Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1999-07-27
2002-06-11
Davenport, Avis M. (Department: 1653)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S003100, C514S012200, C530S350000, C530S351000, C424S084000, C424S084000, C424S184100
Reexamination Certificate
active
06403562
ABSTRACT:
BACKGROUND OF THE INVENTION
Interferon tau (IFN&tgr;) blocks the development of experimental allergic encephalomyelitis (EAE) in mice without associated toxicity; however, the mechanism of such action has not been fully elucidated (Soos et al., 1995). EAE is a murine model useful for studying the demyelinating disease multiple sclerosis (MS) (Zamvil and Steinman, 1990). Myelin basic protein (MBP) has been shown to be one of the primary central nervous system antigens responsible for induction of autoimmunity in the EAE model. Upon immunization with MBP, mice develop clinically observable tail and limb paralysis due to lymphocyte infiltration into the central nervous system accompanied by acute demyelination (Zamvil and Steinman, 1990).
The type I interferons (IFNs), &agr; and &bgr;, have previously been shown to induce suppressor cells that block in vitro antibody production (Johnson and Blalock, 1980). Further, when type I IFN&tgr;-induced suppressor cells were cultured in vitro, they were shown to produce a soluble factor that mediated immunosuppression. Past studies have suggested that “classic” T suppressor cells bear the CD8 phenotype. In addition, IFN&tgr;-induced suppressor cell function occurs via a mechanism similar to that originally observed for type I IFN&agr; and &bgr; inhibition of antibody production in vitro.
A suppressor mechanism shared by the type I IFNs is the induction of soluble suppressor factors. The identification of the cytokines responsible for the induction of suppressor cells useful in the treatment of autoimmune diseases is provided by the subject invention. Surprisingly, these cytokines act in a synergistic fashion. Although IL-10 (Vieira et al., 1991; Moore et al., 1990) and TGF-&bgr; (for a review see Massague, 1990) have previously been shown to inhibit events associated with autoimmune disease (Chaouat et al., 1995; Rott et al., 1994; Stevens et al., 1994; Johns et al., 1991; Schluesener and Lider, 1989), it was not known that these cytokines are produced by suppressor cells involved in prevention of EAE, nor was the synergistic action of these cytokines or self-reactive T cells known.
BRIEF SUMMARY OF THE INVENTION
The subject invention concerns novel methods for treating autoimmune-related diseases, such as Multiple Sclerosis (MS). The method of the subject invention comprises administering the cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-&bgr;), in combination, to a person afflicted with, or predisposed to, an autoimmune disease. When administered in combination, IL-10 and TGF-&bgr; act as suppressive cytokines in a synergistic manner to inhibit the activation of self-reactive T cells in autoimmune diseases. In a further embodiment of the subject method, IL-10 and TGF-&bgr; can be administered in conjunction with IFN&tgr;.
REFERENCES:
patent: 6083919 (2000-07-01), Johnson et al.
patent: 9628183 (1986-09-01), None
The Merck Manual, Berkow R., Editor, 16th ed., Merck & Co; Inc., pp. 339-342, 1992.*
Chaouat, G., Assal-Meliani, A., Martal, J., Raghupathy, R., Elliot, J., Mosmann, T. and Wegmann, T.G. (1995) “IL10 prevents naturally occurring fetal loss in the CBA X DBA/2 mating combinations, and local defect in IL10 production in this abortion-prone combination is corrected by in vivo injection of IFNT”J. Immunmol. 154:4261-4268.
Johns, L.T., Flanders, K.C., Ranges, G.E. and Sriram, S. (1991) “Successful treatment of experimental allergic encehalomyelitis with transforming growth factor-&bgr;1”J. Immunmol. 147:1792-1796.
Johnson, H.M. and Blalock, J.E. (1980) “Interferon immunosuppression: mediation by a suppressor factor”Infect. Immun. 29:301-305.
Massague, J. (1990) “The transforming growth factor-&bgr; family”Annu. Rev. Cell. Biol. 6:597.
Moore, K.W., Vieira, P., Fiorentino, D.F., Trounstine, M.L., Khan, T.A., and Mosmann, T.R., (1990) “Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRF1”Science248:1230.
Rott, O., Fleischer, B. and Cash, E. (1994) “Interleukin-10 prevents experimental allergic encephalomyelitis in rats”Eur. J. Immunol. 24:1434-1440.
Schluesener, H.J. and Lider, O. (1989) “Transforming growth factors &bgr;1 and &bgr;2: Cytokines with identical immunosuppressive effects and potential role in the regulation of autoimmune T cell function”J. Neuroimmunol. 24:249-258.
Soos, J.M., Subramaniam, P.S., Hobeika, A.C., Schiffenbauer, J. and Johnson, H.M. (1995) “The IFN pregnancy recognition hormone, interferon tau, blocks both development and superantigen reactivation of experimental allergic encephalomyelitis without associated toxicity”J. Immunol. 155:2747-2753.
Stevens, D.B., Gould, K.E. and Swanborg, R.H. (1994) “Transforming growth factor-beta 1 inhibits tumor necrosis factor-alpha/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis”J. Neuroimmunol. 51:77-83.
Viera, P., de Waal Malefyt, R., Dang, M.-N., Johnson, K.E., Kastelein, R., Fiorentino, D.F., de Vries, J.E., Roncarolo, M.-G., Mosmann, T.R., and Moore, K.W. (1991) “Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRF1”Proc. Natl. Acad. Sci. 88:1172.
Zamvil, S.S. and Steinman, L. (1990) “The T lymphocyte in experimental allergic encephalomyelitis”Annu. Rev. Immunol. 8:579-621.
Chen, Y. Inobe, J., Weiner, H.L. (1995) “Induction of Oral Tolerance to Myelin Basic Protein in CD8-Depleted Mice”Journal of Immunology155:910-916.
Reitamo, S. et al. (1992) “Interleukin 10 up-regulates elastin gene expression in vivo and in vitro at the transcription level”Biochemical Journal302:331-333.
Oswald, I.P. et al. (1992) “IL-10 synergizes with IL-4 and transforming growth factor-&bgr; to inhibit macrophage cytotoxic activity”Journal of Immunology148:3578-3582.
Karpus, W. J., Swanborg, R.H. (1991) CD4+ suppressor cells inhibit the function of effector cells of experimental autoimmune encephalomyelitis through a mechanism involving transforming growth factor-&bgr;Journal of Immunology146:1163-1168.
Weckmann, A.L., Alcocer-Varela, J. (1996) Cytokine Inhibitors in Autoimmune Disease Seminars in Arthritis and Rheumatism 26(2):539-557.
Johnson Howard M.
Mujtaba Mustafa G.
Soos Jeanne M.
Davenport Avis M.
Saliwanchik Lloyd & Saliwanchik
University of Florida
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