Granted Patent
B2
US 12,419,933 · App. 17/640,679 · Granted Sep 23, 2025
Ophthalmic composition for the treatment of uveitis
Inventors:
Jörg Haisser (Siegelsbach, DE); Frank Löscher (Schriesheim, DE); Chiara Silvana Leo (Heidelberg, DE); Markus Beier (Weinheim, DE)
Assignee:
NOVALIQ GMBH
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Abstract
The invention provides pharmaceutical compositions comprising cyclosporine dissolved in a semifluorinated alkane for use in the treatment of uveitis.
Claims (17)
1. A method of treating uveitis or a disease or condition associated thereto, the method comprising topically administering to an eye of a human suffering from uveitis or a disease or condition related thereto, a composition comprising cyclosporine at a concentration of from about 0.05% (w/v) to about 0.5% (w/v) dissolved in 1-perfluorobutyl-pentane.
2. The method according to claim 1 , wherein the uveitis is anterior uveitis or posterior uveitis.
3. The method according to claim 1 , wherein the uveitis is iridocyclitis or iritis.
4. The method according to claim 1 , wherein the composition is essentially water-free and/or preservative free.
5. The method according to claim 1 , wherein the cyclosporine is comprised at a concentration of from about 0.05% (w/v) to 0.1% (w/v) based on the total volume of the composition.
6. The method according to claim 1 , wherein the composition comprises ethanol.
7. The method according to claim 6 , wherein the ethanol is present at a concentration of up to 1.0% (w/w) based on the total weight of the composition.
8. The method according to claim 6 , wherein the composition consists of cyclosporine at a concentration of from about 0.05 to about 0.1% (w/v), 1-perfluorobutyl-pentane and up to 1.0% (w/w) ethanol based on the total weight of the composition.
9. The method according to claim 6 , wherein the cyclosporine is present at a concentration of 0.05% (w/v) and the ethanol is present at a concentration of 1.0% (w/w) based on the total weight of the composition.
10. The method according to claim 6 , wherein the cyclosporine is present at a concentration of 0.1% (w/v) and the ethanol is present at a concentration of 1.0% (w/w) based on the total weight of the composition.
11. The method of claim 1 , wherein the composition consists of 0.05% to 0.1% (w/v) cyclosporine in 1-perfluorobutyl-pentane.
12. The method according to claim 1 , wherein the composition is topically administered to the eye of a subject suffering from uveitis as a single dose of about 4 to 60 μg cyclosporine per eye or wherein the composition is topically administered to the eye of a subject suffering from uveitis as a single dose of about 4 to 12 μg cyclosporine per eye.
13. The method according to claim 1 , wherein the composition is topically administered to the eye of a subject suffering from uveitis as a daily dose of about 8 to 120 μg cyclosporine per eye or wherein the composition is topically administered to the eye of a subject suffering from uveitis as a daily dose of about 8 to 24 μg cyclosporine per eye.
14. The method according to claim 1 , wherein the composition is administered as single droplets having a volume of about 8-12 μl or wherein the composition is administered as single droplets having a volume of about 10-12 μl or 11 μl.
15. The method according to claim 1 , wherein the composition is administered up to four times per day or wherein the composition is administered twice per day.
16. The method according to claim 1 , wherein the composition comprises or consists essentially of 0.1% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane, and optionally up to 1% (w/w) ethanol, and wherein the composition is administered twice daily as a single dose of about 20 to 24 μg of cyclosporine per eye.
17. The method according to claim 1 , wherein the composition comprises or consists essentially of 0.05% (w/v) cyclosporine dissolved in 1-perfluorobutyl-pentane, and optionally up to 1% (w/w) ethanol, and wherein the composition is administered twice daily as a single dose of about 10 to 12 μg of cyclosporine per eye.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 3, 2022
From: HAISSER, JÖRG; LÖSCHER, FRANK; LEO, CHIARA SILVANA; BEIER, MARKUS
To: NOVALIQ GMBH
Reel/Frame 060094/0906 →
Priority Claims (1)
EP 19195793
· Sep 6, 2019
· regional
Continuity (1)
References Cited (220)
US 2616927A
· Kauck et al.
