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 .
Current Status
This action is responsive to the amended claims of 12/15/2025. Claims 1-7 are pending and have been examined on the merits.
Election/Restrictions
Applicant’s election of sodium phenylbutyrate in the reply filed on 12/15/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
A search for the elected species returned prior art (see SEARCH 5-6 in the attached search notes). Thus, the Markush search will not be unnecessarily extended in this action.
The elected species reads on claims 1-7. No claims are withdrawn.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date is 09/01/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/09/2023, 11/05/2024, 05/06/2025, and 07/22/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 1-6 are objected to because of the following informalities: claim 1 recites “PERK (PKR-like endoplasmic reticulum kinase)” and “ATF6 (activating transcription factor 6)”. While it is understood that the text within the parentheses refer to the full names of the acronyms PERK and ATF6, it is preferred if parentheses are reserved for use around the acronyms. Thus, it is preferred if Applicant swap the acronyms and full names in claim 1, i.e., “PKR-like endoplasmic reticulum kinase (PERK)” and “activating transcription factor 6 (ATF6)”. Dependent claims 2-6 are similarly objected to since they do not rectify the underlying issue. 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 and 4-6 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. This is a written description rejection.
MPEP 2163(I) states “The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant [inventor] has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee [inventor] was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.”
Factors to be considered in making the determination as to whether one skilled in the art would recognize that the 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 or structural chemical formulas; (c) Sufficient relevant 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 Instant Disclosure:
Claims 1 and 4-6 are very broadly drawn to use of an inhibitor of PERK or ATF6 that is purely defined by function, no structural limitations are given. Dependent claims 2-3 narrow the inhibitor to phenylbutyric acid and salts thereof; however, this disclosure is much narrower in scope than that of parent claim 1. This lack of structural definition does not allow the artisan to envisage the full scope of PERK/ATF6 inhibitors which are part of the invention.
The claimed inhibitor is expected to have a certain mechanism of action and corresponding pharmacological utility (e.g., claims 1 and 4-6). The lack of structural definition in Formula (I) leaves the artisan to question what chemical moieties would impart the proper mechanism of action to the inhibitor. The specification discloses only 6 compounds as inhibitors of PERK and/or ATF6 (Pg. 34 ¶1): sodium phenylbutyrate (exemplary of phenylbutyric acid & salts thereof) and TUDCA as inhibitors of both PERK and ATF6 via inhibition of endoplasmic reticulum stress (Pg. 40); GSK2656157 and GSK2606414 as inhibitors of PERK (Pg. 34); and Nelfinavir and Ceapin-A7 as inhibitors of ATF6 (Pg 34). These compounds do not cover the full scope of inhibitors embraced by the limitations of claims 1 and 4-6.
Moreover, the specification does not provide any further guidelines as to what compounds would be suitable for inhibition of PERK and/or ATF6 to treat myopia. This leaves the artisan to question what compounds (either known to be PERK/ATF6 inhibitors or not known) display the claimed mechanism of action/pharmacological utility. In fact, the instant claim 1 embraces compounds which may be undiscovered at the time of filing and/or unknown to be PERK/ATF6 inhibitors. Thus, the specification and claims do not “demonstrate that the patentee [inventor] was in possession of the invention that is claimed” (see MPEP 2163(I)).
Level of Skill and Knowledge in the Art:
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience. The factor is outweighed, however, by the unpredictable nature of the pharmaceutical art. It is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity (e.g. the ability to inhibit PERK/ATF6).
Examiner cites AXTEN (Axten, J.M., Expert Opinion on Therapeutic Patents, 27(1), 2016, 37-48) and GALLAGHER (Gallagher et al., eLIFE, 2016, 5:e11878, 1-33), as evidentiary references, to provide an overview of the knowledge and challenges in the relevant art concerning PERK/ATF6 inhibition.
AXTEN discloses there are few examples of small molecules that potently and selectively modulate PERK which may be a result of difficulty in finding suitable starting points for PERK inhibitor optimization from screening approaches – pairing adequate PERK potency and selectivity is a major challenge and a limiting factor (Pg. 44 Sect. 4 ¶2). The challenges cited in AXTEN are particularly relevant to the instant claims as the PERK inhibitor is left structurally undefined in claims 1 and 4-6 and the specification only provides a few examples (not commensurate in scope with the claims). Since AXTEN acknowledges it is difficult to develop PERK inhibitors and not many are known and since the instant claims and specification do not provide specific guidance on the full scope of the claimed PERK inhibitor, the artisan is left without any guidance as to what compounds comprise the full scope of claims 1 and 4-6.
