Claims for Patent: 9,681,646

Summary for Patent: 9,681,646

Title:	Dosage compensating transgenes and cells
Abstract:	Methods and compositions for reducing expression of genes on Chromosome 21 (\"Chr 21\") by targeting an XIST transgene to the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene or a Regulator of calcineurin 1 (RCAN1) gene, and cells and transgenic animals comprising an XIST transgene inserted into a DYRK1A or RCAN1 allele, e.g., cells and animals trisomic for human Chr 21 and mouse Chr 16.
Inventor(s):	Lawrence; Jeanne B. (Mapleville, RI), Jiang; Jun (Shrewsbury, MA), Hall; Lisa L. (Framingham, MA)
Assignee:	University of Massachusetts (Boston, MA)
Application Number:	14/215,997
Patent Claims:	1. A silencing vector comprising: a silencing element comprising a silencing sequence flanked by first and second targeting sequences, wherein the first and second targeting sequences target a sequence within intron 1 of the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene comprising GCCACCCCTTTGCCAGTTTACACGGGTGATGAGCAGGCTGTT (SEQ ID NO: 11), wherein the first targeting sequence consists of SEQ ID NO:12 or 14, and/or the second targeting sequence consists of SEQ ID NO:13 or 15; and a promoter operably linked to the silencing element. 2. The silencing vector of claim 1, wherein the vector is a plasmid or a viral vector. 3. The silencing vector of claim 2, wherein the viral vector is vaccinia virus, adeno-associated virus (MV), or herpes virus. 4. The silencing vector of claim 1, wherein the silencing element comprises a human X inactive specific transcript (XIST) cDNA or functional fragment thereof. 5. The silencing vector of claim 4, further comprising a selectable marker sequence. 6. The silencing vector of claim 5, wherein the selectable marker sequence is operably linked to a promoter. 7. A silencing vector comprising SEQ ID NO: 45, 54, or 56. 8. A method of reducing levels of expression of genes on Chromosome 21 in a cell, the method comprising contacting the cell with the silencing vector of claim 1, under conditions sufficient for the silencing vector to undergo homologous recombination with the genomic DNA of the cell, wherein the silencing element is inserted into intron 1 of DYRK1A. 9. The method of claim 8, wherein the cell is trisomic for chromosome 21. 10. The method of claim 8, wherein the cell is a human cell. 11. The method of claim 10, wherein the cell is a stem cell or a fibroblast. 12. The method of claim 11, wherein the stem cell is an induced pluripotent stem cell (iPSC), a hematopoietic stem cell, or a neural stem cell. 13. An isolated cell produced by the method of claim 8. 14. A method of reducing the risk of transient myeloproliferative disorder (TMD) in a subject who has Down Syndrome (Trisomy 21), the method comprising: obtaining a hematopoietic stem cell from the subject; contacting the cell with the silencing vector of claim 1, under conditions sufficient for the silencing vector to undergo homologous recombination with the genomic DNA of the cell, wherein the silencing element is inserted into DYRK1A, to produce a modified cell having reduced levels of expression of genes on Chromosome 21; and administering the modified cell to the subject. 15. The method of claim 8, further comprising contacting the cell with a cleavage vector comprising a sequence that enhances or facilitates homologous recombination. 16. The method of claim 15, wherein the cleavage vector comprises a zinc finger nuclease (ZFN) or a transcription activator-like effector nuclease (TALEN). 17. The method of claim 15, wherein the cleavage vector comprises SEQ ID NO: 45, 54, or 56.

Details for Patent 9,681,646

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		2033-03-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2033-03-15
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2033-03-15