· 1952
[cited by applicant]
US 4452818A
· Haidt
· 1984
[cited by applicant]
US 4649047A
· Kaswan
· 1987
[cited by applicant]
US 5077036A
· Long
· 1991
[cited by applicant]
US 5336175A
· Mames
· 1994
[cited by applicant]
US 5518731A
· Meadows
· 1996
[cited by applicant]
US 5667809A
· Trevino et al.
· 1997
[cited by applicant]
US 5874469A
· Maniar et al.
· 1999
[cited by applicant]
US 5874481A
· Weers et al.
· 1999
[cited by applicant]
US 5904933A
· Riess et al.
· 1999
[cited by applicant]
US 5980936A
· Krafft et al.
· 1999
[cited by applicant]
US 5981607A
· Ding et al.
· 1999
[cited by applicant]
US 6113919A
· Reiss et al.
· 2000
[cited by applicant]
US 6140374A
· May et al.
· 2000
[cited by applicant]
US 6262126B1
· Meinert
· 2001
[cited by applicant]
US 6335335B2
· Higashiyama et al.
· 2002
[cited by applicant]
US 6372243B2
· Kobuch et al.
· 2002
[cited by applicant]
US 6458376B1
· Meadows
· 2002
[cited by applicant]
US 6486212B2
· Meinert
· 2002
[cited by applicant]
US 6489367B1
· Meinert
· 2002
[cited by applicant]
US 7001607B1
· Menz et al.
· 2006
[cited by applicant]
US 7026359B1
· Gross et al.
· 2006
[cited by applicant]
US 7041705B2
· Mishra et al.
· 2006
[cited by applicant]
US 7074827B2
· Ueno
· 2006
[cited by applicant]
US 7258869B1
· Berry et al.
· 2007
[cited by applicant]
US 7732415B2
· Dawson et al.
· 2010
[cited by applicant]
US 8029977B2
· Meinert et al.
· 2011
[cited by applicant]
US 8492334B2
· Lavik et al.
· 2013
[cited by applicant]
US 8501800B2
· Bowman et al.
· 2013
[cited by applicant]
US 8614178B2
· Theisinger et al.
· 2013
[cited by applicant]
US 8669241B2
· Matsumura et al.
· 2014
[cited by applicant]
US 8772337B2
· Pilotaz et al.
· 2014
[cited by applicant]
US 8796340B2
· Theisinger et al.
· 2014
[cited by applicant]
US 8865131B2
· Hagedorn et al.
· 2014
[cited by applicant]
US 8957110B2
· Aleo et al.
· 2015
[cited by applicant]
US 8986738B2
· Meinert
· 2015
[cited by applicant]
US 9000048B2
· Mecozzi et al.
· 2015
[cited by applicant]
US 9023898B2
· Wong et al.
· 2015
[cited by applicant]
US 9241900B2
· Wilson
· 2016
[cited by applicant]
US 9265809B2
· Johnson
· 2016
[cited by applicant]
US 9278120B2
· Cruzat et al.
· 2016
[cited by applicant]
US 9308262B2
· Günther et al.
· 2016
[cited by applicant]
US 9446026B2
· Bingaman et al.
· 2016
[cited by applicant]
US 9757459B2
· Theisinger et al.
· 2017
[cited by applicant]
US 9757460B2
· Günther et al.
· 2017
[cited by applicant]
US 9770508B2
· Günther et al.
· 2017
[cited by applicant]
US 9844530B1
· Anastassov et al.
· 2017
[cited by applicant]
US 9878000B2
· Gu et al.
· 2018
[cited by applicant]
US 9968678B2
· Theisinger et al.
· 2018
[cited by applicant]
US RE50060E
· Graf et al.
· 2024
[cited by applicant]
US 20030018044A1
· Peyman
· 2003
[cited by applicant]
US 20050079210A1
· Gupta
· 2005
[cited by applicant]
US 20050175541A1
· Lanza et al.
· 2005
[cited by applicant]
US 20080050335A1
· Faour et al.
· 2008
[cited by applicant]
US 20100279951A1
· Morgan et al.
· 2010
[cited by applicant]
US 20110223208A1
· Hill et al.
· 2011
[cited by applicant]
US 20140004197A1
· Theisinger et al.