GALLAGHER discloses over 100,000 compounds were screened for their ability to reduce the activity of ATF6 – only a small class of compounds termed Ceapins were found to selectively block ATF6 (Pg. 2 ¶4). Further, the ATF6 signaling pathway is considered undruggable (Pg. 3 ¶4). With the reputation of “undruggable”, the artisan would understand the difficulty of inhibiting the ATF6 pathway. In view of GALLAGHER, the artisan would recognize the challenge in screening and finding compounds that successfully inhibit AFT6. Since the instant claims and specification do not provide specific guidance on the full scope of the claimed ATF6 inhibitor, the artisan is left without any guidance to what compounds comprise the full scope of claims 1 and 4-6.
Thus, in view of the relevant art, the instant disclosure has not “convey[ed] to the public what the applicant claims as the invention” nor “demonstrate[d] that the patentee [inventor] was in possession of the invention that is claimed” (see MPEP 2163(I)).
Conclusions:
Due to the breadth of the inhibitor of PERK and/or ATF6 defined purely by function (not chemical structure), the lack of direction given in the claims/specification regarding embodiments of the full scope of inhibitor, and 3) the challenges presented in the art, the artisan would not be able to immediately envisage the breadth of inhibitors embraced by the scope of claims 1 and 4-6. This is particularly true for any unknown/undiscovered inhibitors of PERK/ATF6, which as discussed above, are embraced by the current drafting.
As such, the instant specification fails to provide guidance to overcome the complexity and difficulties known to the artisan, as discussed above. Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Thus, claims 1 and 4-6 are rejected as lacking written description for the full scope of PERK/ATF6 inhibitor. To overcome this rejection, Applicants are encouraged to structurally/chemically define the inhibitor, such as by amending claim 1 to incorporate the species disclosed in the specification (e.g., Pg. 34) and claim 2.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by IKEDA (WO 2018/164113; cited IDS of 10/09/2023), evidenced by HOU (Hou, W. et al., Eye & Contact Lens, 44(4), 2018, 248-259).
IKEDA teaches eyedrops comprising sodium phenylbutyrate in PBS at a concentration of 0.2% or 2% were administered to juvenile mice (Pg. 20 ¶41) wherein a myopia model that exhibits similar symptoms to human myopia had been induced (Pg. 24 ¶50). IKEDA teaches compared to a non-myopic control, the axial length in sodium phenylbutyrate treated myopic-mice was no different (Pg. 18 ¶35). However, the axial length of PBS administered myopic-mice was significantly longer than that of the sodium phenylbutyrate treatment group (Pg. 18 ¶35). Thus, IKEDA teaches treatment with the sodium phenylbutyrate eyedrops inhibits pathological axial lengthening (instant claim 6), therefore inhibiting progression of the myopia. Further, IKEDA teaches the axial length of the eye increases with growth, but sodium phenylbutyrate does not inhibit this growth (Pg. 18 ¶36). Thus, IKEDA teaches physiological axial elongation is not inhibited (instant claim 5).
IKEDA further teaches sodium phenylbutyrate is an endoplasmic reticulum (ER) stress inhibitor (Pg. 17 ¶33) and the ER stress sensors are PERK and ATF6 (Pg. 10 ¶19). Thus, Examiner understands sodium phenylbutyrate to be an upstream inhibitor of PERK and ATF6. Since sodium phenylbutyrate inhibits ER stress, the ER stress sensor pathways are not activated as they would be under ER stress (i.e., they are inhibited by inhibition of the ER stress).
IKEDA is silent as to the treatment of children specifically. However, IKEDA teaches sodium phenylbutyrate is safe in humans and is a very promising drug for inhibiting the progression of myopia (Pg. 19 ¶37). As evidenced by HOU, during early childhood the axial length of the eye increases by several millimeters to actively match eye growth (Pg. 248 Right Col. ¶1-2); i.e., physiological axial elongation is a normal part of children’s development and growth. HOU further discloses in some children the eyes gradually elongate beyond what is normal to produce myopia (Pg. 248 Right Col. ¶2). With this knowledge, and since IKEDA teaches a method of treating myopia in a juvenile mouse model which mirrors human symptoms and the sodium phenylbutyrate eyedrops do not interfere with physiological axial elongation, the artisan would immediately envisage that the target demographic for IKEDA’s method of treatment is children. The advantage of IKEDA’s method is pathologic inhibition without physiological inhibition, thus, as evidenced by HOU, the target population is children.
