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 .
Claim Objections
Claims 14-17 are 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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 21 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The configuration of components that is required in the product made by the method of claims 21-22 is not clear. Claim 1 now recites that “the ophthalmic formulation comprises nanoparticles self-assembled from components of the carrier or excipient, wherein the nanoparticles comprise the active pharmaceutical ingredient”. This recitation implies an emulsion, liposomes, or a similar arrangement of components that occurs due to self- assembly. Claim 23 recites the preparation of a solution of surfactant and thickener where the active ingredient is subsequently dispersed in the solution. No prior dissolution of the active ingredient is recited, therefore the active ingredient is already in particle form when added to the surfactant solution and such particles did not form due to self-assembly of the carrier or excipient. The method further disperses the active ingredient by mechanical means. If the active ingredient particles are not already a nanoparticle size when added, the conversion to nanoparticle sizes via mechanical dispersion is not a self-assembly process. It is not clear how the result of the mechanical dispersion of a solid in a liquid yields a self-assembled configuration of carrier or excipient comprising the active ingredient. Thus it is not clear how (e.g., scope of particular components and proportions) the method is to be practiced with the recited components such that the configuration of the composition of claim 1 is attained.
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.
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 1-5, 7-8, 10, 12-13, 18, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Davio et al. (US PGPub No. 2013/0210912) in view of Zhang et al. (previously cited) and Kito et al. (JP-2016163851 – English translation referenced for citations) as evidenced by McBurnie et al. (Pharmaceutical Technology 2004 24:S13-S23).
Davio et al. teach a topical emulsion (self-assembled particles) eye composition composed of two thickening polymers, oil, non-ionic surfactant, polyol and water (see abstract and paragraph 141). An active pharmaceutical ingredient useful for application to the eye is also an envisioned component and is dissolved in the oil (see paragraphs 9 and 195). An example is detailed with water, sodium chlorite, polysorbate (non-ionic surfactant) at 0.05 wt%, carbomer (thickener) at 0.2 wt%, alginate (thickener) at 0.2 wt%, hydroxypropylmethyl cellulose (thickener) at 0.07 wt%, propylene glycol (cosolvent) at 0.6 wt%, and glycerin (cosolvent) at 0.6 wt% (see paragraph 110 table 7 composition 13; instant claims 7-8, 10, 12-13, 18 ). The mass ratio of surfactant to thickener to cosolvent is 0.05 to 0.47 to 1.2. They further teach sterile filtering the emulsion which implies the presence of nanoparticles smaller than 220 nm, given that sterile filtration occurs via filters with a 220 nm pore size (see paragraph 164 and McBurnie et al. page S14 first column first full paragraph). First and second thickening polymers are generally envisioned as carbomers present at 0.01 to 2 wt% and anionic polysaccharides present at 0.01 to 2 wt% , respectively (see paragraph 104-107). Viscosity enhancing agents may also be present and are envisioned as polyvinylpyrrolidone. Davio et al. go on to teach administration of the composition as drops (see paragraph 143; instant claim 25). The presence of lanosterol is not detailed.
Zhang et al. teach topical compositions of steroid compounds where lanosterol is embraced and exemplified for treating cataracts and other lens conditions (see paragraph 2-10, 25, 54, 62, and claim 30). They detail concentrations of the compound that range from 1 mg/ml to 500 mg/ml (0.001 mg/ml to 0.5 mg/ml) in a mostly aqueous preparation which corresponds to approximately to 0.0001 wt% to 0.5 wt% (see paragraph 61; instant claims 1-4). Lanosterol is an oil soluble compound according to Kito et al. paragraph 26).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include lanosterol at a proportion as detailed by Zhang et al. as the API in the composition of Davio et al. because they teach their concentrations as also being suitable for treating the eye. This modification would have been obvious as the simple substitution of one known element for anther in order to yield a predictable outcome and as the application of the same technique to a similar product in order to yield the same improvement. The result is a mass ratio of surfactant to thickener to cosolvent to lanosterol of 0.05 to 0.47 to 1.2 to 0.0001-0.05 which translates to 1-500 to 9.4-4700 to 24-12,000 to 1. These ranges of proportions overlap with or embrace those instantly claimed which, 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; instant claims 1 and 5). The particle size similarly overlaps with that instantly claimed, thereby rendering the instantly claimed range obvious (see instant claim 20). Administration as drops to treat cataracts would then follow (see instant claims 23-25). Therefore claims 1-8, 10, 12-13, 18, 20-21, and 23-25 are obvious over Davio et al. in view of Zhang et al. and Kito et al. as evidenced by McBurnie et al.