· 2014
[cited by applicant]
US 20140186350A1
· Ghosh et al.
· 2014
[cited by applicant]
US 20160000941A1
· Keller et al.
· 2016
[cited by applicant]
US 20170087100A1
· Scherer et al.
· 2017
[cited by applicant]
US 20170216204A1
· Theisinger et al.
· 2017
[cited by applicant]
US 20170348285A1
· Hellstrom
· 2017
[cited by applicant]
US 20180360908A1
· Beier et al.
· 2018
[cited by applicant]
US 20190256591A1
· Günther et al.
· 2019
[cited by applicant]
US 20190328717A1
· Günther et al.
· 2019
[cited by applicant]
US 20190343793A1
· Günther et al.
· 2019
[cited by applicant]
US 20210069014A1
· Löscher et al.
· 2021
[cited by applicant]
US 20210121471A1
· Löscher et al.
· 2021
[cited by applicant]
US 20210315832A1
· Scherer et al.
· 2021
[cited by applicant]
US 20210346313A1
· Beier et al.
· 2021
[cited by applicant]
US 20220031844A1
· Mauden et al.
· 2022
[cited by applicant]
US 20220079925A1
· Günther et al.
· 2022
[cited by applicant]
US 20220226426A1
· Löscher et al.
· 2022
[cited by applicant]
US 20220354926A1
· Löscher et al.
· 2022
[cited by applicant]
US 20220362382A1
· Löscher et al.
· 2022
[cited by applicant]
US 20230330056A1
· Günther et al.
· 2023
[cited by applicant]
US 20230398065A1
· Günther et al.
· 2023
[cited by applicant]
EP 0670159A1
· 1995
[cited by applicant]
EP 2708228A1
· 2014
[cited by applicant]
EP 2730291A1
· 2014
[cited by applicant]
GB 2224205A
· 1990
[cited by applicant]
WO WO2007008666A2
· 2007
[cited by applicant]
WO WO2008136034A2
· 2008
[cited by applicant]
WO WO2011073134A1
· 2011
[cited by applicant]
WO WO2016082644A1
· 2016
[cited by applicant]
WO 2018033854A1
· 2018
[cited by applicant]
WO WO2018114557A1
· 2018
[cited by examiner]
WO WO2018115097A1
· 2018
[cited by examiner]
Murphy et al. Cyclosporine vs Tacrolimus Therapy for Posterior and Intermediate Uveitis. Arch Ophthalmol. 2005; 123(5):634-641. doi:10.1001/archopht.123.5.634 (Year: 2005).
[cited by examiner]
Babu et al., “Medical Management of Uveitis—Current Trends,” Indian J Opthalmol., vol. 61, No. 6, p. 277-283, (2013).
[cited by applicant]
Daull et al., “Distribution of Cyclosporine A in Ocular Tissues After Topical Administration of Cyclosporine A Cationic Emulsions to Pigmented Rabbits,” Cornea, vol. 32, No. 3, p. 345-354, (2013); Abstract Only.
[cited by applicant]
Dutescu et al., “Semifluorinated Alkanes as a Liquid Drug Carrier System for Topical Ocular Drug Delivery,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 88, No. 1, p. 123-128, (2014).
[cited by applicant]
Prabhu et al., “Topical Cyclosporine A 0.05% for Recurrent Anterior Uveitis,” Br J Opthalmol, vol. 100, No. 3, p. 345-347, (2016); Abstract Only.
[cited by applicant]
“EvoTears, Product Description” Accessed Online: Dec. 21, 2023. https://evotears.com/at/das-produkt/ (Year: 2017).
[cited by applicant]
“EvoTears—Gebrauchsanweisung,” May 2015, retrieved from the Internet, date retrieved: Jun. 26, 2018, 2 pages, URL: http://video.apo-rot.de/docs/11213615.pdf.
[cited by applicant]
“Keratoconjunctivitis,” Cleveland Clinic, last updated Jul. 8, 2022, downloaded from https://my.clevelandclinic.org/health/diseases/23551-keratoconjunctivitis.