Thus, IKEDA anticipates instant claim 1-6.
Claim Rejections - 35 USC § 103
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 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 (WO 2018/164113; cited IDS of 10/09/2023) and HOU (Hou, W. et al., Eye & Contact Lens, 44(4), 2018, 248-259).
Determining the Scope and Contents of the Prior Art:
The teachings of IKEDA are above, ¶14. Further, IKEDA teaches their mouse myopia model is the first to exhibit symptoms similar to those in humans (Pg. 8 ¶14). IKEDA also teaches myopia is induced by ER stress and that myopia is suppressed by inhibiting ER stress, PERK, and/or ATF6 (Pg. 24 ¶49). IKEDA teaches administration of eyedrops comprising a PERK inhibitor GSK2656157 or an ATF6 inhibitor Nelfinavir were also effective in suppressing myopia (Pg. 22 ¶46 & Pg. 24 ¶48).
HOU teaches during early childhood the axial length increases by several millimeters to actively match eye growth (Pg. 248 Right Col. ¶1-2); i.e., physiological axial elongation is a normal part of children’s development and growth. HOU further teaches in some children the eyes gradually elongate beyond what is normal to produce myopia (Pg. 248 Right Col. ¶2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
IKEDA is silent as to the treatment of children.
HOU does not teach treatment of myopia by PERK/ATF6 inhibition by sodium phenylbutyrate.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for inhibiting myopia progression in children and possesses the technical knowledge necessary to make adjustments to the target patient population to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding pathological vs. physiological axial elongation and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references IKEDA and HOU.
The artisan would find it obvious to inhibit myopia progression in children by administering a PERK/ATF6 inhibitor (e.g., sodium phenylbutyrate) based on the combined teachings. The artisan would be motivated to treat myopia in children via the method of IKEDA since the method is advantageous in that it does inhibit pathological axial elongation (Pg. 18 ¶35) but does not inhibit normal physiological axial elongation (Pg. 18 ¶36). Since HOU teaches physiological axial elongation is normal in child development, but some children experience pathological growth producing myopia (Pg. 248 Right Col. ¶1-2), the artisan would find the method of IKEDA to be advantageous for and applicable to children. Further, since IKEDA teaches sodium phenylbutyrate is safe in humans (Pg. 19 ¶37) and the mouse myopia model exhibits human symptoms (Pg. 8 ¶14), the artisan would have a reasonable expectation of success in utilizing IKEDA’s method to treat human patients, including children. Therefore, in view of the combination of references IKEDA and HOU, the artisan would find the instant claims 1-6 obvious.
Note, since IKEDA teaches that myopia is suppressed by inhibiting ER stress, PERK, and/or ATF6 (Pg. 24 ¶49) and administration of other PERK/ATF6 inhibitors also resulted in inhibition of myopia (Pg. 22 ¶46 & Pg. 24 ¶48), the artisan would find the broadest reading of instant claim 1 obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over IKEDA (WO 2018/164113; cited IDS of 10/09/2023), HOU (Hou, W. et al., Eye & Contact Lens, 44(4), 2018, 248-259), and JANSSENS (Janssens S. et al., Nature Immunology, 2014, 15(10), 910-919).
Determining the Scope and Contents of the Prior Art:
IKEDA teaches eyedrops comprising sodium phenylbutyrate were administered to juvenile mice (Pg. 20 ¶41) wherein a myopia model that exhibits similar symptoms to human myopia had been induced (Pg. 24 ¶50). IKEDA teaches the eyedrops inhibit pathological axial lengthening (Pg. 18 ¶35), but do not inhibit physiological axial growth (Pg. 18 ¶36). IKEDA further teaches sodium phenylbutyrate is an endoplasmic reticulum (ER) stress inhibitor (Pg. 17 ¶33) and the ER stress sensors are PERK and ATF6 (Pg. 10 ¶19). IKEDA further teaches administration of eyedrops comprising a PERK inhibitor GSK2656157 or an ATF6 inhibitor Nelfinavir were effective in suppressing myopia (Pg. 22 ¶46 & Pg. 24 ¶48). Further, IKEDA teaches myopia is induced by ER stress and that myopia is suppressed by inhibiting ER stress, PERK, and/or ATF6 (Pg. 24 ¶49).