Claims 1-4, 8-13, 18, 20, and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Lambert et al. (US PGPub No. 2011/00321443) in view of Piraee (WO 2019/097434), Kito et al., and Andoh et al. (EP 0490305) as evidenced by Aviv et al. (US Patent No. 5,496,811).
Lambert et al. teach a topical emulsion (self-assembled particles) eye composition for delivering an anti-inflammatory agent to address various eye conditions (see paragraphs 2 and 62). An exemplified composition provides the vehicle for the pharmaceutical active with water, a quaternary ammonium salt, 0.3 wt% Tyloxapol® (non-ionic surfactant), 0.01 wt% poloxamer (thickener), 1 wt% polyethylene glycol (cosolvent/thickener), 2.35 wt% glycerin (cosolvent), and an oily phase containing the dissolved anti-inflammatory agent (see paragraphs 69 and 99 and table 8a composition Z61EM001 and Aviv et al. column 5 line 62-column 6 line 12). They go on to teach the droplet size to range from 100-150 nm (see paragraph 48; instant claim 20). The mass ratio of surfactant to thickener to cosolvent is 30:1:330. The presence of lanosterol or 25-hydroxycholesterol is not detailed.
Piraee teaches the utility of lanosterol, 25-hydroxycholesterol, and their derivatives in topical ocular compositions to treat cataracts (see abstract and paragraphs 9 and 25). They detail an emulsion composition for administration as well as the presence of the compounds at 0.01-2% w/v (about 0.1 to 20 mg/ml) in combination with an antioxidant(see paragraphs 25-26; instant claims 2-4). Piraee further teach eye drops of the compounds and administration to the eye (see paragraphs 57-79).
Andoh et al. teach a topical eye composition that is envisioned to provide anti-inflammatory and anti-cataract compounds contained in particles (see abstract and page 3 lines 20-32 and claim 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include lanosterol or 25-hydroxycholoesterol at a proportion as detailed by Piraee in the composition of Lambert et al. because Andoh et al. indicates the recognized usefulness of a combination treatment providing both anti-cataract and anti-inflammatory compounds from particles for eye application. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. The result is a mass ratio of surfactant to thickener to cosolvent to lanosterol/25-hydroxycholetserol of 0.3:0.01:3.35:0.01 to 2 which translates to 0.15:0.005:1.675:1 to 30:1:330:1. These ranges of proportions overlap with or embrace those instantly claimed which renders the instantly claimed ranges obvious (see MPEP 2144.05; instant claims 1 and 5). Alternatively, the polyethylene glycol can be considered the thickener and yields 0.3:1.01:2.35:0.01 to 2 which corresponds to 0.15:0.5:1.175:1 to 30:101:235:1. This is again a set of ranges of ratios that overlap with those claimed in instant claims 11 and 26 and renders them obvious. Administration as drops to treat cataracts would then follow (see instant claims 23-25). Therefore claims 1-4, 8-13, 18, 20, and 23-26 are obvious over Lambert et al. in view of Piraee, Kito et al., and Andoh et al. as evidenced by Aviv et al.
Claims 1-5, 7-8, 12-13, 18, 20-22, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US PGPub No. 2012/03086 – henceforth Liu C).
