Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2000-03-14
2002-03-05
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
Reexamination Certificate
active
06353026
ABSTRACT:
BACKGROUND OF THE INVENTION
Neutrophil (PMN) activation plays a central role in diverse host responses, such as host defense, inflammation and reperfusion injury (Weissmann, G., Smolen, J. E., and Korchak, H. M. (1980) Release of inflammatory mediators from stimulated neutrophils.
N. Engl. J. Med
. 303, 27-34). In response to inflammatory stimuli, PMN phospholipases are activated to remodel cell membranes and generate bioactive lipids that serve as intra- or extracellular mediators in the transduction of functional responses (Serhan, C. N., Haeggstrom, J. Z., and Leslie, C. C. (1996) Lipid mediator networks in cell signaling: update and impact of cytokines.
FASEB J
. 10, 1147-1158). Important components of microbicidal and acute inflammatory responses include reactive oxygen species and granule enzymes that are targeted to phagocytic vacuoles, but aberrant release of these potentially toxic agents can lead to amplification of inflammation as well as tissue injury and are implicated in a wide range of diseases (Weiss, S. J. (1989) Tissue destruction by neutrophils.
N. Engl. J. Med
. 320, 365-376). To prevent an over-exuberant inflammatory response and limit damage to the host, these PMN programs are tightly regulated. The host mediators serving as endogenous anti-inflammatory or protective signals are only recently being appreciated (Serhan, C. N. (1994) Lipoxin biosynthesis and its impact in inflammatory and vascular events.
Biochim. Biophys. Acta
1212, 1-25).
SUMMARY OF THE INVENTION
The present invention pertains to methods for modulating a disease or condition associated with phospholipase D (PLD) activity. The methods include administration to a subject, an effective anti-PLD amount of a lipoxin analog having the formula described infra, such that the PLD initiated activity is modulated.
The present invention also pertains to methods for treating phosphlipase D (PLD) activity in a subject. The methods include administration of an effective anti-PLD amount of a lipoxin analog described infra, such that PLD initiated activity is treated.
The present invention further pertains to methods for modulating a disease or condition associated with phospholipase D (PLD) initiated generation of superoxide or degranulation activity in a subject. The methods include, administration of an effective anti-PLD amount of a lipoxin analog described infra, such that a disease or condition associated with initiated by PLD generation of superoxide or degranulation activity, is modulated.
The present invention further relates to methods for treating phospholipase D (PLD) initiated superoxide generation or degranulation activity in a subject. The methods include administration of an effective anti-PLD amount of a lipoxin analog described infra, such that PLD initiated superoxide generation or degranulation activity 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 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: 5648512 (1997-07-01), Serhan
patent: WO 94/29262 (1994-12-01), None
patent: WO 95/01179 (1995-01-01), None
patent: WO 00/54767 (2000-09-01), None
Olson et al., “Biochemistry and cell biology of phospholipase D in human neutrophils”, Chemistry and Physics of Lipids, 80, pp. 3-19, 1996.*
Takano et al., “Neutrophil-mediated Changes in Vascular Permeability Are Inhibited by Topical Application of Aspirin-triggered 15-epi-lipoxin A4 and Novel Lipoxin B4 Stable Analogues”, J. Clin. Invest. vol. 101, No. 4, Feb. 1998, pp. 819-826.*
Weissmann, G., Smolen, J. E., and Korchak, H. M. (1980) Release of inflammatory mediators from stimulated neutrophils.N. Engl. J. Med. 303, 27-34.
Serhan, C. N., Haeggstrom, J. Z., and Leslie, C. C. (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.
Serhan, C. N. (1994) Lipoxin biosynthesis and its impact in inflammatory and vascular events.Biochim. Biophys. Acta1212, 1-25.
Borgeat, P., and Naccache, P. H. (1990) Biosynthesis and biological activity of leukotriene B4.Clin. Biochem. 23, 459-468.
Yokomizo, T., Izumi, T., Chang, K., Takuwa, T., and Shimizu, T. (1997) A G-protein-coupled receptor for leukotriene B4that mediates chemotaxis.Nature387, 620-624.
