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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-6) in the reply filed on 16 December 2025 is acknowledged.
Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 16 December 2025.
Claims 1-6, submitted on 16 December 2025, represent all claims currently under consideration.
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.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date is 11 December 2020.
Information Disclosure Statement
Five Information Disclosure Statements (IDSs), submitted on 15 February 2024, 1 November 2024, 26 February 2025, 13 May 2025, and 15 July 2025, are acknowledged and have been considered.
Drawings
The drawings are objected to because Figures 1-3, 5, 6, 13, and 14 are of low image quality and are difficult to interpret. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 has the definitions for PERK (PKR-like endoplasmic reticulum kinase) and ATF6 (activating transcription factor 6) in parentheticals following the use of the abbreviation. The definition should be outside of the parenthetical, and followed by the abbreviation within a parenthesis, “such as PRK-like endoplasmic reticulum kinase (PERK)”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4, and 5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and
knowledge in the art and (f) Predictability in the art. While all of these factors are
considered, a sufficient number for a prima facie case are discussed below:
The claims are directed to a method to a method for treating scleral thinning, comprising administering eye drops comprising an inhibitor of PERK and/or ATF6 pathway as an active ingredient to a patient in need thereof. The specification of the examined application states that the inhibitor of PERK pathway and the ATF6 pathway refers to a substance having an inhibitor effect on both the signal transduction system of PERK and signal transduction system of ATF6 (Paragraph 0024). A compound that targets and reduces a gene or a protein involved in signaling transduction of PERK and/or ATF6, or a nucleic acid such as antisense oligonucleotide or siRNA that reduces protein expression in the PERK pathway and/or the ATF6 can be blended in eyedrops as an ingredient effective for treating scleral thinning (Paragraph 0027). The inhibitor of the PERK pathway or the ATF6 pathway refers to a substance having an inhibitory effect on the signal transduction system of PERK or the signal transduction system of ATF6 in the endoplasmic reticulum. The inhibitor effect on these signal transduction systems can be evaluated by using, as an indicator, change in a gene and/or a protein involved in these signal transduction systems by a known method (Paragraph 0027). At least one selected from the group consisting of phenylbutyric acid, tauroursodeoxycholic acid, and pharmacologically acceptable salts thereof has been found to be capable of inhibiting both PERK and ATF6 (Paragraph 0032). It is clear from the claims and specification that applicant is in possession of 4-PBA and tauroursodeoxycholic acid as inhibitors of these pathways. However, there is no support in the specification or the claims for the breadth of what is claimed. The artisan could only determine what comprises a PERK and/or ATF6 pathway inhibitor from a posteriori testing and analysis, and would not know prior to utilizing a compound if it is going to inhibit one or both of these pathways and perform in the invention as claimed. There is no specific core structure defined that provides the basis for the breadth of the claims. The artisan would generally understand what a PERK and/or ATF6 pathway inhibitor functionally does, but without guidance from the specification as to the specific classes of compounds or general structure that can be used to inhibit these pathways, there would be no expectation of predictability for practicing this invention. Thus, there is no support in the specification that Applicant was in possession of the claimed invention in its entirety at the time of filing.
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 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Ikeda (US 2020/0150457; Publication Date: 14 May 2020; Filing Date: 5 September 2019) in view of Rada (Experimental Eye Research, Volume 82, Issue 2, February 2006, Pages 185-200) and Zhu (Journal of Ophthalmology, 10 June 2020).
Ikeda discloses a model for myopia, and shows that myopia induction causes endoplasmic reticulum stress in the sclera and this induces myopia. Furthermore, it is revealed that an endoplasmic reticulum stress suppressant, particularly, phenylbutyrate and tauroursodecoxycholic acid act as myopia prevention/suppression agents (Abstract). The myopia suppressant is administered here by eye drop, although any administration form may be adopted. Specifically, administration by injection, application by eyedrops or eye ointments, or oral administration may be used. Particularly, eye drops or eye ointments are preferable because they can be applied directly to the eyes (Paragraph 0043). Further the endoplasmic reticulum stress suppressant includes here sodium phenylbutyrate (4-PBA) and tauroursodeoxycholic acid (TUDCA), although pharmacologically acceptable salts other than these compounds may be used (Paragraph 0044). Any agents may be used that can suppress ER stress. It is said that chemical chaperones such as 4-PBA may reduce ER stress. In addition, signals downstream of ER stress sensors can be inhibited. Any compounds that have actions of reducing the ER stress or suppressing signals from ER stress sensors may act as myopia prevention/suppression agents (Paragraph 0045). The ER stress is sensed by three stress sensors that then transmit the signal downstream so that unfolded proteins do not excessively accumulate. It is known that ER stress sensors include PERK, IRE1, and ATF6. Therefore, any agent may be used that reduce the ER stress by inhibiting the signal transfer in any of those paths (Paragraph 0046). Paragraph 0071 discloses a pharmaceutical composition of 4-PBA in PBS at 0.2% and 2% concentration. Significant differences were recognized in the refractive value and axial length of the eye in the 2% PBA group compared to the PBS administered group. Therefore, it is indicated that 4-PBA has an effect on myopia suppression by eye drop administration (Paragraph 0072).
