Granted Patent
B2
US 12,661,339 · App. 18/169,553 · Granted Jun 23, 2026
Methods for treating ocular
Inventors:
Bobak Robert Azamian (Newport Coast, CA); Douglas Michael Ackermann (Reno, NV); Shawn D. Hickok (Aliso Viejo, CA); Joseph G. Vehige (Irvine, CA)
Assignee:
Tarsus Pharmaceuticals, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Disclosed herein are methods for treating or preventing ophthalmic and dermatologic conditions in a patient, including ocular surface conditions such as blepharitis. The methods can include topically administering directly to an ocular surface of one or more eyes of a patient in need of treatment thereof an effective amount of an isoxazoline parasiticide, formamidine parasiticide, or other active ingredient, formulated into an ophthalmic composition, the ophthalmic composition further comprising a pharmaceutically acceptable vehicle. Compositions are also disclosed.
Claims (19)
1 . A method for treating an ocular Demodex mite infestation, comprising topically administering to one or more of the eye, eyelid, or eyelashes of a human patient in need of treatment thereof an effective amount of a composition comprising spinosad and an isoxazoline parasiticide.
2 . The method of claim 1 , wherein the composition is formulated as an eye drop.
3 . The method of claim 1 , wherein the composition is formulated as an ointment.
4 . The method of claim 1 , wherein the composition is formulated as a cream.
5 . The method of claim 1 , wherein the composition is formulated as an emulsion.
6 . The method of claim 1 , wherein the composition is formulated as a suspension.
7 . The method of claim 1 , wherein the Demodex mite infestation comprises one or more of Demodex folliculorum mites and Demodex brevis mites.
8 . The method of claim 1 , wherein the isoxazoline parasiticide comprises lotilaner.
9 . The method of claim 1 , wherein the composition further comprises tea tree oil.
10 . The method of claim 1 , wherein the ocular Demodex mite infestation causes blepharitis.
11 . The method of claim 1 , wherein the ocular Demodex mite infestation causes meibomian gland dysfunction.
12 . The method of claim 1 , wherein the ocular Demodex mite infestation causes ocular rosacea.
13 . The method of claim 1 , wherein the composition further comprises an antibiotic agent.
14 . The method of claim 1 , further comprising confirming the presence of Demodex mites prior to the topically administering.
15 . The method of claim 14 , wherein confirming the presence of Demodex mites comprises identifying cylindrical dandruff, identifying Demodex mites, or testing for the presence of a biomarker associated with Demodex mites.
16 . The method of claim 1 , wherein the composition comprises an additional agent having miticidal activity against the Demodex mite.
17 . The method of claim 16 , wherein the additional agent is selected from the group consisting of: ivermectin, moxidectin, metronidazole, and amitraz.
18 . A method for treating meibomian gland dysfunction caused by an ocular Demodex mite infestation, comprising topically administering to one or more of the eyelid or eyelashes of a human patient in need of treatment thereof an effective amount of a composition comprising spinosad and an isoxazoline parasiticide.
19 . A method for treating Demodex blepharitis , comprising topically administering to one or more of the eyelid or eyelashes of a human patient in need of treatment thereof an effective amount of a composition comprising spinosad and an isoxazoline parasiticide.
Assignments (2)
PATENT SECURITY AGREEMENT
Recorded Apr 19, 2024
From: TARSUS PHARMACEUTICALS, INC.
To: BIOPHARMA CREDIT PLC
Reel/Frame 067171/0968 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 28, 2023
From: AZAMIAN, BOBAK ROBERT; ACKERMANN, DOUGLAS MICHAEL; HICKOK, SHAWN D.; VEHIGE, JOSEPH G.
To: TARSUS PHARMACEUTICALS, INC.
Reel/Frame 064426/0024 →
Continuity (8)
Provisional Application
62746498
· Oct 16, 2018
Provisional Application
62689787
· Jun 25, 2018
Provisional Application
62626612
· Feb 5, 2018
Provisional Application
62615855
· Jan 10, 2018
Provisional Application
62599213
· Dec 15, 2017
References Cited (400)
US 3781355A
· Harrison et al.
· 1973
[cited by applicant]
US 3864497A
· Harrison et al.
· 1975
[cited by applicant]
US 4389397A
· Lo et al.
· 1983
[cited by applicant]
US 4957918A
· Martin et al.
· 1990
[cited by applicant]
US 5019392A
· Wallach
· 1991
[cited by applicant]
US 5338533A
· Derrieu
· 1994
[cited by applicant]
US 5614545A
· Martin et al.
· 1997
[cited by applicant]
US 5632999A
· Miller
· 1997
[cited by applicant]
US 5747057A
· Miller
· 1998
[cited by applicant]
US 5776481A
· Karst et al.
· 1998
[cited by applicant]
US 5952372A
· McDaniel
· 1999
[cited by applicant]
US 5968990A
· Jon et al.
· 1999
[cited by applicant]
US 5981500A
· Bishop et al.
· 1999
[cited by applicant]
US 6001822A
· Wicks et al.
· 1999
[cited by applicant]
US 6063394A
· Grosse-Bley et al.
· 2000
[cited by applicant]
US 6255350B1
· Jon et al.
· 2001
[cited by applicant]
US 6500446B1
· Derrieu et al.
· 2002
[cited by applicant]
US 6797701B2
· Lukas et al.
· 2004
[cited by applicant]
US 6881726B2
· Chang et al.
· 2005
[cited by applicant]
US 7064108B2
· Guzzo et al.
· 2006
[cited by applicant]
US 7348317B2
· Chang et al.
· 2008
[cited by applicant]
US 7531186B2
· Boeckh et al.
· 2009
[cited by applicant]
US 7662972B2
· Mita et al.
· 2010
[cited by applicant]
US 7906128B2
· Heaney et al.
· 2011
[cited by applicant]
US 7906130B2
· Sabnis et al.
· 2011
[cited by applicant]
US 7964204B2
· Lahm et al.
· 2011
[cited by applicant]
US 8022089B2
· Mita et al.
· 2011
[cited by applicant]
US 8128968B2
· Gao et al.
· 2012
[cited by applicant]
US 8138213B2
· Mita et al.
· 2012
[cited by applicant]
US 8207206B2
· Nicoletti et al.
· 2012
[cited by applicant]
US 8231888B2
· Lahm et al.
· 2012
[cited by applicant]
US 8242161B2
· Boeckh et al.
· 2012
[cited by applicant]
US 8361974B2
· Kaoukhov et al.
· 2013
[cited by applicant]
US 8362069B2
· Diaz-Astruc et al.
· 2013
[cited by applicant]
US 8383659B2
· Nanchen et al.
· 2013
[cited by applicant]
US 8389738B2
· Kousaka et al.
· 2013
[cited by applicant]
US 8450357B2
· Soll et al.
· 2013
[cited by applicant]
US 8455015B2
· Gao et al.
· 2013
[cited by applicant]
US 8466115B2
· Curtis et al.
· 2013
[cited by applicant]
US 8492311B2
· Mita et al.
· 2013
[cited by applicant]
US 8501799B2
· Derrieu
· 2013
[cited by applicant]
US 8541413B2
· Wong et al.
· 2013
[cited by applicant]
US 8552218B2
· Lahm et al.
