IP Library Granted Patent US 12,213,964
Granted Patent B2
US 12,213,964 · App. 18/325,910 · Granted Feb 4, 2025

Isoxazoline parasiticide formulations

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.
A61K31/422A61K9/0048A61K9/08A61K47/26A61P27/02A61P33/14
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Quick Facts
Patent No.
US 12,213,964
App. No.
18/325,910
Granted
Feb 4, 2025
Kind
B2
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 (27)

1. An ophthalmic composition comprising:

an effective amount of an isoxazoline parasiticide,

wherein the isoxazoline parasiticide is present at between about 0.10% and about 0.50% by weight with respect to the total weight of the composition;

a hydrogenated castor oil;

a polysaccharide thickener;

and glycerin,

wherein the glycerin is present at between about 0.5% and about 4% by weight with respect to the total weight of the composition.

2. The ophthalmic composition of claim 1 , wherein the ophthalmic composition is in eye drop form.

3. The ophthalmic composition of claim 1 , wherein the combination of the hydrogenated castor oil and the polysaccharide thickener forms a long-lasting film layer.

4. The ophthalmic composition of claim 1 , wherein the ophthalmic composition is characterized by a viscosity, wherein the viscosity is sufficiently high to cause the ophthalmic composition to spread over meibomian gland orifices on upper and/or lower lid margins upon blinking or closing of the eye and to slow evacuation of the ophthalmic composition through the puncta of the eye for at least 20 seconds.

5. The ophthalmic composition of claim 1 , wherein the isoxazoline parasiticide comprises lotilaner.

6. The ophthalmic composition of claim 1 , wherein the isoxazoline parasiticide is present at about 0.25% by weight with respect to the total weight of the composition.

7. The ophthalmic composition of claim 1 , wherein the hydrogenated castor oil comprises polyoxyl 35 castor oil.

8. The ophthalmic composition of claim 1 , wherein the hydrogenated castor oil is present at about 5% by weight with respect to the total weight of the composition.

9. The ophthalmic composition of claim 1 , wherein the polysaccharide thickener comprises hydroxypropyl methylcellulose.

10. The ophthalmic composition of claim 1 , wherein the polysaccharide thickener comprises carboxymethyl cellulose.

11. The ophthalmic composition of claim 1 , wherein the polysaccharide thickener is present at between about 0.1% and about 0.5% by weight with respect to the total weight of the composition.

12. The ophthalmic composition of claim 1 , wherein the polysaccharide thickener is present at about 0.2% by weight with respect to the total weight of the composition.

13. The ophthalmic composition of claim 1 , further comprising a preservative agent, wherein the preservative agent comprises potassium sorbate.

14. The ophthalmic composition of claim 13 , wherein the preservative agent does not comprise lauralkonium chloride or benzalkonium chloride.

15. The ophthalmic composition of claim 1 , further comprising a preservative agent, wherein the preservative agent comprises lauralkonium chloride.

16. The ophthalmic composition of claim 1 , further comprising a preservative agent, wherein the preservative agent comprises benzalkonium chloride.

17. The ophthalmic composition of claim 1 , further comprising a preservative agent, wherein the preservative agent is present at between about 0.15% and about 0.4% by weight with respect to the total weight of the composition.

18. The ophthalmic composition of claim 1 , wherein the ophthalmic composition does not comprise tea tree oil.

19. The ophthalmic composition of claim 1 , wherein the isoxazoline parasiticide is the sole active ingredient of the ophthalmic composition.

20. The ophthalmic composition of claim 1 , wherein the ophthalmic composition is only locally therapeutically effective.

