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Last Updated: April 23, 2024

Claims for Patent: 7,795,495

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Summary for Patent: 7,795,495

Title:	Transgenic mice for screening for inhibitors of protein aggregation and methods for making and using them
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), Hashimoto; Makoto (La Jolla, CA)
Assignee:	The Regents of the University of California (Oakland, CA)
Application Number:	11/675,607
Patent Claims:	1. A transgenic mouse comprising a nucleotide sequence integrated into the genome of said mouse encoding a human (h) .alpha.-synuclein operably linked to a neuron-active promoter; wherein the transgenic nucleotide sequence is expressed in a neuron, and as a result of said expression, said transgenic mouse develops protein aggregations comprising the human (h) .alpha.-synuclein. 2. The transgenic mouse of claim 1, wherein said promoter comprises a platelet-derived growth factor .beta. (PDGF-.beta.) promoter. 3. The transgenic mouse of claim 1, wherein a SV40 derived intron operably links the neuron-active promoter with said transgenic nucleotide sequence. 4. A method of screening for agents that inhibit protein aggregations comprising a human (h) .alpha.-synuclein comprising: administering a candidate agent to the transgenic mouse of claim 1, and measuring the effect of said agent upon protein aggregations comprising the human (h) .alpha.-synuclein in the transgenic mouse, wherein the effect measured comprises inhibition by the test agent of formation of protein aggregations comprising the human (h) .alpha.-synuclein in the transgenic mouse. 5. The method of claim 4, wherein the effect measured further comprises measuring neuronal inclusions and motor deficits. 6. A method of screening for agents that inhibit intraneuronal inclusion formation and aggregate formation associated with neurodegenerative disease and aggregation of human (h) .alpha.-synuclein, comprising: contacting the transgenic mouse of claim 1 with a candidate agent; and evaluating the effect of said candidate on intraneuronal inclusion formation in the mouse.

Details for Patent 7,795,495

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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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