DR. THEODORE FRIEDMANN, M.D.
Hospitals at Gilman Dr, La Jolla, CA

6432705, Aug 13, 2002

May 8, 2000

09/566660

Jiing-Kuan Yee - Del Mar CA
Theodore Friedmann - La Jolla CA
Shin-Tai Chen - San Diego CA

The Regents of the University of California - Oakland CA
City of Hope - Duarte CA

C12N 500

435325, 435 691, 4353201, 435455, 536 231, 536 234, 536 235, 530350

The present invention features compositions and methods for the inducible expression of a polypeptide, especially a polypeptide normally cytotoxic to the eukaryotic host cell in which it is to be expressed. A nucleotide sequence encoding a polypeptide of interest is operably linked to an inducible promoter. Expression from the inducible promoter is regulated by a multi-chimeric transactivating factor, composed of a first ligand-binding domain that negatively regulates transcription, a transcriptional activation domain, and a second ligand-binding domain that positively regulates the transcriptional activation function of the transactivator. Transcription of the nucleotide sequence under control of the inducible promoter is activated by the multi-chimeric transactivator when both the ligand that binds the first ligand-binding domain is absent and the ligand that binds the second ligand-binding domain is present. This inducible expression system is particularly useful in the expression of the cytotoxic protein VSV G for the production of pseudotyped retroviral vectors.

6451304, Sep 17, 2002

Mar 9, 1999

09/265013

Theodore Friedmann - La Jolla CA
Atsushi Miyanohara - San Diego CA

The Regents of the University of California - Oakland CA

A01N 6300

424 932, 435 691, 435 932, 4352351, 435236, 4353201, 435455, 435456, 435465, 435466, 514 44, 536 231, 536 2372

The invention provides a system for production of retroviruses which are replication incompetent. In the system, gag and pol retroviral structural proteins are expressed separately by different plasmids in a packaging cell line. Separate gag and pol expressing plasmids are provided, as are packaging cell lines containing such plasmids. Retrovirus products of the retroviral vector production system, including chimeric retroviruses, are also provided.

6133027, Oct 17, 2000

Aug 7, 1996

8/693940

Jiing-Kuan Yee - Del Mar CA
Theodore Friedmann - La Jolla CA
Shin-Tai Chen - San Diego CA

City of Hope - Duarte CA
The Regents of the University of California - Oakland CA

C12N 1585, C12N 1586, C12N 15867

435325

The present invention features compositions and methods for the inducible expression of a polypeptide, especially a polypeptide normally cytotoxic to the eukaryotic host cell in which it is to be expressed. A nucleotide sequence encoding a polypeptide of interest is operably linked to an inducible promoter (e. g, a promoter composed of a minimal promoter linked to multiple copies of tetO, the binding site for the tetracycline repressor (tetR) of the Escherichia coli tetracycline resistance operon Tn10). Expression from the inducible promoter is regulated by a multi-chimeric transactivating factor, composed of a first ligand-binding domain that negatively regulates transcription (e. g. , a prokaryotic tetracycline repressor polypeptide), a transcriptional activation domain, and a second ligand-binding domain that positively regulates the transcriptional activation function of the transactivator (e. g. , a ligand-binding domain of a steroid receptor, preferably an estrogen receptor (ER)).

5739018, Apr 14, 1998

Aug 7, 1996

8/694652

Atsushi Miyanohara - San Diego CA
Jiing-Kuan Yee - Del Mar CA
Shin-Tai Chen - San Diego CA
Charles Edward Prussak - San Diego CA
Theodore Friedmann - La Jolla CA

The Regents of the University of California - Oakland CA
City of Hope - Duarte CA

