Granted Patent
B2
US 12,397,000 · App. 18/893,796 · Granted Aug 26, 2025
Stabilized ophthalmic dexamethasone compositions
Assignee:
Oculis Operations Sàrl
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The present disclosure relates to a method for stabilizing the pH of an aqueous composition comprising a drug which is prone to oxidation, said method comprising the addition of an additive to prevent oxidation of the drug which is prone to oxidation. In particular, the present disclosure relates to a method for stabilizing the pH of an aqueous composition comprising a corticosteroid, said method comprising the addition of an additive to prevent oxidation of the corticosteroid. The present disclosure also relates to a composition comprising a corticosteroid and an additive to prevent oxidation of the corticosteroid.
Claims (36)
1. An aqueous ophthalmic composition comprising:
i) between 1% and 4% weight to volume (w/v) of dexamethasone;
ii) between 5% and 25% w/v of γ-cyclodextrin;
iii) between 0.1% and 0.5% w/v of sodium thiosulfate; and,
iv) water;
wherein the aqueous ophthalmic composition comprises a microsuspension comprising solid complexes of dexamethasone and γ-cyclodextrin;
wherein the aqueous ophthalmic composition is in a container made of plastic that allows oxidation of its contents; and,
wherein the aqueous ophthalmic composition has a pH of between 4.5 and 6.
2. The aqueous ophthalmic composition of claim 1 , wherein the composition comprises 1.5% w/v of dexamethasone.
3. The aqueous ophthalmic composition of claim 1 , wherein the composition comprises 14% w/v of γ-cyclodextrin.
4. The aqueous ophthalmic composition of claim 1 , wherein the composition further comprises between 2.2% and 2.8% w/v of a poloxamer.
5. The aqueous ophthalmic composition of claim 4 , wherein the composition comprises 2.5% w/v of the poloxamer.
6. The aqueous ophthalmic composition of claim 4 , wherein the poloxamer is selected from the group consisting of poloxamer 101, poloxamer 105, poloxamer 108, poloxamer 122, poloxamer 123, poloxamer 124, poloxamer 181, poloxamer 182, poloxamer 183, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 212, poloxamer 215, poloxamer 217, poloxamer 231, poloxamer 234, poloxamer 235, poloxamer 237, poloxamer 238, poloxamer 282, poloxamer 284, poloxamer 288, poloxamer 331, poloxamer 333, poloxamer 334, poloxamer 335, poloxamer 338, poloxamer 401, poloxamer 402, poloxamer 403, poloxamer 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate.
7. The aqueous ophthalmic composition of claim 6 , wherein the poloxamer is poloxamer 407.
8. The aqueous ophthalmic composition of claim 1 , wherein the composition further comprises between 0% and 0.2% w/v of disodium edetate.
9. The aqueous ophthalmic composition of claim 8 , wherein the composition comprises 0.1% w/v of disodium edetate.
10. The aqueous ophthalmic composition of claim 1 , wherein the composition further comprises between 0% and 1% w/v of an electrolyte.
11. The aqueous ophthalmic composition of claim 10 , wherein the electrolyte is selected from the group consisting of sodium chloride and potassium chloride.
12. The aqueous ophthalmic composition of claim 10 , wherein the electrolyte is sodium chloride.
13. The aqueous ophthalmic composition of claim 1 , wherein the composition comprises 0.3% w/v of sodium thiosulfate which corresponds to water-free sodium thiosulfate.
14. The aqueous ophthalmic composition of claim 1 , wherein the sodium thiosulfate is sodium thiosulfate pentahydrate.
15. The aqueous ophthalmic composition of claim 1 , wherein the solid complexes comprise microparticles with a diameter D 50 ranging from 1 μm to 10 μm.
16. The aqueous ophthalmic composition of claim 1 , wherein the container is made of low-density polyethylene (LDPE).
17. An aqueous ophthalmic composition comprising:
i) between 1% and 4% weight to volume (w/v) of dexamethasone;
ii) between 5% and 25% w/v of γ-cyclodextrin;
iii) between 0.1% and 0.5% w/v of sodium thiosulfate; and,
iv) water;
wherein the aqueous ophthalmic composition comprises a microsuspension comprising solid complexes of dexamethasone and γ-cyclodextrin;
wherein the aqueous ophthalmic composition is in a container that allows oxidation of its contents and, wherein the aqueous ophthalmic composition has a pH of between 4.5 and 6.
18. The aqueous ophthalmic composition of claim 17 , wherein the composition further comprises between 0% and 0.2% w/v of disodium edetate.
