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 claims
The status of the claims are as follows
Claims 1, 6, and 8-11 are pending.
Claims 1, 6, and 8-11 are rejected.
Priority
Acknowledgement is made that Instant Application 18/682,111, filed on 02/07/2024, is a National Stage Entry of PCT/CN2022/113024, filed on 08/17/2022, which claims Foreign Priority from CN 202110951369.0, filed on 08/18/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statements
The information disclosure statement (IDS) submitted on 02/07/2024, 03/06/2025, 06/04/2025, and 08/27/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Response to Amendments
Applicants’ amendments, filed on 08/07/2026, are acknowledged and have been carefully considered. Claim 1 is amended to remove the terms “solvate”, “metabolite”, and “prodrug”. In view of Applicants’ amendments to claim 1, all pending 35 U.S.C 112(a) rejections of record are withdrawn. Additionally, all pending 35 U.S.C. 112(b) rejections of record are withdrawn.
Applicant asserts claim 1 has been amended to specify that X is selected from C6 aryl, Q is hydroxyl, and n is 1. It is noted, however, claim 1 has been amended to specify that X is selected from aryl and is not amended to specify that X is selected from C6 aryl.
Claims 2-5 have been canceled.
Claim 6 has been amended to define that the compound of Formula I is the following specific compound:
PNG
media_image1.png
109
159
media_image1.png
Greyscale
.
Claim Rejections - 35 USC § 103 - Maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 1, 6 and 8-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (hereafter, Liu. WO 2018/137683; published 2018, Feb. 08) in view of Nguyen (CN 108472303 A; published 2017, Feb. 02).
Claim 1 is directed to a method of preventing and/or treating floaters comprising administering a steroidal compound, or a composition to a subject in need thereof, wherein the steroidal compound is of Formula I, or a stereoisomer, tautomer, nitrogen oxide, or pharmacologically acceptable salt thereof:
PNG
media_image2.png
230
308
media_image2.png
Greyscale
,
wherein X is selected from aryl, Q is hydroxyl, n is 1, and wherein the composition comprises the steroidal compound and one or more of pharmaceutically acceptable carriers, excipients, diluents, adjuvants, or vehicles.
Claim 6 is directed to the method of claim 1, wherein the compound of Formula I is selected as compound 1:
PNG
media_image3.png
166
203
media_image3.png
Greyscale
.
Claims 8 is directed to the method of claim 1, wherein the composition is an eye drop.
Claims 9-10 are directed to the method of claim 1, wherein the composition comprises compound I and further comprises HPMC E5, Poloxamer P407 and Poloxamer P188, respectively.
Claim 11 is directed to the method of claim 1, wherein the compound or the composition is administered to the subject in need thereof 4 times per day and 1 to 2 drops each time.
Liu discloses lanosterol prodrugs and pharmaceutically acceptable salts and isomers thereof, comprised of formula II and formula III:
PNG
media_image4.png
178
233
media_image4.png
Greyscale
PNG
media_image5.png
192
272
media_image5.png
Greyscale
and their use in a pharmaceutical composition to treat ophthalmic diseases, specifically cataracts (abstract, claim 1). The disclosed lanosterol prodrug compounds, pharmaceutically acceptable salts and isomers (claim 19) are, for example:
PNG
media_image6.png
361
416
media_image6.png
Greyscale
Liu further teaches a drug composition comprising a therapeutic effective amount of the lanosterol prodrug compound or its pharmaceutically acceptable salt as the active ingredient and a pharmaceutically acceptable carrier (paragraph 0088). The prodrug is said to have good permeability and is effectively converted into lanosterol in vivo, greatly improving the drug utilization rate of lanosterol (paragraph 0093). The pharmaceutical composition is drawn to eye drops and comprises 1.5% hydroxypropyl methylcellulose (HPMC, E5 size), 20.5% Poloxamer (P407 size), and 1.6% Poloxamer (P188 size) (paragraph 0255). The lanosterol prodrug eye drops were administered to rabbits 3 times per day for 42 consecutive days (paragraphs 0313).
The difference between the teachings of Liu and those in the instant application is that the lanosterol prodrugs and pharmaceutical compositions thereof as taught by Liu are drawn to the treatment of cataracts and not to preventing and/or treating eye floaters. However, Liu discloses that the use of the prodrug is to increase the effect of lanosterol in treating ophthalmic diseases, so a person skilled in the art would have been motivated to use lanosterol and prodrugs thereof to treat other ophthalmic diseases in which lanosterol can ameliorate.
Nguyen teaches an aqueous ophthalmic composition comprising lanosterol as an effective treatment for eye diseases (abstract), wherein said aqueous ophthalmic composition is defined as being an eye drop or spray (paragraph 0043). The eye diseases include, but are not limited to, cataracts and vitreous opacities (paragraph 0041). The term “vitreous opacity” is defined in the specification of the current application as the official name of “floaters”. Nguyen further discloses an embodiment wherein lanosterol includes prodrugs, such as their esters (paragraph 007).
