ROBERT SIMS MUNFORD, MD
Osteopathic Medicine at Harry Hines Blvd, Dallas, TX

5013661, May 7, 1991

Mar 15, 1989

7/323679

Robert S. Munford - Dallas TX
Catherine L. Hall - Dallas TX

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

C12N 918, A61K 31715, C12P 1926

435197

An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids from their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being being bound in turn to lipopolysaccharide glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight by gel exclusion chromatography between about 50,000 Daltons and about 70,000 Daltons, and a molecular weight by polyacrylamide gel electrophoresis with sodium dodecylsulphate, using reduced molecular weight standards, of approximately 54,000 to 60,000 Daltons. Altered bacterial lipopolysaccharide substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of lipopolysaccharide lipid A are produced. Since the structure of the lipid A moiety is highly conserved, acyloxyacyl hydrolase may act on lipopolysaccharide of many different pathogenic bacteria (for example Salmonella, Escherichia, Hemophilus, and Neisseria). Such altered bacterial lipopolysaccharide, having toxicity reduced more than immunostimulatory activity, may be therapeutically useful: (1) as vaccines to prevent Gram-negative bacterial diseases by inducing antibodies to lipopolysaccharide O-polysaccharide or R-core antigens, (2) as antidotes to treat or prevent Gram-negative bacterial sepsis ("septic shock"), or (3) as adjuvants to enhance formation of antibodies to other antigens.

4929604, May 29, 1990

May 28, 1986

6/868428

Robert S. Munford - Dallas TX
Catherine L. Hall - Dallas TX

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

A61K 31715, C12P 1926, C12N 916, C07H 1310

514 53

An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids form their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being bound in turn to LPS glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight between about 50,000 daltons and about 70,000 daltons. Altered bacterial LPS substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of LPS lipid A are produced. Since the structure of the lipid A moiety is highly conserved, acyloxyacyl hydrolase may act on LPS of many different pathogenic bacteria (for example Salmonella, Escherichia, Hemophilus, and Neisseria). Such altered bacterial LPS, having toxicity reduced more than immunostimulatory activity, may be therapeutically useful: (1) as vaccines to prevent Gram-negative bacterial diseases by inducing antibodies to LPS 0-polysaccharide or R-core antigens, (2) as antidotes to treat or prevent gram-negative bacterial sepsis ("septic shock"), or (3) as adjuvants to enhance formation of antibodies to other antigens. The acyloxyacyl hydrolase itself may be therapeutically useful to detoxify endogenous LPS in patients with gram-negative bacterial diseases or to remove toxic LPS from therapeutic injectants.

5200184, Apr 6, 1993

Jul 8, 1991

7/728763

Robert S. Munford - Dallas TX
Catherine L. Hall - Dallas TX

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

A61K 3754, A61K 31715, C12N 918

424 9461

An acyloxyacyl hydrolase from the human promyelocyte cell line HL-60 has been found to specifically hydrolyze fatty acids from their ester linkages to hydroxy groups of 3-hydroxyfatty acids, the latter being bound in turn to LPS glycosaminyl residues. The hydrolyzed fatty acids may include dodecanoic acid, tetradecanoic acid and hexadecanoic acid. This enzyme showed a molecular weight by gel exclusion chromatography between about 50,000 Daltons and about 70,000 Daltons. Altered bacterial LPS substantially without fatty acids bound in ester linkage to hydroxy groups of 3-hydroxyfatty acids covalently linked to a glucosaminyl moiety of LPS lipid A are produced. Since the structure of the lipid A moiety is highly conserved, ac The U. S. Government may have rights in the present invention because the development was partially supported by NIH grant R01 AI18188 from the Department of Health and Human Services.

