Claims for Patent: 7,393,994

Summary for Patent: 7,393,994

Title:	Transgenic mouse model for neurodegenerative diseases
Abstract:	Alzheimer\'s disease, Parkinson\'s disease and Lewy body disease are the most commonly found neurodegenerative disorders in the elderly. The invention is a transgenic mouse that contains two transgenes, human .alpha.-synuclein and human amyloid precursor protein, which are responsible for the formation of the neuritic plaques, Lewy bodies and neurodegeneration seen in the above mentioned diseases. The transgenic mouse is an accurate model for disease by both functional and pathological assays.
Inventor(s):	Masliah; Eliezer (San Diego, CA), Rockenstein; Edward (Chula Vista, CA), Mallory; Margaret E. (Encinitas, CA)
Assignee:	Regents of the University of California (Oakland, CA)
Application Number:	09/933,640
Patent Claims:	1. A transgenic mouse comprising: a first transgenic nucleotide sequence, integrated into the genome of said mouse, comprising a sequence encoding the wild-type human amyloid precursor protein (hAPP) 751 amino acid isoform (hAPP751) operably linked to a first promoter; and a second transgenic nucleotide sequence, integrated into the genome of said mouse, comprising a sequence encoding the wild-type human (h) .alpha.-synuclein operably linked to a second promoter; wherein the first and second transgenic nucleotide sequences are expressed, the first and the second promoter are neuron-active promoters, and as a result of expression of the hAPP751 and (h) .alpha.-synuclein, said transgenic mouse develops amyloidosis, neurofibrillary tangles and intraneuronal accumulation of (h) .alpha.-synuclein. 2. The transgenic mouse of claim 1, wherein said first promoter is a platelet-derived growth factor .beta. (PDGF-.beta.) promoter. 3. The transgenic mouse of claim 2, wherein a simian virus (SV)40 derived intron operably links said PDGF-.beta. promoter to said first transgenic nucleotide sequence. 4. The transgenic mouse of claim 1, wherein said first promoter is a Thy1 promoter. 5. The transgenic mouse of claim 1, wherein said first promoter is a prion (PrP) promoter. 6. The transgenic mouse of claim 1, wherein said second promoter is a Thy1 promoter. 7. The transgenic mouse of claim 1, wherein said second promoter is a PrP promoter. 8. The transgenic mouse of claim 1, wherein said second promoter is a PDGF-.beta. promoter. 9. The transgenic mouse of claim 8, wherein a SV40 derived intron operably links said PDGF-.beta. promoter to said second transgenic nucleotide sequence. 10. The transgenic mouse of claim 1, wherein the nucleotide coding sequence of hAPP comprises an intron between exons 6 through 9 of the hAPP-encoding sequence. 11. A transgenic mouse comprising: a first transgenic nucleotide sequence, integrated into the genome of said mouse, comprising a sequence encoding the wild-type human amyloid precursor protein (hAPP) 751 amino acid isoform (hAPP751) operably linked to a platelet derived growth factor .beta. (PDGF-.beta.) promoter operably linked to a simian virus (SV) 40 intron; and a second transgenic nucleotide sequence, integrated into the genome of said mouse, comprising a sequence encoding the wildtype human (h) .alpha.-synuclein operably linked to a PDGF-.beta. promoter operably linked to an SV40 intron; wherein the first and second transgenic nucleotide sequences are expressed, and as a result of expression of the hAPP751 and wildtype human (h) .alpha.-synuclein, said transgenic mouse develops amyloidosis, neurofibrillary tangles and intraneuronal accumulation of (h) .alpha.-synuclein. 12. The transgenic mouse of claim 11, wherein said transgenic mouse develops formation of intraneuronal inclusions characteristic of Lewy body disease. 13. The transgenic mouse of claim 11, wherein said transgenic mouse develops formation of fibrillary Lewy body-like inclusions. 14. The transgenic mouse of claim 11, wherein said transgenic mouse exhibits neuronal loss in the brain. 15. The transgenic mouse of claim 11, wherein said transgenic mouse develops a motor deficit. 16. The transgenic mouse of claim 11, wherein age of onset of the amyloidosis, neurofibrillary tangles and intraneuronal accumulation of (h) .alpha.-synuclein occurs at a significantly younger age, with p<0.05, than in a singly transgenic littermate, having only one of either the first or the second transgene. 17. A method for screening therapeutic agents for the prevention or treatment of neurological disease comprising (a) administering an agent to the transgenic mouse of claim 1; and, (b) determining the effect of the agent on amyloidosis, neurofibrillary tangles or intraneuronal accumulation of (h) .alpha.-synuclein in the transgenic mouse; and (c) comparing the effect to an untreated control mouse, wherein an improvement in any of these phenotypes indicates the agent is a therapeutic agent. 18. A method for screening for an agent for the prevention or treatment of intraneuronal accumulation of .alpha.-synuclein, amyloidosis or neurofibrillary tangles, comprising (a) providing a potential therapeutic agent; (b) administering the potential therapeutic agent of (a) to the transgenic mouse of claim 1, and (c) determining whether because of the administering of the potential therapeutic agent in (b) intraneuronal accumulation of .alpha.-synuclein, amyloidosis or neurofibrillary tangles in the transgenic mice is prevented or slowed by comparison to a control mouse not treated with the agent. 19. A method for screening therapeutic agents for the prevention or treatment of neurological disease comprising (a) administering an agent to the transgenic mouse of claim 11; and, (b) determining the effect of the agent on amyloidosis, neurofibrillary tangles or intraneuronal accumulation of (h) .alpha.-synuclein in the transgenic mouse; and (c) comparing the effect to an untreated control mouse, wherein an improvement in any of these phenotypes indicates the agent is a therapeutic agent. 20. A method for screening for an agent for the prevention or treatment of intraneuronal accumulation of .alpha.-synuclein, amyloidosis or neurofibrillary tangles, comprising (a) providing a potential therapeutic agent; (b) administering the potential therapeutic agent of (a) to the transgenic mouse of claim 11, and (c) determining whether because of the administering of the potential therapeutic agent in (b) intraneuronal accumulation of .alpha.-synuclein, amyloidosis or neurofibrillary tangles in the transgenic mice is prevented or slowed by comparison to a control mouse not treated with the agent.

Details for Patent 7,393,994

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		2020-02-18
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2020-02-18
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2020-02-18