· 2013
[cited by applicant]
US 8653116B2
· Nanchen et al.
· 2014
[cited by applicant]
US 8790674B2
· Derrieu et al.
· 2014
[cited by applicant]
US 8796464B2
· Moriyama et al.
· 2014
[cited by applicant]
US 8815816B2
· Manetta et al.
· 2014
[cited by applicant]
US 8871941B2
· Lahm et al.
· 2014
[cited by applicant]
US 8921408B2
· Soll et al.
· 2014
[cited by applicant]
US 8946492B2
· Mita et al.
· 2015
[cited by applicant]
US 8987218B2
· Kaoukhov et al.
· 2015
[cited by applicant]
US 9044389B2
· Nanchen et al.
· 2015
[cited by applicant]
US 9066515B2
· Boeckh et al.
· 2015
[cited by applicant]
US 9089587B2
· Jacovella et al.
· 2015
[cited by applicant]
US 9095566B1
· Yavitz et al.
· 2015
[cited by applicant]
US 9107812B2
· Derrieu
· 2015
[cited by applicant]
US 9131689B2
· Derrieu et al.
· 2015
[cited by applicant]
US 9173728B2
· Wurtz
· 2015
[cited by applicant]
US 9173870B2
· Fuchs et al.
· 2015
[cited by applicant]
US 9186345B2
· Snorrason
· 2015
[cited by applicant]
US 9200003B2
· Billen et al.
· 2015
[cited by applicant]
US 9233117B2
· Jacovella et al.
· 2016
[cited by applicant]
US 9233118B2
· Jacovella et al.
· 2016
[cited by applicant]
US 9260231B2
· Havrileck et al.
· 2016
[cited by applicant]
US 9457038B2
· Kaoukhov et al.
· 2016
[cited by applicant]
US 9532978B2
· Fuchs et al.
· 2017
[cited by applicant]
US 9730919B2
· Snorrason
· 2017
[cited by applicant]
US 9758491B2
· Crouse et al.
· 2017
[cited by applicant]
US 9788994B2
· Nichamin
· 2017
[cited by applicant]
US 20030059382A1
· Brandt
· 2003
[cited by applicant]
US 20030181354A1
· Abdulrazik
· 2003
[cited by applicant]
US 20060154901A1
· Pflugfelder et al.
· 2006
[cited by applicant]
US 20090093421A1
· Kaoukhov et al.
· 2009
[cited by applicant]
US 20090317503A1
· Adkins, Jr.
· 2009
[cited by applicant]
US 20110033395A1
· Kaoukhov et al.
· 2011
[cited by applicant]
US 20110059925A1
· Donnenfeld
· 2011
[cited by applicant]
US 20110274631A1
· Kaoukhov et al.
· 2011
[cited by applicant]
US 20130053374A1
· Inoue et al.
· 2013
[cited by applicant]
US 20130324538A1
· Gauvry et al.
· 2013
[cited by applicant]
US 20160184340A1
· Kritikou
· 2016
[cited by examiner]
US 20160287566A1
· Busby
· 2016
[cited by applicant]
US 20170024748A1
· Haider
· 2017
[cited by applicant]
US 20170232024A1
· Tan et al.
· 2017
[cited by applicant]
US 20170239218A1
· Le Hir de Fallois et al.
· 2017
[cited by applicant]
US 20200338105A1
· Tan et al.
· 2020
[cited by applicant]
US 20210077465A1
· Azamian et al.
· 2021
[cited by applicant]
US 20210077466A1
· Azamian et al.
· 2021
[cited by applicant]
US 20220160682A1
· Azamian et al.
· 2022
[cited by applicant]
US 20220249445A1
· Azamian et al.
· 2022
[cited by applicant]
US 20230218584A1
· Azamian et al.
· 2023
[cited by applicant]
US 20250213602A1
· Tan et al.
· 2025
[cited by applicant]
US 20250312317A1
· Azamian et al.
· 2025
[cited by applicant]
US 20250312318A1
· Azamian et al.
· 2025
[cited by applicant]
CN 102260252
· 2011
[cited by applicant]
CN 102552114A
· 2012
[cited by applicant]
CN 103687594
· 2014
[cited by applicant]
EP 2379537
· 2012
[cited by applicant]
EP 3344611B1
· 2020
[cited by examiner]
JP 5246182
· 2013
[cited by applicant]
RU 2126668C1
· 2012
[cited by applicant]
RU 2472505
· 2013
[cited by applicant]
WO WO94015597
· 1994
[cited by applicant]
WO WO99058131
· 1999
[cited by applicant]
WO WO04093886
· 2004
[cited by applicant]
WO WO06050837
· 2006
[cited by applicant]
WO WO09024541
· 2009
[cited by applicant]
WO WO13039948
· 2013
[cited by applicant]
WO WO16014664
· 2016
[cited by applicant]
WO WO16022066
· 2016
[cited by applicant]
WO WO16073347
· 2016
[cited by applicant]
WO WO16102437
· 2016
[cited by applicant]
WO WO16207234
· 2016
[cited by applicant]
WO WO17147352
· 2017
[cited by applicant]
WO WO17178416
· 2017
[cited by applicant]
WO WO17180788
· 2017
[cited by applicant]
WO WO17176948
· 2017
[cited by applicant]
WO WO18081733
· 2018
[cited by applicant]
WO WO19126541
· 2019
[cited by applicant]
WO WO21013825
· 2021
[cited by applicant]
WO WO21041773
· 2021
[cited by applicant]
WO WO21243014
· 2021
[cited by applicant]
Abd et al., “Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or Oleic Acid: Enhanced Diffusivity and Follicular Targeting”, Pharmaceutics 2018; 10(19) in 12 pages.
[cited by applicant]
Abelson et al., “Demystifying Demulcents: A look at the varieties of this common agent and how they can help soothe patients' eyes.” Review of Ophthalmology 2006: pp. 1-7.
[cited by applicant]
Abelson et al., “Staying Local with Blepharitis Treatment”, Review of Ophthalmology, Oct. 2012, pp. 60-62.
[cited by applicant]
Aldrich et al., “Ophthalmic Preparations”, Stimuli to the Revision Process, 2013, 39(5): in 21 pages.
[cited by applicant]
Ali et al., “Therapeutic efficacy of poly (lactic-co-glycolic acid} nanoparticles encapsulated ivermectin (nano-ivermectin} against brugian filariasis in experimental rodent model.” Parasitol Res. Feb. 2014; 113(2):681-…
[cited by applicant]
Allen, 2016, Ophthalmic preparations, Part 1: Ophthalmic solutions, International Journal of Pharmaceutical Compounding, 20:399-404.
[cited by applicant]
Allergan, Inc. “Restasis® (cyclosporine ophthalmic emulsion)”, Product Description; Dec. 2009 I n 7 pages.
[cited by applicant]
Almasieh et al., “Structural and functional neuroprotection in glaucoma: role of galantamine-mediated activation of muscarinic acetylcholine receptors”, Cell Death and Disease (2010) 1, e27; doi:10.1038/cddis.2009.23: p…
[cited by applicant]
Alphabetic List of all veterinary anti-helminthics—Parasiteopedia Jul. 2017, in 2 pages.
