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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/01/2025 has been entered.
Status of the Claims
Currently, claims 49-57 and 59-67 are pending in the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/01/2025 and 09/22/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103 – Withdrawn
Rejections of claims 49-57 and 59-67:
The rejections of claims 49-57 and 59-67 are hereby withdrawn. However, new grounds of rejection are required and will be detailed herein.
Claim Rejections - 35 USC § 103 – New Grounds of Rejection
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 49-57 and 59-67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chia (previously referenced) in view of Horn (US 2015/0065511 A1).
Claims 49-57 are drawn to ophthalmic compositions which have identical limitations to the compositions recited in the methods of claims 59-67, respectively. Essentially, claims 59-67 are drawn to methods of use of the compositions of claims 49-57 for the purpose of treating myopia. As discussed herein, the methods of claims 59-68 are obviated by Chia in view of Horn. As the methods of use in treating myopia are obviated, so are the compositions being used (i.e. claims 49-57). Accordingly, a person of ordinary skill in the art would have found such compositions prima facie obvious for the same reasons as specified below in the rejections of claims 59-67.
Claim 59 recites a method of treating myopia, comprising administering an ophthalmic composition, comprising:
about 0.001% w/v to about 0.05% w/v atropine;
sodium chloride;
glycerin;
chitosan;
povidone;
water
0.04% w/v citrate buffering agent
At a pH from about 3.8 to 7.5.
Chia teaches the treatment of childhood myopia by administering ophthalmic compositions comprising atropine. More specifically, Chia discloses the treatment of childhood myopia by administering atropine compositions with concentrations of 0.01%, 0.1%, and 0.5% over a two year time period. Chia found that the administering of atropine to subjects resulted in a clinically small dose related response on myopia (page 349)1. The teachings of Chia indicate that the administering of ophthalmic atropine compositions in a concentration range of 0.01% to 0.5% provides an effective treatment for myopia in children (page 353)2. The effective range taught by Chia provides a case of obviousness on the basis of MPEP 2144.05(I) Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions:
“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.").”
While Chia teaches the use of atropine containing composition for use in treating myopia, they do not explicitly teach the use of NaCl, glycerin, chitosan, povidone, or 0.04% citrate buffering agent. However, it would be obvious to use such constituents in an ophthalmic composition because Horn teaches each of these components as common excipients, suitable for use in atropine compositions.
Horn teaches ophthalmic compositions for use in the treatment of presbyopia, wherein the compositions comprise a muscarinic agent and a cycloplegic agent. Horn further indicates that atropine is a suitable cycloplegic agent for use in the disclosed compositions (specification [0162])3. Horn further indicates various excipients for use in the disclosed include tonicity adjustors, viscosity enhancers, and buffers. Sodium chloride and glycerin are suggested by Horn as tonicity adjustors (specification [0167])4, chitosan and polyvinyl pyrrolidone (i.e., povidone) are suggested as viscosity enhancers (specification [0150])5, and citrate buffer is suggested as a buffer, wherein the pH is in a widest range of 4.0-8.0, and a preferable narrower range of 5.0-7.0 (specification [0169])6. Accordingly, Horn obviates the inclusion of each of elements (ii)-(v) and (vii). With regards to the recitation of 0.04% citrate buffering agent, it would be well within the ability of a person of ordinary skill in the art to elucidate such an amount by routine optimization, given that the teachings of Horn provide the inclusion of each of the components not disclosed by Chia, and that the concept of buffer and pH control would be well within the ability of such a person skilled in pharmaceutical formulation.
Given that the teachings of Chia are directed towards methods of use of ophthalmic atropine compositions, a person of ordinary skill in the art would be readily motivated to seek out art relevant to ophthalmic compositions, such as those taught by Horn which implicate atropine as a pharmaceutical active. It would have been obvious for a person of ordinary skill in the art to combine the teachings of Chia and Horn because there would be a reasonable expectation that the combination would yield stable atropine concentrations useful for the treatment of myopia.
Claim 60 recites the method of claim 59, comprising about 0.025% w/v atropine.
As discussed previously in the claim 59 rejection above, Chia teaches an effective dosing range of 0.01-0.5% atropine to treat myopia, wherein the effects are dose-dependent. Accordingly, the instant claim is rejected for the same obviousness reasons as claim 59.
Claim 61 recites the method of claim 59, comprising about 0.01% w/v atropine.
As discussed previously in the claim 59 rejection above, Chia teaches an effective dosing range of 0.01-0.5% atropine to treat myopia, wherein the effects are dose-dependent. Accordingly, the instant claim is rejected for the same obviousness reasons as claim 59.
Claim 62 recites the method of claim 59, comprising about 0.05% w/v atropine.
As discussed previously in the claim 59 rejection above, Chia teaches an effective dosing range of 0.01-0.5% atropine to treat myopia, wherein the effects are dose-dependent. Accordingly, the instant claim is rejected for the same obviousness reasons as claim 59.
Claim 63 recites the method of claim 59, comprising edetate disodium.
