James Macdowell Markert

US Patent:

8420071, Apr 16, 2013

Filed:

Sep 19, 2008

Appl. No.:

12/234246

Inventors:

Richard J. Whitley - Birmingham AL, US
James MacDowell Markert - Birmingham AL, US
George Yancey Gillespie - Birmingham AL, US
Jacqueline Nuss Parker - Birmingham AL, US

Assignee:

The UAB Research Foundation - Birmingham AL

International Classification:

A01N 63/00
A61K 48/00

US Classification:

424 932, 514 44 R, 4353201

Abstract:

An anti-cancer pharmaceutical composition includes a herpes simplex virus (HSV) vector into which a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD has been inserted. A method of treatment of a patient suffering from cancer includes administering to the patient the anti-tumor pharmaceutical composition including a HSV vector having a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD inserted therein.

US Patent:

20040258667, Dec 23, 2004

Filed:

Jul 8, 2004

Appl. No.:

10/886907

Inventors:

Richard Whitley - Birmingham AL, US
James Markert - Birmingham AL, US
George Gillespie - Birmingham AL, US
Jacqueline Parker - Birmingham AL, US

International Classification:

A61K048/00

US Classification:

424/093200

Abstract:

An anti-cancer pharmaceutical composition includes a herpes simplex virus (HSV) vector into which a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD has been inserted. A method of treatment of a patient suffering from cancer includes administering to the patient the anti-tumor pharmaceutical composition including a HSV vector having a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD inserted therein.

US Patent:

20070225245, Sep 27, 2007

Filed:

Apr 27, 2007

Appl. No.:

11/796574

Inventors:

Donald Buchsbaum - Alabaster AL, US
G. Gillespie - Birmingham AL, US
James Markert - Birmingham AL, US
Sergey Kaliberov - Birmingham AL, US

International Classification:

A61K 31/70
C12N 15/869

US Classification:

514044000, 435320100

Abstract:

The instant invention has developed viral vectors encoding a mutant bacterial cytosine deaminase (bCD) gene, which have a higher affinity for cytosine than wild type bCD (bCDwt). The purpose of the present invention was to evaluate cytotoxicity in vitro and therapeutic efficacy in vivo of these vectors in combination with the prodrug 5-FC and ionizing radiation against human glioma. The present study demonstrates that infection with the viral vector expressing the mutant cytosine deaminase gene resulted in increased 5-FC-mediated cell killing, compared with vectors expressing the wild-type gene. Furthermore, a significant increase in cytotoxicity following infection with viral vector expressing the mutant cytosine deaminase gene and radiation treatment of glioma cells in vitro was demonstrated as compared to infection with viral vector expressing the wild-type gene. Animal studies showed significant inhibition of subcutaneous or intracranial tumor growth of D54MG glioma xenografts by the combination of AdbCD-D314A/5-FC with ionizing radiation as compared with either agent alone, and with AdbCDwt/5-FC plus radiation. These data indicate that combined treatment with this mutant enzyme/prodrug therapy and radiotherapy provides a promising approach for cancer therapy.

US Patent:

20080095744, Apr 24, 2008

Filed:

Nov 1, 2005

Appl. No.:

11/718439

Inventors:

Jacqueline Parker - Birmingham AL, US
Richard Whitley - Birmingham AL, US
James Markert - Birmingham AL, US

International Classification:

A61K 39/245
C12N 7/01
A61P 35/00

US Classification:

424093200, 435235100

Abstract:

A conditionally replicating, aneurovirulent recombinant herpes simplex virus is provided that includes a nucleic acid encoding an expressible chemokine. An expression control element is operably linked to the nucleic acid. A therapeutic composition includes a first conditionally replicating, aneurovirulent recombinant herpes simplex virus having a first nucleic acid encoding a first expressible cytokine operatively linked to an expression control element. A second such herpes simplex virus encoding a second expressible cytokine is also provided with a pharmaceutically acceptable carrier. Preferably, the second cytokine is a chemokine. In a particular embodiment, the first expressible cytokine increases availability of an immunoresponsive cell for activation. The activatable cell is CD4+, CD8+, NK, a dendritic cell, or a combination thereof. A second conditionally replicating, aneurovirulent, recombinant herpes simplex virus expresses a second cytokine in the same host cell as the first virus or alternatively, upon expression in a second host cell, resulting in the activation of the immunoresponsive cell. A method of tumor cell growth inhibition is provided that includes introduction of a therapeutically effective amount of an aforementioned therapeutic composition into a tumor of an individual such that two different cytokines are produced within the tumor to enhance the immune response in the individual that inhibits tumor cell growth. The first and second recombinant herpes simplex viruses are administered simultaneously, sequentially. Sequential administration is separated by a time period ranging from a few second to several days.

US Patent:

20080206199, Aug 28, 2008

Filed:

Jun 30, 2006

Appl. No.:

11/994158

Inventors:

Kevin Cassady - Birmingham AL, US
James Markert - Birmingham AL, US

Assignee:

THE UAB RESEARCH FOUNDATION - Birmingham AL

International Classification:

A61K 35/76
C12N 7/01
C12N 15/00
A61P 35/04
C12N 5/02

US Classification:

424 932, 4352351, 435375, 4353201, 435440

Abstract:

Disclosed herein are chimeric herpesviruses as well as methods of making and using such chimeric herpesviruses. The chimeric viruses comprise two nucleic acid sequences, one from a herpesvirus and one from a different virus. The herpesvirus nucleic acid sequence is a modified protein kinase R (PKR) evasion gene. The second viral nucleic acid sequence inhibits PKR-mediate protein shutoff in tumor cells, but is not neurovirulent. Thus, the chimeric virus has reduced neurovirulence as compared to the wild-type herpesvirus but remains replication competent.

US Patent:

6764675, Jul 20, 2004

Filed:

Feb 14, 2002

Appl. No.:

10/009972

Inventors:

Richard J. Whitley - Birmingham AL
James MacDowell Markert - Birmingham AL
George Yancey Gillespie - Birmingham AL
Jacqueline Ness Parker - Brimingham AL

Assignee:

The UAB Research Foundation - Birmingham AL

International Classification:

A01N 6300

US Classification:

424 932, 514 44, 4353201, 435455, 435456

Abstract:

An anti-cancer pharmaceutical composition includes a herpes simplex virus (HSV) vector into which a nucleic acid sequence encoding an anti-cancer agent selected from interleukin-12, GM-CSF, and CD has been inserted. A method of treatment of a patient suffering from cancer includes administering to the patient the anti-tumor pharmaceutical composition including an HSV vector having a nucleic acid sequence encoding an anti-cancer agent selected from interleukin-12, GM-CSF, and CD inserted therein.