21. The ophthalmic composition of claim 1 , wherein the ophthalmic composition is formulated as a gel.

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)
Continuation 17099531 · Nov 16, 2020
Continuation 16221390 · Dec 14, 2018
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
Related Publication 20230301971A1 · Sep 28, 2023
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 10588915B2 · Alster et al. · 2020 [cited by applicant]
US 10688122B2 · Amselem et al. · 2020 [cited by applicant]
US 10835517B2 · Borak · 2020 [cited by applicant]
US 11197847B2 · Azamian et al. · 2021 [cited by applicant]
US 20030059382A1 · Brandt · 2003 [cited by applicant]
US 20030181354A1 · Abdulrazik · 2003 [cited by applicant]
US 20040167084A1 · Parks · 2004 [cited by applicant]
US 20060154901A1 · Pflugfelder et al. · 2006 [cited by applicant]
US 20080039519A1 · Heine · 2008 [cited by applicant]
US 20080089958A1 · Diehl et al. · 2008 [cited by applicant]
US 20090093421A1 · Kaoukhov et al. · 2009 [cited by applicant]
US 20090317503A1 · Adkins, Jr. · 2009 [cited by applicant]
US 20100266628A1 · Razzak et al. · 2010 [cited by applicant]
US 20100273870A1 · Gao et al. · 2010 [cited by applicant]
US 20110033395A1 · Kaoukhov et al. · 2011 [cited by applicant]
US 20110059925A1 · Donnenfeld · 2011 [cited by applicant]
US 20110217249A1 · Dreher · 2011 [cited by applicant]
US 20110274631A1 · Kaoukhov et al. · 2011 [cited by applicant]
US 20120053140A1 · Kaoukhov et al. · 2012 [cited by applicant]
US 20130023490A1 · Boeckh et al. · 2013 [cited by applicant]
US 20130053374A1 · Inoue et al. · 2013 [cited by applicant]
US 20130101655A1 · Storm et al. · 2013 [cited by applicant]
US 20130324538A1 · Gauvry et al. · 2013 [cited by applicant]
US 20130344128A1 · Gao et al. · 2013 [cited by applicant]
US 20150086596A1 · Spallitta · 2015 [cited by applicant]
US 20160243116A1 · Jain · 2016 [cited by applicant]
US 20160256442A1 · Cady et al. · 2016 [cited by applicant]
US 20160287566A1 · Busby · 2016 [cited by applicant]
US 20160317439A1 · Lehay et al. · 2016 [cited by applicant]
US 20170020849A1 · Soll et al. · 2017 [cited by applicant]
US 20170024748A1 · Haider · 2017 [cited by applicant]
US 20170065565A1 · Mita et al. · 2017 [cited by applicant]
US 20170135978A1 · Spallitta · 2017 [cited by applicant]
US 20170196928A1 · McAnnally et al. · 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 20170311601A1 · Yang et al. · 2017 [cited by applicant]
US 20200031859A1 · Santos et al. · 2020 [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 20210220360A1 · Kolhe · 2021 [cited by applicant]
US 20220160682A1 · Azamian et al. · 2022 [cited by applicant]
US 20220249445A1 · Azamian et al. · 2022 [cited by applicant]
US 20220354829A1 · Azamian et al. · 2022 [cited by applicant]
US 20220354830A1 · Azamian et al. · 2022 [cited by applicant]
US 20220362218A1 · Azamian et al. · 2022 [cited by applicant]
US 20230190711A1 · Azamian et al. · 2023 [cited by applicant]
US 20230218584A1 · Azamian et al. · 2023 [cited by applicant]
US 20230293496A1 · Azamian et al. · 2023 [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]
JP 5246182 · 2013 [cited by applicant]
RU 2126668C1 · 2012 [cited by applicant]
RU 2472505 · 2013 [cited by applicant]
RU 2017100031 · 2018 [cited by applicant]
WO WO94015597 · 1994 [cited by applicant]
WO WO9415597A1 · 1994 [cited by examiner]
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 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 WO18081733 · 2018 [cited by applicant]
WO WO19126541 · 2019 [cited by applicant]
WO WO20257663 · 2020 [cited by applicant]
WO WO21013825 · 2021 [cited by applicant]
WO WO21041773 · 2021 [cited by applicant]
WO WO21243014 · 2021 [cited by applicant]
Lee et al. (“Comparison of cytotoxicity and wound healing effect of carboxymethylcellulose and hyaluronic acid on human corneal epithelial cells,” Int. J. Ophthalmot. 2015, vol. 8, No. 2, pp. 215-221) (Year: 2015). [cited by examiner]
Bandyopadhyay et al. “Development of Ophthalmic formulations,” Pharmaceutical Dosage forms: Parenteral Medications, Third Ed. vol. 1: Formulation and Packing, Edited by Nema et al. Informa Healthcare, 2010, pp. 255-286 … [cited by examiner]
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 y-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 Folliculorium”, 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”, ScientificWorldJournal, 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 oftwo oral treatments for dogs containing either afoxolaner orfluralaner”, 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 demodexfolliculorum-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 Rhipicephalus sanguineus (sensu lato) ticks attached to d… [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]
Carmignani et al., 2002, Ophthalmic vehicles containing polymer-solubilized tropicamide: “in vitro/in vivo” evaluation, Drug Development and Industrial Pharmacy, 28(1):101-105. [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 Dermacentor reticulatus transmission of [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]
Chhadva et al., 2017, Meibomian glad disease, American Academy of Ophthalmology, pp. S20-S26. [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]
Člović 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 Ile-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 PharmSciTech, 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 Phama 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 [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 & Drug Administration [FDA], “21-169_Reminyl_medr_P4”, 2001, Part 4, Medical Review, retrieved from URL: <. [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 Dematol. 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 Demodex viability” Contact Lens Anterior Eye 2018, 41(6):527-530. [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]
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 exctoparasiticide 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 lolitaner 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 Demodex folliculorum by Systemic Ivermectin” Am J Ophthalmol., 2011, 151:1030-1034. [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 infecte… [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 Alzheimers 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 Demodex in Blepharitis With Cylindrical Dandruff” Cornea 2007;26:697-700. [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 toBacillus 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 Azadirachta indica: its Action Against Insects” An. Soc. Entomol. Brasil. 2000, 29(4):615-632. [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, pp. 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]
Mayo Clinic, 2022, Blepharitis, https://www.mayoclinic.org/diseases-conditions/blepharitis/symptoms-causes/syc-20370141. [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—Braveclo@ (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 Ixodes ricinus ticks on dogs, Parasit Vectors, 10:541, 8 pp.. [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., “Demodex species in human ocular disease: new clinicopathological aspects.” Int Ophthalmol. Epub May 9, 2016, (Abstract) in 2 pages. [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]
Ozoe et al., “The antiparasitic isoxazoline443 is a potent blocker of insect ligand-gated chloride channels”, Biochem Biophys Res Comm. 2010, 391:744-749. [cited by applicant]
Pacque et al., “Safety of and compliance with community-based ivermectin therapy”, The Lancet, 1990, 335:1377-1380. [cited by applicant]
Padula et al., “Assessment of the adverse effects of the acaricide amitraz: in vitro evaluation of genotoxicity”, Toxicol Mech Methods., 2012; 22(9):657-661. [cited by applicant]
Palopoli et al., “Global divergence of the human follicle mite [cited by applicant]
Panic et al., “Repurposing drugs for the treatment and control of helminth infections”, Int J Parasitol Drugs Drug Resist. 2014, 4(3):185-200. [cited by applicant]
Pass et al., “Pharmacokinetics and metabolism of amitraz in ponies and sheep.” J Vet Pharmacol Ther. Jun. 1995; 18(3):210-5, Abstract in 2 pages. [cited by applicant]
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