Horn teaches the inclusion of ethylenediaminetetraacetic acid (i.e., EDTA) as a preservative (specification [0168])7. Accordingly, the instant claim is rejected for the same obviousness reasons as claim 59.
Claim 64 recites the method of claim 59 wherein the composition has a pH of about 5.5.
As iterated in the claim 59 rejection, the teachings of Horn indicate a narrowest preferable pH range of 5.0-7.0. Additionally, Horn indicates that the pH of the composition may be adjusted as needed using acids and bases as pH adjustors. It would be well within the ability of a person of ordinary skill in the art to arrive at the recited pH by routine optimization of the composition pH within the bounds of Horn’s preferred pH range.
Claim 65 recites the method of claim 59 wherein the composition has a dose-to-dose ophthalmic concentration variation of less than 40%.
The composition components of both Chia and Horn would generally be expected to yield homogenous solutions as each of the components appear to be water soluble. Absent of evidence of an unexpected interaction between the components, one of ordinary skill in the art would reasonably expect dose concentration variation to be lower than 40% between doses.
Claim 66 recites the method of claim 59 wherein the ophthalmic composition comprises at least about 80% of the atropine based on initial concentration after at least three months under storage temperature of from about 2°C to about 10°C or from about 16°C to about 26°C.
The instant claim recites a property of the composition used in the method of claim 59. As iterated in the claim 59 rejection, the method and composition are obviated by the teachings of Chia in view of Horn. As the teachings of Chia and Horn obviate both the composition and method, any physiochemical properties conferred to the final composition by its constituency would also be obviated.
Claim 67 further limits the method of claim 66 wherein the ophthalmic composition further has a potency of at least 80% after at least three months under storage temperature of from about 2°C to about 10°C or from about 16°C to about 26°C.
The instant claim recites a property of the composition used in the method of claim 59. As iterated in the claim 59 rejection, the method and composition are obviated by the teachings of Chia in view of Horn. As the teachings of Chia and Horn obviate both the composition and method, any physiochemical properties conferred to the final composition by its constituency would also be obviated.
Conclusion
Claims 49-57 and 59-67 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC TRAN whose telephone number is (571)272-7854. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “A dose-related response on myopia was noted among the 3 treatment arms, but differences between treatment arms were clinically small (Fig 2). An initial hyperopia shift of 0.3 to 0.4 D was noted in the 0.1% and 0.5% groups but not in the 0.01% group (Table 1). At the end of 1 year, there was a significant difference in myopia progression between the 0.5% atropine group and the 0.01% (P 0.001) and 0.1% (P0.01) groups, but there was no statistical significant difference between the 0.01% and 0.1% groups. The final myopia progression over 2 years was 0.490.60, 0.380.60, and 0.300.63 D in the atropine 0.01%, 0.1%, and 0.5% groups, respectively (P0.07), with a significant difference only between the 0.01% and 0.5% groups (Table 2). There was no significant difference in spherical equivalent levels between groups (P0.20). Fifty percent of the 0.01% group had progressed by less than 0.5 D, compared with 58% and 63% in the 0.1% and 0.5% groups, respectively, with approximately 18% progressing by 1.0 D in all 3 groups (Fig 3).”
2 “In conclusion, our results suggest that 0.5%, 0.1%, and 0.01% atropine remain effective in reducing myopia progression, compared with placebo treatment, and that the clinical differences in myopia progression among these 3 groups are small. The lowest concentration of 0.01% atropine thus seems to retain efficacy and is a viable concentration for reducing myopia progression in children, while attaining a clinically significant improved safety profile in terms of accommodation, pupil size, and near visual acuity, and subsequently reduced adverse impact on visual function.”
3 “Cycloplegic agents suitable for the present invention include, but are not limited to, atropine…”
4 “A tonicity adjustor can be, without limitation, a salt such as sodium chloride (“NaCl”), potassium chloride, mannitol or glycerin…”
5 “Viscosity enhancers suitable for the present invention include, but are not limited to, carboxymethyl cellulose (“CMC”), methylcellulose, methyl cellulose 4000, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyl propyl methyl cellulose 2906, carboxypropylmethyl cellulose, hydroxyethyl cellulose, or hydroxyethyl cellulose, hyaluronic acid, dextran, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone”
6 “Various buffers and means for adjusting pH can be used to prepare ophthalmological compositions of the invention. Such buffers include, but are not limited to, acetate buffers, citrate buffers, phosphate buffers and borate buffers. It is understood that acids or bases can be used to adjust the pH of the composition as needed, preferably of I to 10 mM concentration, and more preferably about 5 mM. In a preferred embodiment the pH is from about 4.0 to about 8.0, in a more preferred embodiment the pH is from about 5.0 to about 7.0.”
7 “Preservatives that can he used with the present invention include, but are not limited to. benzalkonium chloride (“BAK”), chlorobutanol, thimerosal, phenylmercuric acetate, disodium ethylenediaminetetraacetic acid”