Granted Patent
B2
US 12,653,779 · App. 18/239,045 · Granted Jun 16, 2026
Compositions and methods for the treatment of presbyopia
Assignee:
LENZ THERAPEUTICS OPERATIONS, INC.
A61K9/0048A61K9/08A61K31/439A61K31/4409A61K45/06A61K47/02A61K47/10A61K47/26A61K47/32A61K47/34A61K47/38A61P27/10
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The invention provides compositions and methods for the treatment of presbyopia. The compositions comprise aceclidine hydrochloride, polysorbate 80, mannitol, anhydrous hypromellose, disodium edetate dihydrate, benzalkonium chloride, sorbic acid and anhydrous sodium citrate and optionally tropicamide.
Claims (17)
1 . A method of treating presbyopia in a subject in need thereof, the method comprising:
a. providing a stable aqueous ophthalmological composition comprising from about 1.25% to about 1.85% w/v aceclidine as the only ophthalmologically active agent in the stable aqueous ophthalmological composition, wherein the stable aqueous ophthalmological composition does not comprise an in situ gelling agent;
b. storing the stable aqueous ophthalmological composition for 1 to 3 months at a temperature from about 2° C. to about 8° C., wherein a therapeutically effective amount of aceclidine remains in solution in the stable aqueous ophthalmogical composition for 1 to 3 months when stored at about 2° C. to about 8° C.; and
c. administering the stable aqueous ophthalmological composition to an eye of the subject.
2 . The method of claim 1 , wherein the ophthalmological composition is administered to both eyes of the subject.
3 . The method of claim 2 , wherein the administration of the ophthalmological composition to both eyes of the subject enhances near vision of the subject greater than the administration to one eye of the subject.
4 . The method of claim 1 , wherein the pupil size of the eye is reduced to from about 1.5 to about 2.5 millimeters subsequent to the administering of the ophthalmological composition to the eye of the subject.
5 . The method of claim 1 , wherein degradation of the aceclidine is inhibited in the stable ophthalmological composition.
6 . The method of claim 1 , wherein the ophthalmological composition further comprises a viscosity enhancer.
7 . The method of claim 6 , wherein the viscosity of the ophthalmological composition is from about 1 to about 5,000 centipoise during the step of storing.
8 . The method of claim 1 , wherein the ophthalmological composition further comprises a surfactant selected from the group consisting of an anionic surfactant, a nonionic surfactant, and a combination thereof.
9 . The method of claim 8 , wherein the surfactant is a nonionic surfactant.
10 . The method of claim 1 , wherein the ophthalmological composition comprises a pH of about 4.0 to about 8.0.
11 . The method of claim 10 , wherein the ophthalmological composition comprises a pH of about 4.0 to about 6.0.
12 . The method of claim 1 , wherein the viscosity of the ophthalmological composition is above 20 cps at 1/s shear during the step of administering.
13 . The method of claim 1 , wherein at least 88% of the aceclidine remains in solution in the ophthalmological composition after 1 to 3 months when the ophthalmological composition is maintained at about 2° C. to about 8° C.
14 . The method of claim 1 , wherein a therapeutically effective amount of aceclidine remains in solution in the ophthalmological composition for 3 months when stored at about 2° C. to about 8° C.
Assignments (2)
CHANGE OF NAME
Recorded Apr 2, 2024
From: LENZ THERAPEUTICS, INC.
To: LENZ THERAPEUTICS OPERATIONS, INC.
Reel/Frame 066978/0082 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 13, 2023
From: HORN, GERALD
To: LENZ THERAPEUTICS, INC.
Reel/Frame 065857/0144 →
Continuity (10)
References Cited (303)
US 4474751A
· Haslam
· 1984
[cited by examiner]
US 4906467A
· Schwartzman et al.
· 1990
[cited by applicant]
US 5073560A
· Wu et al.
· 1991
[cited by applicant]
US 5286864A
· Walther et al.