[cited by applicant]
American Academy of Ophthalmology [AAO] Cornea/External Disease Panel. Preferred Practice Pattern® Guidelines. Blepharitis. San Francisco, CA: American Academy of Ophthalmology; 2013. Available at: www.aao.org/ppp in 31…
[cited by applicant]
American Academy of Ophthalmology [AAO] Cornea/External Disease Panel. Preferred Practice Pattern® Guidelines. Blepharitis. San Francisco, CA: American Academy of Ophthalmology; 2018. Available at: www.aao.org/ppp in 38…
[cited by applicant]
Ames et al., “Cyclosporine ophthalmic emulsions for the treatment of dry eye: a review of the clinical evidence”, Clin Investig (Lond). 2015, 5(3):267-285.
[cited by applicant]
Anadón et al., “Use and abuse of pyrethrins and synthetic pyrethroids in veterinary medicine”, The Vet J. 2009, 182:7-20.
[cited by applicant]
Animalytix LLC. “Bimectin®—Injection for Cattle & Swine”, Bimedia Inc., 2016: in 5 pages.
[cited by applicant]
Anonymous (2014). “Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics,” Cosmetics Ingredient Review, Washington, DC, 36 total pages.
[cited by applicant]
Anonymous (1984). “Final Report on the Safety Assessment of Fossil and Synthetic Waxes,” International Journal of Toxicology 3:43-99.
[cited by applicant]
Anonymous (1992). “Final Report on the Safety Assessment of Methylisothiazolinone and Methylchloroisothiazlinone,” Journal of the American College of Toxicology 11 :75-128.
[cited by applicant]
Anonymous (2002). “Final Report on the Safety Assessment of EDTA, calcium disodium EDTA, diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, tetrasodium EDTA, tripotassium EDTA, trisodium EDTA, HEDTA, and trisod…
[cited by applicant]
Anonymous (2013). “Amended Safety Assessment of Alkyl Esters as Used in Cosmetics,” Cosmetics Ingredient Review, Washington, DC, 82 total pages.
[cited by applicant]
Armstrong Rob., “The conclusion of a comparative efficacy study of fluralaner and sarolaner against the tick
[cited by applicant]
Arrúa et al., “Comparative study of the efficacy of different treatment options in patients with chronic blepharitis”, Arch Soc Esp Oftalmol. 2015, 90(3):112-118.
[cited by applicant]
Asahi et al., “Differential mechanisms of action of the novel γ-aminobutyric acid receptor antagonist ectoparasiticides fluralaner (A1443) and fipronil”, Pest Manag Sci. 2015, 71:91-95; Epub Mar. 31, 2014.
[cited by applicant]
Asahi et al., Feb. 5, 2018, Fluxametamide: A novel isoxazoline insecticide that acts via distinctive antagonism of insect ligand-gated chloride channels, Pesticide Biochemistry and Physiology (2018), https://dot.org/10.…
[cited by applicant]
Asbell et al., “The International Workshop on Meibomian Gland Dysfunction: Report of the Clinical Trials Subcommittee”, IOVS, Special Issue 2011, 52(4):2065-2085.
[cited by applicant]
Asoklis et al., “Ocular Rosacea”, N Engl J Med. 2016, 374(8):771.
[cited by applicant]
Australian Pesticides & Veterinary Medicines Authority; “Pastoral Ag Fluazuron pour-on tick development inhibitor for cattle”, Application Summary for Application No. 104014, 2015, in 5 pages.
[cited by applicant]
Australian Pesticides and Veterinary Medicines Authority [APVMA], “Safety of Fipronil in Dogs and Cats: A review of literature”, 2011, pp. 1-21.
[cited by applicant]
Avdeef Alex, “Solubility Temperature Dependence Predicted from 2D Structure”, ADMET & DMPK 2015, 3(4):298-344.
[cited by applicant]
Ayres et al., “Acne Rosacea Response to Local Treatment for Demodex Folliculorum”, JAMA. 1933, 100(9):645-647.
[cited by applicant]
Bahmani et al., “Comparison of effect of nicotine and levamisole and ivermectin on mortality of leech”, Asian Pac J Trop Dis. 2014, 4(Suppl 1):S477-S480.
[cited by applicant]
Baranowski et al., “Ophthalmic Drug Dosage Forms: Characterization and Research Methods”, Scientific World Journal, 2014, Article ID 861904 in 15 pages.
[cited by applicant]
Barnhorst et al., “The Efficacy of Topical Metronidazole in the Treatment of Ocular Rosacea”, Ophthalmology 1996; 103:1880-1883.
[cited by applicant]
Becskei et al., “Comparative speed of kill of oral treatments with Simparica™(sarolaner) and Bravecto®(fluralaner) against induced infestations of hipicephalus sanguineus on dogs”, Parasit Vectors. 2016: pp. 1-6.
[cited by applicant]
Bernigaud et al. “Efficacy and Pharmacokinetics Evaluation of a Single Oral Dose of Afoxolaner against Sarcoptes scabiei in the Porcine Scabies Model for Human Infestation”, Antimicrob Agents Chemother. 2018, 62(9):e023…
[cited by applicant]
Beugnet et al., “Comparative efficacy of two oral treatments for dogs containing either afoxolaner or fluralaner against Rhipicephalus sanguineus sensu lato and Dermacentor reticulatus” Veterinary Parasitology 209 (2015…
[cited by applicant]
Beugnet et al., “Comparative speed of efficacy against Ctenocephalides felis of two oral treatments for dogs containing either afoxolaner or fluralaner”, Vet Parasitol. 2015, 207: pp. 297-301.
[cited by applicant]
Beugnet et al., “Insecticide and acaricide molecules and/or combinations to prevent pet infestation by ectoparasites”, Trends Parasitol. 2012, 28(7):267-279.
[cited by applicant]
Bezerra Da Silva et al., “Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina” Molecules 2016, 21, 53:1-11.
[cited by applicant]
Biernat et al., “Occurrence of Demodex species in patients with blepharitis and in healthy individuals: a 10-year observational study”, Japanese Ophthalmological Society, Sep. 2018, 62:628-633.
[cited by applicant]
Bimeda, “Bimectin Pour-On (Ivermectin Pour-On)”, Safety Data Sheet, 2015, 77(58): in 8 pages.
[cited by applicant]
Bos et al., “The 500 Dalton rule for the skin penetration of chemical compounds and drugs”, Exp Dermatol. 2000, 9:165-169.
[cited by applicant]
Brayden et al., “Drug Delivery Systems in Domestic Animal Species”, in Handbook of Experimental Pharmacology by F. Cunningham et al. (eds.), 2010; (199):79-112.
[cited by applicant]
Brimecombe et al., “Electrochemical investigation of the effect of pH and solvent on amitraz stability.” J Agric Food Chem. Oct. 18, 2006, 54(21):8139-8143; Abstract in 2 pages.
[cited by applicant]
Bron Anthony, “Ocular rosacea”, UpToDate 2016 (www.uptodate.com), Wolters Kluwer in 24 pages.
[cited by applicant]
Brown, M. et al. (2014). “Severe demodex folliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin,” JAMA Dermatol. 150:61-63.
