DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-19 and 22-23 are pending. Claims 3,8-10,13-14 and 17 are withdrawn. Claims 1-2,4-7,11-12,15-16,18-19 and 22-23, are under examination as being directed to elected Formulation 51 (see paragraph 39 of the specification).
Information Disclosure Statement
The information disclosure statements (IDS)s submitted on 8/18/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Terminal Disclaimer
The terminal disclaimer filed on Aug 18, 2026, disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of
Application No. 17721838 (reference application)
Application No. 17721831 (reference application) in view of Akorn PI
Application No. 17681560 (reference application)
Application No. 17/894882 (reference application)
Application No. 17894884 (reference application)
Application No. 17894885 (reference application)
Application No. 19235538 (reference application).
has been reviewed and is accepted. The terminal disclaimer has been recorded.
Response to Arguments
Applicant’s arguments and amendment of Claims 1-2,4-7,11-12,15-16,18-19 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over as unpatentable over Chia, Ophthalmology Volume 119, Number 2, February 2012)), in view of Akorn Atropine Prescribing Information (PI) (Revised July 2014 ), have been considered and are considered persuasive. The rejection of claims 1-2,4-7,11-12,15-16,18-19 and 22-23 has been withdrawn. However, claims 1-2,4-7,11-12,15-16,18-19 and 22-23 are newly rejected as obvious over Chia, in view of Akorn Atropine Prescribing Information (PI) and WoldeMussie (U.S. 5,716,952).
Claim Rejections - 35 U.S.C. § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4-7, 11-12, 15-16, 18-19 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Chia (Atropine for the Treatment of Myopia 2), Ophthalmology Volume 119, Number 2, February 2012, in view of Akorn Atropine Prescribing Information (PI) (Akorn Atropine Care™((atropine sulfate ophthalmic solution), NDA 206289 Product Label (Revised July 2014 ) and WoldeMussie (U.S. 5,716,952). 2
Examined amended claim 1 is directed to a method of treating myopia in an individual in need thereof,
comprising administering to an eye of the individual a stabilized ophthalmic composition comprising from about 0.01 wt% to about 0.05 wt% atropine or atropine sulfate, water, and tropic acid, and wherein the stabilized ophthalmic composition comprises a pH between about 4.5 and 6.0, and comprises less than 10 % of tropic acid based on the concentration of atropine or atropine sulfate after storage at a temperature of about 25°C for at least 2 weeks.
Similar to claim 1, claim 15 is directed to a similar method of administering the same composition of amended claim 1 to a subject in need, but also includes other conditions such as pre-myopia or progression of myopia, as well as myopia.
Similar to claim 1, claim 23 is directed to a similar method of treating myopia in an individual in need thereof, comprising administering to an eye of the individual an ophthalmic composition comprising from about 0.01 wt% to about 0.05 wt% atropine or atropine sulfate, water, and tropic acid, wherein the stabilized composition comprises a pH between about 4.5 and 6.0, and wherein the topic acid is present in the composition in an amount less than 10% based on the concentration of atropine or atropine sulfate after storage at a temperature of about 25°C for at least 2 weeks. For claims 1, 15 and 23, a tropic acid range of less than 10% that of atropine, would have a broad and reasonable interpretation of 0% tropic acid in the ophthalmic composition.
Regarding claims 1, 15 and 23 and the limitations of treating myopia with an aqueous ophthalmic formulation of atropine 0.01% (eye drops), Chia discloses atropine eyedrops of 0.01% “has minimal side effects compared with atropine 0.1% and 0.5%, and retains comparable efficacy in controlling myopia progression.” . See abstract.3 Per MPEP 2144.05, where the claimed ranges overlap or lie inside prior art ranges, a prima facie case of obviousness exists.
As required by claims 1, 15 and 23, Chia does not teach the presence of tropic acid in its atropine sulfate formulations.
While Chia teaches treatment of myopia with 0.01% atropine sulphate as required by claims 1, 15 and 23, Chia does not recite an aqueous formulation, nor is there an explicit teaching of tropic acid of less than 10% of atropine after storage at 25°C for at least 2 weeks.
Regarding claims 1 and 23 and the claimed pH range of pH from about 4.4 to about 6.4, WoldeMussie, directed to ophthalmic compositions administered to the eye, teaches the use of the buffering agents, such as phosphate, borate and citrate is taught in column 2, lines 23-29. Further, WoldeMussie teaches a pH adjustor to a pH of 4.5-7.5, see Table 1.
With regard to the water (aqueous solution) limitation, Akorn Atropine Sulfate Prescribing Information (Akorn Atropine PI) teaches atropine sulfate ophthalmic solution for topical application to the eye, where the solution comprises water. See page 1 and bottom of page 3. While Akorn Atropine PI does teach tropic acid as metabolite formed by enzymatic hydrolysis of the liver in the body of a subject (see page 8), it does not teach the presence of tropic acid in the atropine formulation to be administered to the subject as claimed.
With regard to the limitation of tropic acid under 10% of atropine/atropine sulfate after storage at a temperature of about 25°C for at least 2 weeks, “ a PHOSITA would have a reasonable expectation that such stability limitation would be present in formulations of the prior art. Storage of the claimed atropine formulation under vacuum conditions, at an optimal pH to ensure stability with various excipients would lead a PHOSITA to have the reasonable expectation the claimed compositions would be stable as claimed.