· 1994
[cited by applicant]
US 5451587A
· Walther et al.
· 1995
[cited by applicant]
US 5488050A
· Neufeld
· 1996
[cited by applicant]
US 6120758A
· Siddiqui et al.
· 2000
[cited by applicant]
US 6241124B1
· Hoyt
· 2001
[cited by applicant]
US 6291466B1
· Gwon et al.
· 2001
[cited by applicant]
US 6353022B1
· Schneider et al.
· 2002
[cited by applicant]
US 6410544B1
· Gwon et al.
· 2002
[cited by applicant]
US 7067261B2
· Bencherif et al.
· 2006
[cited by applicant]
US 8299079B2
· Kaufman
· 2012
[cited by applicant]
US 8455494B2
· Kaufman
· 2013
[cited by applicant]
US 8501800B2
· Bowman et al.
· 2013
[cited by applicant]
US 8524758B2
· Benozzi
· 2013
[cited by applicant]
US 9089562B2
· Horn et al.
· 2015
[cited by applicant]
US 9314427B2
· Horn et al.
· 2016
[cited by applicant]
US 9320709B2
· Horn et al.
· 2016
[cited by applicant]
US 9833441B2
· Horn et al.
· 2017
[cited by applicant]
US 9844537B2
· Horn et al.
· 2017
[cited by applicant]
US 9968594B2
· Horn et al.
· 2018
[cited by applicant]
US 20020035264A1
· Kararli et al.
· 2002
[cited by applicant]
US 20030104996A1
· Li et al.
· 2003
[cited by applicant]
US 20030140996A1
· Thomson
· 2003
[cited by applicant]
US 20030165545A1
· Huth et al.
· 2003
[cited by applicant]
US 20040106644A1
· Randazzo
· 2004
[cited by applicant]
US 20050196370A1
· Yu et al.
· 2005
[cited by applicant]
US 20060172972A1
· Bhushan et al.
· 2006
[cited by applicant]
US 20060177430A1
· Bhushan et al.
· 2006
[cited by applicant]
US 20070297990A1
· Shah et al.
· 2007
[cited by applicant]
US 20090156581A1
· Dillon et al.
· 2009
[cited by applicant]
US 20090297566A1
· Brinkman et al.
· 2009
[cited by applicant]
US 20110250294A1
· Tien et al.
· 2011
[cited by applicant]
US 20110251285A1
· Tien et al.
· 2011
[cited by applicant]
US 20120028910A1
· Combal et al.
· 2012
[cited by applicant]
US 20120315265A1
· Lai et al.
· 2012
[cited by applicant]
US 20130245030A1
· Kaufman
· 2013
[cited by applicant]
US 20140378401A1
· Horn
· 2014
[cited by applicant]
US 20150010634A1
· Knappe et al.
· 2015
[cited by applicant]
US 20160018671A1
· Waite et al.
· 2016
[cited by applicant]
US 20180235946A1
· Horn et al.
· 2018
[cited by applicant]
US 20190038609A1
· Horn
· 2019
[cited by applicant]
US 20190240152A1
· Horn et al.
· 2019
[cited by applicant]
US 20200308168A1
· Banerjee et al.