19. The aqueous ophthalmic composition of claim 18 , wherein the composition further comprises between 0% and 1% w/v of an electrolyte.
20. The aqueous ophthalmic composition of claim 19 , wherein the composition further comprises between 2.2% and 2.8% w/v of a poloxamer.
21. The aqueous ophthalmic composition of claim 20 , wherein the composition comprises 1.5% w/v of dexamethasone.
22. The aqueous ophthalmic composition of claim 20 , wherein the composition comprises 14% w/v of γ-cyclodextrin.
23. The aqueous ophthalmic composition of claim 17 , wherein the solid complexes comprise microparticles with a diameter D 50 ranging from 1 μm to 10 μm.
Assignments (3)
CHANGE OF NAME
Recorded Oct 30, 2024
From: OCULIS OPERATIONS GMBH
To: OCULIS OPERATIONS SÀRL
Reel/Frame 069271/0596 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 4, 2024
From: LOFTSSON, THORSTEINN; FÜLÖP, ZOLTÁN
To: OCULIS SA
Reel/Frame 068804/0492 →
Priority Claims (2)
EP 19183719
· Jul 1, 2019
· regional
EP 20174202
· May 12, 2020
· regional
Continuity (2)
Continuation
17624311
References Cited (193)
US 5051402A
· Kurihara et al.
· 1991
[cited by applicant]
US 5472954A
· Loftsson et al.
· 1995
[cited by applicant]
US 5951971A
· Kawashima et al.
· 1999
[cited by applicant]
US 6969706B1
· Chang et al.
· 2005
[cited by applicant]
US 7893040B2
· Loftsson et al.
· 2011
[cited by applicant]
US 8633172B2
· Loftsson et al.
· 2014
[cited by applicant]
US 8999953B2
· Loftsson et al.
· 2015
[cited by applicant]
US 20020045601A1
· Kawashima et al.
· 2002
[cited by applicant]
US 20020198174A1
· Lyons
· 2002
[cited by applicant]
US 20040077562A1
· Chandavarkar
· 2004
[cited by applicant]
US 20050234018A1
· Lyons et al.
· 2005
[cited by applicant]
US 20060292099A1
· Milburn et al.
· 2006
[cited by applicant]
US 20070148192A1
· Laddha
· 2007
[cited by applicant]
US 20080119448A1
· Friedlaender et al.
· 2008
[cited by applicant]
US 20080145430A1
· Panmai et al.
· 2008
[cited by applicant]
US 20090312724A1
· Pipkin et al.
· 2009
[cited by applicant]
US 20140163080A1
· Horn
· 2014
[cited by applicant]
US 20160346347A1
· Loftsson
· 2016
[cited by applicant]
US 20190105264A1
· Higuchi et al.
· 2019
[cited by applicant]
CN 1559413A
· 2005
[cited by applicant]
CN 1785192A
· 2006
[cited by applicant]
CN 101926760A
· 2010
[cited by applicant]
CN 115837027A
· 2023
[cited by applicant]
DE 19957788A1
· 2001
[cited by applicant]
EP 0579435B1
· 1994
[cited by applicant]
EP 0709099A2
· 1996
[cited by applicant]
EP 1047406B1
· 2003
[cited by applicant]
JP S60149530A
· 1985
[cited by applicant]
KR 20140026953A
· 2014
[cited by applicant]
WO WO1997010805A1
· 1997
[cited by applicant]
WO WO199806381A1
· 1998
[cited by applicant]
WO WO199936055
· 1999
[cited by applicant]
WO WO2004069280
· 2004
[cited by applicant]
WO WO2004087100
· 2004
[cited by applicant]
WO WO2005105067
· 2005
[cited by applicant]
WO WO2009129155
· 2009
[cited by applicant]
WO WO2010053487A1
· 2010
[cited by applicant]
WO WO2017083799
· 2017
[cited by applicant]
WO WO2017196881
· 2017
[cited by applicant]
WO WO2018100434
· 2018
[cited by applicant]
WO WO2020139525
· 2020
[cited by applicant]
WO WO2021001366
· 2021
[cited by applicant]
2.9.31 Particle size analysis by laser light diffraction, European Pharmacopeia 9.0, pp. 349-352.
[cited by applicant]
Ammar et al. “Cyclodextrins in acetazolamide eye drop formulations” Pharmazie, vol. 53, pp. 559-562, Govi-Verlag Pharmazeutischer Verkag GmbH, Eschborn, Germany, 1998.
