Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2002-01-11
2004-03-23
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S558000, C514S552000
Reexamination Certificate
active
06710084
ABSTRACT:
BACKGROUND OF THE INVENTION
Lipid and protein mediators of inflammation such as cytokines and chemokines have a profound impact on the formation and actions of each other (Serhan, C. N., J. Z. Haeggstrom, and C. C. Leslie. 1996. Lipid mediator networks in cell signaling: update and impact of cytokines.
FASEB J.
10:1147-1158). In particular, the cytokines TNF&agr; and IL-1&bgr; play major roles in inflammation, septic shock and tissue injury. PMN perform a range of well-appreciated specialized functions, including chemotaxis, generation of reactive oxygen species and biosynthesis of potent lipid mediators (Weiss, S. J. 1989. Tissue destruction by neutrophils.
N. Engl. J. Med.
320:365-376). In this regard, TNF&agr; stimulates PMN to transcribe and release cytokines such as IL-1&bgr;, enhances leukotriene biosynthesis, and up-regulates adhesion molecules (Marucha, P. T., R. A. Zeff, and D. L. Kreutzer. 1991. Cytokine-induced IL-1&bgr; gene expression in the human polymorphonuclear leukocyte: transcriptional and post-transcriptional regulation by tumor necrosis factor and IL-1
. J. Immunol.
147:2603-2608). Since PMN represent approximately 70% of the peripheral blood leukocytes and are in many instances the initial cell type recruited to interstitial sites, they are now considered a significant source of “proinflammatory” cytokines including TNF&agr; and IL-1&bgr;. These as well as other PMN-derived cytokines and chemokines can, in turn, affect the course of inflammatory and immune responses (Lloyd, A. R., and J. J. Oppenheim. 1992. Poly's lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response.
Immunology Today
13:169-172). In certain clinical settings, including respiratory distress syndrome, myocardial reperfusion injury, gout and rheumatoid arthritis, PMN contribute to ongoing damage of host tissues (Weiss, S. J. 1989. Tissue destruction by neutrophils.
N. Engl. J. Med.
320:365-376; Hachicha, M., P. H. Naccache, and S. R. McColl. 1995. Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein-1 and interleukin-8 by human neutrophils: A possible mechanism of neutrophil recruitment to sites of inflammation in synovitis.
J. Exp. Med.
182:2019-2025; Hansen, P. R. 1995. Role of neutrophils in myocardial ischemia and reperfusion.
Circulation
91:1872-1885). Thus, it is of interest to understand the complex relationships between lipid mediators and TNF&agr;-evoked PMN responses in order to gain insight for new approaches in controlling these events.
SUMMARY OF THE INVENTION
The present invention pertains to methods for modulating a disease or condition associated with TNF&agr; initiated polymorphoneutrophil (PMN) inflammation. The methods include administration to a subject, an effective anti-inflammatory amount of a lipoxin analog having the formula described infra, such that the TNF&agr; initated PMN inflammation is modulated.
The present invention also pertains to methods for treating TNF&agr; initiated polymorphoneutrophil (PMN) inflammation in a subject. The methods include administration of an effective anti-inflammatory amount of a lipoxin analog described infra, such that TNF&agr; initiated polymorphoneutrophil (PMN) inflammation is treated.
The present invention further pertains to methods for modulating a disease or condition associated with TNF&agr; initiated cytokine activity in a subject. The methods include, administration of an effective anti-TNF&agr; amount of a lipoxin analog described infra, such that a disease or condition associated with TNF&agr; initiated cytokine activity, is modulated.
The present invention further relates to methods for treating TNF&agr; initiated cytokine activity in a subject. The methods include administration of an effective anti-TNF&agr; amount of a lipoxin analog described infra, such that TNF&agr; initiated cytokine activity, e.g., inflammation, is treated.
The present invention also relates to methods for modulating a disease or condition associated with TNF&agr; initiated IL-1&bgr; activity in a subject. The methods include administration of an effective anti-inflammatory amount of a lipoxin analog described infra, such that a disease or condition associated with TNF&agr; initiated IL-1&bgr;, is modulated.
