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 .
DETAILED ACTION
Claims 1, 3-8, 10-14 and 18, 21-27 are pending.
Receipt and consideration of Applicants amended claim set and remarks/arguments filed on 8/17/2026 are acknowledged. Claims 14 and 18 remain withdrawn, as being drawn to an unelected invention or species. Claims 1, 14 and 22 are amended and new claims 21-27 are added. Claims under consideration in the instant office action are claims 1, 3-8, 10-13 and 21-27.
Applicants' arguments, filed 8/17/2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
In the interest of compact prosecution, examiner tried several times to contact the applicants and left messages, but did not hear back from them,
Information Disclosure Statement
The information disclosure statement (IDS) dated 8/17//2026 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits.
Claim Objections
Claim 27 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 103
New Grounds of rejection necessitated by the amendment filed on 8/17/2026
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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, 3-8, 10-13 and 21-26.are rejected under 35 U.S.C. 103(a) as being unpatentable over by Mizutare et al. (US 2017/0105934) in view of Makley et al. (US 2018/0250313).
Mizutare et al. discloses a aqueous ophthalmic compositions which comprises an anti-inflammatory or anti-bacterial agents (abstract), at least one surfactant which include Poloxamer 407, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene castor oil 3, polyoxyethylene castor oil 10, polyoxyethylene castor oil 35, polyoxyl 40 stearate and polyoxyl 140 stearate are preferable, and Poloxamer 407, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene castor oil 10, polyoxyethylene castor oil 35, and polyoxyl 40 stearate [0037-0039]. They disclose the inclusion of thickening agents and the preferred agents are cellulose based polymers such as carboxymethyl cellulose, carboxymethyl cellulose sodium and methyl cellulose [0043]. They disclose the use of acidic polysaccharides in their formulation which includes chondroitin sulfate, hyaluronic acid, xanthan gum, gellan gum, alginic acid, or a salt thereof, and is particularly preferably sodium chondroitin sulfate, sodium hyaluronate, alginic acid, or gellan gum[0027]. They disclose the total amount of active ingredient in their composition to be 0.001- 0.01 w/v%[0049], the polysaccharide component to be between 0.0001 w/v% to 6 w/v% [0050], surfactant 0.001 w/v% to 5 w/v% [0059]. Mizutare et al describes in detail all the different active agents and additives that can be used in ophthalmologic solutions and in their inventive compositions [0085-0102]
Mizutare et el. does not specifically recite the ratios between the different components in the composition as instantly claimed, however, they disclose the total amount of active ingredient in their composition to be 0.001- 0.01 w/v%[0049], the polysaccharide component to be between 0.0001 w/v% to 6 w/v% [0050], surfactant 0.001 w/v% to 5 w/v% [0059]. Mizutare et al describes in detail all the different active agents and additives that can be used in ophthalmologic solutions and in their inventive compositions [0085-0102]. It would have been obvious to a person of ordinary skill in the art to optimize the concentrations of these agents with guidelines provided by Mizutare et al. and arrive at the instantly claimed ratio’s. These ranges yield a range of ratios that overlap with those instantly claimed, thereby rendering the claimed ranges obvious. “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)" (see MPEP 2144.05).
Mizutare et al. fails to disclose the instantly claimed active agents as recited in claims 10 and the ophthalmic preparation as nanospheres (claim 12-13) comprising nanobodies having a particle size 350 nm
However, Makley et al. discloses ophthalmic formulations for treatment of ocular conditions such as cataract (abstract). They disclose compounds of formula (IIIC) in their composition which can be used in combination with an anti-apoptotic compound such as lipoic acid [0278] or other anti-inflammatory compounds [0282] or antibiotic agents such as doxycycline and tetracycline [0283]. They disclose their compositions to comprise of surfactants such as sorbitan ether esters at a concentration of 0.05 wt % to about 0.3 wt % of surfactant such as polysorbate -80 [0179] and a viscosity increasing agents which includes carboxymethylcellulose also disclose the use of their compositions as nanosuspension [0186] comprising nano particles of 50 nm droplets([0153], [0301]).