· 2020
[cited by applicant]
US 20210251970A1
· Horn
· 2021
[cited by applicant]
US 20220031608A1
· Horn
· 2022
[cited by applicant]
US 20220105090A1
· Horn
· 2022
[cited by applicant]
US 20220233434A1
· Horn
· 2022
[cited by applicant]
US 20220347170A1
· Horn
· 2022
[cited by applicant]
US 20230190738A1
· Horn
· 2023
[cited by applicant]
US 20230190739A1
· Horn
· 2023
[cited by applicant]
US 20230248644A1
· Horn
· 2023
[cited by applicant]
US 20230310392A1
· Horn
· 2023
[cited by applicant]
US 20230398113A1
· Horn
· 2023
[cited by applicant]
US 20230404912A1
· Horn
· 2023
[cited by applicant]
US 20230414494A1
· Horn
· 2023
[cited by applicant]
CN 101262886A
· 2008
[cited by applicant]
CN 101616640A
· 2009
[cited by applicant]
EP 0197718A2
· 1986
[cited by applicant]
JP S62194861A
· 1987
[cited by applicant]
JP H06211666A
· 1994
[cited by applicant]
JP H07330604A
· 1995
[cited by applicant]
JP 2852607B2
· 1999
[cited by applicant]
JP H11292151A
· 1999
[cited by applicant]
JP 2002521429A
· 2002
[cited by applicant]
JP 2004168709A
· 2004
[cited by applicant]
JP 2008536866A
· 2008
[cited by applicant]
JP 2010514517A
· 2010
[cited by applicant]
JP 2012508793A
· 2012
[cited by applicant]
KR 0165667B1
· 1999
[cited by applicant]
WO WO9612711A1
· 1996
[cited by applicant]
WO WO0006135A2
· 2000
[cited by applicant]
WO WO02080915A2
· 2002
[cited by applicant]
WO WO02100437A2
· 2002
[cited by applicant]
WO WO2007011874A2
· 2007
[cited by applicant]
WO WO2008083118A1
· 2008
[cited by applicant]
WO WO2009015286A2
· 2009
[cited by applicant]
WO WO2009077736A2
· 2009
[cited by applicant]
WO WO2010070664A1
· 2010
[cited by applicant]
WO WO2010125416A1
· 2010
[cited by applicant]
WO WO2010135731A1
· 2010
[cited by applicant]
WO WO2012119070A2
· 2012
[cited by applicant]
WO WO2013041967A2
· 2013
[cited by applicant]
WO WO2014161002A2
· 2014
[cited by applicant]
WO WO2015031186A1
· 2015
[cited by applicant]
WO WO2015031187A1
· 2015
[cited by applicant]
WO WO2015094392A1
· 2015
[cited by applicant]
WO WO2016205068A1
· 2016
[cited by applicant]
WO WO2016205069A1
· 2016
[cited by applicant]
WO WO2016205071A1
· 2016
[cited by applicant]
WO WO2017053646A1
· 2017
[cited by applicant]
WO WO2017160548A1
· 2017
[cited by applicant]
WO WO2019135927A1
· 2019
[cited by applicant]
WO WO2020076769A1
· 2020
[cited by applicant]
WO WO2020117637A1
· 2020
[cited by applicant]
WO WO2020219707A1
· 2020
[cited by applicant]
WO WO2022081204A1
· 2022
[cited by applicant]
WO WO2022232205A1
· 2022
[cited by applicant]
WO WO2023091439A1
· 2023
[cited by applicant]
WO WO2023114347A1
· 2023
[cited by applicant]
WO WO2024220441A1
· 2024
[cited by applicant]
Co-pending U.S. Appl. No. 18/239,072, inventor Horn; Gerald, filed Aug. 28, 2023.
[cited by applicant]
Co-pending U.S. Appl. No. 18/239,087, inventor Horn; Gerald, filed Aug. 28, 2023.
[cited by applicant]
Co-pending U.S. Appl. No. 18/241,733, inventor Horn; Gerald, filed Sep. 1, 2023.
[cited by applicant]
Co-pending U.S. Appl. No. 18/369,737, inventor Horn; Gerald, filed Sep. 18, 2023.
[cited by applicant]
Co-pending U.S. Appl. No. 18/465,918, inventor Horn; Gerald, filed Sep. 12, 2023.
[cited by applicant]
U.S. Appl. No. 18/239,072 Office Action dated Nov. 21, 2023.
[cited by applicant]
U.S. Appl. No. 18/239,087 Office Action dated Oct. 10, 2023.
[cited by applicant]
Akorn Incorporated MSDS: Tropicacyl (R); Rev. 11-11 (date unknown).
[cited by applicant]
Berge et al. Pharmaceutical Salts. Journal of Pharmaceutical Sciences 66(1):1-19 (Jan. 1977).
