Douglas E Brough

US Patent:

6440728, Aug 27, 2002

Filed:

Nov 30, 1999

Appl. No.:

09/450972

Inventors:

Duncan L. McVey - Derwood MD
Douglas E. Brough - Olney MD
Mohammed Zuber - Frederick MD
Imre Kovesdi - Rockville MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 1563

US Classification:

4353201, 435477, 536 231

Abstract:

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.

US Patent:

6458578, Oct 1, 2002

Filed:

Dec 22, 2000

Appl. No.:

09/748044

Inventors:

Douglas E. Brough - Olney MD
Imre Kovesdi - Rockville MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 700

US Classification:

4352351, 435325, 435 691, 4353201, 4242331, 4241991

Abstract:

The present invention provides a recombinant cell line, specifically one that produces adenoviral E1 and DEF-A and/or DEF-B gene products.

US Patent:

6465253, Oct 15, 2002

Filed:

Jan 29, 1999

Appl. No.:

09/101751

Inventors:

Thomas J. Wickham - Falls Church VA
Imre Kovesdi - Rockville MD
Douglas E. Brough - Olney MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 15861

US Classification:

435456, 4353201, 435325, 435455, 530330, 530329, 530328, 530327, 530326, 530324, 530350

Abstract:

The present invention provides a chimeric adenovirus coat protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence. Such a chimeric adenovirus coat protein according to the invention is able to direct entry into cells of a vector comprising the coat protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus coat protein rather than the chimeric adenovirus coat protein. The chimeric coat protein preferably is a fiber, hexon, or penton protein. The present invention also provides an adenoviral vector that comprises the chimeric adenovirus coat protein, as well as methods of constructing and using such a vector.

US Patent:

6475757, Nov 5, 2002

Filed:

Jul 13, 2001

Appl. No.:

09/905758

Inventors:

Duncan L. McVey - Derwood MD
Douglas E. Brough - Olney MD
Imre Kovesdi - Rockville MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 1563

US Classification:

435 9141, 4353201, 435455, 435456, 435 5, 435 6, 435 914, 435 9152, 435 911, 435463

Abstract:

The present invention provides a dual selection cassette (DSC) comprising first and second DNA segments having homology to a eukaryotic viral vector, positive and negative selection genes, each operably linked to their own promoter, and one or more unique restriction enzyme sites (URES) or sitey-directed homologous recombination sites. The present invention also provides a plasmid, pN/P, comprising an independent positive selection marker gene, an origin of replication, and a dual selection cassette. The dual selection cassette and pN/P plasmid can be used to produce eukaryotic gene transfer vectors without requiring temporally-linked double recombination events or the use of specialized bacterial strains that allow the replication of plasmids comprising defective origins of replication. This method usefully increases the ratio of desired to undesired plasmid and vector constructs. Additionally, this invention provides a method for the creation of eukaryotic viral vector libraries.

US Patent:

6482616, Nov 19, 2002

Filed:

May 27, 1999

Appl. No.:

09/321797

Inventors:

Imre Kovesdi - Rockville MD
Douglas E. Brough - Olney MD
Duncan L. McVey - Derwood MD
Joseph T. Bruder - New Market MD
Alena Lizonova - Rockville MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 510

US Classification:

435 914, 4353201, 435325, 435366, 435456

Abstract:

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.

US Patent:

6579522, Jun 17, 2003

Filed:

Jun 27, 2000

Appl. No.:

09/604694

Inventors:

Douglas E. Brough - Olney MD
C. Richter King - Washington DC
Imre Kovesdi - Rockville MD
Jasper J. Schaible - Arlington VA

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

A01N 6300

US Classification:

424 932, 4353201, 435455, 435456, 514 44

Abstract:

An adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a radiation inducible promoter operably linked to the nucleic acid sequence coding for TNF. This invention also provides an adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a spacer element of at least 15 base pairs in the E4 region of the adenoviral genome. A method of producing an adenoviral vector and a method of treating a tumor or cancer in a host comprising administering an anti-cancer or anti-tumor effective amount of the adenoviral vector of the present invention also is provided.

US Patent:

6649373, Nov 18, 2003

Filed:

Jun 4, 2001

Appl. No.:

09/873486

Inventors:

Douglas E. Brough - Olney MD
Imre Kovesdi - Rockville MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 1509

US Classification:

435 691, 435 911, 435455, 435465, 4353201, 4352351, 435325

Abstract:

Provided are methods of modulating the persistence of the expression in a cell of a transgene, such as a transgene in a non-Herpes vector or in at least E4 adenoviral vector, and related systems. One method comprises contacting the cell with a non-Herpes vector comprising and expressing a gene encoding HSV ICP0, whereupon expression of HSV ICP0 the persistence of expression of the transgene is modulated. Further provided is a system for modulating the persistence of expression of a transgene, which system comprises a non-Herpes vector comprising (i) a gene encoding HSV ICP0 and (ii) a transgene, wherein the HSV ICP0 modulates the persistence of expression of the transgene and either the non-Herpes vector comprises the transgene or the system further comprises a vector, in which case the vector comprises the transgene.

US Patent:

6660521, Dec 9, 2003

Filed:

Jan 29, 2001

Appl. No.:

09/771832

Inventors:

Douglas E. Brough - Olney MD
Imre Kovesdi - Rockville MD

Assignee:

GenVec, Inc. - Gaithersburg MD

International Classification:

C12N 1500

US Classification:

4353201, 424 932, 424 936

Abstract:

The present invention provides a method of modulating the persistence of expression of a transgene in an at least E4 adenoviral vector in a cell. In one embodiment, the method comprises contacting the cell with an at least E4 adenoviral vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. In another embodiment, the method comprises contacting the cell simultaneously or sequentially with (i) an at least E4 adenoviral vector comprising a transgene and (ii) a viral vector comprising a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. In addition, the present invention provides a recombinant at least E4 adenoviral vector for use in the method and a composition comprising the vector and a carrier therefor. Also provided by the present invention is a system for modulation of a recombinant at least E4 adenoviral vector for use in the method and a composition comprising the system and a carrier therefor.