The present invention further pertains to methods for treating TNF&agr; initiated IL-1&bgr; activity in a subject. The methods include administration of an effective anti-TNF&agr; amount of a lipoxin analog described infra, such that TNF&agr; initiated IL-1&bgr;, activity, e.g., inflammation, is treated.
In preferred embodiments, the methods of the invention are performed in vitro or in vivo.
In another aspect, the present invention is directed to a packaged pharmaceutical composition for treating a the activity or conditions listed above in a subject. The packaged pharmaceutical composition includes a container holding a therapeutically effective amount of at least one lipoxin compound having one of the formulae described infra and instructions for using the lipoxin compound for treating the activity or condition in the subject.
REFERENCES:
patent: 5441951 (1995-08-01), Serhan
patent: 6387953 (2002-05-01), Serhan
patent: WO 94/29262 (1994-12-01), None
patent: WO 95/01179 (1995-01-01), None
patent: WO 98/11049 (1998-03-01), None
Takano et al., “Neutrophil-Mediated Changes in Vasculare Permeability are Inhibited by Topical Application of Aspirin-Triggered 15-epi-Lipoxin A4 and Novel Lipoxin B4 Stable Analogs”, J.of Clin. Invest., vol. 101, No. 4, pp. 819-826, Feb. 1998.*
Olson, S. C. et al., Biochemistry and cell biology of phospholipase D in human neutrophils. Chem. Phys. Lipids, 80, 3-19, 1996.*
Lloyd, A.R. et al., 1992. Poly's lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunology Today 13:169-172.*
Serhan, C.N., J.Z. Haeggström, and C.C. Leslie. 1996. Lipid mediator networks in cell signaling: update and impact of cytokines.FASEB J.10:1147-1158.
Weiss, S.J. 1989. Tissue destruction by neutrophils.N. Engl. J. Med.320:365-376.
Marucha, P.T., R.A. Zeff, and D.L. Kreutzer. 1991. Cytokine-induced IL-1&bgr; gene expression in the human polymorphonuclear leukocyte: transcriptional and post-transcriptional regulation by tumor necrosis factor and IL-1,J. Immunol.147:2603-2608.
Lloyd, A.R., and J.J. Oppenheim. 1992. Poly's lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response.Immunology Today13:169-172.
Hachicha, M., P.H. Naccache, and S.R. McColl. 1995. Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin-8 by human neutrophils: A possible mechanism of neutrophil recruitment to sites of inflammation in synovitis.J. Exp. Med.182:2019-2025.
Hansen, P.R. 1995. Role of neutrophils in myocardial ischemia and reperfusion.Circulation91:1872-1885.
Takano, T., S. Fiore, J.F. Maddox, H.R. Brady, N.A. Petasis, and C.N. Serhan. 1997. Aspirin-triggered 15-epi-lipoxin A4and LXA4stable analogs are potent inhibitors of acute inflammation: Evidence for anti-inflammatory receptors.J. Exp. Med.185:1693-1704.
Clària, J., and C.N. Serhan. 1995. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions.Proc. Natl. Acad. Sci. USA92:9475-9479.
Lee, T.H., C.E. Horton, U. Kyan-Aung, D. Haskard, A.E. Crea, and B.W. Spur. 1989. Lipoxin A4and lipoxin B4inhibit chemotactic responses of human neutrophils stimulated by leukotriene B4and N-formyl-L-methionyl-L-leucyl-L-Phenylalanine.Clin. Sci.77:195-203.
Serhan, C.N. 1994. Lipoxin biosynthesis and its impact in inflammatory and vascular events.Biochim. Biophys. Acta1212:1-25.
Papayianni, A., C.N. Serhan, M.L. Phillips, H.G. Rennke, and H.R. Brady. 1995. Transcellular biosynthesis of lipoxin A4during adhesion of platelets and neutrophils in experimental immune complex glomerulonephritis.Kidney Int.47:1295-1302.
Chavis, C., I. Vachier, P. Chanez, J. Bousquet, and P. Godar
Brigham and Women's Hospital
Dorsey & Whitney LLP
Rothenberger Scott D.
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