral vector genomes. Alternatively, homologous recombination between linear DNA molecules and recipient DNA molecules produces a library of viral vector genomes. The library of viral vector genomes is converted into a library of viral vectors.

Methods of preparing and using a viral vector library

The present invention provides a recombinant adenovirus comprising coat proteins that lack native binding. In particular, the present invention provides a recombinant adenovirus comprising a penton base protein and a fiber protein, wherein the penton base protein and the fiber protein lack native binding. The present invention further provides a recombinant adenovirus comprising (a) a penton base protein that lacks native binding and (b) a nonnative amino acid sequence that binds a cell-surface binding site.

Vectors and methods for gene transfer

The present invention is directed to a method for enhancing bone density or formation. In accordance with the method, a nucleic acid encoding an angiogenic protein is administered to a cell in a region of a bone such that the nucleic acid is expressed to produce the angiogenic protein, whereby bone density or formation is enhanced within the region. Optionally, a nucleic acid encoding an osteogenic protein is administered to a cell within the same region such that the nucleic acid is expressed to produce the osteogenic protein. The method can be employed to produce a bone graft having a cell harboring an exogenous nucleic acid encoding an angiogenic protein and, optionally, a cell harboring a nucleic acid encoding an osteogenic protein. To facilitate the inventive method, the invention also pertains to a recombinant viral vector having a nucleic acid encoding an angiogenic protein and a nucleic acid encoding an osteogenic protein.

Method of enhancing bone density

The invention provides cells and methods of using the cells for the propagation of replication-deficient adenoviral vectors. The cells comprise at least one heterologous nucleic acid sequence which upon expression produces at least one non-adenoviral gene product that complements in trans for a deficiency in at least one essential gene function of one or more regions of an adenoviral genome so as to propagate a replication-deficient adenoviral vector comprising an adenoviral genome deficient in the at least one essential gene function of the one or more regions when present in the cell.

Non-adenoviral gene product-based complementing cells for adenoviral vectors

The inventive method of producing a eukaryotic viral vector comprises contacting a eukaryotic cell, which comprises a unique enzyme that nicks or cleaves a DNA molecule, with a recombinant phage vector, or contacting a eukaryotic cell, which does not comprise a unique enzyme that nicks or cleaves a DNA molecule, simultaneously or sequentially, in either order, with (i) a unique enzyme that nicks or cleaves a DNA molecule, and (ii) a recombinant phage vector. The recombinant phage vector comprises the DNA molecule comprising (a) a eukaryotic viral vector genome comprising a coding sequence, (b) a phage packaging site that is not contained within the eukaryotic viral vector genome, and (c) a promoter that is operably linked to the coding sequence. Alternatively, the DNA molecule is not present within the recombinant phage vector. The eukaryotic cell is contacted with the first DNA molecule and a recombinant phage vector. The first DNA molecule comprises a replication deficient eukaryotic viral vector genome comprising at least one adenoviral inverted terminal repeat and a packaging signal. The recombinant phage vector comprises a second DNA molecule and a phage packaging site, wherein the second DNA molecule complements in trans the replication deficient eukaryotic viral vector genome. The DNA molecule(s) enter the eukaryotic cell, and the unique enzyme nicks or cleaves the DNA molecule in the eukaryotic cell in at least one region not contained within the eukaryotic viral vector genome, thereby inducing the production of and ultimately producing a eukaryotic viral vector.

Method of preparing a eukaryotic viral vector

The present invention provides a method of identifying a gene product. The method comprises providing a multiplicity of cells comprising a first gene product. Preferably, the first gene product is produced in the multiplicity of cells by expressing a first exogenous nucleic acid sequence encoding the first gene product. A library of second nucleic acid sequences encoding second gene products is then introduced into the multiplicity of cells. The second nucleic acid sequences are expressed in the multiplicity of cells to produce the second gene products such that the first gene product and at least one of the second gene products contact. The method further comprises causing a complex to form between the first gene product, an affinity molecule that binds the first gene product, and at least one of the second gene products, and subsequently retrieving the complex. At least one second gene product of the complex then is identified.

Method of identifying a gene product

The present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof. The nucleic acid sequence is operably linked to regulatory sequences necessary for expression of PEDF or a therapeutic fragment thereof. Preferably, the viral vector is an adenoviral vector or an adeno-associated viral vector. Also preferably, the viral vector further comprises one or more additional nucleic acid sequences encoding therapeutic substances other than PEDF.

Viral vector encoding pigment epithelium-derived factor

The present invention provides a complex that includes a virion having a ligand that recognizes an epitope present on an immune effector cell surface and at least a first nucleic acid encoding a first non-native antigen. The invention also provides a library including a plurality of such complexes, in which antigens of at least two of the plurality are different. Using such reagents, the invention provides a method of precipitating an immune response within an immune effector cell, wherein such a complex is delivered to the cell under conditions sufficient for the cell to mount an immune response to the antigen. When applied in vivo, the method can serve to immunize an animal from the pathogen. Moreover, using a library including a plurality of complexes, which contains at least one test antigen, the invention provides a method of assessing the antigenicity of the test antigen.

Growing community of inventors

Rockville, MD, United States of America

Imre Kovesdi