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 the Application
Claims 1-2, 4, and 6-22 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 12/12/2025 are acknowledged. Claims 11 and 17-19 remain withdrawn, as being drawn to an unelected invention or specie. Claims 1 and 6 are amended, and new claims 21-22 are added. Claims under consideration in the instant office action are claims 1-2, 4, 6-10, 12-16, and 20-22.
Applicants' arguments, filed 12/12/2025, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claim Rejections - 35 USC § 103
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.
Claims 1-2, 4, 6-10, 12-16, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Donnenfeld (Difluprednate for the prevention of ocular inflammation postsurgery: an update, Clinical Ophthalmology, 2011, 5, pp. 811-816) in view of Baldwin (US 2017/0266294, as disclosed in IDS).
Donnenfeld is drawn towards the use of difluprednate for the prevention of ocular inflammation postsurgery (see abstract). Donnenfeld teaches “difluprednate ophthalmic emulsion, 0.05% (Durezol®, Alcon Laboratories, Inc, Fort Worth, TX) – was approved by the US Food and Drug Administration for the treatment of inflammation and pain associated with ocular surgery. Since then, many physicians have had extensive clinical experience with difluprednate and have incorporated it into their standard anti-inflammatory treatment regimen.” (pg. 811, second paragraph).
Donnenfeld does not teach a formulation further comprising a biocompatible polysaccharide comprising deacetylated gellan gum (DGG).
Baldwin is drawn towards “aqueous formulations containing an anti-infection agent, a biocompatible polysaccharide, an osmotic pressure regulator, a pH regulator, and water, wherein a gel containing the therapeutic agent is formed in situ upon instillation of the formulations onto the skin and a body cavity of a subject.” (see abstract). Baldwin teaches “The mechanism of in situ gel formation is to utilize polymer materials' features of changing dispersion or conformation under different environmental conditions, resulting in a significant increase of solution viscosity, thus forming a gel-state drug reservoir in drug administration sites.” (paragraph 0012). Baldwin teaches such formulations comprising (DGG) in an amount of 0.5% to 1% (paragraphs 0013-0014). Baldwin teaches such formulations further comprising mannitol in an amount of 0.1 to 0.5% (paragraphs 0022-0023), trishydroxymethylaminomethane (Tris) (paragraph 0060), polyoxyethylene/polyoxypropylene surfactants (paragraph 0113), and hydroxyethyl cellulose in an amount of 0.01% to 2% (paragraph 0114). Regarding claim 13, povidone iodine is present in an amount of 0.1% to 5% (paragraphs 0018-0019). Regarding claims 1 and 20, Baldwin is silent as to the presence or requirement of a crystal growth inhibitor for ophthalmic compositions. Regarding the amendment, filed 08/13/2025, Baldwin is completely silent as to the incorporation of castor oil, and would thus read on the limitation of the claimed invention.
It would have been obvious to one of ordinary skill in the art to formulate an ophthalmic formulation further comprising DGG, as suggested by Baldwin, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Baldwin teaches ophthalmic formulations capable of forming a gel-state drug reservoir in drug administration sites, which would provide improved delivery of difluprednate as the primary and sole active agent, with a reasonable expectation of success absent evidence of criticality of the particular steps.
Even though the range for components as taught by Baldwin is not the same as the claimed ranges, Baldwin does teach an overlapping range of concentrations, and it has been held that 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(I). Furthermore, the determination of concentrations is well within the purview of those skilled in the art through routine experimentation, and it has been held that “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). See MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the concentrations in order to increase the efficacy of the ophthalmic formulations.
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
With regards to the limitation claimed in instant claims 15-16, which claims average particle sizes, Donnenfeld does not specifically teach the exact amounts claimed in instant claims 15-16. However, it would be within the skill of an ordinary artisan to be able to modify the particle sizes in order to obtain the desired bioavailability of the agents. 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).
Response to Arguments
Applicant argues that “Baldwin, even in view of Donnenfeld as suggested by the Examiner, would not teach or suggest the currently claimed invention, which comprises difluprednate as the primary active ingredient (e.g., for treatment of inflammation or pain associated with ocular surgery).” The Examiner respectfully disagrees since Baldwin is currently relied on principally for the teachings regarding an in situ gel formulation, and does not teach away from difluprednate being designated as the primary active agent in a formulation that reads on the claimed composition.
Applicant also argues that “Donnenfeld is a review of difluprednate ophthalmic emulsion, which requires castor oil to overcome the low solubility of difluprednate. The Examiner's proposed combination (adding difluprednate into Baldwin's aqueous formulations excluding castor oil) is discouraged by the teachings of Donnefeld, and would fundamentally alter how Donnefeld is designed to work- moving it beyond the scope of what a person of ordinary skill in the art consider an obvious modification with a reasonable expectation of success.” The Examiner respectfully disagrees since Donnenfeld teaches the potent therapeutic activity of difluprednate as a topical corticosteroid in the treatment of inflammation and pain (see Conclusion, pg. 815), which is relied on in the rejection. Given the known issues of castor oil use in ophthalmic formulations, it would have been an obvious modification to formulate difluprednate in an alternative ophthalmic formulation, such as the formulations taught by Baldwin. One of ordinary skill in the art would have been motivated to incorporate an agent with low solubility such as difluprednate into the ophthalmic formulations disclosed by Baldwin since Baldwin teaches alternative co-solvents and surfactants to improve solubility of the formulation’s components, including the active agent (paragraph 0113).
Applicant also argues that “the claimed invention is able to achieve unexpected advantages by providing solutions with difluprednate as primary active ingredient, which can sufficiently overcome the low solubility of difluprednate without the use of crystal growth inhibitor or oil (to avoid undesirable side effects caused thereby). The advantages of overcoming low solubility of difluprednate without use of crystal growth inhibitor or oil is neither taught by Baldwin (which does not mention difluprednate) nor Donnenfeld (which requires castor oil to form the oil-in-water emulsion).” The Examiner respectfully disagrees since the claimed invention does not recite the amount or the range of amounts of difluprednate wherein such advantages occur. Although Applicant has provided a comparative of formulations with and without castor oil (see pp. 7-8), the viscosity differences between Formulation 3 and Formulation 5 may be attributed to the difference in the amount of deacylated gellan gum (DGG), and not to a particular amount of castor oil ( see Comparative of Table 2 and 7, pp. 7-8). Additionally, it would be expected that difluprednate, or other active agents with low solubility, can be formulated without the use of crystal growth inhibitors or oil since, for example, Baldwin teaches alternative co-solvents and surfactants to improve solubility of the formulation’s components, including the active agent (paragraph 0113). Baldwin teaches “The mechanism of in situ gel formation is to utilize polymer materials' features of changing dispersion or conformation under different environmental conditions, resulting in a significant increase of solution viscosity, thus forming a gel-state drug reservoir in drug administration sites.” (paragraph 0012). Baldwin teaches such formulations comprising (DGG) in an amount of 0.5% to 1% (paragraphs 0013-0014).
Conclusion
Claims 1-2, 4, 6-10, 12-16, and 20-22 are rejected.
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 ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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, Renee Claytor can be reached at (571)272-8394. 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.
/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
Prosecution Insights