[cited by applicant]
Bijsluiter: Glaucocare. Available at https://consumed.nl/bijsluiters/glaucocare. Machine Translation Provided.
[cited by applicant]
CAS printout for Mashkovskii, The Relation Between the Chemical Structure and Pharmacological Activity of Some Esters of 3-Hydroxyquinuclidine (Quinuclidine-3-ol), Proc. Intern. Pharmacol., 7:359-366 (1961).
[cited by applicant]
Chung et al., The effect of dioptric blur on reading performance. Vision Res47(12):1584-94 (2007).
[cited by applicant]
Cowan et al., Clinical evaluation of a new mydriatic-mydrilate. Br J Ophthalmol 46(12):730-6 (1962).
[cited by applicant]
Davidson., General medicine and visual side effects. Br Med J 1(6166):821 (1979).
[cited by applicant]
Drance et al., Dose response of human intraocular pressure to aceclidine. Arch Ophthalmol 88(4):394-6 (1972).
[cited by applicant]
Edwards., Behaviour of the fellow eye in acute angle-closure glaucoma. Br J Ophthalmol 66(9):576-9 (1982).
[cited by applicant]
Edwards et al., Effect of brimonidine tartrate 0.15% on night-vision difficulty and contrast testing after refractive surgery, J Cataract Refract Surg. 34(9):1538-41 (2008).
[cited by applicant]
Ehlert et al. The interaction of the enantiomers of aceclidine with subtypes of the muscarinic receptor. J Pharmacol Exp Ther 279(3):1335-1344 (1996).
[cited by applicant]
Fechner et al., Accomodative effects of aceclidine in the treatment of glaucoma. Amer J Ophth. 79 (1):104-106 (1975).
[cited by applicant]
Francois et al. Ultrasonographic study of the effect of different miotics on the eye components. Ophthalmologica 175(6):328-338 (1977).
[cited by applicant]
Fricke et al. Global Prevalence of Presbyopia and Vision Impairment from Uncorrected Presbyopia: Systematic Review, Meta-analysis, and Modelling. Ophthalmology 125(10):1492-1499 (2018).
[cited by applicant]
Gardiner., ABC of Ophthalmology: accidents and first aid. Br Med J 2(6148):1347-50 (1978).
[cited by applicant]
Gardiner., ABC of Ophthalmology: Methods of examination. Br Med J 2(6152):1622-6 (1978).
[cited by applicant]
Glaucadrine, poudre et solvant pour collyre en solution, boite de 1 acon de lyophilisat + acon le solvant de 10 ml GI. Available at Http://www.doctissimo.fr/medicament-GLAUCADRINE.htm Machine Translation Provided.
[cited by applicant]
Glaunorm toma all'Indice farmaci. Available at http://www.anibaldi.eu/farmaci/schedetecniche/GLAUNORM.html. (last updated Dec. 15, 2012) Machine Translation Provided.
[cited by applicant]
Grünberger et al., The pupillary response test as a method to differentiate various types of dementia. Neuropsychiatr 23(1):52-57 (2009).
[cited by applicant]
Hoyng et al., The combination of guanethidine 3% and adrenaline 0.5% in 1 eyedrop (GA) in glaucoma treatment. Br J Ophthalmol 63(1):56-62 (1979).
[cited by applicant]
Ishikawa et al. Selectivity of muscarinic agonists including (+/−)-aceclidine and antimuscarinics on the human intraocular muscles. J Ocul Pharmacol Ther 14(4):363-373 (1998).
[cited by applicant]
Josefa Valcarcel, Glaucostat(R) 2% colirio. Machine Translation Provided.
[cited by applicant]
Kaufman et al. Presbyopia and Glaucoma: Two Diseases, One Pathophysiology? The 2017 Friedenwald Lecture. Invest Ophthalmol Vis Sci 60(5):1801-1812 (2019).
