Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-04-10
2002-08-20
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06436983
ABSTRACT:
BACKGROUND OF THE INVENTION
Alzheimer's disease is a degenerative disorder of the human brain. Clinically, it appears as a progressive dementia. Its histopathology is characterized by degeneration of neurons, gliosis, and the abnormal deposition of proteins in the brain. Pathological hallmarks include neurofibrillary tangles (paired helical filaments) and amyloid deposits within the parenchyma and cerebral vasculature.
Recent studies indicate that a major component of the pathology of Alzheimer's disease is chronic inflammation. See, J. Schnabel,
Science,
260:1719-1720 (1993). Administration of nonsteroidal anti-inflammatory drugs appears to slow the advance of Alzheimer's disease. Understanding this inflammatory component of Alzheimer's disease may lead to advances in methods of treating patients suffering from this disease.
The structure and physical properties of human non-pancreatic secretory phospholipase A
2
(hereinafter called, “sPLA
2
”) has been described in two articles, namely, “Cloning and Recombinant Expression of Phospholipase A
2
Present in Rheumatoid Arthritic Synovial Fluid” by Seilhamer, Jeffrey J.; Pruzanski, Waldemar; Vadas Peter; Plant, Shelley; Miller, Judy A.; Kloss, Jean; and Johnson, Lorin K.;
The Journal of Biological Chemistry,
Vol. 264, No. 10, Issue of April 5, pp. 5335-5338, 1989; and “Structure and Properties of a Human Non-pancreatic Phospholipase A
2
” by Kramer, Ruth M.; Hession, Catherine; Johansen, Berit; Hayes, Gretchen; McGray, Paula; Chow, E. Pingchang; Tizard, Richard; and Pepinsky, R. Blake;
The Journal of Biological Chemistry,
Vol. 264, No. 10, Issue of April 5, pp. 5768-5775, 1989; the disclosures of which are incorporated herein by reference.
It is believed that sPLA
2
is a rate limiting enzyme in the arachidonic acid cascade which hydrolyzes membrane phospholipids.
The scientific literature suggests NSAIDs may be beneficial in the treatment of Alzheimer's Disease. Moreover, COX-2 inhibitors are currently being tested for treatment of Alzheimer's.
PLA
2
inhibitors have been proposed as treatment for Alzheimer's disease (see, U.S. Pat. No. 5,478,857), but tykpically these have been cytosolic phospholipase A
2
inhibitors.
Because of the debilitating effects of Alzheimer's disease there continues to exist a need for effective treatments. This invention provides methods for the treatment of Alzheimer's disease in mammals.
SUMMARY OF THE INVENTION
This invention is a method of treating a mammal, including a human, susceptible to having Alzheimer's disease, to prevent or delay the onset of Alzheimer's disease; said method comprising administering to said mammal a prophylactically effective amount of 1H-indole-3-glyoxylamide sPLA
2
inhibitor or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof.
This invention is also a method of treating a mammal, including a human, already afflicted with Alzheimer's disease to prevent or diminish the rate of further deterioration; said method comprising administering to said mammal a therapeutically effective amount of 1H-indole-3-glyoxylamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof.
REFERENCES:
patent: 5654326 (1997-08-01), Bach et al.
Benjamin Roger S.
Criares Theodore J.
Eli Lilly and Company
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