[cited by applicant]
Burgio et al., “A comparative laboratory trial evaluating the immediate efficacy of fluralaner, afoxolaner, sarolaner and imidacloprid + permethrin against adult
[cited by applicant]
Campbell William C., “Ivermectin as an Antiparasitic Agent for Use in Humans”, Annu Rev Microbial. 1991, 45:445-474.
[cited by applicant]
Cardwell et al., “New developments in the treatment of rosacea—role of once-daily ivermectin cream”, Clin Cosmetic Invest Dermatol. 2016, 100(9):71-77.
[cited by applicant]
Carson et al., “
[cited by applicant]
Casida et al., “Novel GABA receptor pesticide targets”, Pest Biochem Physiol. Jun. 2015, (121):22-30.
[cited by applicant]
Casida, “Golden Age of RyR and GABA-R Diamide and Isoxazoline Insecticides: Common Genesis, Serendipity, Surprises, Selectivity, and Safety”, Chem Res Toxicol. 2015; 28:560-566.
[cited by applicant]
Casida, “Radioligand Recognition of Insecticide Targets” J. Agric. Food Chem. 2018, 66: pp. 3277-3290.
[cited by applicant]
Cavalleri et al., “A randomised, blinded, controlled field study to assess the efficacy and safety of lotilaner tablets (Credelio™) in controlling fleas in client-owned dogs in European countries” Parasit Vectors. 2017,…
[cited by applicant]
Cavalleri et al., “A randomized, controlled study to assess the efficacy and safety of lotilaner (Credelio™) in controlling ticks in client-owned dogs in Europe” Parasit Vectors. 2017, 10:531 in 8 pages.
[cited by applicant]
Cavalleri et al., “Assessment of the onset of lotilaner (Credelio™) speed of kill of fleas on dogs” Parasit Vectors (2017) 10:521 in 5 pages.
[cited by applicant]
Cavalleri et al., “Assessment of the speed of flea kill of lotilaner (Credelio™) throughout the month following oral administration to dogs”, Parasit Vectors (2017) 10:529 in 8 pages.
[cited by applicant]
Cavalleri et al., “Laboratory evaluations of the immediate and sustained effectiveness of lotilaner (Credelio™) against three common species of ticks affecting dogs in Europe” Parasit Vectors. 2017, 10:527 in 7 pages.
[cited by applicant]
Cavalleri et al., “Two randomized, controlled studies to assess the efficacy and safety of lotilaner (Credelio™) in preventing
[cited by applicant]
Chavez Fernando, “Case Report of Afoxolaner Treatment for Canine Demodicosis in Four Dogs Naturally Infected with Demodex Canis” Intern J Appl Res Vet Med 2016, 14(2):123-127.
[cited by applicant]
Chen et al., “Human demodicosis: revisit and a proposed classification”, Br J Dermatol. 2014, 170:1219-1225.
[cited by applicant]
Cheng et al., 2015, Recent advances on ocular Demodex infestation, Current Opinion in Ophthalmology, 26(4):295-300.
[cited by applicant]
Cheung et al., “In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid cleansers”, Contact Lens Anterior Eye. 2018, 41:513-517.
[cited by applicant]
Chiodini et al., “Parenteral ivermectin in Strongyloides hyperinfection”, The Lancet. 2000, 335:43-44.
[cited by applicant]
Clark et al., “Long-term delivery of ivermectin by use of poly(D,L-lactic-co-glycolic)acid microparticles in dogs”, AJVR, 2004, 65(6):752-757.
[cited by applicant]
Cliradex® Blepharitis Kit, available at https://cliradex.com/product/cliradex-blepharitis-kit/ (accessed Apr. 4, 2022) 6 pp.
[cited by applicant]
Cliradex® Towelettes Patient Brochure, CX-003 Rev D, Mar. 9, 2016, available at https://cliradex.com/wp-content/uploads/2019/12/cliradex-instructions-for-use.pdf (accessed Apr. 4, 2022) 1 p.
[cited by applicant]
Čolović et al., “Acetylcholinesterase Inhibitors: Pharmacology and Toxicology” Current Neuropharmacology, 2013, 11(3):315-335.
[cited by applicant]
Corta et al., “Kinetics and mechanism of amitraz hydrolysis in aqueous media by HPLC and GC-MS.” Talanta. 1999, 48(1):189-99; Abstract in 1 page.
[cited by applicant]
Cosmetic Ingredient Report Expert Panel Meeting (2010). Cosmetic Ingredient Review, 29 total pages.
[cited by applicant]
Costa et al., “Alpha 2-adrenoceptors as a target for formamidine pesticides: in vitro and in vivo studies in mice.” Toxicol Appl Pharmacol. 1988, 93(2):319-28, Abstract in 2 pages.
[cited by applicant]
Costa et al., “Ivermectin for spasticity in spinal-cord injury” The Lancet 1994, 343:739.
[cited by applicant]
Cresswell James E., “A meta-analysis of experiments testing the effects of a neonicotinoid insecticide (imidacloprid) on honey bees”, Ecotoxicology Nov. 16, 2010 in 9 pages.
[cited by applicant]
Crosaz et al., “Open field study on the efficacy of oral fluralaner for long-term control of flea allergy dermatitis in client-owned dogs in lle-de-France region”, Parasit Vectors . . . 2016, 9:174 in 5 pages.
[cited by applicant]
Dadzie et al., “Ocular findings in a double-blind study of ivermectin versus diethylcarbamazine versus placebo in the treatment of onchocerciasis”, Br J Ophthalmol. 1987, 71:78-85.
[cited by applicant]
De Oliveira et al., “Toxicity effect of the acaricide fipronil in semi-engorged females of the tick
[cited by applicant]
De Sole et al., “Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials”, WHO Bulletin, 1989, 67(6):707-719.
[cited by applicant]
De Sole et al., “Lack of adverse reactions in ivermectin treatment of onchocerciasis” The Lancet, 1990, 335:1106-1107.
[cited by applicant]
Del Pino et al., “Molecular Mechanisms of Amitraz Mammalian Toxicity: A Comprehensive Review of Existing Data” Chem. Res. Toxicol. 2015, 28:1073-1094.
[cited by applicant]
Do, et al., Setting of ADI for MRLs establishment of insecticide fluxametamide, URL: http://www.dbpia.co.kr/Article/NODE027269043; The 59th Biannual Conference of the Korean Society of Analytical Sciences, Nov. 2017, p.…
[cited by applicant]
Doan et al., “The efficacy of avermectins (ivermectin, doramectin and abamectin) as treatments for infestation with the tick
[cited by applicant]
Dorati et al., “Stability Evaluation of Ivermectin-Loaded Biodegradable Microspheres”, AAPS Pharm Sci Tech, 2015, 16(5):1129-1139.
[cited by applicant]
Doshi et al., “Effect of Viscosity, Surface Tension and Mucoadhesion on Ocular Residence Time of Lubricant Eye Drops” Invest Ophthal Visual Science. Apr. 2009, 50:4641; ARVO Annual Meeting Abstract in 2 pages.
[cited by applicant]
Dourmishev et al., “Ivermectin: pharmacology and application in dermatology”, Intern J Dermatol. 2005, 44:981-988.
[cited by applicant]
DrugBank, “Levamisole”—Accession No. DB00848 (APRD01067)—DrugBank, 2017, in 10 pages.
