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Last Updated: April 16, 2024

Claims for Patent: 7,276,643

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Summary for Patent: 7,276,643

Title:	Transgenic animals, cell lines derived therefrom, and methods for screening for anti-amyloidogenic agents
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. .beta.-Synuclein, the non-amyloidogenic homologue of .alpha.-synuclein, is a negative modulator of .alpha.-synuclein and A.beta. aggregation, having neuroprotective properties against .alpha.-synuclein and A.beta. neurotoxicity and that .beta.-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that .beta.-synuclein blocks A.beta. aggregation either by direct inhibition of A.beta. amyloidogenesis or indirectly via either .alpha.-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 .alpha.-synuclein characterizes the mechanisms by which .beta.-synuclein blocks .alpha.-synuclein and A.beta. 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.
Inventor(s):	Masliah; Eliezer (San Diego, CA), Rockenstein; Edward (Chula Vista, CA), Mallory, legal representative; Hersey (Encinitas, CA), Mallory, deceased; Margaret (Encinitas, CA)
Assignee:	The Regents of the University of California (Oakland, CA)
Application Number:	10/204,337
Patent Claims:	1. A transgenic mouse whose genome comprises a first and second transgenic nucleotide sequence, wherein the first transgenic nucleotide sequence comprises a human .alpha.-synuclein coding sequence or a human non-A.beta. (NAC) region; and, the second transgenic nucleotide sequence comprises a human amyloid precursor protein (APP) coding sequence, each operably linked to a neuronal specific promoter and the human APP coding sequence comprises a Swedish or a Indiana mutation, wherein expression of said first and second transgenic nucleotide sequence results in amyloid deposits in the brain of said mouse. 2. An isolated neuronal cell from a transgenic mouse set forth in claim 1, wherein cells of the cell line overexpress a human .alpha.-synuclein coding sequence or a human non-A.beta.(NAC) region. 3. A method of screening for agents that inhibit amyloidogenesis or .alpha.-synuclein aggregation, comprising: (a) providing a candidate agent, wherein optionally the candidate agent is a candidate therapeutic agent; (b) providing a transgenic mouse as set forth in claim 1, or a cell line as set forth in claim 2; (c) administering the candidate agent to the cell line or transgenic mouse; and (d) evaluating the effect of said candidate agent on amyloidogenesis or amyloid deposition. 4. The method of claim 3, wherein the effect of the candidate agent on amyloidogenesis or amyloid deposition comprises inhibition of .alpha.-synuclein aggregation in neurons. 5. The transgenic mouse of claim 1, wherein an SV40-derived intron operably links the promoter with the first or second transgenic nucleotide sequence. 6. The transgenic mouse of claim 1, wherein the first or second transgenic nucleotide sequence comprises an intron. 7. The transgenic mouse of claim 1, wherein the intron comprises an SV40-derived intron.

Details for Patent 7,276,643

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Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986	⤷ Try a Trial	2020-02-18
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132		⤷ Try a Trial	2020-02-18
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132		⤷ Try a Trial	2020-02-18
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

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