[cited by applicant]
Kibbe. Handbook of Pharmaceutical Excipients. 3rd Edition, American Pharmaceutical Association and Pharmaceutical Press (pp. 416-419) (2000).
[cited by applicant]
Latanoprost Label (2006).
[cited by applicant]
Lubrizol Pharmaceutical Bulletin 21 (Lubrizol Advanced Materials, Inc.) May 31, 2011.
[cited by applicant]
Mayama et al. Myopia and advanced-stage open-angle glaucoma. Ophthalmology 109(11):2072-2077 (2002).
[cited by applicant]
Mayo Clinic: Tropicamide (Opthalmic Route), 2015, http://www.mayoclinic.org/drugs-supplements/tropicamide-ophthalmic-route/description/drg-20066481.
[cited by applicant]
Mohan et al., Optimal dosage of cyclopentolate 1% for cycloplegic refraction in hypermetropes with brown irides. Indian J Ophthalmol 59(6):514-6 (2011).
[cited by applicant]
Muller and R.P. Dessing (Eds.) 4th Edition, European Drug Index, European Society of Clinical Pharmacy, Jeutscher Apotheker Verlag Suttgart (p. 550) (1997).
[cited by applicant]
Nayak et al., A comparison of cycloplegic and manifest refractions on the NR-1000F (an objective Auto Refractometer). Br J Ophthalmol 71(1):73-5 (1987).
[cited by applicant]
Park., The comparison of mydriatic effect between two drugs of different mechanism. Korean J Ophthalmol 23(1):40-2 (2009).
[cited by applicant]
PCT/US2014/052256 International Search Report and Written Opinion dated Dec. 18, 2014.
[cited by applicant]
PCT/US2016/036687 International Search Report and Written Opinion dated Sep. 9, 2016.
[cited by applicant]
PCT/US2016/036692 International Search Report and Written Opinion dated Sep. 22, 2016.
[cited by applicant]
PCT/US2016/036694 International Search Report and Written Opinion dated Oct. 26, 2016.
[cited by applicant]
PCT/US2017/021244 International Search Report and Written Opinion dated May 22, 2017.
[cited by applicant]
PCT/US2019/055116 International Search Report and Written Opinion dated Dec. 19, 2019.
[cited by applicant]
PCT/US2019/063923 International Invitation to Pay Additional Fees dated Feb. 3, 2020.
[cited by applicant]
PCT/US2019/063923 International Search Report and Written Opinion dated Apr. 23, 2020.
[cited by applicant]
PCT/US2021/029536 International Search Report and Written Opinion dated Aug. 9, 2021.
[cited by applicant]
PCT/US2022/026435 International Invitation to Pay Additional Fees dated Jul. 5, 2022.
[cited by applicant]
PCT/US2022/026435 International Search Report and Written Opinion dated Sep. 28, 2022.
[cited by applicant]
PCT/US2022/050028 International Search Report and Written Opinion dated Mar. 2, 2023.
[cited by applicant]
Primožič et al. Influence of the acyl moiety on the hydrolysis of quinuclidinium esters catalyzed by butyrylcholinesterase. Croatica Chemica Acta 84(2):245-249 (2011).
[cited by applicant]
Prospectus/Technical Sheet for Glaucostat Josefa Valcarecel Glaucostat® 2% colirio (2000).
[cited by applicant]
PubChem 233021624 deposited on Feb. 12, 2015 (Feb. 12, 2015).
[cited by applicant]
PubChem 427198483 deposited Aug. 13, 2020 (Aug. 13, 2020).
[cited by applicant]
PubChem-CID-22416839, Create Date: Dec. 5, 2007.
[cited by applicant]
Romano., Double-blind cross-over comparison of aceclidine and pilocarpine in open-angle glaucoma. Br J Ophthalmol 54(8):510-21 (1970).
[cited by applicant]
Smith et al., Subsensitivity to cholinoceptor stimulation of the human iris sphincter in situ following acute and chronic administration of cholinomimetic miotic drugs. Br J Pharmacol 69(3):513-8 (1980).