HOU teaches during early childhood the axial length increases by several millimeters to actively match eye growth (Pg. 248 Right Col. ¶1-2); i.e., physiological axial elongation is a normal part of children’s development and growth. HOU further teaches in some children the eyes gradually elongate beyond what is normal to produce myopia (Pg. 248 Right Col. ¶2).
JANSSENS teaches ER stress is detected by sensors PERK and ATF6 which trigger the unfolded protein response (UPR) (Pg. 910 Left Col. ¶1). JANSSENS teaches, as part of the UPR, the PERK pathway triggers expression of ATF4, CHOP, and GADD34 (Pg. 911 Fig. 1), while the ATF6 pathway triggers release of BiP (i.e., Grp78) (Pg. 911 Fig. 1 & Left Col. ¶3).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
IKEDA does not teach a step of selecting the candidate substance using a change in a protein/gene of the PERK/ATF6 pathways as an indicator.
HOU and JANSSENS do not teach contacting a candidate substance with an eye-derived cell.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a screening method useful for selecting myopia inhibitors and possesses the technical knowledge necessary to make adjustments to the screening indicators to optimize/enhance the screening outcomes. Said artisan has also reviewed the problems in the art regarding the role of PERK and ATF6 in myopia and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references IKEDA, HOU, and JANSSENS.
Since IKEDA teaches the role of ER stress, PERK, and ATF6 in myopia induction and that inhibition thereof suppresses myopia (Pg. 24 ¶49), and since JANSSENS teaches ER stress triggers a response in the PERK/ATF6 pathways resulting in release/expression of certain proteins/genes (Pg. 911 Fig. 1 & Left Col. ¶3), the artisan would be motivated to utilize the PERK/ATF6 pathways as indicators of successful myopia inhibitors. In view of these teachings, the artisan would have a reasonable expectation of success in administering an eyedrop containing a candidate substance (e.g., sodium phenylbutyrate) and measuring the expression of the PERK/ATF6 pathways to determine the extent of ER stress and therefore the extent of myopia pathology. Since ER stress is taught by IKEDA to induce myopia, the artisan would find it reasonable to track ER stress via the stress sensor pathways PERK and ATF6 which express and release factors including ATF4, CHOP, GADD34, and BiP (see JANSSENS). The artisan would expect a decrease in ER stress factors to correlate to a decrease in ER stress and therefore a decrease in myopia progression/induction. Thus, the artisan would recognize these PERK/ATF6 factors as an indicator of a successful candidate substance and would select the candidate based on such indication.
Note, since IKEDA teaches various PERK and/or ATF6 inhibitors are given via eyedrops (Pg. 18 ¶35, Pg. 22 ¶46, & Pg. 24 ¶48), the method of IKEDA teaches the candidate substance is contacted with an eye-derived cell.
Further, since IKEDA teaches inhibition of PERK/ATF6 inhibits pathological axial lengthening (Pg. 18 ¶35), but does not inhibit physiological axial growth (Pg. 18 ¶36) and since HOU teaches physiological axial elongation is a normal part of children’s development and growth (Pg. 248 Right Col. ¶1-2), the artisan would be motivated to use this screening protocol to find an inhibitor suitable for treating myopia in children.
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 anticipatory nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,478,597. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference claims 1, 3-4, and 6 recite a method of suppressing (i.e., inhibiting) axial elongation/progression of myopia in a pediatric subject (i.e., children) by administering an eye drop comprising 4-phenylbutyric acid or salts thereof including sodium phenylbutyrate. These claims recite species of the instantly claimed inhibitor of PERK and/or ATF6 of instant claim 1, as exemplified by instant claims 2-3 drawn to phenylbutyric acid and salts thereof such as sodium phenylbutyrate.
Reference claim 2 is drawn to the eyedrop comprising 0.2-2% phenylbutyric acid/salt thereof; this falls within the instantly claimed range of 0.01-5% (instant claim 4).
