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Method of treatment using interferon-tauRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Lymphokine, InterferonMethod of treatment using interferon-tau description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070190026, Method of treatment using interferon-tau. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF THE INVENTION [0001] The present invention relates to pharmaceutical compositions containing interferon-tau and methods of uses thereof. More particularly, the invention relates to methods for treating conditions responsive to interferon-tau by orally administering interferon-tau in a dose sufficient to alter the blood level of 2',5'-oligoadenylate synthetase. BACKGROUND OF THE INVENTION [0002] Interferon-tau (hereinafter "IFN.tau." or "interferon-.tau.") was discovered originally as a pregnancy recognition hormone produced by the trophectoderm of ruminant conceptuses (Imakawa, K. et al, Nature, 330:377-379, (1987); Bazer, F. W. and Johnson, H. M., Am. J. Repro. Immunol, 26:19-22, (1991)). The distribution of the IFN.tau. gene is restricted to ruminants, including cattle, sheep, and goats, (Alexenko, A. P. et al., J. Interferon and Cytokine Res., 19:1335-1341, (1999)) but has been shown to have activity in cells belonging to other species including humans and mice (Pontzer, C. H. et al., Cancer Res., 51:5304-5307, (1991); Alexenko, A. P. et al., J. Interferon and Cytokine Res., 20:817-822, (2000)). For example, IFN.tau. has been demonstrated to possess antiviral, (Pontzer, C. H. et al., Biochem. Biophys. Res. Commun., 152:801-807, (1988)), antiproliferative, (Pontzer, C. H., et al., 1991) and immunoregulatory activities (Assal-Meliani, A., Am. J. Repro. Immunol, 33:267-275 (1995)). [0003] While IFN.tau. displays many of the activities classically associated with type I IFNs, such as interferon-.alpha. and inteferon-.beta., considerable differences exist between IFN.tau. and the other type I IFNs. The most prominent difference is the role of IFN.tau. in pregnancy in ruminant species. The other IFNs have no similar activity in pregnancy recognition. Also different is viral induction. All type I IFNs, except IFN.tau., are induced readily by virus and dsRNA (Roberts, et al, Endocrine Reviews, 13:432 (1992)). Induced IFN-.alpha. and IFN-.beta. expression is transient, lasting approximately a few hours. In contrast, IFN.tau. synthesis, once induced, is maintained over a period of days (Godkin, et al., J. Reprod. Fert., 65:141 (1982)). On a per-cell basis, 300-fold more IFN-.tau. is produced than other type I IFNs (Cross, J. C. and Roberts, R. M., Proc. Natl. Acad Sci. USA 88:3817-3821 (1991)). [0004] Another difference lies in the amino acid sequences of IFN-.tau. and other type I interferons. The percent amino acid sequence similarity between the interferons .alpha..sub.2b, .beta..sub.1, .omega..sub.1, .gamma., and .tau. are summarized in the table below. TABLE-US-00001 rHuIFN.alpha..sub.2b rHuIFN.beta..sub.1 rHuIFN.sub.1.omega..sub.1 rHuIFN.sub..gamma. rOvIFN.tau. RhuIFN.alpha..sub.2b 33.1 60.8 11.6 48.8 RhuIFN.beta..sub.1 33.1 33.1 12.2 33.8 RhuIFN.omega..sub.1 60.8 33.1 10.2 54.9 RhuIFN.sub..gamma. 11.6 12.2 10.2 10.2 rovIFN.tau. 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). Streuli et al., Science, 209: 1343 (1980). Imakawa et al., Nature, 330: 377 (1987). [0005] Recombinant ovine IFN.tau. (rIFN.tau.) is 48.8 percent homologous to IFN.alpha..sub.2b and 33.8 percent homologous to IFN.beta..sub.1. Because of this limited homology between IFN.tau. and IFN.alpha. and between IFN.tau. and IFN.beta., it cannot be predicted whether or not IFN.tau. would behave in the same manner as IFN.alpha. or IFN.beta. when administered orally. IFN.tau. is also reported to have a low receptor binding affinity for type I receptors on human cells (Brod, S., J. Interferon and Cytokine Res., 18:841 (1999); Alexenko, A. et al., J. Interferon and Cytokine Res., 17:769 (1997)). Additionally, the fact that IFN.tau. is a non-endogeneous human protein generates the potential for systemic neutralizing antibody formation when IFN.tau. is introduced into the human body (Brod, S., J. Interferon and Cytokine Res., 18:841 (1999). These differences between IFN.tau. and the other interferons make it difficult to predict whether IFN.tau. when administered to a human will provide a therapeutic benefit. Teachings in the art relating to oral administration of IFN.alpha., IFN.beta., or any other non-tau interferon, fail to provide a basis for drawing any expectations for IFN.tau.. [0006] One limiting factor in the use of IFN.tau., as well as proteins and polypeptides in general, is related to biodistribution, as affected by protein interaction with plasma proteins and blood cells, when given parenterally. The oral route of administration is even more problematic due to proteolysis in the stomach, where the acidic conditions can destroy the molecule before reaching its intended target. For example, polypeptides and protein fragments, produced by action of gastric and pancreatic enzymes, are cleaved by exo- and endopeptidases in