[cited by applicant]
Beeley et al. Fabrication, implantation, elution, and retrieval of a steroid-loaded polycaprolactone subretinal implant Journal of biomedical materials research, vol. 74, pp. 437-444, Wiley Periodicals, Inc., USA, 2005.
[cited by applicant]
Bhatia, Saurabh “Chapter 2: Nanparticles Types, classification, characterization, fabrication methods and drug delivery applications” Natural Polymer Drug Delivery Systems, pp. 33-93, 2016.
[cited by applicant]
Bonini, M. et al. Self-assembly of beta-cyclodextrin in water. Part 1: Cryo-TEM and dynamic and static light scattering. Langmuir 22, pp. 1478-1484, 2006.
[cited by applicant]
Brewster, Marcus E. et al. “Cycolodextrins as pharmaceutical solubilizers”, Advanced Drug Delivery Reviews, vol. 59, pp. 645-666, 2007.
[cited by applicant]
Chadha, Renu et al. “Kinetics of degradation of diclofenac sodium in aqueous solution determined by a calorimetric method,” Die Pharmazie, vol. 58, pp. 631-635, 2003.
[cited by applicant]
Chen, Bin et al. “A comparative study of enol aldehyde formation from betamethasone, dexamethasone, beclomethasone and related compounds under acidic and alkaline conditions” Steroids, vol. 74, No. 1, pp. 30-41, 2009.
[cited by applicant]
Chen, Quan et al. “A validated, stability-indicating HPLC method for the determination of dexamethasone related substances on dexamethasone-coated drug-eluting stents” Journal of Pharmaceutical and Biomedical Analysis, …
[cited by applicant]
Cohen, E.M. “Dexamethasone, Analytical Profiles of Drug Substances,” vol. 2, pp. 163-197, 1973.
[cited by applicant]
Conrow, Raymond E. et al. “Corticosteroid Decomposition via a Mixed Anhydride”, The Journal of Organic Chemistry, vol. 67, pp. 6835-3836, 2002.
[cited by applicant]
Dalton, K. et al. Physical Properties of soft contact lens solutions, Optometry and Vision Science, vol. 85m No. 2, pp. 122-128, Feb. 2008.
[cited by applicant]
Dalton, P.H. “Osmolality and viscosity of artificial tears” American Academy of Optometry, downloaded from <URL https://www.aaopt.org/detail/kowledge-base-article/ph-osmolality-and-viscosity-artificial-tears> on Sep. 24…
[cited by applicant]
Duan et al. “Cyclodextrin solubilization of the antibacterial agents triclosan and tricloscarban; formation of aggregates and higher-order complexes” International Journal of Pharmaceutics, vol. 297, pp. 213-222, Nether…
[cited by applicant]
Fenyvesi, E. “Approved Pharmaceutical Products Continuing Cyclodextrins,” Cyclodextrin News, vol. 27, No. 2, Feb. 2013.
[cited by applicant]
Frioriksdottir, Hafru “Polymer enhancement of cyclodextrin complexation in vivo and in vitro observations,” A Doctoral Thesis, pp. 6-117, University, IS, 1997.
[cited by applicant]
Gan, L. et al. “Recent advances in topical ophthalmic drug delivery with lipid-based nanocarriers” Drug Discov. Today, vol. 18, pp. 290-297, 2013.
[cited by applicant]
Gonzalez-Gaitano et al. “The aggregation of cyclodextrins as studied by Photon Correction Spectroscopy” Journal of Inclusion Phenomena and Macrocylclic Chemistry, vol. 44, pp. 101-105, Kluwer Academic Publishers, Nether…
[cited by applicant]
Gudmundsdottir, B.S. et al. γ-Cyclodextrin nanoparticle eye drops with dorzolamide: effect on intraocular pressure in man. J Ocul Pharmacol Ther. 30:35-41, 2014.
[cited by applicant]
He, Y. et al. “Cyclodextrin-based aggregates and characterization by microscopy” Micron, vol. 39, pp. 495-516, 2008.
[cited by applicant]
Hidaka, Teturo, et al. “Studies on betamethasone: Behavior of betamethasone in acid or alkaline medium, Photolysis and Oxidation” Yakugaku Zasshi, vol. 100, No. 1, pp. 72-80, 1980.
[cited by applicant]
Higuchi, T. et al. “Phase solubility techniques. Advances in Analytical Chemistry of Instrumentation” vol. 4, pp. 117-212, 1965.
