Arch Development Corporation

The University of Chicago

The UAB Research Foundation (The University of Alabama at Birmingham)

Medimmune Limited

University Patents, Inc.

Institut Merieux

Aviron

Institute Merieux

Dana-farber-cancer Institute Inc.

Bernard Roizman

Donald W Kufe

Rosario Leopardi

George William Kemble

Dennis E Hallahan

Ralph R Weichselbaum

Guoying Zhou

Richard J Whitley

Nikolai Khodarev

Joany Chou

Richard R Spaete

Ravi Sood

Fenyong Liu

Renato Bruni

Leonard Edwin Post

Bin He

Lewis B Schwartz

Andy Minn

Edwardine Labay

Frances C Purves

Mark Prichard

Frances C Spector

M Robert Lang

Gouying Zhou

Te Du

Guo J Ye

Guo Jie Ye

Gregory S Sibley

Compositions, kits and methods for treating cancer in a subject in need thereof are disclosed involving one or more inhibitors of the JAK/STAT pathway which renders the cancer chemosensitive and/or radiosensitive.

Anti-tumor therapy

The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells renders the HSV particles, particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor.

Targeting of herpes simplex virus to specific receptors

Panels, compositions, and methods for treating cancer in a subject in need thereof are disclosed involving one or more genes the suppression of which renders the cancer chemosensitive and/or radiosensitive.

The disclosure relates to methods of controlling the state of a virus (lytic or lysogenic) in an individual, such as a method of reactivating a latent virus in an individual, comprising administering one or more agents that modulates the activity of signal transducer and activator of transcription 3 (STAT3) or any of p300, CBP or p300/CBP. Also contemplated are methods further comprising administering an HDAC modulating agent, such as an HDAC inhibiting agent or an HDAC activating agent.

Modulation of reactivation of a latent virus

The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells render the HSV particles. particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor.

Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

Treatment of tumors with genetically engineered herpes virus

Disclosed is a set of genes differentially expressed in chemotherapy and radiation resistant tumors useful in predicting response to therapy and assessing risk of local-regional failure, survival and metastasis in cancer patients. Also disclosed are methods for characterizing tumors according to gene expression and kits for use in the methods of the invention.

Prognosis and therapy predictive markers and methods of use

Recombinant herpes simplex viruses comprising DNA encoding cytokines and methods for treating neoplastic diseases using the inventive recombinant viruses are disclosed.

Recombinant herpes simplex virus useful for treating neoplastic disease

Live, attenuated, phenotypically stable HSV-2 viruses and methods of making and using the virus are provided. Live, attenuated HSV-2 viruses are constructed using recombinant techniques and can be used in a pharmaceutical composition for prophylactic treatment of HSV-2 infections and for treatment of recurrent HSV-2 related diseases and conditions.

Methods and compositions for treatment and prevention of HSV-2 infections and conditions

The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells renders the HSV particles particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor.

Targeting of Herpes simplex virus to specific receptors

The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific receptors. Also, recombinant vectors for producing such HSV particles. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention may be used for targeting cells that express the selected receptor. The ability to selectively target cells renders the HSV particles particularly useful in selectively killing the selected receptor-bearing cells (such as tumor cells), imaging cells bearing the selected receptor, and providing gene replacement therapy to cells bearing the selected receptor.

The present invention provides methods of expressing a nucleic acid or producing a proteinaceous composition encoded by a nucleic acid in vascular and cardiovascular cells by administration of a herpesvirus vector. The present invention provides methods of producing a therapeutic benefit in vascular and cardiovascular tissue by administration of a herpesvirus vector. In additional aspects, the invention concerns combination therapies for vascular and cardiovascular diseases comprising administration of a herpesvirus vector and treatment with at least one addition pharmacological agent or surgical procedure.

Genetically engineered herpes virus for the treatment of cardiovascular disease

The ICP4 protein of herpes simplex virus plays an important role in the transactivation of viral genes. The present invention discloses that ICP4 also has the ability to inhibit apoptosis. This function appears to reside in functional domain distinct from the transactivating function, as indicated by studies using temperature sensitive mutants of ICP4 that transactivating function at elevated temperatures. Also disclosed are methods for inhibition of apoptosis using ICP4 or an ICP4 encoding gene, such as an &agr;4 gene, methods of inhibiting ICP4's apoptosis-inhibiting function, and methods for the production of recombinant proteins and treatment of HSV infections.

Herpes simplex virus ICP4 is an inhibitor of apoptosis

The present invention relates to the identification and purification of a herpes protease and a nucleic acid segment coding for two proteins. The first protein is the herpes protease which is able to cleave itself and also cleave the second protein. This protease is required for the assembly of the herpes virus capsid, therefore is essential for replication. The second protein has previously been designated as the family of proteins in viral infected cells, ICP35. The protease and its substrates are encoded by overlapping nucleic acid segments. This invention also relates to a promoter sequence for the second protein. Methods are presented of producing a viral protease, screening a protease inhibitor which may be used in a drug designed for the treatment of herpes disease, methods for treating herpes and other viral infections wherein the virus employs a protease substantially similar to the herpes protease, for capsid production. Methods for detecting herpes infections and other viral infections are also disclosed.

Growing community of inventors

Chicago, IL, United States of America

Bernard Roizman