Multicellular living organisms and unmodified parts thereof and – Nonhuman animal – Transgenic nonhuman animal
Reexamination Certificate
2007-10-02
2007-10-02
Kaushal, Sumesh (Department: 1632)
Multicellular living organisms and unmodified parts thereof and
Nonhuman animal
Transgenic nonhuman animal
C800S003000, C435S325000
Reexamination Certificate
active
10204337
ABSTRACT:
The methodologies of the present invention demonstrate that a critical balance between pro- and anti-amyloidogenic molecules exists that regulates amyloid formation and cell death in Alzheimer's disease and Parkinson's disease. β-Synuclein, the non-amyloidogenic homologue of α-synuclein, is a negative modulator of α-synuclein and Aβ aggregation, having neuroprotective properties against α-synuclein and Aβ neurotoxicity and that β-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that β-synuclein blocks Aβ aggregation either by direct inhibition of Aβ amyloidogenesis or indirectly via either α-synuclein or its 35 a.a. NAC region, inferring neuroprotective characteristics within the effected cells. The generation of a transgenic mouse line and a cell system overexpressing α-synuclein characterizes the mechanisms by which β-synuclein blocks α-synuclein and Aβ aggregation and that this mechanism offers protection to the cell against amyloid formation as seen in the pathologies of Alzheimer's disease and Parkinson's disease.
REFERENCES:
Kahle PJ, Physiology and pathophysiology of alpha-synuclein cell culture and transgenic animal models based on a parkinson's disease-associated protein, 2000, Annals of the New York Academy of Sciences, vol. 920, pp. 33-41.
Schneider MR, Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins, FASEB, 2000, vol. 14, pp. 629-640.
Gotz J, In vivo analysis of wild-type and FTPD-17 tau transgenic mice, Annal of NY Acad of Sci, 2000, vol. 920, pp. 126-133.
Ristevski S, Making better transgenic models, 2005, Molecular Biotechnology, vol. 29, pp. 153-163.□□
Houdebine LM, The methods to generate transgenic animals and to control transgene expression, 2002, J. of Biotechnology, vol. 98, pp. 145-160.
Smith KR, Gene transfer in higher animals: theoretical considerations and key concepts, J. of Biotechnology, vol. 99, pp. 1-22.
Cole, G.M. et al. Amyloid-Associated α-Synuclein (NACP) Pathology in Aged Amyloid Precursor Transgenic Mice. Society for Neuroscience Abstracts, 1999, vol. 25, No. 1-2, pp. 298, lines 7-19.
Davis, Stephen W. et al. Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation. Cell, 1997, vol. 90, 537-548.
Games, Dora et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature, 1995, vol. 373, 523-527.
Goldberg, M.S. et al. Studies of Human α-Synuclein in Transgenic Mice. Society for Neuroscience Abstracts, 1999, vol. 25, No. 1-2, lines 6-20.
Hashimoto, Makoto et al. Human recombinant NACP/α-synuclein is aggregated and fibrillated in vitro: Revelance for Lewy body disease. Brain Research, 1998, vol. 799, No. 2, 301-306.
Jensen, Paul H. et al. Binding of Aβ to α- and β-synucleins: identification of segments in α-synuclein/NAC precursor that bind Aβ and NAC. Biochem J. 1997, vol. 323, 539-546.
Mucke, L. et al. Potential Roles of α1-Antichymotrypsin and α-Synuclein in Alzheimer's Pathogenesis Assessed in Bigenic Mice Expressing Human Amyloid Precursor Proteins. Society for Neuroscience Abstracts, 1999, vol. 25, No. 1-2, p. 302, lines 4-21.
Mucke, Lennart et al. Protection Against HIV-1 gp120-induced Brain Damage by Neuronal Expression of Human Amyloid Precursor Protein. J.Exp.Med., 1995, vol. 181, 1551-1556.
Takeda, Ayako et al. Abnormal Accumulation of NACP/α-Synuclein in Neurodegenerative Disorders, Am. J. of Pathology, 1998, vol. 152, No. 2, 367-372.
Mallory, legal representative Hersey
Masliah Eliezer
Rockenstein Edward
Kaushal Sumesh
Montanari David A.
Morrison & Foerster / LLP
The Regents of the University of California
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