Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-03-02
1999-08-17
Hutzell, Paula K.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
5303873, 436512, G01N 3353
Patent
active
059392690
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to agents that neutralize the activity of inhibitors of insulin receptor tyrosine kinase activity, especially PC-1, and their uses in the diagnosis and treatment of diseases and disorders involving inappropriate insulin receptor tyrosine kinase inhibitor expression. In particular the invention relates to agents useful in detecting or treating diseases or disorders associated with an inappropriate expression of PC-1. In a preferred aspect, the invention relates to agents and methods useful in diagnosing the presence of insulin resistance in an individual suspected of having insulin resistance or related disorders, in particular, noninsulin dependent diabetes mellitus. The invention also provides for methods of treating mammals, preferably humans, who suffer from diseases associated with inappropriate expression of PC-1. In a particular embodiment, the invention provides for methods of preventing, treating, or suppressing the effects of inappropriate expression of PC-1, such as insulin resistance and non-insulin dependent diabetes mellitus.
DESCRIPTION OF RELATED ART
Diabetes mellitus in humans is a complex disorder which can be subdivided into two major clinical syndromes. Each category, in turn, subsumes a number of differing etiologies. About 10% of persons with diabetes have insulin-dependent diabetes mellitus (IDDM). IDDM is characterized by selective destruction of insulin-producing .beta. cells, absolute insulin deficiency, youthful onset, and evidence of autoimmune pathogenesis. Noninsulin-dependent diabetes mellitus (NIDDM) is more common and often seen in the context of obesity. NIDDM is characterized by onset in middle age, resistance to the effects of insulin, and relative insulin deficiency without .beta. cell destruction. The terms Type 1 and Type 2 diabetes have been used to refer to IDDM and NIDDM respectively. It has been suggested, however, that the terms be used as modifiers of the physiological states, i.e., Type 1 is sometimes used to describe an immune mediated pathogenic mechanism and Type 2 used to describe a non-immune mediated pathogenesis. In Type 1 diabetes, for example, the immune system mediates destruction of beta cells. Using this classification there are three major clinal syndromes: Type 1 insulin dependent diabetes, 2) Type 1 noninsulin dependent diabetes, and 3) Type 2 noninsulin dependent diabetes. The NIDDM stage of Type 1 then would describe the late, slower progressing autoimmune onset.
The pathogenesis of Type 2 NIDDM has not previously been clearly understood. Descriptively, three phases can be recognized in individuals. The first phase is characterized by demonstrable insulin resistance with normal plasma glucose levels and elevated plasma insulin levels. In the second stage, postprandial hyperglycemia and increased insulin resistance characterize the disease. In the third phase, insulin resistance continues and secreted insulin levels decline resulting in fasting hyperglycemia. In all stages the plasma levels of insulin do not correspond to plasma glucose levels, i.e. relative insulin deficiency is perceived. Type 2 NIDDM is typified, therefore, by insulin resistance, as well as, insulin secretory defects. (Harrison's. Prncpls. of Int. Med., 11th Ed., McGraw-Hill, publisher, New York, N.Y.)
Several recent studies suggest that the presence of insulin resistance precedes the onset of NIDDM. Patients with NIDDM secrete insulin, but not in a normal fashion, and have resistance to both endogenous and exogenous insulin in muscle and other insulin sensitive tissues. Moller et al., N. Eng. J. Med, 325:938 (1991). The presence of insulin resistance suggests that it may be an initial abnormality in the disease. In the majority of patients with NIDDM, however, the molecular basis of the insulin resistance is unknown.
Dermal fibroblasts, derived from a patient exhibiting insulin resistance and NIDDM, produced an inhibitor of insulin receptor tyrosine kinase activation. Insulin receptor content was normal in the patient a
REFERENCES:
patent: 4748018 (1988-05-01), Strolle et al.
patent: 5124147 (1992-06-01), Wissner et al.
patent: 5128270 (1992-07-01), Dela Croix et al.
Harahap, A.R. et al. 1988. J. Immunol. 141:2317-2320.
Feinstein, R. et al. Dec. 15, 1993. J. Biol. Chem. 268:26055-8.
Osband, M.E. et al. 1990. Immonol. Today, 11: 193-195.
Hotamisligil, G.S. 1994. Diabetes, 43: 1271-1278.
Stefair, C. et al. 1996. Diabetes, 45:980-983.
Yamo, T. et al. 1987. Biochem. Biophys. Res. Comm. 147(3):1061-1069.
Buckley, MF et al. 1990 JBC 265(29):17506-17511.
Bauki, K. et al. 1994. JBC 269:2847-2851.
