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(12) United States Patent (10) Patent No.: US 9,504,645 B2 Ackermann, Jr

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(12) United States Patent (10) Patent No.: US 9,504,645 B2 Ackermann, Jr USOO9504645B2 (12) United States Patent (10) Patent No.: US 9,504,645 B2 Ackermann, Jr. et al. (45) Date of Patent: Nov. 29, 2016 (54) PHARMACEUTICAL FORMULATIONS FOR (56) References Cited TREATING OCULAR CONDITIONS U.S. PATENT DOCUMENTS (71) Applicant: Oyster Point Pharma, Inc., South San 6,277,855 B1 8, 2001 Yerxa, Francisco, CA (US) 2006, OO84656 A1 4/2006 Ziegler et al. 2011 OO86086 A1 4/2011 Johnson et al. (72) Inventors: Douglas Michael Ackermann, Jr., San 2011 O274628 A1 11/2011 Borschke Francisco, CA (US); James Loudin, 2012,0289572 A1 1 1/2012 Mazurov et al. Houston, TX (US); Kenneth J. Mandell, Arlington, MA (US) FOREIGN PATENT DOCUMENTS EP 1214062 B1 11, 2003 (73) Assignee: OYSTER POINT PHARMA, INC., WO WO-03005998 A2 1, 2003 WO WO-03045394 A1 6, 2003 South San Francisco, CA (US) WO WO-2004039366 A1 5, 2004 WO WO 2006/100075 * 9/2006 (*) Notice: Subject to any disclaimer, the term of this WO WO-2008O57938 A1 5, 2008 patent is extended or adjusted under 35 WO WO-2009111550 A1 9, 2009 WO WO-2010O28011 A1 3, 2010 U.S.C. 154(b) by 0 days. WO WO-2010O28033 A1 3, 2010 (21) Appl. No.: 14/887,259 OTHER PUBLICATIONS (22) Filed: Oct. 19, 2015 Mazzanti (Int. J. Devi Neuroscience 25 (2007) 259-264).* PCT/US2015/56273 International Search Report and Written Opin (65) Prior Publication Data ion dated Jan. 8, 2016. Co-pending U.S. Appl. No. 14/887,243, filed Oct. 19, 2015. US 2016/0106746 A1 Apr. 21, 2016 Co-pending U.S. Appl. No. 14/887,248, filed Oct. 19, 2015. Co-pending U.S. Appl. No. 14/887.253, filed Oct. 19, 2015. U.S. Appl. No. 14/887.243 Office Action dated Mar. 24, 2016. U.S. Appl. No. 14/887,248 Office Action dated Mar 18, 2016. Related U.S. Application Data U.S. Appl. No. 14/887.253 Office Action dated Mar. 23, 2016. Albietz et al. Dry eye: an update on clinical diagnosis, management (60) Provisional application No. 62/066,280, filed on Oct. and promising new treatments. Clinical and Experimental Optom 20, 2014, provisional application No. 62/100,844, etry 84(1):4-18 (2001). filed on Jan. 7, 2015. Alimohammadi et al. Evidence for nicotinic acetylcholine receptors on nasal trigeminal nerve endings of the rat. Chem Senses 25:61-66 (2000). (51) Int. Cl. Beule. Physiology and pathophysiology of respiratory mucosa of A6 IK 9/00 (2006.01) the nose and the paranasal sinuses. GMS Curr Top Otorhinolaryngol A6 IK 3/439 (2006.01) Head Neck Surg 9:1-24 (2010). A6 IK 3/4439 (2006.01) Thuerauf et al. Dose-dependent stereoselective activation of the A6 IK 3/4427 (2006.01) trigeminal sensory system by nicotine in man. Psychopharmacology A6 IK 3/4985 (2006.01) (Berl) 142(3):236-243 (1999). A6 IK 45/06 (2006.01) U.S. Appl. No. 14/887,248 Office Action dated Jun. 28, 2016. A 6LX 3L/21995 (2006.01) (52) U.S. Cl. * cited by examiner CPC ............. A61K 9/0043 (2013.01); A61K 9/007 Primary Examiner — Devang Thakor (2013.01); A61K 31/439 (2013.01); A61 K (74) Attorney, Agent, or Firm — Wilson, Sonsini, 3 1/4427 (2013.01); A61K 31/4439 (2013.01); Goodrich & Rosati A6 IK3I/4985 (2013.01); A61K 31/4995 (2013.01); A61K 45/06 (2013.01) (57) ABSTRACT (58) Field of Classification Search Described herein are pharmaceutical formulations for treat USPC .......................................................... 424/400 ing ocular conditions. See application file for complete search history. 13 Claims, 2 Drawing Sheets U.S. Patent Nov. 29, 2016 Sheet 1 of 2 US 9,504,645 B2 : U.S. Patent Nov. 29, 2016 Sheet 2 of 2 US 9,504,645 B2 i i {x : x x . (uu) it tuoidus US 9,504,645 B2 1. 2 PHARMACEUTICAL FORMULATIONS FOR nicotinic acetylcholine receptor and in an amount that does TREATING OCULAR CONDITIONS not result in undesired systemic side effects. Provided herein, in some embodiments, is a method of CROSS-REFERENCE increasing tear production, comprising the local administra tion of a therapeutically effective amount of a nicotinic This application claims benefit of U.S. Provisional Appli acetylcholine receptor agonist into the nasal cavity of an cation No. 62/066,280, filed on Oct. 20, 2014, and U.S. individual in need thereof, wherein the agonist selectively Provisional Application No. 62/100,844, filed on Jan. 7, binds to the peripheral nicotinic acetylcholine receptor and 2015, both of which are herein incorporated by reference in does not cross the blood-brain barrier in a pharmacologically 10 relevant concentration. In some embodiments is method of their entirety. increasing tear production, comprising the local administra tion of a therapeutically effective amount of a nicotinic BACKGROUND OF THE INVENTION acetylcholine receptor agonist into the nasal cavity of an Dry Eye Disease (“DED) is a condition that affects individual in need thereof, wherein the agonist does not 15 cross the blood-brain barrier in a pharmacologically relevant millions of people worldwide. Approximately 40 million concentration and selectively binds to at least one of the people in North