[cited by applicant]
Stella. Prodrugs: Some Thoughts and Current Issues. J Pharm Sci 99(12):4755-4765 (2010).
[cited by applicant]
Tataru et al., Antiglaucoma pharmacotherapy. J Med Life 5(3):247-51 (2012).
[cited by applicant]
Trinavarat et al., Effective pupil dilatation with a mixture of 0.75% tropicamide and 2.5% phenylephrine: A randomized controlled trial. Indian J Ophthalmol 57(5):351-4 (2009).
[cited by applicant]
U.S. Appl. No. 14/223,639 Office Action dated Jan. 5, 2015.
[cited by applicant]
U.S. Appl. No. 14/223,639 Office Action dated Sep. 30, 2014.
[cited by applicant]
U.S. Appl. No. 14/742,903 Office Action dated Dec. 2, 2015.
[cited by applicant]
U.S. Appl. No. 14/742,903 Office Action dated Jul. 17, 2015.
[cited by applicant]
U.S. Appl. No. 14/742,921 Office Action dated Jul. 15, 2015.
[cited by applicant]
U.S. Appl. No. 14/860,770 Office Action dated Dec. 13, 2016.
[cited by applicant]
U.S. Appl. No. 14/860,777 Office Action dated Mar. 9, 2017.
[cited by applicant]
U.S. Appl. No. 15/073,089 Office Action dated May 8, 2017.
[cited by applicant]
U.S. Appl. No. 15/073,089 Office Action dated Nov. 30, 2016.
[cited by applicant]
U.S. Appl. No. 15/073,139 Office Action dated Dec. 1, 2016.
[cited by applicant]
U.S. Appl. No. 15/235,431 Office Action dated Mar. 9, 2018.
[cited by applicant]
U.S. Appl. No. 15/864,703 Office Action dated Apr. 8, 2019.
[cited by applicant]
U.S. Appl. No. 15/864,703 Office Action dated Feb. 11, 2019.
[cited by applicant]
U.S. Appl. No. 15/864,703 Office Action dated Mar. 26, 2018.
[cited by applicant]
U.S. Appl. No. 15/956,931 Office Action dated Oct. 2, 2018.
[cited by applicant]
U.S. Appl. No. 15/956,936 Office Action dated Feb. 11, 2019.
[cited by applicant]
U.S. Appl. No. 15/956,936 Office Action dated Sep. 28, 2018.
[cited by applicant]
U.S. Appl. No. 16/106,730 Office Action dated Jun. 11, 2021.
[cited by applicant]
U.S. Appl. No. 16/106,730 Office Action dated Jun. 2, 2020.
[cited by applicant]
U.S. Appl. No. 16/106,730 Office Action dated Oct. 19, 2020.
[cited by applicant]
U.S. Appl. No. 16/156,276 Office Action dated Jun. 26, 2020.
[cited by applicant]
U.S. Appl. No. 16/156,276 Office Action dated Oct. 22, 2020.
[cited by applicant]
U.S. Appl. No. 16/700,088 Office Action dated May 28, 2021.
[cited by applicant]
U.S. Appl. No. 16/700,088 Office Action dated Nov. 2, 2021.
[cited by applicant]
U.S. Appl. No. 16/747,070 Office Action dated Jun. 25, 2021.
[cited by applicant]
U.S. Appl. No. 16/747,070 Office Action dated Oct. 30, 2020.
[cited by applicant]
U.S. Appl. No. 16/796,364 Office Action dated Apr. 30, 2021.
[cited by applicant]
U.S. Appl. No. 16/796,364 Office Action dated Dec. 30, 2020.
[cited by applicant]
U.S. Appl. No. 16/796,364 Office Action dated Jun. 11, 2021.
[cited by applicant]
U.S. Appl. No. 16/881,570 Office Action dated Oct. 7, 2020.