Ikeda does not explicitly disclose a method for the treatment of scleral thinning.
Rada provides a review of the sclera and myopia. High myopia is characterized by scleral thinning (Abstract). Scleral thinning and localized ectasia of the posterior sclera are characteristic changes of the myopic eye that have been noted by many observers. This overall scleral thinning observed in highly myopic human eyes is associated with thinning of collagen fibrils with a preponderance of unusually small diameter fibrils averaging below 6070 nm (5. Scleral changes during myopia development).
Zhu investigated the role of endoplasmic reticulum stress in scleral remodeling in a guinea pig model of form-deprivation myopia (FDM). Scleral fibroblasts were cultured and exposed to the ER stress induced tunicamycin (TM) or the ER stress inhibitor 4-phenylbutyric acid (4-PBA). The sclera of FDM eyes exhibited swollen and distended ER at 4 weeks, as well as significantly increased protein expression of GRP78 and CRT at 1 week and 4 weeks compared to the sclera of control eyes. In vitro, TM induced ER stress in scleral fibroblasts which was suppressed by 4-PBA. The mRNA expression of TGFβ1 and COL1A1 was upregulated after TM stimulation for 24 hours. ER stress is an important modulator which could influence the expression of scleral collagen (Abstract). Myopic scleral remodeling is a dynamic process that leads to reduced collagen content and thinner collagen fiber bundles, followed by scleral thinning (Introduction). Emerging evidence has indicated that ER stress facilitates remodeling in fibrotic diseases. During ER stress, the ER stress sensors, IRE1, PERK, and ATF6 trigger the unfolded protein response (UPR). Calreticulin is a calcium-binding chaperone localized in the ER lumen, playing a crucial role in protein folding, calcium homeostasis, and many other processes. CRT is found to be an ER stress chaperone, which was required for ER stress and TGFβ1 induced collagen production in many fibrotic diseases (Introduction).
Ikeda, Rada, and Zhu are considered analogous to the claimed invention as all are involved in the study and treatment of ocular conditions. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply the method of utilizing 4-PBA to treat myopia as taught by Ikeda for the treatment of scleral thinning, as Rada shows that it is known in the art that myopia results in scleral thinning, and Zhu demonstrates that the use of 4-PBA in models of scleral thinning results in downregulation of ER stress, which causes scleral thinning. The use of the method of Ikeda for the treatment of scleral thinning is prima facie obvious combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)); the method of Ikeda utilizes 4-PBA to treat myopia, which is known in the art to inhibit ER stress. Rada demonstrates that myopia is associated with scleral thinning, while Zhu shows that inhibition of ER stress can result in improvements in scleral thinning. The artisan would recognize this, and have a reasonable expectation of success as 4-PBA is a known inhibitor of PERK and ATF6, which are associated with ER stress. Moreover, the specification of the examined application defines “scleral thinning” as a shape change of the eye due to ocular axis elongation (Paragraphs 0008, 0009, and 0022). Ikeda states that 4-PBA suppresses the elongation of ocular axial length due to myopia. Thus, it can be said that the shape changes of the eye due to ocular axis elongation (“scleral thinning”) of the invention of the examined application can be treated in the same way, and the artisan would recognize this, and apply the method of Ikeda.
Regarding Claim 6, each of these conditions are associated with myopia and scleral thinning. In view of the teachings of Ikeda, Rada, and Zhu, it would be obvious to one of ordinary skill in the art to specifically treat these conditions as scleral thinning and myopia are associated with one another, and Ikeda demonstrates that their method results in suppression of changes of the eye due to ocular axis elongation, which is a form of scleral thinning.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of U.S. Patent No. 12,478,597 (Patent Date: 25 November 2025) (‘597) in view of Rada (Experimental Eye Research, Volume 82, Issue 2, February 2006, Pages 185-200) and Zhu (Journal of Ophthalmology, 10 June 2020).