[cited by applicant]
“Novaliq Announces Positive Topline Results of Phase 2 Clinical Trial Evaluating CyclASol® in Adults with Moderate to Severe Dry Eye Disease,” Businesswire, Jan. 5, 2017, URL: <https://www.businesswire.com/news/home/201…
[cited by applicant]
“Novaliq begins Phase 2 trial of Cyclasol for dry eye disease,” Optometry Times, vol. 8, No. 3, (2016), p. 24.
[cited by applicant]
“Novaliq GmbH Begins Phase II Clinical Trial of Cyclasol for the Treatment of Moderate to Severe Dry Eye Disease,” (online), 5 pages, (2016); retrieved on Jan. 2021, from the Internet: https://www.biospace.com/article/r…
[cited by applicant]
“Ocular Surface Disease Index (OSDI),” Dec. 1, 2003, pp. 1-2, Retrieved from the Internet: URL: http://www.supereyecare.com/resources/OSDI.pdf.
[cited by applicant]
“Semifluorinated alkane technology brings advantages for topical therapy,” Ophthalmology Times, 2016, pp. 1-2.
[cited by applicant]
“Topical drug dosage forms for eye conditions,” The Pharmaceutical Journal, (Pharmaceutical Press, May 31, 2017), available at https://pharmaceutical-journal.com/article/Id/topical-drug-dosage-forms-for-eye-conditions.
[cited by applicant]
“Xerophthalmia,” Eye Clinic, 4 pages, archived Dec. 30, 2014.
[cited by applicant]
Agarwal et al., “Modern Approaches to the Ocular Delivery of Cyclosporine A,” Drug Discovery Today, vol. 21, No. 6, pp. 977-988, (2016); doi: 10.1016/j.drudis.2016.04.002.
[cited by applicant]
Agrahari, et al., “A comprehensive insight on ocular pharmacokinetics,” Drug Delivery and Translational Research, vol. 6, No. 6, pp. 735-754, (2016).
[cited by applicant]
Ahmed, S. et al., “Ocular Drug Delivery: a Comprehensive Review,” AAPS PharmSciTech, vol. 24, No. 66, pp. 1-29, (2023).
[cited by applicant]
Ann Marie Griff, O.D., & Ann Pietrangelo, “Everything you need to know about keratoconjunctivitis,” Healthline.com, Nov. 22, 2019, downloaded from https://www.healthline.com/health/keratoconjunctivitis.
[cited by applicant]
Benezra, D. et al., “Cyclosporine eyedrops for the treatment of severe vernal keratoconjunctivitis,” American Journal of Ophthalmology, vol. 101, pp. 278-282, (1986).
[cited by applicant]
Bertilla et al., “Semifluorinated Alkanes as Stabilizing Agents of Fluorocarbon Emulsions,” Springer, vol. 12, 24 pages, (2005).
[cited by applicant]
Blackie et al., “Getting to the Root Cause of Dry Eye”, Review of Optometry, pp. 1-12, (2012).
[cited by applicant]
Bron, A. et al., “Grading of Corneal and Conjunctival Staining in the Context of Other Dry Eye Tests,” Cornea, vol. 22, No. 7, pp. 640-650, (2003).
[cited by applicant]
CEQUA® Prescribing Information, available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210913s000lbl.pdf (Aug. 2018) (last accessed Feb. 28, 2023).
[cited by applicant]
Chaglasian, E. et al., “Recycling Cyclosporine,” Review of Cornea & Contact Lenses, 2016, 5 pages.
[cited by applicant]
Chao, W. et al., “Report of the Inaugural Meeting of the TFOS i2 = initiating innovation Series: Targeting the Unmet Need for Dry Eye Treatment,” (London, United Kingdom, Mar. 21, 2015) Accepted Manuscript, Accepted Dat…
[cited by applicant]
Chhadva et al., “Meibomian Gland Disease The Role of Gland Dysfunction in Drye Eye Disease,” Ophthalmology, Vo. 124, No. 11 Supplement, pp. S20-S26, (2017).
[cited by applicant]
Davies, N., “Biopharmaceutical Considerations in Topical Ocular Drug Delivery,” Clinical and Experimental Pharmacology and Physiology, vol. 27, pp. 558-562, (2000).