[cited by applicant]
U.S. Appl. No. 17/069,155 Office Action dated Aug. 19, 2021.
[cited by applicant]
U.S. Appl. No. 17/242,398 Office Action dated Apr. 27, 2023.
[cited by applicant]
U.S. Appl. No. 17/242,398 Office Action dated Oct. 14, 2022.
[cited by applicant]
U.S. Appl. No. 17/502,066 Office Action dated Jun. 22, 2023.
[cited by applicant]
U.S. Appl. No. 17/502,066 Office Action dated Mar. 31, 2022.
[cited by applicant]
U.S. Appl. No. 17/502,066 Office Action dated Nov. 14, 2022.
[cited by applicant]
U.S. Appl. No. 17/552,622 Office Action dated Feb. 9, 2023.
[cited by applicant]
U.S. Appl. No. 17/552,654 Office Action dated Apr. 20, 2022.
[cited by applicant]
U.S. Appl. No. 17/552,654 Office Action dated Dec. 2, 2022.
[cited by applicant]
U.S. Appl. No. 17/988,366 Office Action dated Jul. 19, 2023.
[cited by applicant]
Varma et al. Concentration of Latanoprost Ophthalmic Solution after 4 to 6 Weeks' Use in an Eye Clinic Setting. Invest Ophthalmol Vis Sci. 47(1):222-225 (2006).
[cited by applicant]
Ward et al., 1,2,5-Thiadiazole analogues of aceclidine as potent ml muscarinic agonists. J Med Chem 41(3):379-392 (1988).
[cited by applicant]
Wood et al., Pupil dilatation does affect some aspects of daytime driving performance. Br J Ophthalmol (11):1387-90 (2003).
[cited by applicant]
Zhang et al. Reactive impurities in large and small molecule pharmaceutical excipients—A review. TrAC Trends in Analytical Chemistry 101:34-42 (2018).
[cited by applicant]
Aceclidine (Hydrochloride) Item No. 1790. Product Information. Cayman Chemical Company (1 pg) (Dec. 2, 2022).
[cited by applicant]
Barot et al. Prodrug Strategies. Ocular Drug Delivery Med. Chem. 8(4):753-768 (2012).
[cited by applicant]
Bartlett, Paul, et al., Exploiting Chemical Diversity for Drug Discovery. The Royal Society of Chemistry (pp. 113-118) (2006).
[cited by applicant]
Charman, W. Neil. Pinholes and presbyopia: solution or sideshow? Ophthalmic Physiol Opt 39(1):1-10 (2019).
[cited by applicant]
Co-pending U.S. Appl. No. 18/606,372, inventor Horn; Gerald, filed Mar. 15, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/606,433, inventor Horn; Gerald, filed Mar. 15, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/606,475, inventor Horn; Gerald, filed Mar. 15, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/606,489, inventor Horn; Gerald, filed Mar. 15, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/606,509, inventor Horn; Gerald, filed Mar. 15, 2024.
[cited by applicant]
Diamonds-BCdVA and Refraction Guideline, Version 1.0, Jan. 12, 2016 (10 pages).
[cited by applicant]
Drug information Q&A “Q29”. What is the expiry date of drugs and how to store them properly?, Japan Pharmaceutical Manufacturers Association [online], Mar. 2014, [retrieved on Mar. 25, 2024], Retrieved from the Internet…
[cited by applicant]
Find ETDs Home Thesis Resources Find ETDs. Available at https://ndltd.org/thesis-resources/find-etds/ (Retrieved on Jan. 31, 2023).
[cited by applicant]
Irwin, John et al., ZINC—a Free Database of Commercially Available Compounds for Virtual Screening. Journal of Chemical Information and Modeling. 45(1):177-182 (2005).
[cited by applicant]
Jiao, Jim. Polyoxyethylated nonionic surfactants and their applications in topical ocular drug delivery. Advanced Drug Delivery Reviewed 60:1663-1673 (2008).
