Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1998-06-12
2002-05-21
Saunders, David (Department: 1644)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C435S375000, C514S021800, C530S350000
Reexamination Certificate
active
06391852
ABSTRACT:
BACKGROUND OF THE INVENTION
Hereditary hemochromatosis (HH) is a common disease characterized by excess iron deposition in the major organs of the body (Dadone, M. M. et al.
AM. J. Clin. Pathol.
78:196-207 (1982); Edwards, C. Q. et al.
N. Engl. J. Med.
18:1355-1362. (1988); McLaren, C. E., et al.
Blood
86:2021-2027 (1995); Bothwell, T. H. et al.,
The metabolic and molecular basis of inherited disease
(ed. C. R. Scriver, E. A.) 2237-2269 (McGraw-Hill, New York 1995); Bacon, B. R. et al.,
Hepatology, A textbook of liver disease
(eds. Zakim, D. & Boyer, T. D.) 1439-1472 (W. B. Saunders, Philadelphia, 1996). A candidate gene for this disease, HFE, was identified by positional cloning (Feder, J. N., et al.
Nature Genetics
13:399-408 (1996)). The gene, a novel member of the MHC class I family, was found to have a mutation, cysteine 282→tyrosine (C282Y), in 83% of patient chromosomes (Feder, J. N., et al.
Nature Genetics
13:399-408 (1996)). This mutation eliminates the ability of HFE to associate with &bgr;
2
-microglobulin (&bgr;
2
m) and prevents cell-surface expression (Feder, J. N., et al.,
J. Biol. Chem.
272:14025-14028 (1997)). However, the relationship of this class I-like molecule to the regulation of iron metabolism has remained obscure.
Thus, an object of the instant invention is to provide a molecular basis for the relationship of HFE to iron metabolism, and diagnostic and therapeutic agents for the treatment of iron overload diseases and iron deficiency diseases.
SUMMARY OF THE INVENTION
One aspect of the invention is a method of treating an iron overload disease by administering to a patient an HFE polypeptide having the sequence of SEQ ID NO:1,
RLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE,
wherein the HFE polypeptide is provided in a complex with full length, wild type human &bgr;
2
m.
A further aspect of the invention is a composition of an HFE polypeptide having the amino acid sequence of SEQ ID NO:1,
RLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE,
wherein the HFE polypeptide is provided in a complex with full length, wild type human &bgr;
2
m.
A further aspect of the invention is a method of treating an iron deficiency disease by administering to a patient an HFE polypeptide, i.e., H63D-HFE mutant, having the sequence of SEQ ID NO:2,
RLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDDESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE,
wherein the HFE polypeptide is provided in a complex with full length, wild type human &bgr;
2
m.
A further aspect of the invention is a composition of an HFE polypeptide, i.e., H63D-HFE mutant, having the amino acid sequence of SEQ ID NO:2,
RLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDDESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNHSKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDHLEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE,
wherein the HFE polypeptide is provided in a complex with full length, wild type human &bgr;
2
m.
A further aspect of the invention is a method of treating an iron deficiency disease by administering to a patient an HFE polypeptide, i.e., H111A/H145A-HFE mutant, having having the sequence of SEQ ID NO:3,
RLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNASKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDALEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE,
wherein the HFE polypeptide is provided in a complex with full length, wild type human &bgr;
2
m.
A further aspect of the invention is a composition of an HFE polypeptide, i.e., H111A/H145A-HFE mutant, having the amino acid sequence of SEQ ID NO:3,
RLLRSHSLHYLFMGASEQDLGLSLFEALGYVDDQLFVFYDHESRRVEPRTPWVSSRISSQMWLQLSQSLKGWDHMFTVDFWTIMENHNASKESHTLQVILGCEMQEDNSTEGYWKYGYDGQDALEFCPDTLDWRAAEPRAWPTKLEWERHKIRARQNRAYLERDCPAQLQQLLELGRGVLDQQVPPLVKVTHHVTSSVTTLRCRALNYYPQNITMKWLKDKQPMDAKEFEPKDVLPNGDGTYQGWITLAVPPGEEQRYTCQVEHPGLDQPLIVIWE,
wherein the HFE polypeptide is provided in a complex with full length, wild type human &bgr;
2
m.