[cited by applicant]
Dembinski, R. et al., “Semi-fluorinated Alkanes as Carriers for Drug Targeting in Acute Respiratory Failure,” Experimental Lung Research, vol. 36, pp. 499-507, (2010).
[cited by applicant]
English-language machine translation of EP0670159 (A1) issued in U.S. Appl. No. 14/122,025 on Apr. 1, 2015, 10 pages.
[cited by applicant]
Eva M. del Amo, “Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?” Frontiers in Drug Discovery 2:954771 (Sep. 8, 2022), available at https://www.fro…
[cited by applicant]
Gayton, J., “Etiology, Prevalence, and Treatment of Dry Eye Disease,” Clinical Ophthalmology, vol. 3, pp. 405-412, (2009).
[cited by applicant]
Gehlsen et al., “A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye,” Graefe's Arch. Clin. Exp. Ophthalmol., vol. 255, N…
[cited by applicant]
Gehlsen, U., et al. “Cyclosporine A using F4H5 as liquid drug carrier is effective in treating experimental dry-eye disease,” Investigative Ophthalmology & Visual Science, Abstract Only (2 pages) vol. 56, No. 7, p. 319,…
[cited by applicant]
Gehlsen, U., et al., “Omega-3 Fatty Acids Using F6H8-Carrier as Topical Therapy in Experimental Dry-Eye Disease,” Investigative Ophthalmology & Visual Science, Abstract Only (1 page), vol. 57, pp. 417, (2016).
[cited by applicant]
German, E.J., et al., “Reality of drop size from multi-dose eye drop bottles: is it cause for concern?” Eye, Vo. 13, pp. 93-100, (1999).
[cited by applicant]
Gunther, B., “Breaking the Vicious Circle of Dry Eye Disease,” OIS@ SECO, Feb. 21, 2019, pp. 1-14, New Orleans, URL: https://ois.net/wp-content/uploads/2019/02/DryEye-Novaliq.pdf.
[cited by applicant]
Hardung, H., “Semifluorierte und perfluorierte Verbindungen zur topischen und parenteralen Anwendung,” 2008, English Language Abstract, 2 pages, retrieved from https://freidok.uni-freiburg.de/data/5682 (retrieved on Jul…
[cited by applicant]
Hardung, H., “Semifluorierte und perfluorierte Verbindungen zur topischen und parenteralen Anwendung,” 2008, retrieved from http://www.freidok.uni-freiburg.de/volltexte/5682/pdf/Dissertation_Hardung.pdf (retrieved on Oc…
[cited by applicant]
Hoerauf, H. et al., “Combined Use of Partially Fluorinated Alkanes, Perfluorocarbon Liquids and Silicone Oil: An Experimental Study,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 239, No. 5, pp. 37…
[cited by applicant]
Holm, R. et al., “A novel excipient, 1-perfluorohexyloctane shows limited utility for the oral delivery of poorly water-soluble drugs,” European Journal of Pharmaceutical Sciences, vol. 42, pp. 416-422, (2011).
[cited by applicant]
IKERVIS® Prescribing Information, available at https://www.medicines.org.uk/emc/product/6937/smpc/print (Updated Mar. 2, 2022) (last accessed Apr. 27, 2023).
[cited by applicant]
Kaercher et al., “NovaTears® as new Therapy in Dry Eye Results from three prospective, multicenter, non-interventional studies in different patient populations”, TFOS Conference (Tear Film & Ocular Surface), Sep. 7-10, …
[cited by applicant]
Kumar, S. et al., “Reduction in drop size of ophthalmic topical drop preparations and the impact of treatment,” J. Adv. Pharm. Tech. Res., vol. 2, No. 3, (2011).
[cited by applicant]
Lallemand et al., “Cyclosporine A delivery to the eye: a pharmaceutical challenge,” European Journal of Pharmaceutics and Biopharmaceutics, Abstract Only, 1 page, vol. 56, No. 3, pp. 307-318, (2003).
[cited by applicant]
Lallemand et al., “Cyclosporine Delivery to the Eye: A comprehensive Review of Academic and Industrial Efforts,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 117, pp. 14-28, (2017).
[cited by applicant]
Lemp, M., “Management of Dry Eye Disease,” The American Journal of Managed Care, vol. 14, No. 3, pp. S88-S101, (2008).
