Claims for Patent: 9,101,647

Summary for Patent: 9,101,647

Title:	Composition and method for inner ear sensory hair cell regeneration and replacement
Abstract:	A composition and method for replacement and regeneration of hair cells of the inner ear is provided. The composition comprises an active agent in an amount effective to decrease Hes1 gene expression in a tissue of the inner ear. The active agent can be short interfering RNA (siRNA) molecules encapsulated in a biodegradable nanoparticle. The method involves administering a solution to the inner ear where the solution contains an active agent in an amount effective to decrease Hes1 gene expression.
Inventor(s):	Kopke; Richard D. (Oklahoma City, OK)
Assignee:	HOUGH EAR INSTITUTE (Oklahoma City, OK)
Application Number:	13/701,550
Patent Claims:	1. A composition for regenerating hair cells of the inner ear comprising: (a) magnetically responsive nanoparticles comprising poly(lactic-co-glycolic acid) and an siRNA molecule that decreases expression of a Hes1 gene in a tissue of the inner ear and (b) a pharmaceutically acceptable carrier. 2. The composition of claim 1, wherein the composition comprises one or more of: (i) an siRNA molecule comprising SEQ ID NO. 3 and a complementary sequence thereof; (ii) an siRNA molecule comprising SEQ ID NO. 4 and a complementary sequence thereof; (iii) an siRNA molecule comprising SEQ ID NO. 5 and a complementary sequence thereof; (iv) an siRNA molecule comprising SEQ ID NO. 6 and a complementary sequence thereof; (v) an siRNA molecule comprising SEQ ID NO. 7 and a complementary sequence thereof; and (vi) an siRNA molecule comprising SEQ ID NO. 8 and a complementary sequence thereof. 3. The composition of claim 1, wherein the composition comprises one or more of (i) an siRNA molecule comprising SEQ ID NO. 3 and SEQ ID NO. 4, (ii) an siRNA molecule comprising SEQ ID NO. 5 and SEQ ID NO. 6, and (iii) an siRNA molecule comprising SEQ ID NO. 7 and SEQ ID NO. 8. 4. The composition of claim 1, wherein the siRNA molecule comprises SEQ ID NO. 7 and SEQ ID NO. 8. 5. The composition of claim 1, wherein the nanoparticles comprise superparamagnetic iron oxide. 6. The composition of claim 1, wherein the nanoparticles comprise from about 500 to about 1000 siRNA molecules per nanoparticle. 7. The composition of claim 1, wherein the nanoparticles are dispersed in the pharmaceutically acceptable carrier. 8. The composition of claim 7 in which a concentration of the siRNA molecules per milliliter of dispersion ranges from about 50 .mu.g/mL to about 100 .mu.g/mL. 9. The composition of claim 1, wherein the pharmaceutically acceptable carrier is selected from a group consisting of artificial perilymph, 5% dextrose in sterile water, sterile physiologic saline, and phosphate-buffered physiologic saline. 10. The composition of claim 1, where the composition comprises nanoparticles comprising a biodegradable polymer and one or both of (i) an siRNA molecule that decreases expression of a Hes5 gene in a tissue of the inner ear and (ii) an siRNA molecule that decreases expression of a MAPK1 gene in a tissue of the inner ear. 11. The composition of claim 10, wherein the siRNA molecule that decreases expression of the Hes5 gene comprises (i) SEQ ID NO. 9 and a complementary sequence thereof, (ii) SEQ ID NO. 10 and a complementary sequence thereof, (iii) SEQ ID NO. 11 and a complementary sequence thereof, (iv) SEQ ID NO. 12 and a complementary sequence thereof, (v) SEQ ID NO. 13 and a complementary sequence thereof, (vi) SEQ ID NO. 14 and a complementary sequence thereof, or (vii) combinations of any of these. 12. The composition of claim 10, wherein the siRNA molecule that decreases expression of the MAPK1 gene comprises (i) SEQ ID NO. 15 and a complementary sequence thereof, (ii) SEQ ID NO. 16 and a complementary sequence thereof, or (iii) a combination of these. 13. A method of regenerating hair cells of an inner ear of a mammal comprising: applying to the inner ear of a mammal in need thereof an amount of biodegradable nanoparticles comprising an siRNA molecule that decreases expression of a Hes 1 gene in a tissue of the inner ear effective to regenerate hair cells in an inner ear of said mammal. 