A PHOSITA following the teachings of Chia would have found it prima facie obvious to treat the myopia with aqueous formulations of atropine sulfate known to be commercially available and FDA approved in the art, that is absent any amounts of tropic acid, where WoldeMussie teaches the claimed pH range. Further, a person having ordinary skill in the art (PHOSITA) would have had a reasonable expectation of success in formulating the atropine ophthalmic formulation of Chia into known atropine aqueous formulations in known concentrations as cited in the art and also achieving the tropic acid less than 10 % of atropine/atropine sulfate after storage 25°C for at least 2 weeks, where WoldeMussie teaches the claimed pH range. Further, a person having ordinary skill in the art (PHOSITA), recognizing the capability and purposes of buffers to maintain a stable pH would routinely do so as known in the art.
The rationale to support a finding of obviousness are the known prior art elements of atropine formulated at a concentration of 0.01% to treat myopia in combination with known method, use of an aqueous formulation, to predictably arrive at the claimed invention. It would be routine for a PHOSITA to optimize a method treating myopia as claimed with aqueous formulations of such as the cited prior art discloses such methods per Chia and where a commercial and FDA approved atropine formulation is an aqueous formulation.
Claims 2 and 16 and the limitation of atropine sulphate concentration of about 0.01 wt% is taught by Chiba. Chia teaches the concentration of 0.01 wt% of atropine where it notes in terms of efficacy “atropine 0.01 % also had significant clinical effects as evident by its effect on myopia progression, accommodation and pupil size.” See page 353, column 1.
As per claims 4-6 and 18-19 and the limitation of topical administration to the eye, via instillation (drop by drop to the eye), administered at least once a day, Chia teaches its child subjects were administered 0.01% atropine once nightly. See abstract. See also Akorn Atropine PI that discloses atropine sulfate ophthalmic solution for topical application to the eye, administered 1 drop topically to the eye, up to twice daily as needed. See page 1.
As required by claim 7 and the limitation of a tonicity adjusting agent, it is noted that sodium chloride is a known tonicity agent in aqueous solution as per Akorn Atropine PI, where page 3 notes hydrochloric acid and sodium hydroxide in aqueous solution. See page 3.
Regarding claims 11-12 and the limitations of the preservative benzalkonium chloride, Akorn Atropine PI teaches a benzalkonium chloride at a concentration of 0.01 % of its formulation is also taught. See page 3, reproduced in part below.
PNG
media_image1.png
50
660
media_image1.png
Greyscale
Similar to claims 1, 15 and 23, claim 22 is directed to a method of treating myopia in an individual in need comprising administering an ophthalmic composition comprising from about 0.01 wt% to about 0.05 wt% atropine or atropine sulfate, water, and tropic acid, and wherein the composition comprises less than .005 % of tropic acid.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response states Applicant has amended claims 1 and 23 to clarify the claimed subject matter; Applicant stated that neither Chia, nor Akorn, taken alone or in combination, teach each and every element of claims 1 and 23 as amended
Applicant argues the Office has acknowledged in the Notice of Allowance dated July 20, 2026, for co-pending application 17/721,838
PNG
media_image2.png
88
508
media_image2.png
Greyscale
The Attorney response states Akorn does not resolve these deficiencies of Chia because it describes a 1 % atropine composition.
In response, it is pointed out that allowed claim 46 of 17/721,838
PNG
media_image3.png
162
628
media_image3.png
Greyscale
is of different scope from examined amended claim 1. Note the difference in atropine concentration, presence of benzalkonium chloride, lack of tropic acid, etc..
PNG
media_image4.png
184
634
media_image4.png
Greyscale
Accordingly, the basis for allowance in Application 17/721,838 claim 46, i.e. Chia does not teach the claimed pH range, is not applicable here.
Further, as detailed above in the new obviousness rejection, Wolde-Mussie teaches an ophthalmically administered composition with excipients, to address the pH amendments of claim 1. WoldeMussie, directed to ophthalmic compositions administered to the eye, teaches the use of the buffering agents, such as phosphate, borate and citrate is taught in column 2, lines 23-29. WoldeMussie teaches a pH adjustor to a pH of 4.5-7.5, see Table 1.
Conclusion and Correspondence
No claims are allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 Formulation 5 (see Specification, para. [00393], Table 23A) as the species for substantive examination. Formulation 5 comprises (%w/v) 0.01 Atropine sulfate monohydrate, 0.04 Citric Acid, 0.9 Sodium Chloride, 0.01 Benzalkonium Chloride (BAK), and Q.S. H 20. Tropic acid concentration of Formulation 5 is provided at least at para. [00381 ], Table 25A.
2 Chia (NPL No. 024), and Akorn Atropine PI (NPL No. 006) are cited on the July 30, 2024 IDS. WoldeMussie - provided as Pat cite 12 in IDS dated 7/30/2024.
3 Chia teaches the concentration of 0.01 wt% of atropine where it notes in terms of efficacy “atropine 0.01 % also had significant clinical effects as evident by its effect on myopia progression, accommodation and pupil size.” See page 353, column 1. Chia teaches that “[o]verall, atropine-related adverse effects were uncommon at the 0.01% dose.” See page 353, column 2. Table 3 of Chia teaches reduced instances of adverse/severe adverse events at atropine 0.01 % when compared to higher concentrations 0.1% and 0.5%. See page 353 top of page, noting reduced adverse events of 0.01 % atropine in treating childhood myopia in terms of allergic conjunctivitis, dermatitis involving eyelids, etc. compared with 0.1% and 0.5%.
Prosecution Insights