[cited by applicant]
Horsky, J et al. “Inclusion complexes of proteins: interaction of cyclodextrins with peptides containing aromatic amino acids studies by competitive spectrophotometry” J. Inclusion Phenom. Mal. Recognit, Chem., vol. 18,…
[cited by applicant]
International Search Report and Written Opinion for PCT/IB20417/001659, dated May 3, 2018, 10 pages.
[cited by applicant]
International Search Report and Written Opinion for PCT/EP2020/068398, dated Aug. 17, 2020, 11 pages.
[cited by applicant]
Jansook, Phatsawee et al. “γCD/HPγCD mixtures as solubilizer: solid-state characterization and sample dexamethasone eye droop suspension” Journal of Pharmacy & Pharmaceutical Sciences, vol. 13, No. 3, pp. 336-350, 2010.
[cited by applicant]
Jansook, Phatsawee et al. “Effect of self-aggregation of γ-cyclodextrin on drug solubilization” Journal of Inclusion Phenomena and Macrocyclic Chemistry, vol. 68, pp. 229-236, 2010.
[cited by applicant]
Jansook, P. et al “Cyclodextrin-poloxamer aggregates as nanocarriers in eye drop formulations: dexamethasone and amphotericin B” Taylor & Francis, 2016.
[cited by applicant]
Johannessen, G. et al. “Kinetics of y-cyclodextrin nanoparticle suspension eye drops in tear fluid. Acta Ophthalmologica” vol. 92, pp. 550-556, 2014.
[cited by applicant]
Johannsdoltir, S. et al. “Formulations and toxicologic in vivo studies of aqueous cyclosporin an eye drops with cyclodextrin nanoparticles” In J. Pharm. vol. 529, pp. 486-490, 2017.
[cited by applicant]
Johannsdoltir, S. et al. “Development of a cyclodextrin-based aqueous cyclosporin a eye drop formulations” Int. J. Pharm. Vol. 493, pp. 86-95, 2015.
[cited by applicant]
Jonas “Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and neovascular diseases” Acta Ophalmologica Scandinavia, vol. 83, 99. 645-663, Munksgaard, Denmark, 2005.
[cited by applicant]
Jozwiakowski, M. et al. “Aqueous solubility behavior of three cyclodexteins” Carbohydrate Research, vol. 143, pp. 51-59, 1985.
[cited by applicant]
Kabat et al. “Not all tears are created equal”, Review of Optometry, vol. 142(1), 3 pages, 2005.
[cited by applicant]
Kanai, A. et al. “The effect on the cornea of alpha cyclodextrin vehicle for cyclosporin eye drops” Transplant Proc., vol. 21, pp. 3150-3152, 1989.
[cited by applicant]
Korenfeld et al. OCS-01 (Novel Topical Dexamethasone Formulation) in Inflammation and Pain Post Cataract Surgery: A Randomized, Double-Masked, Vehicle-Controlled Study, Clinical Therapeutics, vol. 44, Issue 12, pp. 1577…
[cited by applicant]
Kristinsson et al. “Dexamethasone-Cyclodextrin-Polymer Co-complexes in aqueous eye drops” Investigative ophthalmology & Visual science, vol. 37, No. 6 pp. 1199-1203, Lippincott-Raven Publication USA, 1996.
[cited by applicant]
Kunert, K.S. et al. “Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine” Archives of Ophthalmology, vol. 120, pp. 330-337, 2002.
[cited by applicant]
Kurkov, S.V. et al. “Cyclodextrins”, Int. J. Pharm. vol. 453, pp. 167-180, 2013.
[cited by applicant]
Laupacis, A. et al. “Cyclosporin A: a powerful immunosuppressant” Canadian Medical Association Journal, vol. 126, pp. 1041-1046, 1982.
[cited by applicant]
Lawen, A. “Biosynthesis of cyclosphorins and other natural peptidyl proyl cis/trans isomerase inhibitors” Biochimica et Biophysica Acta, vol. 1850, pp. 2111-2120, 2015.
[cited by applicant]
Le Bourlais, C. et al. “Ophthalmic drug delivery systems-recent advances. Progress in Retinal and Eye Research” vol. 17, pp. 33-58, 1998.
[cited by applicant]
Li, Min Various Types and Mechanisms of Degradation Reactions, Chapter 4, RSC Drug Discovery Series No. 29, Organic Chemistry of Drug Degradation, 2012.
