Aβ 42 lowering agents

Details Aβ 42 lowering agents Aβ 42 lowering agents

2006-08-29

2006-08-29

Weber, Jon (Department: 1655)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving hydrolase

C514S002600

Reexamination Certificate

active

07097998

ABSTRACT:
The invention provides a method of preventing, delaying, or reversing the progression of Alzheimer's disease by administering an Aβ42lowering agent to a mammal under conditions in which levels of Aβ42are selectively reduced, levels of Aβ38are increased, and levels of Aβ40are unchanged. The invention provides methods and materials for developing and identifying Aβ42lowering agents. In addition, the invention provides methods for identifying agents that increase the risk of developing, or hasten progression of, Alzheimer's disease. The invention also provides compositions of Aβ42lowering agents and antioxidants, Aβ42lowering agents and non-selective secretase inhibitors, as well as Aβ42lowering agents and acetylcholinesterase inhibitors. The invention also provides kits containing Aβ42lowering agents, antioxidants, non-selective secretase inhibitors, and/or acetylcholinesterase inhibitors as well as instructions related to dose regimens for Aβ42lowering agents, antioxidants, non-selective secretase inhibitors, and acetylcholinesterase inhibitors.

REFERENCES:
patent: 5192753 (1993-03-01), McGeer et al.
patent: 5434170 (1995-07-01), Andrulis
patent: 5455169 (1995-10-01), Mullan
patent: 5603959 (1997-02-01), Horrobin et al.
patent: 5643960 (1997-07-01), Breitner et al.
patent: 5695774 (1997-12-01), Clark
patent: 6025395 (2000-02-01), Breitner et al.
patent: 6160018 (2000-12-01), Wechter et al.
patent: 6160618 (2000-12-01), Garner
patent: 6184248 (2001-02-01), Lee et al.
patent: 6255347 (2001-07-01), Xiaotao et al.
patent: 6469055 (2002-10-01), Lee et al.
patent: WO 01/78721 (2001-10-01), None
Breitner et al. 1994. Neurology, vol. 44, pp. 227-232.
Netland et al. 1998. Neurobiology of Aging, vol. 19, pp. 201-204.
Rogers et al 1993. Neurology, vol. 43, pp. 1609-1611.
Akoho et al., “A Study on Binding Modes of Nonsteroidal Anti-inflammatory Drugs to COX1 and COX2 as Obtained by Dock4.0,”J. Chem. Software, 1999, 5(3):1-13.
Amin et al., “The pleiotropic functions of aspirin: mechanisms of action,”Cell. Mol. Life Sci., 1999, 56:305-312.
Andreasen et al., “Cerebrospinal Fluid β-Amyloid(1-42)in Alzheimer Disease,”Arch. Neurol., 1999, 56:673-680.
Bayly et al., “Structure-Based Design of Cox-2 Selectivity Into Flurbiprofen,”Bioor. Med. Chem. Lett., 1999, 9:307-312.
Bickford et al., “Long-Term Treatment of Male F344 Rats with Deprenyl: Assessment of Effects on Longevity, Behavior, and Brain Function,”Neurobiology of Aging, 1997, 18(3):309-318.
Blacker et al., “The Genetics of Alzheimer Disease,”Arch. Neurol., 1998, 55:194-296.
Braak et al., “Neuropathological stageing of Alzheimer-related changes,”Acta. Neuropathol., 1991, 82:239-259.
Breitner et al., “Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs,”Neurobiol. Aging, 1995, 16(4):523-30.
Cammisuli et al., “Effects of extended electrical kindling on exploratory behavior and spatial learning,”Behav. Brain Res., 1997, 89:179-190.
Canaparo et al., “Determination Ibuprofen in human plasma by high-performance liquid chromatography: validation and application in pharmacokinetic study,”Biomed. Chromatogr., 2000, 14:219-226.
Chen et al., “A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimder's disease,”Nature, 2000, 408:975-979.
Citron et al., “Evidence that the 42- and 40-amino acid forms of amyloid β protein are generated from the β-amyloid precursor protein by different protease activities,”Proc. Natl. Acad. Sci. USA, 1996, 93:13170-13175.
