US0096.03796 B2 (12) United States Patent (10) Patent No.: US 9,603.796 B2 Lichter et al. (45) Date of Patent: *Mar. 28, 2017 (54) CONTROLLED RELEASE ANTIMICROBIAL A63L/43 (2006.01) COMPOSITIONS AND METHODS FOR THE A6II 3/522 (2006.01) TREATMENT OF OTC DISORDERS A 6LX 3/573 (2006.01) A63L/7036 (2006.01) (71) Applicants: Otonomy, Inc., San Diego, CA (US); (52) U.S. Cl The R ts of the University of AV e. we (NEON y O CPC .......... A61K 9/0046 (2013.01); A61K 9/0019 s s (2013.01); A61K 9/0024 (2013.01); A61K 9/06 (72) Inventors: Jay Lichter, San Diego, CA (US); (2013.01); A61K 9/10 (2013.01); A61K 9/1641 Andrew M. Trammel, Olathe, KS (2013.01); A61K 31/43 (2013.01); A61 K (US); Fabrice Piu, San Diego, CA 3 1/496 (2013.01); A61 K3I/522 (2013.01); (US); Qiang Ye, San Diego, CA (US); A6 IK3I/573 (2013.01); A61K 3 1/7036 Luis A. Delianary, San Marcos, CA (2013.01); A61K 47/02 (2013.01); A61K 47/10 (US); Carl Lebel Malibu CA (US); (2013.01); A61K 47/34 (2013.01); A6 IK 8/042 Jeffrey P. Harris, La Jolla, CA (US) (2013.01); A61 K 9/14 (2013.01) (58) Field of Classification Search (73) Assignees: OTONOMY, INC., San Diego, CA CPC ... A61K 31/43; A61K 31/496; A61K 31/522; (US): THE REGENTS OF THE A61K 3 1/573; A61K 3 1/7036; A61 K UNIVERSITY OF CALIFORNIA, 47/02: A61K 47/10; A61K 47/34: A61 K Oakland, CA (US) 8/042: A61 K9/0019; A61K 9/0024; A61 K9/0046; A61K 9/06; A61 K9/10: (*) Notice: Subject to any disclaimer, the term of this A61K 9/14: A61 K 9/1641 patent is extended or adjusted under 35 See application file for complete search history. U.S.C. 154(b) by 0 days. This patent is Subject to a terminal dis- (56) References Cited claimer. U.S. PATENT DOCUMENTS (21) Appl. No.: 14/836,184 4,188,373 A 2, 1980 Krezanoski (22) Filed: Aug. 26, 2015 4,268,519 A 5/1981 Turner 4,478,822 A 10, 1984 Haslam et al. (65) Prior Publication Data 4,938,763. A 7, 1990 Dunn et al. 4,968,507 A 11/1990 Zentner et al. US 2016/0051547 A1 Feb. 25, 2016 (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS (63) Continuation of application No. 13/645,126, filed on CN 101664381 A 3, 2010 Oct. 4, 2012, now Pat. No. 9,233,068, which is a EP O551626 A1 7, 1993 continuation of application No. 12/506,127, filed on (Continued) Jul. 20, 2009, now Pat. No. 8,318,817, and a continuation-in-part of application No. 12/427,663, OTHER PUBLICATIONS filed on Apr. 21, 2009, now Pat. No. 9,132,087, and a continuation-in-part of application No. 12/466,310, PCT/US2014/052754 International Preliminary Report on Patent filed on May 14, 2009, now Pat. No. 8,030,297. ability dated Mar. 10, 2016. (60) Provisional application No. 61/082,450, filed on Jul. (Continued) 21, 2008, provisional application No. 61/082,871, filed on Jul. 23, 2008, provisional application No. 61/094,384, filed on Sep. 4, 2008, provisional Primary Examiner — Sarah Pihonak application No. 61/101,112, filed on Sep. 29, 2008, (74) Attorney, Agent, or Firm — Wilson, Sonsini, provisional application No. 61/140,033, filed on Dec. Goodrich & Rosati 22, 2008. (51) Int. Cl. (57) ABSTRACT A6 IK 9/00 (2006.01) Disclosed herein are compositions and methods for the A6 IK 9/10 (2006.01) treatment of otic diseases or conditions with antimicrobial A6 IK 9/16 (2006.01) agent compositions and formulations administered locally to A6 IK 9/06 (2006.01) an individual afflicted with an otic disease or condition, A6 IK 9/14 (2006.01) through direct application of these compositions and formu A6 IK 8/04 (2006.01) lations onto or via perfusion into the targeted auris A6 IK 47/34 (2006.01) structure(s). 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