[cited by applicant]
Loftsson et al. “Cyclodextrins in eye drop formulations: Enhanced topical delivery of corticosteroids to the eye”, Acta Ophthalmologica Scandinavica, Hvidovre, Dk. vol. 80, No. 2, p. 144-150, Apr. 1, 2002.
[cited by applicant]
Loftsson et al. “Cyclodextrins and topical drug delivery to the anterior and posterior segments of the eye” International Journal of Pharmaceutics, 2017.
[cited by applicant]
Loftsson et al. “Pharmaceutical applications of cyclodextrins: basic science and product development” Journal of Pharmacy and Pharmacology, vol. 62, pp. 1607-1621, 2010.
[cited by applicant]
Loftsson, T. “Self-assembled cyclodextrin nanoparticles and drug delivery” J. Incl. Phenom. Macro. vol. 80, pp. 1-7, 2014.
[cited by applicant]
Loftsson et al. “Pharmaceutical applications of cyclodextrins: effects on drug permeation through biological membranes” J. Pharm. Pharmacol. 63, pp. 1119-1135, 2011.
[cited by applicant]
Loftsson et al. “Determination of aqueous solubility by heating and equilibration: A technical note” AAPS PharmSciTech 7, article No. 4, 2006.
[cited by applicant]
Loftsson et al. “Topical drug delivery to the posterior segment of the eye: anatomical and physiological considerations” Pharmazie, vol. 63, pp. 171-179, 2008.
[cited by applicant]
Loftsson et al. “Cyclodextrins in drug delivery” Expert Opinion, vol. 2, Drug Delivery, pp. 335-351, Ashley Publications Ltd. London, 2005.
[cited by applicant]
Loftsson et al. “Cyclodextrins in ophthalmic drug delivery” Advanced Drug Delivery Reviews, vol. 36, pp. 59-79, Netherlands, 1999.
[cited by applicant]
Loftsson et al. “Topical dexamethasone delivery to the retina: An aqueous cyclodextrin-based microsuspension” Journal of drug delivery science and technology, 81, 2023.
[cited by applicant]
Loftsson et al. “The effects of organic salts on the cyclodextrins solubilization of drugs” International Journal of Pharmaceutics, vol. 262, pp. 101-107, Netherlands, 2003.
[cited by applicant]
Loftsson et al. “The effects of water-soluble polymers on cyclodextrins and cyclodextrin solubilization of drugs” J. Drug Del. Sci. Tech. vol. 14, pp. 35-43, Ed. De Sante, France, 2004.
[cited by applicant]
Loftsson et al. “Topical drug delivery to the eye: dorzolamide” Acta Ophthalmologica vol. 90, pp. 603-608, 2012.
[cited by applicant]
Loftsson et al. “Self-Association of Cyclodextrins and Cyclodextrin Complexes”, Journal of Pharmaceutical Sciences, vol. 93, No. 5, pp. 1091-1099, Wiley-Liss, Inc. and the American Pharmacists Association, USA, 2004.
[cited by applicant]
Loftsson et al. “Cyclodextrins solubilization of the antibacterial agents Triclosan and Triclocarban; Effect of ionization and polymers” Journal of inclusion phenomena and macrocyclic chemistry, vol. 52, pp. 109-117, Ne…
[cited by applicant]
Loftsson et al. “Pharmaceutical applications of cyclodextrins. 1 Drug solubilization and stabilization” Journal of Pharmaceutical Sciences, vol. 85, pp. 1017-1025, 1996.
[cited by applicant]
Loftsson et al. “Evaluation of cyclodextrin solubilization of drugs” International Journal of Pharmaceutics, vol. 302, pp. 18-28, Netherlands, 2005.
[cited by applicant]
Loftsson et al. “Topically effective ocular hypotensive acetazolamide and ethoxyzolamide formulations in rabbits” J. Pharm. Pharmacol. vol. 46, pp. 503-504, Pharmaceutical Press England, 1994.
[cited by applicant]
Loftsson et al. Cyclodextrin Microparticles for drug delivery to the posterior segment of the eye: Aqueous dexamethasone Eye Drops, vol. 59, No. 5 J. Pharm. Pharmacol. 629-635, 2007.
[cited by applicant]
Loftsson et al. “Cyclodextrin solubilization of benzodiazephines: formulation of midazolam nasal spray” International Journal of Pharmaceutics, vol. 212, pp. 29-40, Netherlands, 2001.
[cited by applicant]
Loftsson et al. “Aqueous eye drops containing drug/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment” Acta Ophthalmologica, 2022.