C12N 510, C12N 1563, C12N 1586

4351723

The present invention features packaging cell lines and recombinant retroviral particles produced thereby, particularly pseudotyped retroviral particles. Preferably, the packaging cell lines are derived from HeLa, Cf2Th, D17, MDCK, or BHK cells, most preferably from Cf2Th cells. Retroviral particles are produced by inducibly expressing an envelope protein of interest (e. g. , a retroviral envelope or the envelope protein of vesicular stomatitis virus (VSV G)). Inducible expression of the envelope protein is accomplished by operably linking an envelope protein-encoding nucleotide sequence to an inducible promoter (e. g. , a promoter composed of a minimal promoter linked to multiple copies of tetO, the binding site for the tetracycline repressor (tetR) of the Escherichia coli, tetracycline resistance operon Tn10). Expression from the inducible promoter is regulated by a multi-chimeric transactivating factor, composed of a first ligand-binding domain that negatively regulates transcription from the inducible promoter (e. g. , a prokaryotic tetracycline repressor polypeptide (tetR)), a transcriptional activation domain, and a second ligand-binding domain (e. g.

5670354, Sep 23, 1997

Jun 7, 1995

8/480453

Jane C. Burns - La Jolla CA
Jiing-Kuan Yee - Del Mar CA
Theodore Friedmann - La Jolla CA

The Regents of the University of California - Oakland CA

C12N 1500, C12N 1506, C12N 506, C12N 516

4351723

The present application discloses retrovirus-derived vectors in which the retroviral envelope glycoprotein has been replaced by the G glycoprotein of vesicular stomatitis virus, and the use of these vectors in the transfer of exogenous genes into the cells of a wide variety of non-mammalian organisms. Also disclosed is a method for the generation of retroviral vectors in high titers, wherein a recombinant, stable host cell line is provided which harbors the retroviral vector of interest without envelope protein. High-titer retroviral vector production is initiated by introducing nucleic acid encoding a functional membrane-associated protein into the cell line. The vectors disclosed in the present application can be concentrated by ultracentrifugation to titers greater than 10. sup. 9 cfu/ml which are especially useful in human gene therapy trials, and can also infect cells, such as hamster and fish cells, that are ordinarily resistant to infection with vectors containing the retroviral envelope protein.

5674486, Oct 7, 1997

Jun 6, 1995

8/473123

Robert E. Sobol - La Jolla CA
Fred H. Gage - La Jolla CA
Ivor Royston - La Jolla CA
Theodore Friedmann - La Jolla CA

San Diego Regional Cancer Center - San Diego CA

A61K 4800, A61K 3576, C12N 500

424 9321

A novel method of tumor immunotherapy is described comprising the genetic modification of cells resulting in the secretion of cytokine gene products to stimulate a patient's immune response to tumor antigens. In one embodiment, autologous fibroblasts genetically modified to secrete at least one cytokine gene product are utilized to immunize the patient in a formulation with tumor antigens at a site other than an active tumor site. In another embodiment, cells genetically modified to express at least one tumor antigen gene product and to secrete at least one cytokine gene product are utilized in a formulation to immunize the patient at a site other than an active tumor site.

5650148, Jul 22, 1997

Mar 10, 1994

8/209609

Fred H. Gage - La Jolla CA
Theodore Friedmann - La Jolla CA
Michael B. Rosenberg - San Diego CA
Jon A. Wolff - Madison WI
Malcolm Schinstine - San Diego CA
Michael D. Kawaja - Toronto, CA
Jasodhara Ray - San Diego CA

The Regents of the University of California - Oakland CA

A61K 4800, A61K 3100, C12N 1500, C12N 500

424 932

Methods of genetically modifying donor cells by gene transfer for grafting into the central nervous system to treat defective, diseased or damaged cells are disclosed. The modified donor cells produce functional molecules that effect the recovery or improved function of cells in the CNS. Methods and vectors for carrying out gene transfer and grafting are described.

5082670, Jan 21, 1992

Dec 15, 1988

7/285196

Fred H. Gage - La Jolla CA
Michael B. Rosenberg - San Diego CA
Theodore Friedmann - La Jolla CA

The Regents of the University of California - Oakland CA

A61K 3500, A61K 4800, C12N 1500

424520