America have some form of dry eye, and peripheral nicotinic acetylcholine receptor Subtypes selected many millions more suffer worldwide. DED results from the from alpha3beta4, alpha-4beta2, and alpha7. In some disruption of the natural tear film on the surface of the eye, embodiments is a method of increasing tear production, and can result in ocular discomfort, visual disturbance and comprising the local administration of a therapeutically a reduction in vision-related quality of life. Patients with effective amount of a nicotinic acetylcholine receptor ago severe cases of DED are at risk for serious ocular health nist into the nasal cavity of an individual in need thereof, deficiencies such as corneal ulceration, and can experience wherein the agonist selectively binds to the peripheral a quality of life deficiency comparable to that of moderate nicotinic acetylcholine receptor and is administered in an Severe angina. 25 amount that is not systemically bioavailable. In some embodiments is a method of increasing tear production, SUMMARY OF THE INVENTION comprising the local administration of a therapeutically effective amount of a nicotinic acetylcholine receptor ago Provided herein, in some embodiments, is a method of nist into the nasal cavity of an individual in need thereof, increasing tear production, comprising the local administra 30 wherein the agonist selectively binds to the peripheral tion of a therapeutically effective amount of a nicotinic nicotinic acetylcholine receptor and in an amount that does acetylcholine receptor agonist into the nasal cavity of an not result in undesired psychoactive side effects. In some individual in need thereof, wherein the agonist selectively embodiments is a method of increasing tear production, binds to the peripheral nicotinic acetylcholine receptor. In comprising the local administration of a therapeutically Some embodiments, is a method of increasing tear produc 35 effective amount of a nicotinic acetylcholine receptor ago tion, comprising the local administration of a therapeutically nist into the nasal cavity of an individual in need thereof, effective amount of a nicotinic acetylcholine receptor ago wherein the agonist selectively binds to the peripheral nist into the nasal cavity of an individual in need thereof, nicotinic acetylcholine receptor and in an amount that does wherein the agonist selectively binds to the peripheral not result in undesired systemic side effects. nicotinic acetylcholine receptor and does not cross the 40 Further provided herein, in some embodiments, is a blood-brain barrier in a pharmacologically relevant concen method of treating dry eye, comprising the local adminis tration. In some embodiments is method of increasing tear tration of a therapeutically effective amount of a nicotinic production, comprising the local administration of a thera acetylcholine receptor agonist into the nasal cavity of an peutically effective amount of a nicotinic acetylcholine individual in need thereof, wherein the agonist selectively receptoragonist into the nasal cavity of an individual in need 45 binds to the peripheral nicotinic acetylcholine receptor. In thereof, wherein the agonist selectively binds to at least one Some embodiments, is a method of treating dry eye, com of the peripheral nicotinic acetylcholine receptor Subtypes prising the local administration of a therapeutically effective selected from alpha3beta4, alpha-4beta2, and alpha7. In amount of a nicotinic acetylcholine receptor agonist into the Some embodiments is a method of increasing tear produc nasal cavity of an individual in need thereof, wherein the tion, comprising the local administration of a therapeutically 50 agonist selectively binds to the peripheral nicotinic acetyl effective amount of a nicotinic acetylcholine receptor ago choline receptor and does not cross the blood-brain barrier nist into the nasal cavity of an individual in need thereof, in a pharmacologically relevant concentration. In some wherein the agonist selectively binds to the peripheral embodiments is method of treating dry eye, comprising the nicotinic acetylcholine receptor and is administered in an local administration of a therapeutically effective amount of amount that is not systemically bioavailable. In some 55 a nicotinic acetylcholine receptor agonist into the nasal embodiments is a method of increasing tear production, cavity of an individual in need thereof, wherein the agonist comprising the local administration of a therapeutically selectively binds to at least one of the peripheral nicotinic effective amount of a nicotinic acetylcholine receptor ago acetylcholine receptor subtypes selected from alpha3beta4, nist into the nasal cavity of an individual in need thereof, alpha-4-beta2, and alpha7. In some embodiments is a method wherein the agonist selectively binds to the peripheral 60 of treating dry eye, comprising the local administration of a nicotinic acetylcholine receptor and in an amount that does therapeutically effective amount of a nicotinic acetylcholine not result in undesired psychoactive side effects.
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