Fiore, S., Romano, M., Reardon, E. M., and Serhan, C. N. (1993) Induction of functional lipoxin A4receptors in HL-60 cells.Blood81, 3395-3403.
Isakson, P., Seibert, K., Masferrer, J., Salvemini, D., Lee, L., and Needleman, P. (1995) Discovery of a better aspirin.Advances in Prostaglandin, Thromboxane&Leukotriene Research23, 49-54.
Chiang, N., Takano, T., Clish, C. B., Petasis, N. A., Tai, H.-H., and Serhan, C. N. (1998) Aspirin-triggered 15-epi-lipoxin A4(ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4ELISA.J. Pharmacol Exper. Ther. 287, 779-790.
Serhan, C. N., Maddox, J. F., Petasis, N. A., Akritopoulou-Zanze, I., Papayianni, A., Brady, H. R., Colgan, S. P., and Madara, J. L. (1995) Design of lipoxin A4stable analogs that block transmigration and adhesion of human neutrophils.Biochemistry34, 14609-14615.
Takano, T., Fiore, S., Maddox, J. F., Brady, H. R., Petasis, N. A., and Serhan, C. N. (1997) Aspirin-triggered 15-epi-lipoxin A4(LXA4) and LXA4Stable analogues are potent inhibitors of acute inflammation: Evidence for anti-inflammatory receptors.J. Exp. Med. 185, 1693-1704.
Owman, C., Garzino-Demo, A., Cocchi, F., Popovic, M., Sabirsh, A., and Gallo, R. (1998) The leukotriene B4receptor functions as a novel type of coreceptor mediating entry of primary HIV-1 isolates into CD4-positive cells.Proc. Natl. Acad. Sci. 95, 9530-9534.
Marcus, A. J. (1995) Aspirin as prophylaxis against colorectal cancer.N. Engl. J. Med. 333, 656-658.
Vainio, H., and Morgan, G. (1997) Aspirin for the second hundred years: new uses for an old drug.Pharmacol Toxicol81, 151-152.
Herschman, H. R. (1998) Recent progress in the cellular and molecular biology of prostaglandin synthesis.Trends in Cardiovasc. Med. 8, 145-150.
Takano, T., Clish, C. B., Gronert, K., Petasis, N., and Serhan, C. N. (1998) Neutrophil-mediated changes in vascular permeability are inhibited by topical application of aspirin-triggered 15-epi-lipoxin A4and novel lipoxin B4stable analogues.J. Clin. Invest. 101, 819-826.
Billah, M. M., Eckel, S., Mullmann, T. J., Egan, R. W., and Siegel, M. I. (1989) Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phsophatidate phosphohydrolase in signal transduction.J. Biol. Chem. 264, 17069-17077.
Wakelam, M. J. O., Martin, A., Hodgkin, M. N., Brown, F., Pettit, T. R., Cross, M. J., De Takats, P. G., and Reynolds, J. L. (1997) Role and regulation of phospholipase D activity in normal and cancer cells.Advances in Enzyme Regulation37, 29-34.
Olson, S. C., and Lambeth, J. D. (1996) Biochemistry and cell biology of phospholipase D in human neutrophils.Chem. Phys. Lipids80, 3-19.
Steed, P. M., Clark, K. L., Boyar, W. C., and Lasala, D. J. (1998) Characterization of human PLD2 and the analysis of PLD isoform splice variants.FASEB J. 12, 1309-1317.
Martin, A., Saqib, K. M., Hodgkin, M. N., Brown, F. D., Pettit, T. R., Armstrong, S., and Wakelam, M. J. O. (1997) Role and regulation of phospholipase D signalling.Biochem. Soc. Trans. 25, 1157-1160.
Levy, B. D., Petasis, N. A., and Serhan, C. N. (1997) Polyisoprenyl phosphates in intracellular signalling.Nature389, 985-989.
Agwu, D. E., McPhail, L. C., Sozzani, S., Bass, D. A., and McCall, C.
Brigham and Women's Hospital
Dorsey & Whitney LLP
Jones Dwayne C.
Rothenberger Scott D.
LandOfFree
Regulation of phospholipase D activity does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Regulation of phospholipase D activity, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Regulation of phospholipase D activity will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2835229