5356778, Oct 18, 1994

Feb 5, 1993

7/972498

Eric J. Hansen - Plano TX
Robert S. Munford - Dallas TX
Jussi Mertsola - Kaarina, FI

Board of Regents, The University of Texas - Austin TX

G01N 33579, G01N 3353, G01N 33569

435 72

The invention relates to a method of detecting gram-negative bacterial endotoxin using antibody capture combined with amoebocyte lysate chromogenic detection. The method is highly sensitive and rapid and may be used for detection of specific endotoxin. In a particular application, picogram levels of Haemophilus influenzae type b endotoxin are detected in plasma taken from previously infected mammals. In another particular application, the method is applied to the detection and diagnosis of disease, through the detection of endotoxin from disease-causing organisms. A specific example is the diagnosis of chancroid through the detection of endotoxin from H. ducreyi.

5281520, Jan 25, 1994

Sep 12, 1990

7/581342

Patrick J. O'Hara - Seattle WA
Frederick S. Hagen - Seattle WA
Francis J. Grant - Seattle WA
Robert S. Munford - Dallas TX

ZymoGenetics, Inc. - Seattle WA
Board of Regents University of Texas System - Austin TX

C12N 1500, C12N 1556, C12N 1580, C12N 1585

435 691

Methods are disclosed for producing acyloxyacyl hydrolase. The protein is produced from eukaryotic host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of acyloxyacyl hydrolase. The DNA constructs generally include the following operably linked elements: a transcriptional promoter; DNA sequence encoding acyloxyacyl hydrolase, the small subunit of acyloxyacyl hydrolase or the large subunit of acyloxyacyl hydrolase; and a transcriptional terminator. In addition, isolated DNA sequences encoding acyloxyacyl hydrolase and isolated DNA sequences encoding the small or large subunit of acyloxyacyl hydrolase are disclosed.

5851822, Dec 22, 1998

Apr 28, 1998

/067908

Robert S. Munford - Dallas TX

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

C12N 1586

4353201

The present invention describes methods of controlling and regulating the inflammatory reaction generated in response to various toxins, immunogens, pathogens and autoimmune insults. The method employs a vector that includes an anti-cytokine protein or antibacterial protein gene under the control of a cytokine responsive promoter. In animal models, adenoviral vectors successfully delivered the vectors to hepatic cells and were subsequently shown to respond only to stimulation by induced cytokines.

5744304, Apr 28, 1998

May 30, 1995

8/456103

Robert S. Munford - Dallas TX

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

C12Q 168

435 6

The present invention describes methods of controlling and regulating the inflammatory reaction generated in response to various toxins, immunogens, pathogens and autoimmune insults. The method employs a vector that includes an anti-cytokine protein or antibacterial protein gene under the control of a cytokine responsive promoter. In animal models, adenoviral vectors successfully delivered the vectors to hepatic cells and were subsequently shown to respond only to stimulation by induced cytokines.

2002015, Oct 17, 2002

Jan 3, 2002

10/039171

Robert Haley - Dallas TX, US
Alan Varley - Plano TX, US
Robert Munford - Dallas TX, US

Board of Regents, The University of Texas System

A61K048/00, C12N015/86, C12N015/861, C12N015/867

435/456000, 514/044000, 435/320100

The present invention provides methods of gene therapy to prevent or treat exposure to organophosphate (OP) toxins, such as that observed in Gulf War Syndrome patients. In particular, vectors comprising the PON1 gene, which express the enzyme paraoxonase, can be used to prevent damage from OP toxins when given prior to exposure, or to reduce the toxic effects after exposure. Depending on the PON1 isotype (R or Q), protection against particular toxins may be achieved.

5198339, Mar 30, 1993

Jul 13, 1990

7/553072

Eric J. Hansen - Plano TX
Robert S. Munford - Dallas TX
Jussi Mertsola - Kaarina, FI

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

G01N 3353, G01N 33579

435 72

The invention relates to a method of detecting gram-negative bacterial endotoxin using antibody capture combined with amoebocyte lysate chromogenic detection. The method is highly sensitive and rapid and may be used for detection of specific endotoxin. In a particular application, picogram levels of Haemophilus influenzae are detected in plasma taken from previously infected mammals.