CATHERINE LELA HALL, MD
Osteopathic Medicine at Harry Hines Blvd, Dallas, TX

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.

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.

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.