JACK A. ROTH, M.D.
Radiology at Holcombe Blvd, Houston, TX

6630344, Oct 7, 2003

Aug 29, 2000

09/650946

Bingliang Fang - Houston TX
Jack A. Roth - Houston TX

Texas Systems, University of the Board of Regents - Austin TX

C12N 15861

4353201, 536 235, 536 2372, 536 241

The present invention provides viral vectors that have been engineered to contain a synthetic promoter that controls at least one essential gene. The synthetic promoter is induced by a specific gene product not normally produced in the cells in which the viral vector is to be transferred. The vectors are propagated in producer or helper cells that express the inducing factor, thereby permitting the virus to replicate to high titer. The lack of the inducing factor in the target cells precludes viral replication, however, meaning that no vector toxicity or immunogenicity arises. Where the virus carries a gene of interest, this should provide for higher level expression for longer periods of time than with current vectors. Methods for making the vectors, helper cells, and their use in protein production, vaccines and gene therapy are disclosed.

2007009, Apr 26, 2007

Mar 9, 2006

11/372246

Lin Ji - Sugar Land TX, US
Bingliang Fang - Pearland TX, US
Jack Roth - Houston TX, US

C12N 15/86

435456000

Promoters that include a tissue-selective promoter sequence and a second promoter sequence operatively coupled to the tissue-selective promoter sequence, wherein the second promoter sequence includes a minimal viral promoter sequence, are disclosed. Nucleic acids and compositions that include these promoter sequences are also disclosed. Also disclosed are methods of improving the function of a tissue-selective promoter, involving operatively coupling a tissue-selective promoter sequence with a second promoter sequence that includes a minimal viral promoter sequence. Also disclosed are methods of delivering a gene into a cell, methods of treating a subject with a hyperproliferative disease, and methods of imaging a cell that involve use of the novel promoter sequences set forth herein.

6740320, May 25, 2004

Jun 2, 1995

08/459713

Wei-Wei Zhang - Sugar Land TX
Jack A. Roth - Houston TX

Board of Regents, The University of Texas System - Austin TX

A61K 4800

424 932, 424 931, 424 936, 435 691, 4353201, 435455, 435456

Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.

6069134, May 30, 2000

Oct 17, 1997

8/953290

Jack A. Roth - Houston TX
Toshiyoshi Fujiwara - Okayama, JP
Elizabeth A. Grimm - Houston TX
Tapas Mukhopadhyay - Houston TX
Wei-Wei Zhang - Houston TX

Board of Regents, The University of Texas System

A61K 4800

514 44

The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

2003003, Feb 27, 2003

Nov 23, 1999

09/447681

JACK A. ROTH - HOUSTON TX, US

A61K048/00

424/093200, 424/093600, 514/044000, 435/320100

Disclosed are methods and compositions for the selective manipulation of gene expression through the preparation of retroviral expression vectors for expressing antisense sequences, such as K-ras oncogene antisense sequences, or sequences encoding a desired product, such as wild type p53 sequences. Preferred retroviral vectors of the present invention incorporate the -actin promoter in a reverse orientation with respect to retroviral transcription. Preferred antisense RNA constructs of the present invention employ the use of antisense intron DNA corresponding to distinct intron regions of the gene whose expression is targeted for down-regulation. In an exemplary embodiment, a human lung cancer cell line (NCI-H460a) with a homozygous spontaneous K-ras mutation was transfected with a recombinant plasmid that synthesizes a genomic segment of K-ras in antisense orientation. Translation of the mutated K-ras mRNA was specifically inhibited, whereas expression of H-ras and N-ras was unchanged. A three-fold growth inhibition occurred in H460a cells when expression of the mutated ras p21 protein was down-regulated by antisense RNA and cells remained viable. The growth of H460a tumors in nu/nu mice was substantially reduced by expressed K-ras antisense RNA.

2007019, Aug 16, 2007

Oct 14, 2005

11/251111

Wei-Wei Zhang - Sugar Land TX, US
Jack Roth - Houston TX, US

A61K 48/00, C12N 5/08, C12N 15/861, C12N 15/88, C12N 7/00

424093210, 435456000, 435458000, 435235100, 435366000

Described are simplified and efficient methods for preparing recombinant adenovirus using liposome-mediated cotransfection and the direct. observation of a cytopathic effect (CPE) in the transfected cells. Also disclosed are compositions and methods involving novel p53 adenovirus constructs, including methods for restoring p53 function and tumor suppression in cells and animals having abnormal p53.

2003008, May 1, 2003

Sep 19, 2002

10/246696

Wei-Wei Zhang - Sugar Land TX, US
Jack Roth - Houston TX, US

Board of Regents, The University of Texas System

A61K048/00, C12N007/00, C12N015/861

514/044000, 424/093200, 435/456000, 435/235100, 435/320100

An adenoviral supervector system is disclosed that is capable of expressing more than 7.5 kilobases of heterologous DNA in a replication defective adenoviral vector. The supervector system comprises an adenoviral vector construct and a helper cell. The vector construct is capable of being replicated and packaged into a virion particle in the helper cell. In particular, the helper cell expresses DNA from the E2 region of the adenovirus 5 genome and complements deletions in that region in the vector construct. In certain embodiments, the disclosed invention comprises tissue specific expression of up to 30 kb of heterologous DNA directed by an adenoviral vector. Also disclosed are methods of transferring heterologous DNA into mammalian cells.

7163925, Jan 16, 2007

May 19, 1998

09/080935

Xiaomei Jin - Houston TX, US
Jack A. Roth - Houston TX, US

Board of Regents, The University of Texas System - Austin TX

A61K 48/00, C12N 15/63, C12N 15/86, C12N 15/861

514 44, 4353201, 435455, 435456

A variety of genetic constructs are disclosed that will find both in vitro and in vivo use in the area of tumor biology and cancer therapy. In particular, expression constructs are provided that contain a p16 encoding region and other regulatory elements necessary for the expression of a p16 transcript. One version of the expression construct is a replication-deficient adenoviral vector. Also provided are methods for the transformation of cell lines and the inhibition of cancer cell proliferation.

6133416, Oct 17, 2000

Aug 22, 1997

8/918712

Deborah R. Wilson - Houston TX
Therese M. Timmons - Houston TX
Julia A. Lee - Houston TX
Brian D. Almond - Houston TX
Jack A. Roth - Houston TX

The University of Texas System Board of Regents - Austin TX

C07K 200, C07K 400, C07K 500, A61K 4500

530300

The present invention involves the identification of a factor or factors that are anti-proliferative and can be used in the treatment of cancers and other hyperproliferative disease states. The factor or factors are induced from cells follow contact of the cells with viral or plasmid expression vectors. One factor is between about 3 kDa and 300 kDa in size, while another is less than about 3 kDa in size. Both are heat stable and is resistant to both protease and nuclease treatment. Methods for purification and use of the factor also are disclosed.