[cited by applicant]
Kim, Sunghwan, et al., Pubchem in 2021: New Data Content and Improved Web Interfaces . Nucleic Acids Research 49(D1):D1388-D1395 (2021).
[cited by applicant]
Krise et al. A novel prodrug approach for tertiary amines. 2. Physicochemical and in vitro enzymatic evaluation of selected N-phosphonooxymethyl prodrugs. J Pham Sci 88(9):922-927 (1999).
[cited by applicant]
Mäntylä et al. Design, synthesis and in vitro evaluation of novel water-soluble prodrugs of buparvaquone. Eur J Pharm Sci 23(2):151-158 (2004).
[cited by applicant]
Pramanik et al. A new route to cevimeline. Tetrahedron Letters 54(24):3043-3045 (2013).
[cited by applicant]
PubChem CID-22416839, Dec. 5, 2007.
[cited by applicant]
Santvliet, et al. Determinants of Eye Drop Size. Survey of Ophthamology 49(2):197-213 (2004).
[cited by applicant]
Schuster, Bradley L. Is There a Best Technique for Putting in Eye Drops?. Glaucoma Research Foundation, Mar. 23, 2022; [retrieved on Jun. 14, 2024]. Available at URL: https://glaucoma.org/articles/is-there-a-best-techni…
[cited by applicant]
STN Registry/Zregistry (CAS Registrysm) Sep. 2016 (2 pages.).
[cited by applicant]
U.S. Appl. No. 17/502,066 Office Action dated Mar. 27, 2024.
[cited by applicant]
U.S. Appl. No. 17/988,366 Office Action dated Apr. 29, 2024.
[cited by applicant]
U.S. Appl. No. 17/988,366 Office Action dated Jan. 8, 2024.
[cited by applicant]
U.S. Appl. No. 18/239,072 Office Action dated Mar. 27, 2024.
[cited by applicant]
U.S. Appl. No. 18/239,087 Office Action dated Jan. 25, 2024.
[cited by applicant]
U.S. Appl. No. 18/241,733 Office Action dated Jan. 30, 2024.
[cited by applicant]
U.S. Appl. No. 18/369,737 Office Action dated Jun. 6, 2024.
[cited by applicant]
U.S. Appl. No. 18/465,918 Office Action dated Feb. 1, 2024.
[cited by applicant]
U.S. Appl. No. 18/606,372 Office Action dated Jun. 20, 2024.
[cited by applicant]
White, et al. Effect of Blinking on Tear Elimination as Evaluated by Dacryoscintigraphy. Ophthalmology 98(3):367-369 (1991).
[cited by applicant]
Xu, Renfeng et al. Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic Eyes. Optom Vis Sci 93(11):1409-1419 (2016).
[cited by applicant]
Barman, Purna Chandra et al. An Overview of Non-Newtonian Fluid. International Journal of Applied Science and Engineering 4(2):97-101 (2016).
[cited by applicant]
Co-pending U.S. Appl. No. 18/763,722, inventors Horn; Gerald et al., filed Jul. 3, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/765,066, inventors Horn; Gerald et al., filed Jul. 5, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/765,156, inventors Horn; Gerald et al., filed Jul. 5, 2024.
[cited by applicant]
Co-pending U.S. Appl. No. 18/766,429, inventors Horn; Gerald et al., filed Jul. 8, 2024.
[cited by applicant]
PCT/US2024/024819 International Search Report and Written Opinion dated Jul. 15, 2024.
[cited by applicant]
PubChem SID 500830745. Talsaclidine. Available from: https://pubchem.ncbi.nlm.nih.gov/substance/500830745 (2024).
[cited by applicant]
Randazzo et al., Pharmacological management of night vision disturbances after refractive surgery Results of a randomized clinical trial. J Cataract Refract Surg 31(9):1764-1772 (2005).
[cited by applicant]
Zimmerman et al. Side Effects and Ways to Avoid Them. Ophthalmology 89(1):P76-80 (1982).
[cited by applicant]