[cited by applicant]
Lin, H. et al., “Dry eye disease: A review of diagnostic approaches and treatments,” Saudi Journal of Ophthalmology, vol. 28, pp. 173-181, (2014).
[cited by applicant]
Majumdar, S. et al., “A Low Concentration of Tacrolimus/Semifluorinated Alkane (SFA) Eyedrop Suppresses Intraocular Inflammation in Experimental Models of Uveitis,” Current Molecular Medicine, vol. 17, No. 3, pp. 211-22…
[cited by applicant]
Meinert, H. et al., “Semifluorinated Alkanes—A New Class of Compounds with Outstanding Properties for Use in Ophthalmology,” European Journal of Ophthalmology, vol. 10, No. 3, pp. 189-197, (2000).
[cited by applicant]
Meinert, H. et al., “The Use of Semifluorinated Alkanes in Blood-Substitutes,” Biomaterials, Artificial Cells, and Immobilization Biotechnology, vol. 21, No. 5, pp. 583-595, (1993).
[cited by applicant]
Messmer, E.M., “The Pathophysiology, Diagnosis, and Treatment of Dry Eye Disease,” Deutsches Arzteblatt International, vol. 112, No. 5, pp. 71-82, (2015).
[cited by applicant]
Messmer, et al. “Semifluorierte Alkane als Therapie bei Meibomdrüsen-Dysfunktion Ergebnisse einer prospektiven, multizentrischen Beobachtungsstudie,” DOG-Kongress, Sep. 29-Oct. 2, 2016, Berlin DOG (Deutsche Ophtalmologi…
[cited by applicant]
Messmer, et al. “Semifluorinated Alkanes as a Therapy for Meibomian Gland Dysfunction Results of a prospective, multi-centered observational study,” DOG-Kongress, Sep. 29-Oct. 2, 2016, Berlin DOG (Deutsche Ophtalmologis…
[cited by applicant]
Messmer, et al. “Semifluorinated Alkanes as a Therapy for Meibomian Gland Dysfunction Results of a prospective, multi-centered observational study,” Presentation, DOG-Kongress, Sep. 29-Oct. 2, 2016, Berlin DOG (Deutsche…
[cited by applicant]
Miller, K. et al., “Minimal Clinically Important Difference for the Ocular Surface Disease Index,” Socioeconomics and Health Services, Arch Ophthalmol, vol. 128, No. 1, pp. 94-101, (2010).
[cited by applicant]
Murphy, C. et al., “Cyclosporine vs Tacrolimus Therapy for Posterior and Intermediate Uveitis,” Arch Ophthalmol., vol. 123, pp. 634-641, (2005).
[cited by applicant]
O'Rourke, M. et al., “Enhancing Delivery of Topical Ocular Drops,” Cataract & Refractive Surgery Today Europe, 2016, 2 pages.
[cited by applicant]
Perry, H., “Dry Eye Disease: Pathophysiology, Classification, and Diagnosis,” The American Journal of Managed Care, vol. 14, No. 3, pp. S79-S87, (2008).
[cited by applicant]
Pflugfelder et al., “The Pathophysiology of Dry Eye Disease What We Know and Future Directions for Research,” Ophthalmology, vol. 124, No. 11 Supplement, pp. S4-S13, (2017).
[cited by applicant]
Qiao, J. et al., “Emerging treatment options for meibomian gland dysfunction,” Clinical Ophthalmology, vol. 7, pp. 1797-1803, (2013).
[cited by applicant]
RESTASIS® Prescribing Information, available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050790s020lbl.pdf (Nov. 2012) (last accessed Feb. 28, 2023).
[cited by applicant]
Sall, K. et al., “Two Multicenter, Randomized Studies of the Efficacy and Safety of Cyclosporine Ophthalmic Emulsion in Moderate to Severe Dry Eye Disease,” Ophthalmology, vol. 107, No. 4, pp. 631-639, (2000).
[cited by applicant]
Scherer et al., “Eyesol: A Novel Topical Ocular Drug Delivery System for Poorly Soluble Drugs,” Drug Development & Delivery, vol. 13, No. 1, pp. 40-44, (2013).
