Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2003-04-15
2004-08-17
Shah, Mukund (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S186000, C514S228800, C514S230500, C514S299000, C514S300000, C544S063000, C544S088000, C544S090000, C544S091000, C544S095000
Reexamination Certificate
active
06777404
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to compositions and methods of achieving a therapeutic effect, including the treatment or prevention of Syndrome X, in an animal, preferably a mammal, including a human subject, and a companion animal, using a corticotropin releasing factor (CRF) antagonist alone or together with a glucocorticoid receptor (GR) antagonist.
Syndrome X, also known as metabolic syndrome, plurimetabolic syndrome or insulin resistance syndrome, encompasses a complex of disturbances of carbohydrate and fat metabolism characterized by obesity, dyslipoproteinemia (low HDL and high LDL, VLDL and triglycerides), hyperinsulinemia, insulin resistance, glucose intolerance and hypertension (Atherosclerosis X, F. P. Woodford, J. Davignon, A. Sniderman (Eds.), Elsevier Science BV, Amsterdam (1995): 520-524.). Syndrome X is associated with an elevated risk for cardiovascular disease.
There are striking similarities between Cushing's disease and Syndrome X, both being characterized by visceral obesity, hypertension, insulin resistance, glucose intolerance and hyperlipidemia (Endocrine Research, 22(4), 701-708 (1996)). Cushing's disease is caused by hypersecretion of cortisol, the most important human glucocorticoid, by the adrenal cortex. Cortisol is known to cause visceral fat accumulation and insulin resistance (Pennington Cent. Nutr. Ser. (1996), 5 (Molecular and Genetic Aspects of Obesity), 340-352; Nutrition, 13:795-803 (1997); and Prog. Obes. Res., 7:505-510 (1996)). Cortisol promotes hepatic gluconeogenesis and glycogen deposition and increases blood glucose levels. Cortisol also increases the sensitivity of adipose tissue to lipolytic hormones, elevating fatty acid levels and thereby stimulating triglyceride synthesis and VLDL (very low density lipoprotein) secretion. The VLDL is converted to VLDL remnants or LDL (low density lipoprotein) which are largely taken up by the liver via the LDL receptors, resulting in down-regulation of the LDL receptor and consequently hypertriglyceridemia and hyper-apobetalipoproteinemia. Abnormalities of glucocorticoid secretion and sensitivity in men have been shown to be associated with hypertension and insulin resistance (Endocrine Research, 22(4), 701-708 (1996); and Hypertension, 1998;31:891-895). Hypersecretion of cortisol is the result of excessive secretion of ACTH (adrenocorticotropic hormone). Administration of ACTH has been shown to increase blood pressure in animals (J. Hypertension, 16:593-600 (1998)). The secretion of ACTH is controlled by the releasing hormone, corticotropin releasing factor (CRF or CRH). Thus, a CRF (CRH) antagonist, by decreasing ACTH secretion, will amelioralte the hypersecretion of glucocorticoids and thereby be of therapeutic benefit in the treatment of Syndrome X.
In addition, the levels of glucocorticoids present in the body are primarily, but not solely, determined by the concentration of CRF, so the use of a combination of a CRF antagonist and a GR antagonist will be of greater therapeutic benefit in the treatment of Syndrome X than the use of a CRF antagonist alone.
International Patent Application Publication No. WO 97/25042, published Jul. 17, 1997, discloses methods for the treatment and/or prophylaxis of Syndrome X by the administration of an agonist of PPAR&agr; and PPAR&ggr;, or a pharmaceutically acceptable derivative thereof, to a human or non-human animal in need of such treatment.
International Patent Application Publication No. WO 99/17761, published Apr. 15, 1999, discloses the use of nordihydroguaiaretic acid to treat or ameliorate the characteristic manifestations of Syndrome X in a non-diabetic animal with normal serum glucose levels.