Combs et al., “Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARγ Agonists,”J. Neurosci., 2000, 20(2):558-567.
Corton et al., “Central Role of Peroxisome Proliferator-Activated Receptors in the Actions of Peroxisome Proliferators,”Annu. Rev. Pharmacol., 2000, 40:491-518.
Cotran et al.,Pathologic Basis of Disease, Sixth Edition, 1999, W.B. Saunders Company, Philadelphia, p. 1332, Table. 30-2.
Cronstein et al., “Targets for Antiinflammatory Drugs,”Annu. Rev. Pharmacol. Toxicol., 1995, 35:449-462.
Cryer et al., “Cyclooxygenase-1 and Cyclooxygenase-2 Selectivity of Widely Used Nonsteroidal Anti-Inflammatory Drugs,”Am. J. Med., 1998, 104:413-421.
DeWitt, “Cox-2-Selective Inhibitors: The New Super Aspirins,”Mol. Pharmacol., 1999, 55(4):625-631.
Dubois et al., “Cyclooxygenase in biology and disease,”FASEB J., 1998, 12:1063-1073.
Eriksen et al., “NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo,”J. Clin. Invest., 2003, 112(3):440-449.
Folstein et al., “Mini-Mental State”—A Practical Method for Grading the Cognitive State of Patients for the Clinician,J. Psychiat. Res., 1975, 12:189-198.
Frautschy et al., “Animal Model—Microglial Response to Amyloid Plaques in APPsw Transgenic Mice,”Am. J. Pathol., 1998, 152:307-317.
Galasko et al., “An Inventory to Assess Activities of Daily Living for Clinical Trials in Alzheimer's Disease,”Alzheimer Disease and Associated Disorders, 1997, 11(Suppl. 2):S33-S39.
Galasko et al., “High Cerebrospinal Fluid Tau and Low Amyloid β42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype,”Arch. Neurol., 1998, 55:937-945.
Halliday et al., “Alzheimer's Disease and Inflammation: A Review of Cellular and Therapeutic Mechanisms,”Clin. Exp. Pharmacol. Physiol., 2000, 27:1-8.
Haugabook et al., “Reduction of Aβ accumulation in the Tg2576 animal model of Alzheimer's disease after oral administration of the phosphatidylinositol kinase inhibitor wortmannin,”FASEB J., 2000, 12 pgs.
He et al., “PPARδ Is an APC-Regulated Target of Nonsteroidal Anti-Inflammatory Drugs,”Cell, 1999, 99:335-345.
Higaki et al., “Inhibition of β-Amyloid Formation Identifies Proteolytic Precursors and Subcellular Site of Catabolism,”Neuron, 1995, 14:651-659.
Hsiao et al., “Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice,”Science, 1996, 274:99-102.
Kalgutkar et al., “Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors: Facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors,”Proc. Natl. Acad. Sci. USA, 2000, 97(2):925-930.
Kalgutkar et al., “Ester and Amide Derivatives of the Nonsteroidal Antiinflammatory Drug, Indomethacin, as Selective Cyclooxygenase-2 Inhibitors,”J. Med. Chem., 2000, 43:2860-2870.
Kato et al., “Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes,”Journal of Pharmacy and Pharmacology, 2001, 53:1679-1685.
Kawarabayashi et al., “Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzhelmer's Disease,”J. Neurosci., 2001, 21(2):372-381.
Khachaturinan, “Diagnosis of Alzheimer's Disease,”Arch. Neurol., 1985, 42:1097-1105.
Kitamura et al., “Increased Expression Cyclooxygenases and Peroxisom Proliferator-Activated Receptor-γ in Alzheimer's Disease Brains,”Biochem. Biophys. Res. Comm., 1999, 254:582-586.
Klafki et al., “The Carboxyl Termini of β-Amyloid Peptides 1-40 and 1-42 Are Generated by Distinct γSecretase Activities,”J. Biol. Chem., 1996, 271(45):28655-28659.
Koo et al., “Evidence That Production and Release of Amyloid β-Protein Involves the Endocytic Pathway,”J. Biol. Chem., 1994, 269(26):17386-17389.
Koo et al., “Trafficking of cell-surface amyloid β-p

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