Liu C teaches submicron emulsions of paclitaxel complexed with a steroid, where the molar ratio of paclitaxel to steroid is 1:0.2 to 4 (see abstract). They teach the emulsion (self-assembled nanoparticles) with a diameter of less than 400 nm (spherical particles) (see paragraph 16; instant claim 20). Liu C also teaches lanosterol as an envisioned steroid (see paragraph 15). Submicron emulsion 23 prepares a 200 ml composition that employs 0.145 g of complex with a 1:1 molar ratio of the steroid to paclitaxel and includes water (solvent), 3 g fatty glyceride (non-ionic surfactant), 3 g poloxamer (thickener/surfactant), and 5 g glycerol (cosolvent) (see examples 1 and 7; instant claims 1, 7-8, 10, and 12-13). Liu C teach preparing their submicron emulsion by mixing the solvent, surfactant, and the instant thickener into a first solution then dispersing a second solution of the dissolved steroid containing complex via high pressure homogenization into the first solution (see examples 3 and 7; instant claims 21-22). The desired size is attained via homogenization and ranges from 100 to 300 nm (see paragraphs 32-35; instant claim 27). Liu C also teach alginate as an alternative to the fatty glyceride (see paragraph 26).
While a full example for each embodiment that follows from the teachings of Liu C is not detailed, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare an embodiment of Liu et al. where lanosterol is the steroid, for example, by modifying their submicron emulsion 23. The 1:1 molar ratio of paclitaxel to lanosterol corresponds to a 2:1 mass ratio (as calculated by the examiner based on a 426 g/mol lanosterol molar mass and 853 g/mol paclitaxel molar mass). The composition would then provide 200 ml with 3000 mg surfactant, 3000 mg thickener, 5000 mg cosolvent, and 48 mg lanosterol which is a 62.5:62.5:101:1 ratio with 0.24 mg/ml lanosterol (as calculated by the examiner; instant claims 1-5). A small portion of the glycerol could also be considered the osmotic pressure regulator and a portion of the poloxamer could be considered part of the surfactant and shift the ratio to 75:50:101:1 (see instant claims 5, 7 and 18). Preparation via the method Liu C teaches would follow. It also would have been obvious to exchange alginate for the fatty glyceride which would yield a composition with the poloxamer fulfilling the role of the instant surfactant and the alginate fulfilling the role of the instant thickener (see instant claims 7-8). The modification is obvious as simple substitution of one known element for another in order to yield a predictable outcome. The desired particle size overlaps with that instantly claimed, thereby rendering obvious the claimed range (see MPEP 2144.05; instant claims 20 and 27). Although the composition of Liu C is not described as ophthalmic, this recitation is an intended use for the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Here the composition of Liu C is capable of performing the recited use since it can be applied to the eye, therefore it meets the intended use limitations. Thus claims 1-5, 7-8, 12-13, 18, 20-22, and 27 are obvious over Liu C.
Allowable Subject Matter
The limitations of instant claims 14-16 recite compositions with self assembled nanoparticles with particular options for the surfactant, cosolvent, and thickener as well as ranges of proportions for each of these components and the oxysterol. While Zheng et al. (previously cited) detail overlapping ranges for the recited components and name emulsions as contemplated general forms, their teachings do not clearly connect a self-assembled configuration of component’s and the proportions necessary to achieve them. Examples of Zheng et al. note a cloudy liquid and/or white visible particles in the prepared compositions which are features that are not suggestive of the presence of self-assembled nanoparticles. The prior art does not appear to provide for both the presence of a claimed oxysterol and the excipient component’s required by the instant claims at the recited proportions and in a configuration that includes self-assembled nanoparticle of the excipients and oxysterol. Therefore the claims are non-obvious.
Response to Arguments
Applicant's arguments filed April 28, 2026 have been fully considered. In light of the amendment to the claims, the previous grounds of rejection are hereby withdrawn. New grounds of rejection are detailed to address the new combination of claim limitations.
Conclusion
No claim is 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 CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
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, Robert Wax can be reached at (571) 272-0623. 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.
/CARALYNNE E HELM/ Examiner, Art Unit 1615
/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615
Prosecution Insights