[cited by applicant]
Magnusdottir et al. “Self-association and cyclodextrin solubilizations of NSAIDs” Journal of Inclusion phenomena and macrocyclic chemistry, vol. 44, pp. 213-218, Kluwer Academic Publishers, Netherlands, 2002.
[cited by applicant]
Mele et al. “Non-covalent associations of cyclomaltooligosaccharides (cyclodextrins) with trans-B-carotene in water: evidence for the formation of large aggregates by light scattering and NMR spectroscopy”, Carbohydrate…
[cited by applicant]
Messner, M. et al. “Self-assembled cyclodextrin aggregates and nanoparticles” Int. J. Pharm. vol. 387, pp. 199-208, 2010.
[cited by applicant]
Miyake, K. et al. Enhanced absorption of cyclosporin A by complexation with dimethyl-beta-cyclodextrin in bile duct-cannulated and -noncannulated rats: Biological & Pharmaceutical Bulletin, vol. 22, pp. 66-72, 1999.
[cited by applicant]
Moya-Ortega et al. “Dexamethasone eye drops containing γ-cyclodextrin-based nanogels” Int J. Pharm. 441, 507-515, 2013.
[cited by applicant]
Muankaew, C. et al. “Cyclodextrin-based telmisartan Ophthalmic Suspension: Formulation development for water-insoluble drugs” International Journal of Pharmaceutics, vol. 507, pp. 21-31, 2016.
[cited by applicant]
Muankaew, C. et al. “Effect of y-cyclodextrin on solubilization and complexion of irbesartan: influence of pH and excipients” Int. J. Pharm. vol. 474, pp. 80-90, 2014.
[cited by applicant]
Myles et al. “Recent progress in ocular drug delivery for posterior segment disease: Emphasis on transscleral iontophoresis” Advanced drug delivery reviews, vol. 57, pp. 2063-2079, Netherlands, 2005.
[cited by applicant]
Oculis Holding AG—Form F-4 Registration Statement; Securities and Exchange Commission; Registration No. 333, filed Nov. 7, 2022.
[cited by applicant]
Oculis announces positive top line results from DIAMOND Stage 1 Phase 3 Trial in Diabetic Macular Edema with OCS-01 Eye Drops, May 22, 2023.
[cited by applicant]
Oculis Completes Series A Financing, Internet website https://www.businesswire.com/news/home/20160816005055/en/Oculi . . . ; accessed Aug. 1, 2023, Reykjavik, Iceland, Aug. 16, 2016.
[cited by applicant]
Ohira, Akihiro et al. “Topical dexamethasone c-cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema” Acta Ophthalmologica, 93:610-615, 2015.
[cited by applicant]
Peel, M. et al. “Semi-synthesis of cyclosphorins” Biochimica et Biophysica Acta, vol. 1850, pp. 2121-2144, 2015.
[cited by applicant]
Raghava et al. “Periocular routes for retinal drug delivery”, Expert Opinion, Drug Delivery, vol. 1 pp. 99-114, Ashley Publications Ltd., England, 2004.
[cited by applicant]
Rowe, Raymond C., et al. “Cyclodextrins”, Handbook of Pharmaceutical Excipients, 4
[cited by applicant]
Russo, S. et al. Dexamethasone-netilmicin: a new ophthalmic steroid-antibiotic combination. Effcacy and safety after cataract surgery, Eye 21, 58-64, 2007.
[cited by applicant]
Sabadini, E. et al. “Solubility of cyclomaltooligosaccharides (cyclodextrins) in H2O and D2O: a comparative study” Carbohydrate Research vol. 341, No. 2, pp. 207-274, 2006.
[cited by applicant]
Salminen et al. “Disposition of ophthalmic timolol in treated and untreated rabbit eyes. A multiple and single dose study” Exp. Eye Res. vol. 38, pp. 203-206, Academic Press Inc. London, 1984.
[cited by applicant]
Schloesser, Paul “Oculis eye drop secures another late-stage win, this time in post-cataract surgery inflammation and pain” Endpoint News https://endpts.com/oculis-eye-drop-meets-primary-endpoints-in-phiii-post-surgery-…
[cited by applicant]
Shah, Tirth J et al. “Intracameral dexamethasone injection in the treatment of cataract surgery induced inflammation: design, development, and place in therapy” Clinical Ophthalmology, 12; 2223-2235; 2018.
[cited by applicant]
Spangler, M. et al. “A validated, stability-indicating method for the assay of dexamethasone in drug substance and drug product analyses, and the assay of preservatives in drug product”, Chromatographia, vol. 54, pp. 32…
[cited by applicant]
Stamm, Hermann: Overview of the methods and techniques of measurement of nanoparticles Nanotrust-Possible Health Effects of Manufactured Nanomaterials, 52 pages, 2009.
[cited by applicant]
Stefansson, Einar et al. Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double-masked, vehicle-controlled study, Acta Ophthalmologica, 101:22-33; 2023.
[cited by applicant]
Stella, V.J. et al. Cyclodextrins Tox. Pathol. vol. 36, pp. 30-42, 2008.
[cited by applicant]
Sugrue, M.F. “The pharmacology of antiglaucoma drugs”, Pharmacology & Therapeutics, vol. 43, pp. 91-138, 1989.
[cited by applicant]
Tanito, M et al. “Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular edema” Invest. Ophth. Vis. Sci. vol. 52, pp. 7944-7948, 2011.
[cited by applicant]
Tayar, El et al. Solvent-dependent conformation and hydrogen-bonding capacity of cyclosphorin A: evidence from partition coefficients and molecular dynamics simulations, J. Med. Chem. vol. 36, pp. 3753-3764, 1993.
[cited by applicant]
Urtti, A. “Challenges and obstacles of ocular pharmacokinetics and drug delivery” Drug Del. Rev., vol. 58, pp. 1131-1135, 2006.
[cited by applicant]
Usayapant, A. et al. “Effect of 2-Hydroxypropyl-β-cyclodextrin on the Ocular Absorption of dexamethasone and dexamethasone acetate,” Pharmaceutical Research, vol. 8, No. 12, pp. 1495-1499, 1991.
[cited by applicant]
Utine, C.A. et al. Topical Ophthalmic use of cyclosporin A. Ocular Immunology & Inflammation: vol. 18, pp. 352-361, 2010.
[cited by applicant]
Yasukawa et al. “Intracular sustained drug delivery using implantable polymeric devices” Advanced drug delivery reviews, vol. 57, pp. 2033-2046, Netherlands, 2005.
[cited by applicant]
Zimmer et al. “Microspheres and nanoparticles used in ocular delivery systems” Advanced Drug Delivery Reviews, vol. 16.pp. 61-73, Netherlands, 1995.
[cited by applicant]
U.S. Pat. No. 7,893,040 B2, U.S. Appl. No. 11/489,466, Loftsson et al., Feb. 22, 2011.
[cited by applicant]
U.S. Pat. No. 8,633,172 B2, U.S. Appl. No. 13/758,955, Loftsson et al., Jan. 21, 2014.
[cited by applicant]
U.S. Pat. No. 8,999,953 B2, U.S. Appl. No. 14/106,265, Loftsson et al., Apr. 7, 2015.
[cited by applicant]
U.S. Pat. No. 11,135,311 B2, U.S. Appl. No. 15/826,247, Loftsson et al., Oct. 5, 2021.
[cited by applicant]
U.S. Pat. No. 11,491,240 B2, U.S. Appl. No. 17/487,354, Loftsson et al., Nov. 8, 2022.
[cited by applicant]
U.S. Pat. No. 12,090,160 B2, U.S. Appl. No. 18/383,991, Loftsson et al., Sep. 17, 2024.
[cited by applicant]
U.S. Pat. No. 12,090,161 B2, U.S. Appl. No. 18/383,993, Loftsson et al., Sep. 17, 2024.
[cited by applicant]
U.S. Pat. No. 12,090,162 B2, U.S. Appl. No. 18/384,000, Loftsson et al., Sep. 17, 2024.
[cited by applicant]
U.S. Pat. No. 12,097,209 B2, U.S. Appl. No. 17/624,311, Loftsson et al., Sep. 24, 2024.
[cited by applicant]
US, 2023/0042785, A1, U.S. Appl. No. 17/973,749, Loftsson et al., Feb. 9, 2023.
[cited by applicant]
US, 2024/0058358, A1, U.S. Appl. No. 18/383,987, Loftsson et al., Feb. 22, 2024.
[cited by applicant]
US, 2024/0058361, A1, U.S. Appl. No. 18/383,999, Loftsson et al., Feb. 22, 2024.
[cited by applicant]
US, 2024/0091377, A1, U.S. Appl. No. 18/517,529, Loftsson et al., Mar. 21, 2024.
[cited by applicant]
U.S. Appl. No. 18/792,377, Loftsson et al., filed Aug. 1, 2024.
[cited by applicant]
U.S. Appl. No. 18/893,790, Loftsson et al., filed Sep. 23, 2024.
[cited by applicant]
U.S. Appl. No. 18/893,798, Loftsson et al., filed Sep. 23, 2024.
[cited by applicant]
U.S. Appl. No. 18/893,805, Loftsson et al., filed Sep. 23, 2024.
[cited by applicant]
U.S. Appl. No. 18/893,806, Loftsson et al., filed Sep. 23, 2024.
[cited by applicant]
U.S. Appl. No. 18/893,810, Loftsson et al., filed Sep. 23, 2024.
[cited by applicant]
Delaney-Gesing, Alex “Positive topline data reported in phase 3 DME trial of OCS-01” Glance by Eyes On Eyecare, XP093155144, Retrieved from the Internet: URL: https://glance.eyesoneyecare.com/stories/2023-05-23/positive…
[cited by applicant]
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), “Scientific Opinion on the re-evaluation of sorbic acid (E 200), potassium sorbate (E 202) and calcium sorbate (E 203) as food additives.” EFSA Jour…
[cited by applicant]
Jansook, Phatsawee et al., “Cyclodextrin solubilization of carbonic anhydrase inhibitor drugs: formulation of dorzolamide eye drop microparticle suspension” European journal of pharmaceutics and biopharmaceutics 76.2, 2…
[cited by applicant]
Johannsdottir, S. et al. “Topical drug delivery to the posterior segment of the eye: Dexamethasone concentrations in various eye tissues after topical administration for up to 15 days to rabbits” Journal of Drug Deliver…
[cited by applicant]
Li, Xiaolin, et al., “Development of dexamethasone suspension eye drops: A comparative investigation of ternary and quaternary cyclodextrin aggregates.” Journal of Drug Delivery Science and Technology 82: 104383, 2023.
[cited by applicant]
Study details of clinical trial NCT05608837—Multicenter Study on the Efficacy and Safety of OCS-01 in Subjects With Uveitis Related and Post Surgical Macular Edema (LEOPARD) earliest version, Retrieved from the Internet…
[cited by applicant]
Tatsumi, Tomoaki, “Current treatments for diabetic macular edema.” International Journal of Molecular Sciences 24.11: 9591, 2023.
[cited by applicant]
Yau, Joanne W. Y. et al. “Global prevalence and major risk factors of diabetic retinopathy” Diabetes care 35.3, 556-564, 2012.
[cited by applicant]
U.S. Pat. No. 12,233,133 B2, U.S. Appl. No. 18/517,529, Loftsson et al., Feb. 25, 2025.
[cited by applicant]
US, 2024/0390515, A1, U.S. Appl. No. 18/792,377, Loftsson et al., Nov. 28, 2024.
[cited by applicant]
US, 2025/0009757, A1, U.S. Appl. No. 18/893,790, Loftsson et al., Jan. 9, 2025.
[cited by applicant]
US, 2025/0009759, A1, U.S. Appl. No. 18/893,798, Loftsson et al., Jan. 9, 2025.
[cited by applicant]
US, 2025/0009760, A1, U.S. Appl. No. 18/893,805, Loftsson et al., Jan. 9, 2025.
[cited by applicant]
US, 2025/0009761, A1, U.S. Appl. No. 18/893,806, Loftsson et al., Jan. 9, 2025.
[cited by applicant]
US, 2025/0009762, A1, U.S. Appl. No. 18/893,810, Loftsson et al., Jan. 9, 2025.
[cited by applicant]
US, 2025/0120985, A1, U.S. Appl. No. 18/917,928, Loftsson et al., Apr. 17, 2025.
[cited by applicant]
U.S. Appl. No. 19/051,044, Loftsson et al., filed Feb. 11, 2025.
[cited by applicant]
Allen et al. “Packaging/Container Issues: Unit-dose, Pre-filled Syringes, Pre-packs, Etc.” Science & Technology for the Hospital Pharmacist, an internet article obtained from the website: https://compoundingtoday.com/ne…
[cited by applicant]
Genentech, Diabetic Macular Edema (DME) Fact Sheet, www.gene.com, printed from https://web.archive.org/web/20150320111749/https://gene.com/patients/disease-education/diabetic-macular-edema, 3 pages, Mar. 20, 2015.
[cited by applicant]
NHS, “How and when to use dexamethasone eye drops” www.nhs.uk, https://www.nhs.uk/medicines/dexamethasone-eye-drops/how-and-when-to use-dexamethasone-eye-drops/, Google data sheet, 5 pages, Jul. 21, 2022.
[cited by applicant]