[cited by applicant]
Drugs.com, “Ivermectin”, Monograph for Professionals, Am Society of Health-Sys Pharmacists, Inc. [AHFS DI Essentials] 2013, in 19 pages.
[cited by applicant]
Drugs.com, “Metronidazole”, Monograph for Professionals, Am Society of Health-Sys Pharmacists, Inc. [AHFS] 2007 in 36 pages.
[cited by applicant]
Dryden et al., “Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida …
[cited by applicant]
Dryden et al., “Efficacy of fluralaner flavored chews (Bravecto®) administered to dogs against the adult cat flea,
[cited by applicant]
Durvet, “Ivermectin Injection”, Bimeda—MTC Animal Health Inc., Material Safety Data Sheet, ANADA 200-447, 2011, in 6 pages.
[cited by applicant]
Durvet, “Ivermectin Sheep Drench”, Material Safety Data Sheet, First Priority Inc. Jun. 2, 2002, in 3 pages.
[cited by applicant]
Egeberg et al., “Patients with Rosacea Have Increased Risk of Dementia”, Ann Neurol. 2016, 79(6):921-928.0.
[cited by applicant]
Eizadi-Mood et al., “Amitraz Poisoning Treatment: Still Supportive?” Iranian J Pharma Res. 2011, 10(1):155-158.
[cited by applicant]
Elston, “Demodex mites: facts and controversies.” Clin Dermatol 2010; 28(5):502-504 [Abstract].
[cited by applicant]
Environmental Protection Agency [EPA], “Amitraz Approval Summary”, in 182 pages.
[cited by applicant]
Environmental Protection Agency [EPA], Amitraz R.E.D. Facts Sheet EPA-738-F-96-031, 1996, in 11 pages.
[cited by applicant]
Environmental Protection Agency [EPA], “Carbaryl” Summary (1992): pp. 1-4.
[cited by applicant]
Environmental Protection Agency [EPA], “Fipronil—Environmental Impact Summary for DP Barcode D338854”, (2007): pp. 1-71.
[cited by applicant]
Environmental Protection Agency [EPA], Fipronil—New Pesticide Fact Sheet CAS #120068-37-3; (1996): pp. 1-10.
[cited by applicant]
Environmental Protection Agency [EPA], “Margosan-O”, Azadirachtin Summary and Registration for Vikwood Ltd. (1984): pp. 1-11.
[cited by applicant]
Erdemir et al., “Demodex mites in acne rosacea: reflectance confocal microscopic study”, Australas J Dermatol. 2017, 58(2):e26-e30.
[cited by applicant]
Estermann et al., “Effect of Oral Donepezil on Intraocular Pressure in Normotensive Alzheimer Patients” J Ocular Pharma Thera. 2006, 22(1):62-67.
[cited by applicant]
Ethiopia Sheep and Goat Productivity Improvement Program (ESGPIP), “Control of External Parasites of Sheep and Goats” Technical Bulletin No. 41 , 2010: pp. 1-16.
[cited by applicant]
European Medicines Agency [EMA]—Committee for Human Medicinal Products (CHMP/463/00 Rev.1), “Background review for the excipient propylene glycol”, Summary of Propylene Glycol Excipient, EMA. Nov. 2014, in 96 pages.
[cited by applicant]
European Medicines Agency [EMA]—Veterinary Medicines and Inspections; “Fluazuron—Summary Report”, European Medicines Agency; EMEA/CVMP/77290/05-Final; 2005 in 5 pages.
[cited by applicant]
European Medicines Agency [EMA]—Veterinary Medicines Division, “CVMP assessment report for Bravecto for spot-on solution for dogs and cats (EMEA/V/C/002526/X/0005)”; Mar. 18, 2016: pp. 1-34.
[cited by applicant]
European Medicines Agency [EMA], “European public MRL assessment report (EPMAR)—Fluralaner (poultry)”, Feb. 15, 2017: pp. 1-12.
[cited by applicant]
European Medicines Agency [EMA]—Veterinary Medicines Division, “CVMP Assessment Report for NexGard”, Committee for Medicinal Products for Veterinary Use (CVMP), Dec. 12, 2013, in 21 pages.
[cited by applicant]
European Medicines Agency [EMA]—Veterinary Medicines Division, “CVMP Assessment Report for Simparica”, Committee for Medicinal Products for Veterinary Use (CVMP), Sep. 10, 2015, in 26 pages.
[cited by applicant]
European Medicines Agency [EMA]—Veterinary Medicines Evaluation Unit, “Cymiazole”, Committee for Veterinary Medical Products, Summary Report, Mar. 1996 in 7 pages.
[cited by applicant]
European Union [EU], “Directive 98/8/EC concerning the placing of biocidal products on the market—Imidacloprid”, Assessment Report, Feb. 18, 2011, in 131 pages.
[cited by applicant]
Farkouh et al., “Systemic side effects of eye drops: a pharmacokinetic perspective” Clin Ophthalmol. 2016, 10:2433-2441.
[cited by applicant]
FDA Center for Veterinary Medicine, “Animal Drug Safety Communication: FDA Alerts Pet Owners and Veterinarians About Potential for Neurologic Adverse Events Associated with Certain Flea and Tick Products” dated Aug. 5, …
[cited by applicant]
Federal Drug Administration [FDA], “Afoxolaner, Fluralaner and Sarolaner”, FDA-CVM FOIA Response 2017-963: pp. 1-26.
[cited by applicant]
Filho et al., “The efficacy of oral ivermectin for the treatment of chronic blepharitis in patients tested positive for Demodex spp.”, Br J Ophthalmol. Jun. 2011, 95(6): 893-895.
[cited by applicant]
Fisara et al., “A randomized controlled trial of the efficacy of orally administered fluralaner (Bravecto™) against induced
[cited by applicant]
Fisara et al., “A small-scale open-label study of the treatment of canine flea allergy dermatitis with fluralaner”, Vet Dermatol. 2015, 26: pp. 417-e98.
[cited by applicant]
Flajs et al., “Ivermectin Pharmacokinetics”, Slov Vet Res 2002; 39(3/4):167-178.
[cited by applicant]
Fluralaner—Bravecto—for veterinary use in Dogs and Cats against fleas and ticks (Jul. 11, 2017), Retrieved from: http://parasilipedia.net/index.php?option=com_content&view=article&id=2731&Itemid=2955, in 3 pages.
[cited by applicant]
Folz et al., “Clinical evaluation of Amitraz as a treatment for canine demodicosis” Vet Parasit. 1984, 16:335-341.
[cited by applicant]
Folz et al., “Evaluation of a topical treatment, alone and in combination with a detergent, for generalized demodicosis” Vet Parasitol., 1984/85, 17:165-172.
[cited by applicant]
Food & Drug Administration [FDA] Veterinary Freedom of Information Summary “Nexgard—Afoxolaner”, 2013, in 22 pages.
[cited by applicant]
Food and Drug Administration [FDA], “Bravecto”, Freedom of Information Summary NADA 141-426, May 15, 2014; in 39 pages.
[cited by applicant]
Food and Drug Administration [FDA], CFR 21, vol. 5, Part 349 “Ophthalmic Drug Products for over-the-counter human use”, [Revised as of Apr. 1, 2016] in 9 pages.