[cited by applicant]
Schmutz et al., “Fluorinated Vesicles Made from Combinations of Phospholipids and Semifluorinated Alkanes. Direct Experimental Evidence of the Location of the Semifluorinated Alkane within the Bilayer”, Langmuir, vol. 1…
[cited by applicant]
Sheppard, J. et al., “A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 Essence Study,” Cornea, vol. 40, No. 10, pp. 1290-1297, (2021).
[cited by applicant]
Spöler et al., “Towards a New in vitro Model of Dry Eye: The ex vivo Eye Irritation Test,” Developments in Ophthalmology, vol. 45, pp. 93-107, (2010).
[cited by applicant]
Steven et al., “Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease Due to Meibomian Gland Disease,” Journal of Ocular Pharmacology and Therapeutics, vol. 33, No. 9, pp. 1-8, (2017).
[cited by applicant]
Steven, P. et al. “Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease—A Prospective, Multicenter Noninterventional Study” Journal of Ocular Pharmacology and Therapeutics, vol. 31, No. 8, pp. 498-503, (201…
[cited by applicant]
Steven, P. et al., “Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease—A Prospective, Multicenter Noninterventional Study,” Investigative Ophthalmology & Visual Science, vol. 56, p. 4493, (2015), Abstract…
[cited by applicant]
Torkildsen, G. et al., “A Clinical Phase 2 Study to Assess Safety, Efficacy, and Tolerability of CyclASol for the Treatment of Dry Eye Disease,” Poster Presentation at American Academy of Ophthalmology (AAO), New Orlean…
[cited by applicant]
Wirta, David L. et al., “A Clinical Phase II Study to Assess Efficacy, Safety and Tolerability of Waterfree Cyclosporine Formulation for the Treatment of Dry Eye Disease,” Ophthalmology, vol. 126, pp. 792-800, (2019).
[cited by applicant]
Wong, D. et al., “Perfluorocarbons and Semifluorinated Alkanes,” Seminars in Ophthalmology, vol. 15, No. 1, pp. 25-35, (2000).
[cited by applicant]
Xalatan, Latanoprost Ophthalmic Solution, 50 μg/mL Prostaglandin F 2α analogue, Product Monograph, Jul. 21, 2014, 30 pages.
[cited by applicant]
Yaoxue Zhuanye Zhishi II (Editor: Jin Xiangqun), Military Medical Science Press, 1st Printing of 2nd Edition, Mar. 2009, p. 158.
[cited by applicant]
Yaoxue Zhuanye Zhishi II (Editor: Jin Xiangqun), Military Medical Science Press, 1st Printing of 2nd Edition, Mar. 2009, p. 158, 3 pages (English Machine Translation).
[cited by applicant]
Zeng, Y., “Atlas of Clinical Keratoconjunctival Disease,” Hubei Science and Technology Press, pp. 287-299, (2011).
[cited by applicant]
Zeng, Y., “Atlas of Clinical Keratoconjunctival Disease,” Hubei Science and Technology Press, pp. 287-299, (2011), English Translation.
[cited by applicant]
Zhang, X. et al., “Dry Eye Management: Targeting the Ocular Surface Microenvironment,” International Journal of Molecular Sciences, vol. 18, pp. 1398, 28 pages, (2017).
[cited by applicant]
“PharmaNews,” Kompass Ophthalmologie, vol. 2, No. 2, pp. 98-99, (2016).
[cited by applicant]
Agarwal, P. et al., “Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs,” International Journal of Pharmaceutics, vol. 538, No. 1-2, pp. 119-129, (2018).
[cited by applicant]
English language machine translation for “PharmaNews,” Kompass Ophthalmologie, vol. 2, No. 2, pp. 98-99, (2016).
[cited by applicant]
Pensyl, D., “Chapter 14: Preparations for Dry Eye and Ocular Surface Disease,” Clinical Ocular Pharmacology, Fifth Edition, pp. 263-278, 18 pages, (2008).
[cited by applicant]
Utine, C. et al., “Clinical Review: Topical Ophthalmic Use of Cyclosporin A,” Ocular Immunology & Inflammation, vol. 18, No. 5, pp. 352-361, (2010).
[cited by applicant]