CRF antagonists are disclosed in U.S. Pat. Nos. 4,605,642 and 5,063,245. They are also disclosed in International patent publications WO 95/33750; WO 95/34563; WO 94/13661; WO 94/13644; WO 94/13643; WO 94/13676; WO 94/13677; WO 95/33727; WO 98/05661; WO 98/08847; WO 98/08846; and European patent publications EP 778277 and EP 773023. CRF antagonists are also disclosed in the following patent publications: EP 576350; EP 659747; EP 812831; WO 95/10506; WO 96/35689; WO 96/39400; WO 97/00868; WO 97/14684; WO 97/29109; WO 97/29110; WO 97/35539; WO 97/35580; WO 97/35846; WO 97/44038; WO 97/45421; WO98/03510; WO 98/08821; WO 98/11075; WO 98/15543; WO 98/21200; WO 98/27066; WO 98/29397; WO 98/29413; WO 98/42699; WO 98/35967; WO 98/42706; WO 98/45295; WO 98/47874; WO 98/47903; WO 98/51312; WO 99/01454; WO 99/01439; WO 99/10350; WO 99/12908; WO 99/00373; WO 99/38868; WO 99/51597; WO 99/51599; WO 99/40089; WO 99/51598; and WO 99/51600. They are also disclosed in U.S. Pat. Nos. 5,109,111; 5,132,111; 5,245,009; 5,464,847; 5,493,006; 5,510,458; 5,644,057; 5,663,292; 5,668,145; 5,705,646; 5,712,303; and 5,723,608. An overview of the patent literature on CRF antagonists is provided in T. E. Christos and A. Arvanitis, Exp. Opin. Ther. Patents (1998) 8(2):143-152.
The importance of CRF antagonists is set out in the literature, e.g., P. Black, Scientific American: “Science & Medicine,” 1995, 2:16-25; T. Lovenberg, et al., Current Pharmaceutical Design, 1995, 1: 305-316; D. T. Chalmers et al., Trends in Pharmacological Sciences, April 1996, pages 166-172; and U.S. Pat. No. 5,063,245. An outline of the activities possessed by CRF antagonists is found in M. J. Owens et al., 1991, Pharm. Rev., 43:425-473. CRF antagonists are described in the art as being effective in the treatment of stress-related illnesses, mood disorders such as depression, major depressive disorder, single episode depression, recurrent depression, child abuse induced depression, postpartum depression, dysthemia, bipolar disorders, and cyclothymia; chronic fatigue syndrome; eating disorders such as anorexia and bulimia nervosa; generalized anxiety disorder; panic disorder; phobias; obsessive-compulsive disorder; post-traumatic stress disorder; pain perception such as fibromyalgia; headache; gastrointestinal diseases; hemorrhagic stress; ulcers; stress-induced psychotic episodes; fever; diarrhea; post-operative ileus; colonic hypersensitivity; irritable bowel syndrome; Crohn's disease; spastic colon; inflammatory disorders such as rheumatoid arthritis and osteoarthritis; pain; asthma; psoriasis; allergies; osteoporosis; premature birth; hypertension, congestive heart failure; sleep disorders; neurodegenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, multiinfarct dementia, Parkinson's disease, and Huntington's disease; head trauma; ischemic neuronal damage; excitotoxic neuronal damage; epilepsy; stroke; spinal cord trauma; psychosocial dwarfism; euthyroid sick syndrome; syndrome of inappropriate antidiuretic hormone; obesity; chemical dependencies and addictions; drug and alcohol withdrawal symptoms; infertility; cancer; muscular spasms; urinary incontinence; hypoglycemia and immune dysfunctions including stress induced immune dysfunctions, immune suppression and human immunodeficiency virus infections; and stress-induced infections in humans and animals.
GR antagonists are disclosed in the following references: International patent application PCT/IB00/00366, filed Mar. 27, 2000, and assigned to the assignee hereof, which published as International patent publication WO 00/66522; International patent publications WO 99/41256 and WO 99/41257; U.S. Pat. No. 5,696,127; European patent publication 188396; European patent publication 683172; International patent publication WO 98/26783; International patent publication WO 98/27986; International patent publication WO 98/31702; European patent publication 903146; and International patent publications WO 99/41256 and WO 99/41257.
GR modulators (e.g., agonists, partial agonists, antagonists and partial antagonists) can be used in the treatment of diseases associated with an excess or a deficiency of glucocorticoids in the body. As such, they may be used to treat the following: obesity, diabetes, cardiovascular disease, hypertension, Syndrome X, depression, anxiety, gla
Chen Yuhpyng Liang
Hamanaka Ernest S.
Dorigo Andrea E.
Ginsburg Paul H.
Patel Sudhaker B.
Pfizer Inc
Richardson Peter C.
LandOfFree
Use of corticotropin releasing factor antagonists and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of corticotropin releasing factor antagonists and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of corticotropin releasing factor antagonists and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3315419