[cited by applicant]
Forton et al., “Demodex folliculorum and topical treatment: acaricidal action evaluated by standardized skin surface biopsy.”, Br J Dermatol. Mar. 1998, 138(3):461-466 [Abstract].
[cited by applicant]
Foster et al., “Fipronil (Frontline Top Spot)”, Information on Use Sheet, etc. in 2 pages.
[cited by applicant]
Foster et al., “The Use of Fipronil (Frontline Top Spot) in Dogs and Cats”, from www.peteducation.com in 4 pages.
[cited by applicant]
Foulks et al., [Eds.], “Special Issue—International Dry Eye Workshop (DEWS) Report”, The Ocular Surface, Apr. 2007, 5(2):59-142.
[cited by applicant]
Fourie et al., “Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of sarcoptic mange in dogs” Vet Parasitol. 2007, 150:275-281.
[cited by applicant]
Fourie et al., “Efficacy of a topical application of Certifect (fipronil 6.26% w/v, amitraz 7.48% w/v, (S)-methoprene 5.63% w/v) for the treatment of canine generalized demodicosis” Parasite 2013, 20:46 in 6 pages.
[cited by applicant]
Fourie et al., “Efficacy of orally administered fluralaner (Bravecto™) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs” Fourie et al. Parasit Vectors., 2015, 8:187 in 7 p…
[cited by applicant]
Frame et al., “Comparing the in vitro effects of MGO™ Manuka honey and tea tree oil on ocular
[cited by applicant]
G Production Inc., Metrogel® (metronidazole) Gel: Highlights of Prescribing Information in 2 pages.
[cited by applicant]
Galderma Laboratories, LP., “Soolantra™ (ivermectin) cream”, Highlights of Prescription Information: Dec. 2014, in 8 pages.
[cited by applicant]
Gao et al., “Clinical Treatment of Ocular Demodicosis by Lid Scrub With Tea Tree Oil”, Cornea, Mar. 2007, 26:136-143.
[cited by applicant]
Gao et al., “High Prevalence of Demodex in Eyelashes with Cylindrical Dandruff” Invest Ophthalmol Vis Sci. 2005; 46(9):3089-3094.
[cited by applicant]
Gao et al., “In vitro and in vivo killing of ocular Demodex by tea tree oil” Br J Ophthalmol 2005; 89:1468-1473.
[cited by applicant]
Gao et al., Sep. 2005, High prevalence of Demodex in eyelashes with cylindrical dandruff, IOVS, 46(9):3089-3094.
[cited by applicant]
Gardon et al., “Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection” The Lancet, 1997, 350:18-22.
[cited by applicant]
Gassel et al., “The novel isoxazoline ectoparasiticide fluralaner: Selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/ acaricidal activity”, Insect Biochem Mo…
[cited by applicant]
Geerling et al., “The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Management and Treatment of Meibomian Gland Dysfunction”, IOVS, Special Issue 2011, 52(4):2050-2064.
[cited by applicant]
Gibbons et al., “A review of the direct and indirect effects of neonicotinoids and fipronil on vertebrate wildlife”, Environ Sci Pollut Res. 2015, 22:103-118.
[cited by applicant]
Gonzalez-Salinas et al., Sep. 21, 2021, Safety and efficacy of topical lotilaner ophthalmic solution 0.25% for the treatment of demodex blepharitis: a pilot study, Journal of Ophthalmology, 2021:1-7.
[cited by applicant]
Gordon D.M., “Dimethyl Sulfoxide in Ophthalmology, with Especial Reference to Possible Toxic Effects”, Biol Actions of Dimethyl Sulfoxide, 1967, 141:392 in 4 pages.
[cited by applicant]
Government Publishing Office, “Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution”, 21 CFR Part 524; FR 2011, 76(250):81806-7.
[cited by applicant]
Green-Church et al., “The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Tear Film Lipids and Lipid-Protein Interactions in Health and Disease” IOVS, Special Issue 2011, 52(4):1979-…
[cited by applicant]
Grubbs Jr. et al., “Instrument Development of the UNC Dry Eye Management Scale”, Cornea. Nov. 2014, 33(11):1186-1192.
[cited by applicant]
Gupta et al., “Ivermectin 1% Cream for Rosacea”, SkinTherapyLetter.com, Dec. 15, 2015, in 6 pages.
[cited by applicant]
Gupta Ramesh C. [Ed.], “Amitraz”, Vet Toxicol. 2007, Chapter 46, pp. 514-517.
[cited by applicant]
Guzzo et al., “Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects”, J Clin Pharmacol. 2002, 42:1122-1133.
[cited by applicant]
Hainzl et al., “Mechanisms for Selective Toxicity of Fipronil Insecticide and Its Sulfone Metabolite and Desulfinyl Photoproduct”, Chem Res Toxicol. 1998, 11(12):1529-1535.
[cited by applicant]
Halos et al., “Preference of Dogs between Two Commercially Available Oral Formulations of Ectoparasiticide Containing Isoxazolines, Afoxolaner or Fluralaner”, Open J Vet Med. 2015, 5:25-29.
[cited by applicant]
Herath et al., “Amitraz poisoning: A case report of an unusual pesticide poisoning in Sri Lanka and literature review” BMC Pharmacol Toxicol. (2017) 18(6):1-6.
[cited by applicant]
Herrero, V.R., “Preservatives in Ophthalmic Formulations: An Overview”, Arch Soc Esp Oftalmol. 2007; 82(9):531-532.
[cited by applicant]
Holland et al., “Lifitegrast for the Treatment of Dry Eye Disease—Results of a Phase III Trial (OP3)”, Ophthalmol. Jan. 2017, 124(1):53-60.
[cited by applicant]
Holzchuh et al., “Clinical Treatment of Ocular
[cited by applicant]
Hom et al. Randomized Controlled Trial to Evaluate the Safety and Efficacy of TP-03 for the Treatment of Blepharitis Due to Demodex Infestation (Jupiter Study—Phase 2B—Presented at AOA 2020 Virtual Meeting Jun. 26, 2020…
[cited by applicant]
Hom et al., “Understanding Emulsion Eye Drop Technology”, Rev Optometry. Mar. 2003, 140(3) in 6 pages.
[cited by applicant]
Hosseini et al., “Development and evaluation of a measure of patient-reported symptoms of Blepharitis” Health and Quality of Life Outcomes, 2018, 16:11 in 6 pages.
[cited by applicant]
Inceboz et al., “Diagnosis and Treatment of Demodectic Blepharitis” Türkiye Parazitoloji Dergisi, 2009; 33 (1):p. 32-36.
[cited by applicant]
Intervet Australia Pty Limited, “Bravecto Fluralaner Chewable Tablets for Dogs”, Material Safety Data Sheet Feb. 2015, Version 1: pp. 1-11.
[cited by applicant]
Ismailos et al., “Unusual solubility behaviour of cyclosporin A in aqueous media” J Pharm Pharmacol. 1991, 43:287-289.
[cited by applicant]
Jackson Jeremy D., “Infectious folliculitis”, UpToDate 2016 (www.uptodate.com) Wolters Kluwer. 2016, in 39 pages.