Reference claim 5 is drawn to the method of reference claim 1 wherein the method does not affect the extension of normal axial length of the eye associated with growth. This reads on instant claim 5 wherein physiological (i.e., normal) axial elongation is not inhibited.
Regarding instant claim 6, since the reference claim 1 suppresses a symptom of myopia that is axial elongation, Examiner understands the reference claim to be drawn to inhibition of pathological axial elongation.
Claim 7 is provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-3 of copending Application No. 18/600,985 (reference application – claims of 03/11/2024) in view of IKEDA (WO 2018/164113; cited IDS of 10/09/2023), HOU (Hou, W. et al., Eye & Contact Lens, 44(4), 2018, 248-259), and JANSSENS (Janssens S. et al., Nature Immunology, 2014, 15(10), 910-919) as applied to claim 7 above.
Determining the Scope and Contents of the Prior Art:
Reference claims 1-2 are drawn to a myopia medicine screening method comprising administering a candidate material to a mouse model having myopia. Reference claim 3 is drawn to the method of reference claim 1 wherein the candidate material is administered by eyedrop (i.e., contacting with an eye-derived cell).
IKEDA, HOU, and JANSSENS teach the instant claim 7, see ¶20 above for the relevant teachings.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
App. No. ‘985 does not teach wherein the candidate substance is selected based on a change in the PERK and/or ATF6 pathway.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a screening method useful for identifying inhibitors of myopia and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcome. Said artisan has also reviewed the problems in the art regarding the role of PERK and ATF6 in myopia and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references App. No. ‘985, IKEDA, HOU, and JANSSENS.
The artisan would be motivated to select the candidate substance based on the change in a protein/gene of the PERK and/or ATF6 pathway since IKEDA teaches the role of ER stress, PERK, and ATF6 in induction of myopia and that inhibition thereof inhibits myopia (Pg. 24 ¶49). Further, since in view of HOU, IKEDA’s method is suitable for use in children (see ¶20 above), the artisan would have a reasonable expectation of success that the screening would provide an inhibitor for myopia progression in children. Finally, since JANSSENS teaches the proteins/genes involved in the signaling pathways of both PERK and ATF6 are known and their activation under ER stress is understood (Pg. 911 Fig. 1) and since IKEDA teaches ER stress and downstream stress sensors PERK and ATF6 have a role in myopia induction (Pg. 24 ¶49), the artisan would have a reasonable expectation of success in utilizing these markers to track the success of candidate substances in inhibiting myopia (see ¶20 above).
This is a provisional nonstatutory double patenting rejection.
Claims 1-6 are provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 9-17 of copending Application No. 18/847,501 in view of IKEDA (WO 2018/164113; cited IDS of 10/09/2023) and HOU (Hou, W. et al., Eye & Contact Lens, 44(4), 2018, 248-259).
Determining the Scope and Contents of the Prior Art:
The reference claims 9-17 are drawn to an aqueous composition of 4-phenylbutyric acid or salts thereof. See MPEP 804: "In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed.” See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02. The reference specification teaches the aqueous composition is preferably eye drops (Pg. 12 ¶38) which is suitably used as a therapeutic agent for myopia (Pg. 12 ¶37).
IKEDA and HOU teach the method of instant claims 1-6, see ¶19 above for the relevant teachings.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
App. No. ‘501 claims do not teach the instant method of use or inhibitor content of the eyedrops.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for inhibiting myopia and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding phenylbutyric acid-based eyedrops and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references App. No. ‘501, IKEDA, and HOU.
Since the claims of ‘501 are drawn to an aqueous composition of 4-phenylbutyric acid and salts thereof and the supporting disclosure teaches eyedrops as the preferable form and treatment of myopia as suitable (Pg. 12 ¶37-38), the artisan would recognize IKEDA as an equivalent reference since IKEDA teaches sodium phenylbutyrate eyedrops for inhibition of myopia (Pg. 20 ¶41). Thus, in view of the advantages of IKEDA’s method and applicability to inhibition of myopia in children, as discussed in ¶19 above, the artisan would find it obvious to use the aqueous composition of ‘501 in the form of eyedrops (as disclosed by IKEDA) in order to inhibit progression of myopia in children. The same motivation and expectation of success discussed in ¶19 applies here due to the equivalency between IKEDA and App. No. ‘501.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-7 are rejected.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625