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US 2005/0226845 A1 Liu Et Al US 20050226845A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0226845 A1 Liu et al. (43) Pub. Date: Oct. 13, 2005 (54) METHOD OF TREATMENT USING Continuation-in-part of application No. 10/825,382, INTERFERON-TAU filed on Apr. 14, 2004, which is a continuation-in-part of application No. 10/825,457, filed on Apr. 14, 2004. (76) Inventors: Chih-Ping Liu, San Francisco, CA (US); Lorelie H. Villarete, Alameda, (60) Provisional application No. 60/552,279, filed on Mar. CA (US) 10, 2004. Provisional application No. 60/552,279, filed on Mar. 10, 2004. Correspondence Address: PERKINS COE LLP Publication Classification P.O. BOX 21.68 MENLO PARK, CA 94026 (US) (51) Int. Cl. ................................................. A61K 38/21 (52) U.S. Cl. ............................................................ 424/85.4 (21) Appl. No.: 11/040,706 (22) Filed: Jan. 21, 2005 (57) ABSTRACT Related U.S. Application Data Methods of treating a disease or condition responsive to interleukin-10 therapy in a mammal are provided. In one (63) Continuation-in-part of application No. 10/884,741, form, a method includes orally administering a therapeuti filed on Jul. 2, 2004, which is a continuation-in-part cally effective amount of interferon tau to the mammal. In of application No. 10/824,710, filed on Apr. 14, 2004. other forms of the invention, the method includes adminis Continuation-in-part of application No. 10/825,068, tering a Second therapeutic agent to the mammal in addition filed on Apr. 14, 2004. to interleukin-10 either simultaneously or Sequentally. US 2005/02268.45 A1 Oct. 13, 2005 METHOD OF TREATMENT USING 0004 While IFNT displays many of the activities classi INTERFERON-TAU cally associated with type I IFNs, such as interferon-C. and CROSS-REFERENCE TO RELATED interferon-?3, considerable differences exist between IFNT APPLICATIONS and the other type I IFNs. The most prominent difference is the role of IFNT in pregnancy in ruminant species. The other 0001. This application is a continuation-in-part of U.S. IFNS have no similar activity in pregnancy recognition. Also patent application Ser. No. 10/884,741, filed Jul. 2, 2004, which is a continuation-in-part of U.S. patent application different is viral induction. All type IIFNs, except IFNL, are Ser. No. 10/824,710, filed Apr. 14, 2004, and which claims induced readily by virus and dsRNA (Roberts, et al., Endo the benefit of U.S. Provisional Patent Application Ser. No. crine Reviews, 13:432 (1992)). Induced IFN-O. and IFN-?3 60/552,279, filed Mar. 10, 2004. This application is also a expression is transient, lasting approximately a few hours. In continuation-in-part of U.S. patent application Ser. NoS. contrast, IFNT Synthesis, once induced, is maintained over a 10/825,068; 10/825,382; and 10/825,457, all of which were period of days (Godkin, et al., J. Reprod. Fert, 65:141 filed on Apr. 14, 2004, and all of which claim the benefit of (1982)). On a per-cell basis, 300-fold more IFNT is produced U.S. Provisional Patent Application Ser. No. 60/552,279, than other type IIFNs (Cross, J. C. and Roberts, R. M., Proc. filed Mar. 10, 2004. Natl. Acad. Sci. USA 88:3817-3821 (1991)). FIELD OF THE INVENTION 0005 Another difference lies in the amino acid sequences 0002 The present invention relates to pharmaceutical of IFNT and other type I interferons. The percent amino acid compositions containing interferon-tau and methods of uses Sequence Similarity between the interferons C, B, (), Y, thereof. More particularly, the invention relates to methods and T are Summarized in the table below. rHuIFNC, rHuIFNB rHuIFNC) rHuIFN, rOvIFN rHuIFNC, 33.1 60.8 11.6 48.8 rHuIFNB, 33.1 33.1 12.2 33.8 rHuIFNG) 60.8 33.1 10.2 54.9 rHuIFN, 11.6 12.2 10.2 10.2 rOvIFN 48.8 33.8 54.9 10.2 Sequence comparison determined from the following references: Taniguchi et al., Gene, 10(1): 11 (1980). Adolf et al., Biochim. Biophys. Acta, 1089(2): 167 (1991). Streuliet al., Science, 209: 1343 (1980). Imakawa et al., Nature, 330: 377 (1987). of treating diseases or conditions responsive to interleukin 0006 Recombinant Ovine IFNT is 48.8 percent homolo 10 (IL-10) therapy in a mammal by administering inter gous to IFNC, and 33.8 percent homologous to IFNB. feron-tau (IFNt) either alone or in combination with one or Because of this limited homology between IFNT and IFNC. more therapeutic agents. and between IFNT and IFNB, it cannot be predicted whether or not IFNT would behave in the same manner as IFNC. or BACKGROUND OF THE INVENTION IFNB when administered orally. IFNT is also reported to have a low receptor binding affinity for type I receptors on 0003) Interferon-tau (hereinafter “IFNt” or “interferon human cells (Brod, S., J. Interferon and Cytokine Res., t”) was discovered originally as a pregnancy recognition 18:841 (1999); Alexenko, A. et al., J. Interferon and Cytok hormone produced by the trophectoderm of ruminant con ine Res., 17:769 (1997)). Additionally, the fact that IFNT is ceptuses (Imakawa, K. et al, Nature, 330:377-379, (1987); a non-endogeneous human protein generates the potential Bazer, F. W. and Johnson, H. M., Am. J. Repro. Immunol, for systemic neutralizing antibody formation when IFNT is 26:19-22, (1991)). The distribution of the IFN1 gene is injected into the human body (Brod, S., J. Interferon and restricted to ruminants, including cattle, sheep, and goats, Cytokine Res., 18:841 (1999). These differences between (Alexenko, A. P. et al., J. Interferon and Cytokine Res., IFNT and the other interferons make it difficult to predict 19:1335-1341, (1999)) but has been shown to have activity whether IFNT will provide a therapeutic benefit when in cells belonging to other species including humans and administered to a human. Teachings in the art relating to oral mice (Pontzer, C. H. et al., Cancer Res., 51:5304-5307, administration of IFNC, IFNB, or any other non-tau inter (1991); Alexenko, A. P. et al., J. Interferon and Cytokine feron, fail to provide a basis for drawing any expectations Res., 20:817-822, (2000)). For example, IFNT has been for IFN. demonstrated to possess antiviral, (Pontzer, C. H. et al., 0007. One limiting factor in the use of IFNT, as well as Biochem. Biophys. Res. Commun., 152:801-807, (1988)), proteins and polypeptides in general, is related to biodistri antiproliferative, (Pontzer, C. H., et al., 1991) and immuno bution, as affected by protein interaction with plasma pro regulatory activities (ASSal-Meliani, A., Am. J. Repro. teins and blood cells, when given parenterally. The oral route Immunol, 33:267-275 (1995)). of administration is even more problematic due to proteoly US 2005/02268.45 A1 Oct. 13, 2005 sis in the Stomach, where the acidic conditions can destroy and compositions have drawbackS Such that there is a the molecule before reaching its intended target. For continuing need for Safe and effective methods and compo example, polypeptides and protein fragments, produced by Sitions to treat Such diseases or conditions. The present action of gastric and pancreatic enzymes, are cleaved by invention addresses this need. eXO- and endopeptidases in the intestinal brush border membrane to yield di- and tri-peptides. If proteolysis by SUMMARY OF THE INVENTION pancreatic enzymes is avoided, polypeptides are Subject to degradation by brush border peptidases. Polypeptides or 0009 Interleukin 10 has been found to be associated with proteins that might Survive passage through the Stomach are a wide variety of disease States. Accordingly, methods of Subject to metabolism in the intestinal mucosa where a treating a disease or condition responsive to interleukin-10 penetration barrier prevents entry into cells. For this reason, therapy in a mammal are provided. much effort has been focused on delivering proteins to the 0010. In one aspect of the invention, a method of treating oral-pharyngeal region in the form of a lozenge or Solution a disease or condition responsive to interleukin-10 therapy held in the oral cavity for a period of time. in a mammal includes orally administering a daily dosage of greater than about 5x10 Units of interferon tau to the 0008. The role of cytokines in various diseases and mammal. correlations between cytokine blood levels with disease onset and Severity is of interest to the medical community. 0011. The method may be amenable for treating a wide For example, it has been shown or Suggested that the variety of diseases or conditions, including Alzheimer's following diseases may be benefited by interleukin-10 disease, liver fibrosis, pulmonary fibrosis, optic neuritis, therapy or otherwise show Some linkage between interleu Stroke, atherOSclerosis, anti-phospholipid syndrome, chronic kin-10 and the particular disease or condition: liver fibrosis obstructive pulmonary disease, autism, rejection from organ Nelson, D. R. et al. Hepatology 38(4):859-868 (2003); transplantation and a wide variety of autoimmune disorders. Louis, H., Acta Gastr. Belg. 66(1):7-14 (2003); pulmonary 0012. In certain forms of the invention, the method fibrosis Aral, T., et al., Am. J. Physiol. Lung. Cell. Mol. includes administering a Second therapeutic agent to the Physiol. 278:L914-L922 (2000); Alzheimer's disease De mammal in addition to interleukin-10 either Simultaneously Luigi, A. et al., Mech. Age. Dev (16): 1985-1995 (2001); or Sequentially. Such combination therapy can result in Remarzue, E. J., and Bollen, E. L., Exp. Gerontol. additive or Synergic improvements in ameliorating the dis 36(1):171-176 (2001); Town, T. et al., J. Neuroimmunol. ease or condition, including ameliorating the progression 132(1-2):49-59 (2002); stroke Frenkel, D.
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