14. The method of claim 13, wherein the applying comprises transtympanic administration. 15. The method of claim 13, wherein the applying comprises a direct injection through the round window membrane. 16. The method of claim 13, wherein the nanoparticles further comprise superparamagnetic iron oxide. 17. The method of claim 16, wherein the applying comprises using magnetic force to transport the nanoparticles across the round window membrane. 18. The method of claim 13, wherein the nanoparticles comprise one or more of: (i) an siRNA molecule comprising SEQ ID NO. 3 and a complementary sequence thereof; (ii) an siRNA molecule comprising SEQ ID NO. 4 and a complementary sequence thereof; (iii) an siRNA molecule comprising SEQ ID NO. 5 and a complementary sequence thereof; (iv) an siRNA molecule comprising SEQ ID NO. 6 and a complementary sequence thereof; (v) an siRNA molecule comprising SEQ ID NO. 7 and a complementary sequence thereof; and (vi) an siRNA molecule comprising SEQ ID NO. 8 and a complementary sequence thereof. 19. The method of claim 13, wherein the nanoparticles comprise one or more of (i) an siRNA molecule comprising SEQ ID NO. 3 and SEQ ID NO. 4, (ii) an siRNA molecule comprising SEQ ID NO. 5 and SEQ ID NO. 6, and (iii) an siRNA molecule comprising SEQ ID NO. 7 and SEQ ID NO. 8. 20. The method of claim 13, wherein the siRNA molecule comprises SEQ ID NO. 7 and SEQ ID NO. 8. 21. A magnetically responsive nanoparticle for regenerating hair cells of the inner ear, comprising a poly(lactic-co-glycolic acid) and an siRNA molecule that decreases expression of a Hes1 gene in a tissue of the inner ear. 22. The nanoparticle of claim 21, wherein the nanoparticle comprises one or more of: (i) an siRNA molecule comprising SEQ ID NO. 3 and a complementary sequence thereof; (ii) an siRNA molecule comprising SEQ ID NO. 4 and a complementary sequence thereof; (iii) an siRNA molecule comprising SEQ ID NO. 5 and a complementary sequence thereof; (iv) an siRNA molecule comprising SEQ ID NO. 6 and a complementary sequence thereof; (v) an siRNA molecule comprising SEQ ID NO. 7 and a complementary sequence thereof; and (vi) an siRNA molecule comprising SEQ ID NO. 8 and a complementary sequence thereof. 23. The nanoparticle of claim 21, wherein the nanoparticle comprises one or more of (i) an siRNA molecule comprising SEQ ID NO. 3 and SEQ ID NO. 4, (ii) an siRNA molecule comprising SEQ ID NO. 5 and SEQ ID NO. 6, and (iii) an siRNA molecule comprising SEQ ID NO. 7 and SEQ ID NO. 8. 24. The nanoparticle of claim 21, wherein the siRNA molecule comprises SEQ ID NO. 7 and SEQ ID NO. 8. 25. The nanoparticle of claim 21, wherein the nanoparticle comprises superparamagnetic iron oxide. 26. The nanoparticle of claim 21, wherein nanoparticle comprises from about 500 to about 1000 siRNA molecules. 27. The nanoparticle of claim 21, where the nanoparticle further comprises one or both of (i) an siRNA molecule that decreases expression of a Hes5 gene in a tissue of the inner ear and (ii) an siRNA molecule that decreases expression of a MAPK1 gene in a tissue of the inner ear. 28. The nanoparticle of claim 27, wherein the siRNA molecule that decreases expression of the Hes5 gene comprises (i) SEQ ID NO. 9 and a complementary sequence thereof, (ii) SEQ ID NO. 10 and a complementary sequence thereof, (iii) SEQ ID NO. 11 and a complementary sequence thereof, (iv) SEQ ID NO. 12 and a complementary sequence thereof, (v) SEQ ID NO. 13 and a complementary sequence thereof, (vi) SEQ ID NO. 14 and a complementary sequence thereof, or (vii) combinations of any of these. 29. The nanoparticle of claim 27, wherein the siRNA molecule that decreases expression of the MAPK1 gene comprises (i) SEQ ID NO. 15 and a complementary sequence thereof, (ii) SEQ ID NO. 16 and a complementary sequence thereof, or (iii) a combination of these. 30. The composition of claim 1, where the nanoparticles further comprise one or both of (i) an siRNA molecule that decreases expression of a Hes5 gene in a tissue of the inner ear and (ii) an siRNA molecule that decreases expression of a MAPK1 gene in a tissue of the inner ear.

Details for Patent 9,101,647

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2030-06-04