Claim 1 of ‘597 is directed to a method of suppressing a symptom or progression of pediatric myopia, the method comprising administering an eye drop comprising 4-phenylbutyric acid or a pharmacologically acceptable salt thereof to a pediatric patient thereof with progressing myopia in need thereof, wherein the symptom of pediatric myopia comprises an elongated axial length of the eyeball. Claim 2 of ‘597 is the method of claim 1 wherein a content of 4-PBA or pharmacologically acceptable salt thereof in the eye drop if from 0.2% to 2%. Claim 6 of ‘597 is directed to the method of claim 6 wherein the 4-PBA is sodium phenylbutyrate.
‘597 fails to teach a method for treating scleral thinning.
The teachings of Rada and Zhu are previously described and are fully incorporated into this rejection.
‘597, Rada, and Zhu are considered analogous to the claimed invention as all are involved in the study and treatment of ocular conditions. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply the method of utilizing 4-PBA to treat pediatric myopia or a symptom thereof as taught by ‘597 for the treatment of scleral thinning, as Rada shows that it is known in the art that myopia results in scleral thinning, demonstrating that scleral thinning is a symptom of pediatric myopia, and Zhu demonstrates that the use of 4-PBA in models of scleral thinning results in downregulation of ER stress, which causes scleral thinning. The use of the method of ‘597 for the treatment of scleral thinning is prima facie obvious combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)); the method of ‘597 utilizes 4-PBA to treat symptoms of pediatric myopia, which is known in the art to inhibit ER stress. Rada demonstrates myopia is associated with scleral thinning, while Zhu shows that inhibition of ER stress can result in improvements in scleral thinning. The artisan would recognize this, and have a reasonable expectation of success as 4-PBA is a known inhibitor of PERK and ATF6, which are associated with ER stress.
Regarding Claim 6, each of these conditions are associated with myopia and scleral thinning. In view of the teachings of Rada and Zhu, it would be obvious to one of ordinary skill in the art to specifically treat these conditions as scleral thinning and myopia are associated with one another.
Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of copending Application No. 18/266,102 (Amended Claims of 15 December 2025) (‘102) in view of Rada (Experimental Eye Research, Volume 82, Issue 2, February 2006, Pages 185-200) and Zhu (Journal of Ophthalmology, 10 June 2020).
Claim 1 of ‘102 is directed to a method for inhibiting myopia progression in children, comprising administering eyedrops comprising an inhibitor of PERK and/or ATF6 pathway as an active ingredient. Claim 2 of ‘102 is directed to the method of claim 1, wherein the inhibitor is at least one selected from the group consisting of phenylbutyric acid and pharmacologically acceptable salts thereof. Claim 3 of ‘102 is directed to the method of claim 2 wherein the inhibitor is sodium phenylbutyrate. Claim 4 of ‘102 is directed to the method of claim 1 wherein a content of the inhibitor is 0.01 to 5% by mass based on a total amount of the eyedrops.
‘102 does not teach a method for treating scleral thinning.
The teachings of Rada and Zhu are previously described and are fully incorporated into this rejection.
‘102, Rada, and Zhu are considered analogous to the claimed invention as all are involved in the study and treatment of ocular conditions. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply the method of utilizing 4-PBA to inhibit myopia progression as taught by ‘102 for the treatment of scleral thinning, as Rada shows that it is known in the art that myopia results in scleral thinning, demonstrating that scleral thinning is a symptom of myopia , and Zhu demonstrates that the use of 4-PBA in models of scleral thinning results in downregulation of ER stress, which causes scleral thinning. Thus, inhibition of scleral thinning would inhibit myopia progression by slowing or reversing scleral thinning. The use of the method of ‘102 for the treatment of scleral thinning is prima facie obvious combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)); the method of ‘102 utilizes 4-PBA to inhibit myopia progression, which is known in the art to inhibit ER stress. Rada demonstrates myopia is associated with scleral thinning, while Zhu shows that inhibition of ER stress can result in improvements in scleral thinning. The artisan would recognize this, and have a reasonable expectation of success as 4-PBA is a known inhibitor of PERK and ATF6, which are associated with ER stress.
Regarding Claim 6, each of these conditions are associated with myopia and scleral thinning. In view of the teachings of Rada and Zhu, it would be obvious to one of ordinary skill in the art to specifically treat these conditions as scleral thinning and myopia are associated with one another.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-6 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625