[cited by applicant]
Jacobi et al., “Demodex Follicularum in dry eye patients” TFOS 2016 poster in 2 pages.
[cited by applicant]
Jańczak et al., “Clinical aspects of demodicosis in veterinary and human medicine”, Med Weter. 2017, 73(5):265-271.
[cited by applicant]
Jarmuda, S. et al. (2012). Potential role of Demodex mites and bacteria in the induction of rosacea, J. Med. Microbial. 61 (Pt. 11):1504-1510.
[cited by applicant]
Jarmuda, S. et al. (2014). “Correlation between serum reactivity to Demodex-associated Bacillusoleronius proteins, and altered sebum levels and Demodex populations in erythematotelangiectaticrosacea patients,” J. Med. M…
[cited by applicant]
Jelic et al., “Donepezil: A Review of Pharmacological Characteristics and Role in the Management of Alzheimer Disease” Clin Med Insights: Therapeutics 2010, 2:771-788.
[cited by applicant]
Jia et al., “Acute Toxicity, bioconcentration, elimination and antioxidant effects of fluralaner in zebrafish
[cited by applicant]
Jiang et al., “Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner”, Int J Environ Res Public Health. 2017, 14:154 in 17 pages.
[cited by applicant]
Johnson, W. (2011). “Safety Assessment of Cyclomethicone, Cyclotetrasiloxane, Cyclopentasiloxane, Cyclohexasiloxane, and Cycloheptasiloxane,” International Journal of Toxicology 30(Suppl. 3):149S-227S.
[cited by applicant]
Jon et al., “Liquid matrices for insecticides for “pour on” applications in aqueous medium—Amitraz as a Case Study”, in
[cited by applicant]
Jongejan et al., “Comparative efficacy of oral administrated afoxolaner (NexGard™) and fluralaner (Bravecto™) with topically applied permethrin/imidacloprid (Advantix®) against transmission of Ehrlichia canis by infected
[cited by applicant]
Jonsson et al., “Critical evaluation of the modified-adult immersion test with discriminating dose bioassay for Boophilus microplus using American and Australian isolates” Vet Parasitol. 2007, 146:307-315.
[cited by applicant]
Junquera P., “Fluralaner: Safety Summary for Veterinary use in Dogs & Cats (Bravecto)”, 2017 in 3 pages.
[cited by applicant]
Kabat Alan G., “In-Vitro Demodicidal Activity of Commercial Lid Hygiene Products” Southern College of Optometry. (2018) Poster in 1 page.
[cited by applicant]
Kagaruki, “The efficacy of amitraz against cattle ticks in Tanzania” Onderstepoort J Vet Res. 1996, 63:91-96.
[cited by applicant]
Karadzovska et al., “A randomized, controlled field study to assess the efficacy and safety of lotilaner flavored chewable tablets (Credelio™) in eliminating fleas in client-owned dogs in the USA”, Parasit Vectors. 2017…
[cited by applicant]
Kaushik et al., “Acetylcholinesterase Inhibitors: Beneficial Effects on Comorbidities in Patients With Alzheimer's Disease” Am J Alzheimer's Dis Other Demen. 2018, 33(2):73-85; Epub Oct. 3, 2017 in 13 pages.
[cited by applicant]
Kheirkhah et al., “Fluorescein Dye Improves Microscopic Evaluation and Counting of
[cited by applicant]
Kilp et al., “Comparative pharmacokinetics of fluralaner in dogs and cats following single topical or intravenous administration”, Parasit Vectors. 2016; 9(296) in 7 pages.
[cited by applicant]
Kilp et al., “Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration” Parasit Vectors 2014, 7:85: pp. 1-5.
[cited by applicant]
Kita et al., “Amitraz and its metabolite differentially activate α- and β-adrenergic-like octopamine receptors.” Pest Manag Sci. 2017; 73(5):984-990, Abstract in 2 pages.
[cited by applicant]
Kita et al., “Pharmacological characterization of histamine-gated chloride channels from the housefly
[cited by applicant]
Knop et al., “The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland”, IOVS, Special Issue 2011, 52(4):1938-1978.
[cited by applicant]
Kojima et al., “In Vivo Evaluation of Ocular Demodicosis Using Laser Scanning Confocal Microscopy”, Invest Ophthalmol Visual Science. Jan. 2011, 52(1): 565-569.
[cited by applicant]
Kong et al., “Absolute configuration assignment of (+)-fluralaner using vibrational circular dichroism” Chirality. 2017, 29:854-864.
[cited by applicant]
Kong et al., “Solubility of Imidacloprid in Different Solvents”, J Chem Eng Data, 2008, 53:615-618.
[cited by applicant]
Koo et al., “Ocular Surface Discomfort and Demodex: Effect of Tea Tree Oil Eyelid Scrub in Demodex Blepharitis”, J Korean Med Sci 2012; 27:1574-1579.
[cited by applicant]
Kugadas et al., “Impact of Microbiome on Ocular Health”, The Ocular Surface, Jul. 2016, 14(3):342-349.
[cited by applicant]
Kuntz et al., “Safety evaluation of lotilaner in dogs after oral administration as flavoured chewable tablets (Credelio™)”, Parasit Vectors. 2017, 10:538 in 6 pages.
[cited by applicant]
Lacey et al., “Demodex Mites—Commensals, Parasites or Mutualistic Organisms?” Dermatology 2011; 222:128-130.
[cited by applicant]
Lacey et al., “Mite-related bacterial antigens stimulate inflammatory cells in rosacea”, Br J Dermatol. 2007, 157(3):474-481.8.
[cited by applicant]
Lacey et al., “Study of Demodex mites: Challenges and Solutions” JEADV 2016, 30:764-775.
[cited by applicant]
Lacey et al., “Under the lash:
[cited by applicant]
Laspina et al., “
[cited by applicant]
Lemp et al., “Blepharitis in the United States 2009: A Survey-based Perspective on Prevalence and Treatment” The Ocular Surface, Apr. 2009, 7(2):S1-22.
[cited by applicant]
Lexicomp, Inc. Ivermectin (systemic): Drug information, 2016, in 6 pages.
[cited by applicant]
Li, J. et al. (2010). “Correlation between ocular Demodex infestation and serum immunoreactivity to Bacillus proteins in patients with Facial rosacea,” Ophthalmology 117:870-877.
[cited by applicant]
Liang et al., “High Prevalence of
[cited by applicant]
Lifschitz et al., “Comparative distribution of ivermectin and doramectin to parasite location tissues in cattle”, Vet Parasitol. 2000, 87:327-338.
[cited by applicant]
Lilienfeld Sean, “Galantamine—a Novel Cholinergic Drug with a Unique Dual Mode of Action for the Treatment of Patients with Alzheimer's Disease” CNS Drug Reviews, 2002, 8(2):159-176.
[cited by applicant]
Lindsley et al., “Interventions for chronic blepharitis”, Cochrane Database Syst Rev. Dec. 2014, 5:e in PMC Dec. 18, 2014, CD005556. doi:10.1002/14651858.CD005556.pub2; in 117 pages.
[cited by applicant]
Little Susan E., “Lotilaner—a novel systemic tick and flea control product for dogs”, Parasit Vectors. 2017, 10:539 in 3 pages.