the intestinal brush border membrane to yield di- and tri-peptides. If proteolysis by pancreatic enzymes is avoided, polypeptides are subject to degradation by brush border peptidases. Polypeptides or proteins that might survive passage through the stomach are subject to metabolism in the intestinal mucosa where a penetration barrier prevents entry into cells. For this reason, much effort has been focused on delivering proteins to the oral-pharyngeal region in the form of a lozenge or solution held in the oral cavity for a period of time. SUMMARY OF THE INVENTION [0007] Accordingly, it is an object of the invention to provide a method for treating a condition in a human subject that is responsive to interferon therapy. [0008] It is another object of the invention to provide a method for treating such a condition by oral administration of IFN.tau.. [0009] In one aspect, the invention includes a method for treating a condition responsive to interferon therapy in a human subject, by orally administering IFN.tau. to the intestinal tract of the subject in an amount effective to produce a measurable increase in the subject's blood 2',5'-oligoadenylate synthetase (OAS) level, relative to the OAS level in the subject in the absence of IFN.tau. administration. The oral administration of IFN.tau. to the subject's intestinal tract, in such an effective amount, is continued on a regular basis of at least several times per week, for a period of at least one month. [0010] In another aspect, the invention includes a composition for use in preparation of a medicament for treating a condition in human subject responsive to interferon tau therapy, the condition selected from an autoimmune condition, cancer, or a viral infection. The composition comprises interferon-tau formulated for oral administration to the intestinal tract of the subject in an amount effective to produce an initial measurable increase in the subject's blood 2',5'-oligoadenylate synthetase (OAS) level, relative to the blood OAS level in the subject in the absence of interferon-tau administration, wherein the interferon-tau is administered to the intestinal tract of the subject in such effective amount, on a regular basis of at least several times per week, for a period of at least one month, independent of changes in the subject's blood OAS level. [0011] In one embodiment, the IFN.tau. is ovine IFN.tau.. In specific embodiments, the ovine IFN.tau. has a sequence identified herein as SEQ ID NO:2 or SEQ ID NO:3. More generally, the IFN.tau. has an amino acid sequence that is at least about 80% homologous with ovine IFN.tau.. The IFN.tau. can be a recombinantly produced IFN.tau.. [0012] The continuing administration may be carried out on a daily basis, or several times per week, e.g., every 48 hours. [0013] In yet another embodiment, the IFN.tau. is administered to a subject suffering from an autoimmune disorder, such as multiple sclerosis. In this method, IFN.tau. is administered during the period of patient symptoms, typically over the life of the subject. [0014] The IFN.tau., in another embodiment, is administered to a subject suffering from a viral infection, such as HCV. The method may further include detecting the presence of infection in the subject, and continuing administration of the IFN.tau. for a period of at several months past the time when infection is no longer detected. The subject may be treated with a second antiviral agent during the period of treatment with IFN.tau.. [0015] In another embodiment, the IFN.tau. is administered to a subject suffering from a condition characterized by cellular proliferation, such as cancer. The subject may be treated with a second anticancer agent during the period of treatment with IFN.tau.. [0016] The IFN.tau. dosage form is preferably one that delivers the protein predominantly to the small intestine. For example, the dosage form can be comprised of a mucoadhesive polymer that protects and/or stabilizes the protein from the intestinal environment. The mucoadhesive formulation enhances binding of the interferon to cells lining the intestinal wall. [0017] The treatment can further include monitoring the blood OAS level to ascertain if the OAS level is increased as a result of initial administration of IFN.tau.. In another embodiment, the amount of IFN.tau. initially administered to the patient is adjusted to achieve a measurable increase in blood OAS, relative to the level observed prior to administering oral IFN.tau.. [0018] These and other objects and features of the invention will be more fully appreciated when the following detailed description of the invention is read in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS [0019] FIG. 1 shows blood OAS concentration, in pmol/dL, following intraperitoneal (i.p.) or gastric administration of IFN-.tau. to healthy mice. [0020] FIG. 2 shows blood OAS concentration, in pmol/dL, upon gastric administration of IFN.tau. to mice at dosages of 1.times.10.sup.3 U, 1.times.10.sup.4 U, and 1.times.10.sup.5 U. Continue reading about Method of treatment using interferon-tau... 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