Itoh, et al. 1994. Acta Histochew. lytochem. (Abstract 123) 27(4):406.
Sevier et al., "Monoclonal Antibodies in Clinical Immunology" Clinical Chemistry 27(11):1797-1806 (1981).
Costantino et al., "Insulin-Resistant MDA-MB231 Human Breast Cancer Cells Contain a Tyrosine Kinase Inhibiting Activity" Molecular Endocrinology 7(12):1667-1676 (1993).
Elliott et al., "Treatment of Rheumatoid Arthritis with Chimeric Monoclonal Antibodies to Tumor Necrosis Factor .alpha." Arthritis and Rheumatism 36(12):1681-1690 (1993).
Funakoshi et al., "Molecular Cloning of cDNAs for Human Fibroblast Nucleotide Pyrophosphatase" Arch. of Biochem. and Biophys. 295(1):180-187 (1992).
Goding, "Antibody Production by Hybridomas" Journal of Immunological Methods 39:285-308 (1980).
Goldfine, Ira D., "The Insulin Receptor: Molecular Biology and Transmembrane Signaling" Endocr Rev. 8(3):235-255 (1987).
Goodman, "Immunogenicity & Antigenic Specificity" Basic and Clinical Immunology pp. 32-40 (1976).
Grupe et al., "Inhibition of Insulin Receptor Phosphorylation by PC-1 is Not Mediated by the Hydrolysis of Adenosine Triphosphate or the Generation of Adenosine" Journal of Biological Chemistry 370(38):22085-22088 (1995).
Grupe et al., "Transgenic Knockouts Reveal a Critical Requirement for Pancreatic .beta. Cell Glucokinase in Maintaining Glucose Homeostasis" Cell 83:69-78 (1995).
Harris et al., "Therapeutic Antibodies--The oming of Age" TIBTECH 11:42-44 (Feb. 1993).
Huang et al., "Expression of the Murine Plasma Cell Nucleotide Pyrophosphohydrolase PC-1 is Shared by Human Liver, Bone, and Cartilage Cells" J. Clin. Invest. 94:560-567 (1994).
Maddux et al., "Inhibitors of Insulin Receptor Tyrosine Kinase in Fibroblast from Diverse Patients with Impaired Insulin Action: Evidence for a Novel Mechanism of Postreceptoe Insulin Resistance" J. Clin. Endocrin. Metabol. 77(1):73-79 (1993).
Maddux et al., "Membrane Glycopprotein PC-1 and Insulin Resistance in Non-Insulin-Dependent Diabetes Mellitus" Nature 373:448-451 (1995).
Moller, D.E. & Flier, J.S. "Mechanisms of Disease: Insulin Resistance-Mechanism, Syndromes and Implications" New England J. of Medicine 325(13):938-948 (1991).
Oda et al., "The Plasma Cell Membrane Glycoprotein, PC-1, Is a Threonine-Specific Protein Kinase Stimulated by Acidic Fibroblast Growth Factor"Journal of Biological Chemistry 266(25):16791-16795 (1991).
Rebbe et al., "Expression of Nucleotide Pyrophosphatase and Alkaline Phosphodiesterase I Activities of PC-1, the Murine Plasma Cell Antigen" Molecular Immunology 30(1):87-93 (1993).
Sbraccia et al., "Production of Inhibitor of Insulin-Receptor Tyrosine Kinase in Fibroblasts from Patient with Insulin Resistance and NIDDM" Diabetes 40:295-299 (1991).
Seino S. et al., "Prespectives in Diabetes: Human Insulin-Receptor Gene" Diabetes 39:129-133 (1990).
Stearne et al., "The Murine Plasma Cell Antigen PC-1: Purification and Partial Amino Acid Sequence" J. Immunol. 134(1):443-448 (1985).
Waldmann, T., "Monoclonal Antibodies in Diagnosis and Therapy" Science 252:1657-1622 (Jun. 1991).
Woody et al., "Effective Clinical Therapy of Cardiovascular and Autoimmune Diseases with Chimerized Monoclonal Antibodies" IBS's Second Annual Int'l Conference on Commercializing Human Monoconal Antibodies (abstract only)San Diego, CA:2:35 (1994).
Goldfine Ira D.
Grupe Andrew
Maddux Betty A.
Spencer Steven
Stewart Timothy A.
Davis Minh-Tam
Genentech Inc.
Hutzell Paula K.
Sherwood Pamela
The Regents of the University of California
LandOfFree
Antagonists to insulin receptor tyrosine kinase inhibitor does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antagonists to insulin receptor tyrosine kinase inhibitor, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antagonists to insulin receptor tyrosine kinase inhibitor will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-314219