Claims for Patent: 9,217,020

Summary for Patent: 9,217,020

Title:	Constructs for enhancement of gene expression in muscle
Abstract:	Efficient and muscle-specific gene expression can be obtained with constructs containing two or more copies of USE and/or .DELTA.USE fused to the minimal promoter of the TnISlow gene. USE is a small (about 160-bp) upstream enhancer of the TnISlow gene that confers slow-twitch muscle fiber specificity. .DELTA.USE is generated from a 100-bp deletion at the 5\' end of USE. .DELTA.USE confers expression in slow- and fast-twitch muscle fibers. The strength and relatively small size (less than 600-bp) of these constructs make them useful for gene therapy applications.
Inventor(s):	Blain; Marilyne (Lorraine, CA), Massie; Bernard (Laval, CA), Gilbert; Renald (Montreal, CA)
Assignee:	National Research Council of Canada (Ottawa, CA)
Application Number:	12/450,939
Patent Claims:	1. A construct comprising two or more enhancers from a slow troponin I gene fused in line and operably linked to a muscle cell specific promoter, and a nucleotide sequence of interest, wherein each enhancer comprises the nucleotide sequence as set forth in nucleotides 152 to 218 of SEQ ID NO:17 or as set forth in nucleotides 57-218 of SEQ ID NO: 17, and wherein the construct ensures tissue-specific expression of the nucleotide of interest in muscle cells. 2. The construct of claim 1, wherein the two or more enhancers are upstream of the promoter. 3. The construct of claim 1, wherein the enhancers are oriented in a natural orientation. 4. The construct of claim 1, wherein there are 3 or more enhancers. 5. The construct of claim 1, wherein there are from 2 to 5 enhancers. 6. The construct of claim 1, wherein the promoter comprises minimal promoter from the slow troponin I gene. 7. The construct of claim 1, further comprising an intron downstream of the promoter. 8. The construct of claim 1, wherein the enhancers are three enhancers each comprising the nucleotide sequence as set forth in nucleotides 57 to 218 of SEQ ID NO: 17. 9. The construct of claim 1, wherein the enhancers are three enhancers each comprising the nucleotide sequence as set forth in nucleotides 152 to 218 of SEQ ID NO: 17. 10. The construct of claim 1, wherein the enhancers are four enhancers each comprising the nucleotide sequence as set forth in nucleotides 57 to 218 of SEQ ID NO: 17. 11. The construct of claim 1, wherein the enhancers are four enhancers each comprising the nucleotide sequence as set forth in nucleotides 152 to 218 of SEQ ID NO: 17. 12. The construct of claim 1, wherein the enhancers are five enhancers each comprising the nucleotide sequence as set forth in nucleotides 57 to 218 of SEQ ID NO: 17. 13. The construct of claim 1, wherein the enhancers are five enhancers each comprising the nucleotide sequence as set forth in nucleotides 152 to 218 of SEQ ID NO: 17. 14. A method of specifically expressing a nucleotide sequence of interest in a muscle cell in vitro, comprising transfecting into the muscle cell a construct of claim 1; culturing said cell under suitable condition to express the nucleotide sequence of interest. 15. The method of claim 14, wherein the muscle cell is a skeletal muscle cell. 16. The method of claim 14, wherein the nucleotide sequence of interest codes for a protein. 17. The method of claim 16, wherein the protein mitigates pathology associated with hemophilia, Pompe disease, Fabry's disease, anaemia, emphysema or familial hypercholesterolemia. 18. The method of claim 16, wherein the protein mitigates pathology associated with a neuromuscular disorder. 19. A method of specifically expressing a nucleotide sequence of interest in a muscle cell in a mouse model, comprising administering the construct of claim 1 into a muscle cell of a mouse; measuring the expression of the nucleotide sequence of interest in said muscle cell.

Details for Patent 9,217,020

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		2027-04-17
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2027-04-17
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2027-04-17