Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from a fruit – including berry
Reexamination Certificate
2000-10-30
2002-03-05
Tate, Christopher R. (Department: 1651)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Containing or obtained from a fruit , including berry
C424S725000
Reexamination Certificate
active
06352729
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to a naturally occurring extract Kas from the Melothria Indica Lou plant that inhibits the release of cytokines such as Tumor Necrosis Factor-alpha (TNF-alpha) by immune response cells, such as macrophages, for the therapeutic treatment of disease including sepsis.
Many of the toxic effects of endotoxins can be mimicked in vivo by TNF-alpha or IL-1 beta themselves (Norogrodsky, et. al., 1994, Science 264:1319). Tumor necrosis factor-alpha (TNF-alpha), a 17 Kda protein produced by macrophages and other cells, was discovered by separate groups of investigators pursuing mediators of disparate diseases. The pleiotropic nature of TNF-alpha prevents generalization about whether it is beneficial or injurious. It is clear that, in some instances, the local effects of TNF-alpha improve host defense mechanisms by mobilizing substrate, increasing immune cell function, and stimulating inflammation. But, in other cases, the toxicity of TNF-alpha may cause disease by mediating septic shock, tissue injury, or catabolic illness. TNF-alpha has been implicated in many diseases including: AIDS, Anemia, Autoimmune Disease, Cachexia, Cancer, Cerebral Malaria, Diabetes Mellitus, Disseminated Intravascular Coagulopathy, Eurthyroid Sick Syndrome, Hemorrhagic Shock, Hepatitis, Insulin Resistance, Leprosy, Leukemia, Lymphoma, Meningitis, Multiple Sclerosis, Myocardial Ischemia, Obesity, Rejection Of Transplanted Organs, Rheumatoid Arthritis, Septic Shock, Stroke and Tuberculosis (Tracey, K. J.,
Tumor Necrosis Factor
-
alpha
in The Cytokine Handbook (Academic Press Limited 1994)).
Septic Shock Syndrome, a frequently lethal complication of infectious disease, kills 85,000-150,000 people in the USA annually (Tracey, K. J.,
Tumor Necrosis Factor
-
alpha
in The Cytokine Handbook (Academic Press Limited 1994)). This disease is caused by a massive systemic infection by Gram-negative bacteria. Due to excessive stimulation of the host immune system by the endotoxin lipopolysaccharide (LPS), which is present on the outer membrane of the bacteria, the host immune cells, mainly macrophages, produce several cytokines such as Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin 1-Beta (IL-I Beta), Interleukin 6 (IL-6) and Nitric Oxide (NO), which are the main modulators of the response to LPS (Norogrodsky, et. al., 1994, Science 264:1319). It has been reported that anti-TNF monoclonal antibodies prevent the development of septic shock in animal studies (Tracey, et. al., 1987, Nature 330:66; Beutler, 1985, Science 229:869; Mathison, et. al., 1988, J. Clin. Invest. 81:1925; Grau, et. al., 1987, Science 237:1210). These findings provide a rationale for the removal of TNF for the purpose of the treatment of sepsis shock. We have discovered a component designated as Kas from the extract of plant Melothria Indica Lou that functionally removed TNF-alpha by blocking the release of TNF-alpha by macrophage. In a sepsis animal model, we found that Kas prevents death in sepsis-induced mice.
BRIEF SUMMARY OF THE INVENTION
It is the object of this invention to use an extract of the Melothria Indica Lou plant, designated “Kas,” as a therapeutic agent for the treatment of TNF-related diseases, such as sepsis.
It is another object of this invention to employ a method to isolate and to purify the active component Kas, which is present in the extract of the Melothria Indica Lou plant and inhibits the secretion of TNF by endotoxin-stimulated macrophages.
REFERENCES:
patent: 09-315938 (1997-09-01), None
Novogrodsky, A., et al., Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors, Science, May 27, 1994, p. 1319, vol. 264,.