Additionally, Liu only teaches the use of lanosterol prodrug eye drops 3 times per day, while the instant application teaches the use of lanosterol prodrug eye drops 4 times a day with 1 or 2 drops during each administration. Routine optimization would have led a skilled artisan from the dosage as taught in Liu to the dosage as disclosed in the instant application if the lower dose was not fully effective in treatment of vitreous opacity. Therefore, it would it have been prima facia obvious for one skilled in the art to use a lanosterol prodrug in the eye drop formulation as taught by Liu to treat vitreous opacity as taught by Nguyen and arrive at the current invention.
Response to Arguments
Applicants’ arguments (“Remarks”, filed on 08/07/2026) traversing the rejection of claims 1-6 and 8-11 over Liu in view of Nguyen have been fully considered but are not found persuasive.
Regarding claims 1 and 6, Applicant asserts that Liu does not disclose, teach, or even suggest that the specific compound of Formula I, depicted as compound I above, can be used to treat floaters because Liu is directed to ophthalmic formulations of lanosterol prodrugs for treating cataracts, not vitreous opacity or floaters. Applicant further asserts that Liu neither teaches nor suggests that that compound of the presently amended claim 1 can exhibit a therapeutic, alleviate, or preventive effect on floaters, substantially alleviate and/or cure floaters, or significantly improve visual clarity. Therefore, a person skilled in the art would not have derived from Liu the specific compound or composition and would not have understood the benefit of using the compound to treat floaters with a reasonable expectation of success. Applicant further asserts Nguyen teaches the use of lanosterol, general lanosterol prodrugs (such as esters) for treating vitreous opacities/floaters. However, Nguyen does not disclose or suggest the specific compound of Formula I as now claimed.
It is therefore contended that the rejection depends on a skilled artisan selecting the presently claimed compound for Liu’s disclosed alternatives and applying it to Nguyen’s vitreous opacity indication, of which the Office Action does not provide a compound-specific reason to select that compound for the vitreous target or establish a reasonable expectation of success. Lastly, Applicant asserts that neither reference provides evidence that the selected compound would reach the vitreous humor in an effective amount or produce the clinical effects reported in the Instant Application.
The Examiner acknowledges the above remarks in accurate in that Liu fails to teach lanosterol prodrugs as a treatment method for eye floaters and therefore does not disclose evidence of its success in treating the same. Additionally, Nguyen fails to teach the specific lanosterol prodrug of the instantly amended claims, and therefore also fails to provide evidence that it would treat eye floaters.
However, the rejection of record is not based on either Liu or Nguyen alone, but rather the combination of Liu as modified by Nguyen. 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).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may 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), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would have recognized that both references teach the same field of endeavor of using lanosterol prodrugs to treat ophthalmic disorders. Specifically, Liu teaches the compound of the instantly amended claims (
PNG
media_image3.png
166
203
media_image3.png
Greyscale
) and compositions thereof to treat ophthalmic disorders, such as cataracts. Nguyen teaches lanosterol and general ester prodrugs thereof in treating ophthalmic disorders, such as eye floaters and cataracts. Said skilled artisan would have had a reasonable expectation of success in selecting compound I from the finite list of identified lanosterol prodrugs and using said compound to treat other ophthalmic indications that lanosterol prodrugs are shown to alleviate.
In response to Applicant’s assertion that neither reference provides evidence that the selected compound would reach the vitreous humor, Liu teaches the lanosterol prodrugs, including compound I, are more permeable than lanosterol and converts to lanosterol in vivo. Nguyen teaches compositions comprising lanosterol is sufficient in treating eye floaters. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in using more permeable prodrugs (e.g., compound I) to treat the vitreous-opacity indication because treatment of said indication requires the active agent permeate the lens of the eye to reach the vitreous humor.
Regarding claims 8-11, Applicant asserts the Examiner’s characterization of the dosing difference as “routine optimization” does not, by itself, establish that use of the selected compound to treat eye floaters would have been predictably effective, especially since the claimed invention is distinguished by the specific compound structure, not merely by dosing parameters in general.
The Office Action asserted the lanosterol prodrug eye drop composition of Liu comprised of 1.5% hydroxypropyl methylcellulose (HPMC, E5 size), 20.5% Poloxamer (P407 size), and 1.6% Poloxamer (P188 size). The dosing regimen of which (i.e., 3 times a day) could be “routinely optimized”, based on the needs of the patient, to arrive at the instantly claimed regimen (i.e., 4 times per day with 1 or 2 drops each time). Applicant made no assertion to the contrary.
Reconsidering the entire record, and weighting Applicants’ evidence together with the evidence supporting the prima facie case, the examiner finds that the rebuttal evidence does not outweigh the evidence of obviousness.
Therefore, in view of the foregoing, the rejection of claims 1, 6 and 8-11 are maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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 Paul Arcoria whose telephone number is (571)272-8719. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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, Clinton Brooks can be reached at (571)270-7682. 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.
/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights