Chiron Corporation

Intrexon Corporation

Introgen Therapeutics Inc.

Other

The University of Texas System

University of South Florida

Chiron Viagene, Inc.

Sunil D Chada

James G Respess

Douglas J Jolly

Jack R Barber

Mordechai Bodner

Harry E Gruber

David A Driver

Paul K Laikind

William E Fogler

Charles C Reed

Sybille L Sauter

Nicholas J DePolo

John F Warner

Daniel C St Louis

Brandon Cuthbertson

Jeremiah F Roeth

Thomas W Dubensky, Jr

Jack A Roth

Tapas Mukhopadhyay

Scott Antonia

Stephen M W Chang

Stephen M Chang

Fayaz Khazi

Kerstin Menander

Abner Mhashilkar

Dmitry I Gabrilovich

Caty E DeJesus

This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing vectors for one or more immuunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals. These vector may be provided to treat a variety of disorders, e.g., neoplastic disorders, through direct injection or through in vitro engineered cells, such as dendritic cells.

Vectors conditionally expressing therapeutic proteins, host cells comprising the vectors, and uses thereof

This invention relates to the field of therapeutics. Disclosed are methods of conditionally expressing erythropoietin under the control of an ecdysone receptor-based gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals. The methods of the invention cause an in vivo increase in the expression of erythropoietin and an increase in the hematocrit or volume percentage of red blood cells in blood after administration of the ligand.

Vectors conditionally expressing protein

The present invention relates to immunotherapy methods for treating hyperproliferative disease in humans, particularly to hyperproliferative disease that is refractory to therapy. More specifically, the invention is directed, in one embodiment, to methods for treating a subject with a hyperproliferative disease in which the expression of a self gene is upregulated in therapy-resistant hyperproliferative cells. In another embodiment, an adenoviral expression construct comprising a self gene under the control of a promoter operable in eukaryotic cells is administered to the therapy-resistant hyperproliferative cells. The present invention thus provides immunotherapies for treating therapy-resistant hyperproliferative disease by attenuating the natural immune system's CTL response against hyperproliferative cells or overexpressing mutant p53 antigens, for example.

P53 vaccines for the treatment of cancers

Methods of suppressing or preventing an infection of a subject by a pathogen that involve administering to the subject a composition that includes a therapeutically effective amount of an MDA-7 polypeptide or a nucleic acid encoding the MDA-7 polypeptide, and a pharmaceutically acceptable preparation suitable for delivery to the subject, wherein the MDA-7 suppresses or prevents the infection, are disclosed. Also disclosed are methods of suppressing or preventing a viral infection of a cell, including obtaining an MDA-7 polypeptide or a nucleic acid encoding the MDA-7 polypeptide, and contacting the cell with the MDA-7 polypeptide or the nucleic acid encoding the MDA-7 polypeptide, wherein the MDA-7 suppresses or prevents infection of the cell.

Use of MDA-7 to inhibit pathogenic infectious organisms

The present invention is directed to the use of benzimidazole derivatives for the treatment of tumors and in combination with tumor suppressor gene therapy. In a particular embodiment, treatment of p53-positive tumors with benzimidazole derivatives induces p53 expression and increases its half-life, resulting in apoptotic death of the tumor cells. Similarly, in conjunction with p53 gene therapy, benzimidazole derivatives induce p53 expression and accumulation in tumor cells regardless of their p53 status. The combination treatment subsequently elicits apoptosis of the tumor cells.

Antihelminthic drugs as a treatment for hyperproliferative diseases

Recombinant retroviruses carrying a vector construct capable of preventing, inhibiting, stabilizing or reversing infectious, cancerous or auto-immune diseases are disclosed. More specifically, the recombinant retroviruses of the present invention are useful for (a) stimulating a specific immune response to an antigen or a pathogenic antigen; (b) inhibiting a function of a pathogenic agent, such as a virus; and (c) inhibiting the interaction of an agent with a host cell receptor. In addition, eucaryotic cells infected with, and pharmaceutical compositions containing such a recombinant retrovirus are disclosed. Various methods for producing recombinant retroviruses having unique characteristics, and methods for producing transgenic packaging animals or insects are also disclosed.

Method for inhibiting human tumor cells

Retroviral vector constructs are described which have a 5&prime; LTR, a tRNA binding site, a packaging signal, one or more heterologous sequences, an origin of second strand synthesis and a 3&prime; LTR, wherein the vector construct lacks retroviral gag/pol or env coding sequences. In addition, gag/pol, and env expression cassettes are described wherein the expression cassettes lack a consecutive sequence of more than 8 nucleotides in common. The above-described retroviral vector constructs, gag/pol and env expression cassettes may be utilized to construct producer cell lines which preclude the formation of replication competent virus.

Crossless retroviral vectors

Retroviral vector constructs are described which have a 5' LTR, a tRNA binding site, a packaging signal, one or more heterologous sequences, an origin of second strand synthesis and a 3' LTR, wherein the vector construct lacks retroviral gag/pol or env coding sequences. In addition, gag/pol, and env expression-cassettes are described wherein the expression cassettes lack a consecutive sequence of more than 8 nucleotides in common. The above-described retroviral vector constructs, gag/pol and env expression cassettes may be utilized to construct producer cell lines which preclude the formation of replication competent virus.

Method for making reflection defective retroviral vectors for infecting

Lamboid bacteriophage capable of specifically interacting with and delivering nucleic acid molecules to eukaryotic cells are disclosed. Such bacteriophage-derived gene transfer systems target one or more specific receptors on eukaryotic cells, for instance by incorporating mutant tail fiber proteins or by incorporating known ligands for specific eukaryotic receptors into lambda phage. Also disclosed are methods for identifying and producing modified bacteriophage tail fiber polypeptides capable of specifically interacting with eukaryotic transmembrane proteins. Methods of treating diseases using such gene transfer systems are also disclosed.

Bacteriophage-mediated gene transfer systems capable of transfecting

The present invention provides a method of destroying selected tumor cells comprising administering to a warm-blooded animal a vector construct which directs the expression of at least one immunogenic, non-tumorigenic form of an altered cellular component normally associated with the selected tumor cells. Also provided are vector constructs which direct the expression of altered cellular components. Representative altered cellular components include ras.sup.*, p53.sup.*, Rb.sup.*, alter protein encoded by the Wilms' tumor gene, ubiquitin.sup.*, mucin.sup.*, DCC, APC, MCC, neu, an altered receptor, and bcr/abl. Also provided are recombinant viruses carrying a vector construct, target cells infected with the recombinant virus, and pharmaceutical compositions comprising the recombinant virus and a pharmaceutically acceptable carrier or diluent.

Anti-cancer immunotherapeutics

Growing community of inventors

Vista, CA, United States of America

Sunil D Chada