The references above disclose that their pharmaceutical compositions comprise ophthalmologically acceptable preservatives, surfactants, viscosity enhancers, penetration enhancers, buffers, sodium chloride, and water to form an aqueous, sterile ophthalmic suspension or solution. They teach the key excipients that goes into an ophthalmic formulations which are instantly claimed, the surfactant and the ionic macromolecule, the solvent and the active agents. Further, excipients used in the ophthalmic compositions and formulation of ophthalmic compositions are well known in the pharmaceutical arts. As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by teachings of Boss et al. and what is well known in the art.
Further it is recognized that pharmaceutical excipients may perform more than one function, and are therefore characterized as having different uses depending on the particular application. While the use of an excipient in the context of a particular formulation may determine the function of the excipient, the inclusion of any particular excipient into any one or more categories as set forth above is not meant to limit the function of that excipient
The references above provide clear motivation and suggestions to formulate an ophthalmic composition with the instantly claimed compound suitable for administration to the eyes for the purpose it serves. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention. With regards to the amount of each of the excipients added to the composition. it would be within the skill of an ordinary artisan to be able to optimize the concentrations of each of the excipient to maximize its effect and utility in the composition. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). An ordinarily skilled artisan would arrive at the instantly claimed concentration while conducting routine optimization testing to achieve this goal. As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in formulating the instantly claimed composition absence of evidence to the contrary.
Response to applicant’s arguments filed on 08/17/2026:
Applicant traverses the above rejection with the following arguments:
a. The ophthalmic compositions disclosed in Mizutare are different from the claimed
ophthalmic preparations. Specifically, Mizutare discloses incorporating specific excipients into an aqueous ophthalmic composition to inhibit the wetting, deterioration, or change in weight of polybutylene terephthalate (PBT)-containing resin containers that contain the ophthalmic composition. See, e.g., paragraphs [0001] and [0005]-[0008] of Mizutare
b. Mizutare broadly recites a list of active ingredients. Mizutare discloses several thickening agents, among which the ionic macromolecule CMC-Na is listed together with non-ionic macromolecules PVPs and methyl cellulose without any differentiation, indicating that ionic macromolecules and non- ionic macromolecules are interchangeable in Mizutare's ophthalmic compositions.
c. Makley does not teach or suggest formulating any of the recited APIs, or any of the disclosed combinatorial therapeutic agents for that matter, within its pharmaceutical formulation. None of Makley's working examples incorporates any combinatorial therapeutic agent in addition to the compound of formula IIIC..
d. Applicants demonstrate nexpected results demonstrating that the recited APIs, when formulated with the components at the specific ratios recited in the amended claims, form nanoparticle-comprising ophthalmic preparations with superior stability, high encapsulation efficiency, and high API content in the nanoparticles
Applicant's traversal arguments for this rejection have been fully considered, but are not found to be persuasive.
In response to applicant's arguments against each reference individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The references above disclose that their pharmaceutical compositions comprise ophthalmologically acceptable preservatives, surfactants, viscosity enhancers, penetration enhancers, buffers, sodium chloride, and water to form an aqueous, sterile ophthalmic suspension or solution. They teach the key excipients that goes into an ophthalmic formulations which are instantly claimed, the surfactant and the ionic macromolecule, the solvent and the active agents. Further, excipients used in the ophthalmic compositions and formulation of ophthalmic compositions are well known in the pharmaceutical arts. As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by teachings of Boss et al. and what is well known in the art.
. the examiner recognizes that obviousness can only be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988) and In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). It is also noted that "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Applicants arguments with reference to unexpected results is acknowledged. However, the data shown in the example is not commensurate to the scope of the instant claims as the claims do not specifically recite the exact conditions, concentrations and procedure used in the data generated wherein the Applicants claims unexpected results. For example, in Table 1,, examples 1-21 have used only CMC-Na, Sodium glycolate, PEG2K-(COOH)2 and Sodium alginate as ionic macromolecule, only Polysorbate 80, Poloxamer P188 and Lauryl glucoside as surfactants and HPMC, Xanthan gum, PVPK30 and Polaxomer as adhesive agents. Instant claims are not restricted to the use of these agents for the specific purposes and as such are not commensurate in scope. Accordingly, Examiner is not persuaded with the “unexpected results” argument by the Applicant, and the rejection is hereby maintained.
.
Conclusion
Claims 1, 3-8, 10-13 and 21-26 are rejected. Claim 27 is objected. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7.00 am to 4.00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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