REFERENCES:
Jeffrey, GP, et al. Alternate splicing produces a soluble form of the hereditary hemochromatosis protecin Hfe. Blood Cells, Molecules and Diseases 25:61-67, 1999.*
Dupradeau, Fy, et al. A 3-dimensional model building by homology of the HFE protein: molecular consequences and application to antibody development. Biochim. Biophys. ACTA 148:213-221, 2000.*
GenBank Accession No. NP 000401, Mar. 19, 1999.*
Gupta, S., ed. Immunology of HIV Infection, Plenum Medical Book Co. New York, pp. 402-404, 1996.*
Parkkila, S. et al., Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract. Proc. Natl. Acad. Sci. USA 94:2534-2539, Mar. 1997.*
Fahnestock, ML, et al., The MHC Class I homolog encoded by human cytomegalovirus binds endogenous peptides. Immunity 3:583-590, 1995.*
Ahmed, R and Stevens, JG. Viral Persistence.. In: Fundamental Virology, Second Edition, Fields, et al., eds. Raven Press, Ltd., New York. p. 252, 1991.*
Anderson et al., 1990, “Transferrin receptor distribution and regulation in the rat small intestine. Effect of iron stores and erythropoiesis,”Gastroenterology 98(3):576-585.
Banerjee et al., 1986, “Transferrin receptors in the human gastrointestinal tract. Relationship to body iron stores,”Gastroenterology 91(4):861-869.
Dadone et al., 1982, “Hereditary hemochromatosis. Analysis of laboratory expression of the disease by genotype in 18 pedigrees,”Am. J. Clin. Pathol. 78(2):196-207.
Edwards et al., 1988, “Prevalence of hemochromatosis among 11,065 presumably healthy blood donors,”N. Engl. J. Med. 318(21):1355-1362.
Fahnestock et al., 1992, “Thermal stability comparison of purified empty and peptide-filled forms of a class I MHC molecule,”Science 258(5088):1658-1662.
Fahnestock et al., 1995, “The MHC class I homolog encoded by human cytomegalovirus binds endogenous peptides,”Immunity 3(5):583-590.
Feder et al., 1996, “A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis,”Nat. Genet. 13(4):399-408.
Feder et al., 1997, “The hemochromatosis founder mutation in HLA-H disrupts &bgr;2-microglobulin interaction and cell surface expression,”J. Biol. Chem. 272(22):14025-14028.
Karin and Mintz, 1981, “Receptor-mediated endocytosis of transferrin in developmentally totipotent mouse teratocarcinoma stem cells,”J. Biol. Chem. 256(7):3245-3252.
Lin et al., 1990, “Expression of T cell antigen receptor heterodimers in a lipid-linked form,”Science 249(4969):677-679.
McLaren et al., 1995, “Prevalence of heterozygotes for hemochromatosis in the white population of the United States,”Blood 86(5):2021-2027.
Mulford and Lodish, 1988, “Endocytosis of the transferrin receptor is altered during differentiation of murine erythroleukemic cells,”J. Biol. Chem. 236(11):5455-5461.
Octave et al., 1982, “Transferrin uptake by cultured rat embryo fibroblasts. The influence of lysosomotropic agents, iron chelators and colchicine on the uptake of iron and transferrin,”Eur. J. Biochem. 123(2):235-240.
Omary and Trowbridge, 1981, “Biosynthesis of the human transferrin receptor in cultured cells,”J. Biol. Chem. 256(24):12888-12892.
Parham et al., 1983, “Arginine 45 is a major part of the antigenic determinant of human &bgr;2-microglobulin recognized by mouse monoclonal antibody BB
Bjorkman Pamela J.
Feder John N.
Schatzman Randall C.
Bio-Rad Laboratories, Inc.
DeCloux Amy
Pennie & Edmonds LLP
Saunders David
LandOfFree
Methods and compositions for diagnosis and treatment of iron... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for diagnosis and treatment of iron..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for diagnosis and treatment of iron... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2863326