[cited by applicant]
Liu et al., “Pathogenic role of Demodex mites in blepharitis”, Curr Opin Allergy Clin Immunol. Oct. 2010, 10(5):505-510.
[cited by applicant]
Lu, G.W., “Recent advances in developing ophthalmic formulations: a patent review”, Recent Pat Drug Deliv Formul. Jan. 2010, 4(1):49-57; Abstract in 1 page.
[cited by applicant]
Luntz et al., “Azadirachtin from the Neem Tree
[cited by applicant]
Mabrouk ST. The Preparation and Testing of a Common Emulsion and Personal Care Product: Lotion. Journal of Chemical Education vol. 81, No. 1, p. 83-86, 2004. (Year: 2004).
[cited by applicant]
Maier, “Management of rosacea” UpToDate 2016 (www.uptodate.com), Wolters Kluwer, in 28 pages.
[cited by applicant]
Marie Miglianico, et al., Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases; PNAS; vol. 115, No. 29, pages E6920-E6926 (6 pages). URL: www.pnas.org/cgi/doi/10.1073/pnas.1801338115.
[cited by applicant]
Marty et al., “Treatment of Human Disseminated Strongyloidiasis with a Parenteral Veterinary Formulation of Ivermectin”, Clin Infect Diseases. 2005, 41: e5-8.
[cited by applicant]
Matricoti et al., “The use of oral fluralaner for the treatment of feline generalized demodicosis: a case report” Journal of Small Animal Practice (2017) 58, pp. 476-479.
[cited by applicant]
McKellar et al., “Clinical and pharmacological properties of ivermectin in rabbits and guinea pigs”, The Veterinary Record. 1992, 130(4):71-73; Abstract in 2 pages.
[cited by applicant]
McTier et al., “Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs”, Vet Parasitol. 2016, 222:3-11.
[cited by applicant]
Meadows et al., “A randomized, blinded, controlled USA field study to assess the use of fluralaner tablets in controlling canine flea infestations”, Parasit Vectors. 2014, 7:375 in 8 pages.
[cited by applicant]
Medisca Inc., “Doxycycline Hyclate USP—Safety Data Sheet”, Jul. 2014, in 6 pages.
[cited by applicant]
Medvedev et al., “Clinical-Laboratory Parallels in Patients with Demodectic Blepharitis at Cosmecevtic's Use”, Ophthalmology 2015: 12 (4):50-57.
[cited by applicant]
Merck & Co., Inc., “Stromectol® (Ivermectin) Tablets”, Prescription Information, May 2010, in 7 pages.
[cited by applicant]
Merck Animal Health, “Compendium of Veterinary Products—Bravecto@ (fluralaner topical solution) for Dogs,” dated Aug. 5, 2019: https://merckusa.cvpservice.com/product/basic/view/1047520 (4 pages).
[cited by applicant]
Merck, “Pyrethrins and Synthetic Pyrethroids” Retrieved from: http://www.merckvetmanual.com/pharmacology/ectoparasiticides/ectoparasiticides-used-in-large-animals, downloaded Dec. 11, 2017 in 1 page.
[cited by applicant]
Merial Ltd., “Ivermectin—IVOMEC Injection for Cattle and Swine”, Material Safety Data Sheet; Jan. 7, 2010, in 7 pages.
[cited by applicant]
Merial Ltd., “NexGard (afoxolaner) Chewables”, Safety Data Sheet 2014, in 5 pages.
[cited by applicant]
Merial Ltd., “NexGard (afoxolaner) Chewables”, Technical Monograph, 2014, in 21 pages.
[cited by applicant]
Missel et al., “Design and Evaluation of Ophthalmic Pharmaceutical Products”, in
[cited by applicant]
Miyajima et al., “Effect of high fat intake on the pharmacokinetic profile of ivermectin in rabbits” Drug Metabolism and Pharmacokinetics 30 (2015): pp. 253-256.
[cited by applicant]
Moser VC., “Amitraz” Encyclopedia of Toxicology, vol. 1, 2014, pp. 200-202.
[cited by applicant]
Mueller et al., “Treatment of canine generalized demodicosis with a ‘spot-on’ formulation containing 10% moxidectin and 2.5% imidacloprid (Advocate, Bayer Healthcare)”, Vet Dermatol. 2009, 20:441-446.
[cited by applicant]
Mueller et al., “Treatment of demodicosis in dogs: 2011 clinical practice guidelines”, Vet Dermatol. 2012, 23:86-e21 in 13 pages.
[cited by applicant]
Mueller Ralf S., “Treatment protocols for demodicosis: An evidence-based review”, Vet Dermatol. 2004, 15:75-89.
[cited by applicant]
Mullen et al., [Eds.] “Mites (Acari)” in
[cited by applicant]
Mullens et al., “Comparative in vitro evaluation of contact activity of fluralaner, spinosad, phoxim, propoxur, permethrin and deltamethrin against the northern fowl mite,
[cited by applicant]
Murphy et al., “Laboratory evaluations of the immediate and sustained efficacy of lotilaner (Credelio™) against four common species of ticks affecting dogs in North America”, Parasit Vectors. 2017, 10:523 in 8 pages.
[cited by applicant]
Murphy et al., 2017, Laboratory evaluation of the speed of kill of lotilaner (Credelio™) against
[cited by applicant]
Narayanan et al., “Use of Carbodiimides as Stabilizing Agents to Deliver Water—Labile Active Ingredients in Liquid Systems Including Aqueous Medium—Amitraz as a Case Study”, J ASTM Inter'l., Feb. 2006, 3(2): pp. 1-7.
[cited by applicant]
Nashat et al. “Characterization of Demodex musculi Infestation, Associated Comorbidities, and Topographic Distribution in a Mouse Strain with Defective Adaptive Immunity”, Compara Med. 2017, 67(4):315-329.
[cited by applicant]
Nau, Jeffrey. “Oyster Point Pharma”, Apr. 12, 2018. PowerPoint in 15 pages.
[cited by applicant]
Nelson et al., “The International Workshop on Meibomian Gland Dysfunction: Report of the Definition and Classification Subcommittee”, IOVS, Special Issue. 2011, 52(4):1930-1937.
[cited by applicant]
Ng, Keng Wooi., “Penetration Enhancement of Topical Formulations”, Pharmaceutics 2018; 10(51) in 3 pages.
[cited by applicant]
Nicholls et al., “
[cited by applicant]
Nicholls et al., “Demodex treatment in external ocular disease: the outcomes of a Tasmanian case series”, Springer Science+Business Media Dordrecht, Int Ophthalmol. 2016, 6 pages.
[cited by applicant]
Nichols et al., “The International Workshop on Meibomian Gland Dysfunction: Executive Summary”, IOVS, Special Issue 2011, 52(4):1922-1929.
[cited by applicant]
Nichols Kelly K., “The International Workshop on Meibomian Gland Dysfunction: Introduction”, IOVS, Special Issue 2011, 52(4):1917-1921.
[cited by applicant]
Ohmes et al., “Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Afoxolaner Chewable (NexGard®) against Tick (
[cited by applicant]
Omura et al., “The life and times of ivermectin—a success story”, Perspectives, Dec. 2004, 2:984-989.
[cited by applicant]