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(12) United States Patent (10) Patent No.: US 9,597,284 B2 Ackermann, Jr

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(12) United States Patent (10) Patent No.: US 9,597,284 B2 Ackermann, Jr USO0959.7284B2 (12) United States Patent (10) Patent No.: US 9,597,284 B2 Ackermann, Jr. et al. (45) Date of Patent: *Mar. 21, 2017 (54) DRY EYE TREATMENTS (58) Field of Classification Search USPC .......................................................... 424/400 (71) Applicant: Oyster Point Pharma, Inc., South San See application file for complete search history. Francisco, CA (US) (56) References Cited (72) Inventors: Douglas Michael Ackermann, Jr., San Francisco, CA (US); James Loudin, U.S. PATENT DOCUMENTS Houston, TX (US); Kenneth J. 6,277,855 B1 8, 2001 Yerxa, Mandell, Arlington, MA (US) 2006, OO84656 A1 4/2006 Ziegler et al. 2011 OO86086 A1 4/2011 Johnson et al. (73) Assignee: Oyster Point Pharma, Inc., San 2011 O274628 A1 11/2011 Borschke Francisco, CA (US) 2012,0289572 A1 1 1/2012 Mazurov et al. (*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 EP 1214062 B1 11, 2003 U.S.C. 154(b) by 0 days. WO WO-03005998 A2 1, 2003 WO WO-03045394 A1 6, 2003 This patent is Subject to a terminal dis WO WO-2004039366 A1 5, 2004 claimer. WO WO 2006/100075 * 9/2006 WO WO-2008O57938 A1 5, 2008 (21) Appl. No.: 14/887,248 WO WO-2009111550 A1 9, 2009 WO WO-2010O28011 A1 3, 2010 (22) Filed: Oct. 19, 2015 WO WO-2010O28033 A1 3, 2010 (65) Prior Publication Data OTHER PUBLICATIONS US 2016/0106745 A1 Apr. 21, 2016 Mazzanti (Int. J. Devl Neuroscience 25 (2007) 259-264.* Beule (GMS Current Topics in Otorhinolaryngology—Head and Neck Surgery 2010, vol. 9, 1-24).* Related U.S. Application Data Thuerauf (Psychopharmacology (1999) 142 : 236-243).* Albietz (Clinical and Experimental Optometry 84.1 Jan.-Feb. 2001, (60) Provisional application No. 62/066,280, filed on Oct. pp. 4-18).* 20, 2014, provisional application No. 62/100,844, PCT/US2015/56273 International Search Report and Written Opin filed on Jan. 7, 2015. ion dated Jan. 8, 2016. Co-pending U.S. Appl. No. 14/887,243, filed Oct. 19, 2015. Co-pending U.S. Appl. No. 14/887.253, filed Oct. 19, 2015. (51) Int. Cl. Co-pending U.S. Appl. No. 14/887.259, filed Oct. 19, 2015. A6 IK 9/00 (2006.01) U.S. Appl. No. 14/887.243 Office Action dated Mar. 24, 2016. A6 IK 3/439 (2006.01) U.S. Appl. No. 14/887.253 Office Action dated Mar. 23, 2016. A6 IK 3/4439 (2006.01) U.S. Appl. No. 14/887.259 Office Action dated Mar. 21, 2016. A6 IK 3/4427 (2006.01) A6 IK 3/4985 (2006.01) * cited by examiner A6 IK 45/06 (2006.01) A 6LX 3L/21995 (2006.01) Primary Examiner — Devang Thakor (52) U.S. Cl. CPC ............ A61K 9/0043 (2013.01); A61K 9/007 (57) ABSTRACT (2013.01); A61K 31/439 (2013.01); A61 K Described herein are methods and pharmaceutical formula 3 1/4427 (2013.01); A61K 31/4439 (2013.01); tions for treating dry eye disease. A6 IK3I/4985 (2013.01); A61K 31/4995 (2013.01); A61K 45/06 (2013.01) 15 Claims, 2 Drawing Sheets U.S. Patent Mar. 21, 2017 Sheet 1 of 2 US 9,597,284 B2 IQunõ14 x: U.S. Patent Mar. 21, 2017. Sheet 2 of 2 US 9,597,284 B2 S && S C S S S '''''''''''''''''''''': O &: i US 9,597,284 B2 1. 2 DRY EYE TREATMENTS Provided herein, in some embodiments, is a method of increasing tear production, comprising the local administra CROSS-REFERENCE tion of a therapeutically effective amount of a nicotinic acetylcholine receptor agonist into the nasal cavity of an This application claims benefit of U.S. Provisional Appli individual in need thereof, wherein the agonist selectively cation No. 62/066,280, filed on Oct. 20, 2014, and U.S. binds to the peripheral nicotinic acetylcholine receptor and Provisional Application No. 62/100,844, filed on Jan. 7, does not cross the blood-brain barrier in a pharmacologically 2015, both of which are herein incorporated by reference in relevant concentration. In some embodiments is method of their entirety. increasing tear production, comprising the local administra 10 tion of a therapeutically effective amount of a nicotinic BACKGROUND OF THE INVENTION acetylcholine receptor agonist into the nasal cavity of an individual in need thereof, wherein the agonist does not Dry Eye Disease (“DED) is a condition that affects 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 15 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. amount that is not systemically bioavailable. In some embodiments is a method of increasing tear production, SUMMARY OF THE INVENTION 25 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 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 30 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 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 35 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 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 40 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 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 45 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 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, 50 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 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 55 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 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. In some 60 receptoragonist into the nasal cavity of an individual in need embodiments is a method of increasing tear production, thereof, wherein the agonist selectively binds to the periph comprising the local administration of a therapeutically eral nicotinic acetylcholine receptor and is administered in effective amount of a nicotinic acetylcholine receptor ago an amount that is not systemically bioavailable. In some nist into the nasal cavity of an individual in need thereof, embodiments is a method of treating dry eye, comprising the wherein the agonist selectively binds to the peripheral 65 local administration of a therapeutically effective amount of nicotinic acetylcholine receptor and in an amount that does a nicotinic acetylcholine receptor agonist into the nasal not result in undesired systemic side effects.
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