US009333171B2 (12) United States Patent (10) Patent No.: US 9,333,171 B2 Lichter et al. (45) Date of Patent: *May 10, 2016 (54) CONTROLLED-RELEASECNS A647/4 (2006.01) MODULATING COMPOSITIONS AND A647/38 (2006.01) METHODS FOR THE TREATMENT OF OTC A647/44 (2006.01) DSORDERS A 6LX3/97 (2006.01) (52) U.S. Cl. (71) Applicants: Otonomy, Inc. San Diego, CA (US); CPC ................. A61 K9/0046 (2013.01); A61 K9/06 Gis they of (2013.01); A61 K3I/00 (2013.01); A61 K s s 31/167 (2013.01); A61K 31/195 (2013.01); (72) Inventors: Jay Lichter, Rancho Santa Fe, CA (US); A6 IK31/197 (2013.01); A61 K3I/5513 Andrew M. Trammel, Olathe, KS (US); (2013.01); A61K 45/06 (2013.01); A61K47/10 FabriceO Piu,TO San Diego, CA (US); (2013.01); A61(2013.01); K47/14 (2013.01);A61 K47744 A61K47/38 (2013.01) Qiang Ye, San Diego, CA (US); Michael • u. fs Christopher Scaife, Los Altos, CA (58) Field of Classification Search (US); Benedikt Vollrath, San Diego, CA None (US); Sergio G. Duron, San Diego, CA See application file for complete search history. (US); Luis A. Dellamary, San Marcos, CA (US); Carl Lebel, Malibu, CA (US); Jeffrey P. Harris, La Jolla, CA (US) (56) References Cited (73) Assignees: OTONOMY, INC., San Diego, CA U.S. PATENT DOCUMENTS (US): THE REGENTS OF THE 4,478,822. A 10/1984 Haslam et al. UNIVERSITY OF CALIFORNLA, 5,292,516 A * 3/1994 Viegas et al. ................. 424/423 Oakland, CA (US) 5,503,848 A 4/1996 Perbellini et al. 5,861,174 A 1/1999 Stratton et al. (*) Notice: Subject to any disclaimer, the term of this 86. R 58: S.E. al patent is extended or adjusted under 35 6,316,011 B1 1 1/2001 Ron et al. U.S.C. 154(b) by 0 days. 6,392,036 B1 5/2002 Karlsson et al. 6,649,621 B2 11/2003 Kopke et al. This patent is Subject to a terminal dis- 6,740,664 B2 5/2004 Cagle et al. claimer. 7,001,615 B1 2/2006 Singh et al. 7,524,834 B2 4/2009 Karlsson et al. (21) Appl. No.: 14/300,011 8,318,817 B2 11/2012 Lichter et al. ................. 514,772 8,349,353 B2 * 1/2013 Lichter et al. ................. 424/437 (22) Filed: Jun. 9, 2014 (Continued) (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2014/03092.17 A1 Oct. 16, 2014 WO WO97/38698 10, 1997 WO WO99,24051 5, 1999 Related U.S. Application Data (Continued) (63) Continuation of application No. 13/425,217, filed on Mar. 20, 2012, now Pat. No. 8,852,626, which is a OTHER PUBLICATIONS origippi. N. 12/494,156, filed on Ahn etal. Lipoic acid rescues DBA mice from early-onset age-related • 1-1 s s hearing impairment. Neuroreport 19(13): 1265-9. 2008. (60) Provisional application No. 61/076,567, filed on Jun. (Continued) 27, 2008, provisional application No. 61/082,450, filed on Jul. 21, 2008, provisional application No. fo Sp i. d s Pys Primary Examiner — Hasan Ahmed provisionalapplicauon applicationNo. No., 112, 61/140,033, Illed on Sep. filed Z9, on Dec.s torney Agent, or Firm — Wilson Sonsini, Goodrich 22, 2008, provisional application No. 61/164,812, filed on Mar. 30, 2009. (57) ABSTRACT (51) Int. Cl. A6DF 9/02 (2006.01) Disclosed herein are compositions and methods for the treat A6 IK9/00 (2006.01) ment of otic disorders with CNS modulating agent composi A6 IK9/06 (2006.01) tions and compositions administered locally to an individual A6 IK3I/00 (2006.01) afflicted with an otic disorder, through direct application of A6 IK3I/67 (2006.01) these compositions and compositions onto or via perfusion A 6LX3L/95 (2006.01) into the targeted auris structure(s). 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