Tracy, K.J., et al., Anti-cachectin/TNF monoclonal antibodies prevent septic schock during lethal bacteraemia, Nature, Dec. 17, 1987, p. 662, vol. 330.
Beutler, B., et al., Passive Immunization Against Cachectin/Tumor Necrosis Factor Protects Mice from Lethal Effect of Endotoxin, Science, Aug. 30, 1985, p. 869, vol. 229.
Mathison, John C., et al., Participation of Tumor Necrosis Factor in the Mediatin of Gram Negative Bacterial Lipopolysaccharide-induced injury in Rabbits, J. Clin. Invest., Jun. 1988, p. 1925, vol. 81.
Grau, G.E., et al., Tumor Necrosis Factor (Cachectin) as an Essential Mediator in Murine Cerebral Malaria, Science, Sep. 4, 1987, p. 1210, vol. 237.
Cayer, J.M., et al., Cachectin/Tumor Necrosis Factor Stimulates Collagenase and Prostaglandin E2Production by Human Synovial Cells and Dermal Fibroblasts, J. Exp. Med., Dec. 1985, p. 2163, vol. 162, The Rockefeller Univ. P.
Haddad, E.K., et al., Early Embryo Loss is Associated with Local Production of Nitric Oxide by Decidual Mononuclear Cells, J. Exp. Med., Oct. 1995, p. 1143. vol. 182, The Rockefeller Univ. Press.
Wei, X.Q., et al., Altered Immune Responses in Mice Lacking Inducible Nitric Oxide Synthase, Nature, Jun. 1, 1995, p. 408, vol. 375.
Spriggs, David, et al., Genomic Structure, Induction, and Production of TNF-60 , Chapter 1 in “Tumor Necrosis Factor”, Marcel Dekker Inc.
Trentham, David E., et al., Autoimmunity to Type II Collagen: an Experimental Model of Arthritis, J. Exp. Med., 1977, p. 857, vol. 146., The Rockefeller Univ. Press.
Bertolini, Donald R., et al., Stimulation of Bone Rescrption and Inhibition of Bone Formation in Vitro by Human Tumour Necrosis Factors, Nature, Feb., 1986, p. 516, vol. 319.
Keffer, J., et. al., Transgenic Mice Expressing Human Tumour Necrosis Factor: a predictive genetic model of arthritis, EMBO J., 1991, pp. 4025-4031, vol. 10, Oxford University Press.
Taylor, G., et. al., A Pathogenic Role for TNF alpha in the Syndrome of Cachexia, Arthritis, and Autoimmunity Resulting from Tristetraprolin (TTP) Deficiency, Immunity, May 1996, pp. 445-454, vol. 4, Cell Press.
Elliott, M., et. al., Repeated Therapy with Monoclonal Antibody to Tumour Necrosis Factor alpha (cA2) in Patients with Rheumatoid Arthritis, The Lancet, pp. 1125-1127, Oct. 22, 1994, vol. 344.
Chomczynski, P., et. al., Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate-Phenol-Chloroform Extraction, Analytical Biochemistry, pp. 156-159, 1987, vol. 162, Academic Press, Inc.
Aviv, H., et. al., Purification of Biologically Active Globin Messenger RNA by Chromatography on Oligothymidylic acid-Cellulose, Proc. Nat. Acad. Sci., pp. 1408-1412, Jun. 1972. vol. 69.
Kriegler, M., et. al., A Novel Form of TNF/Cachectin Is a Cell Surface Cytotoxic Thransmembrane Protein: Ramifications for the Complex Physiology of TNF, Cell, pp. 45-53, Apr. 8, 1988, vol. 53, Cell Press.
Ambryx Biotechnology, Inc.
Srivastava Kailash C.
Tate Christopher R.
Trojan Law Offices
LandOfFree
Plant extract that inhibits the release of tumor necrosis... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Plant extract that inhibits the release of tumor necrosis..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Plant extract that inhibits the release of tumor necrosis... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2854281