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 .
DETAILED ACTION
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 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.
Response to Amendments
Applicant’s amendments, corrected specification, IDSs filed on Feb. 20, 2026 and Jan. 27, 2026, and response filed Jan. 27, 2026 have been received and entered into the case.
Status of the Claims
Claims 1-4, 6, and 12-31 are currently pending.
Claims 1, 6, 13 and 29 are amended.
Claims 15-28 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Claims 29 and 30 now depended from claim 1, the elected invention.
Claims 5 and 7-11 are cancelled.
Claim 31 is new.
Claims 1-4, 6, 12-14 and 29-31 have been considered on the merits.
Drawings
The drawing objections are withdrawn due to amendment.
Specification Objections
Specification objections are withdrawn due to amendment.
Claim Suggestion
It is suggested that the recitation of “a subject who is in drusen stage” in claim 1 be amended to recite “a subject who is in the drusen stage of age-related macular degeneration” in the interest of improving claim form.
Claim Objections
The claim objections are withdrawn due to amendment.
Claim Rejections - 35 USC § 112(a)
The previous claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ), are withdrawn due to amendment. New claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ) have been added to address the claim amendments.
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.
35 USC § 112(a)-written description
Claims 1-4, 6, 12-14 and 29-31 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 claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 1 recites a limitation of “ a method of inhibiting drusen formation in an ocular tissue in a subject who is in drusen stage”. The specification describes the different stage of age-related macular degeneration (AMD) including stage 2 or drusen stage and discloses the “unmet need to develop treatments that either prevent disease progression from the drusen stage to the advanced stages or further progression of GA” (geographic atrophy) (Fig. 18, 0033, and 0128). There is no description of inhibiting drusen formation in the ocular tissue of a subject at the drusen stage or description of treating such a subject with one or more inhibitors of ribosomal protein S6 kinase beta-1 (S6K1).
This is a new matter rejection.
Claim Rejections - 35 USC § 112(a)-scope of enablement
Claims 1-4, 6, 12-14 and 29-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inhibiting drusen formation in ocular tissue by administering to the cells of the ocular tissue one or more inhibitors of S6K1 where the inhibitors comprise an inhibitory nucleic acid that binds to a nucleic acid encoding a S6K1 protein and reduces or prevents expression of the S6K1 protein, does not reasonably provide enablement for inhibiting drusen formation in ocular tissue in a subject who is in the drusen stage. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, the enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to inhibiting drusen formation in ocular tissue in a subject who is in drusen stage by administering to the cells of the ocular tissue one or more inhibitors of S6K1 where the inhibitors comprise an inhibitory nucleic acid that binds to a nucleic acid encoding a S6K1 protein and reduces or prevents expression of the S6K1 protein. Thus, the claims taken together with the specification imply that any inhibitory nucleic acid that binds to a nucleic acid encoding a S6K1 protein and reduces or prevents expression of the S6K1 protein, can be administered to the ocular tissue of a subject who is in the drusen stage and inhibit drusen formation in the ocular tissue with the instantly claimed method.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
Inventions related to treating age-related macular degeneration (AMD) bear a heavy responsibility to provide supporting evidence because of the unpredictability in biological responses to therapeutic treatments. The standard of enablement is high for such inventions because as the state of the art stands, there is no current gene therapy for age-related macular degeneration or related retinal diseases. In support, Amaxilati et al. (Cells, 2026) reports key challenges for gene therapy for age-related macular degeneration include intraocular inflammation and neutralizing antibodies, variability and durability of transgene expression, surgical risks associated with subretinal delivery, and long-term safety (abstract). Amaxilati reports that current treatment strategies for AMD focus on managing symptoms and slowing disease progression and not actually curing AMD (pg. 3 last para.). Additionally, Amaxilati reports that “for dry AMD, antioxidant vitamin supplementation remains the only American Academy of Ophthalmology-recommended option, and may slow progression from earlier to later stages of the disease” (pg. 3 last para.). Amaxilati further states that gene therapy for dry AMD remains to be investigated (pg. 4 para. 1) and that vector platforms, delivery routes, and target tissues need to be determined for AMD subtypes (Figure 2 and pg. 6 para. 2). In further support, Jain et al. (Cureus, 2024) reports that there still several challenges and limitations to be addressed in gene therapy for inherited retinal dystrophies including the potential for side effects and immune responses, the long-term effects and durability of the treatments are largely unknown, there are technical and biological challenges such as efficient delivery, and there is variability in patient response to gene therapy (pg. 5 para. 1).
Thus, as the state of the art stands, gene therapy for AMD and other inherited retinal dystrophies is highly unpredictable. In the instant case, the applicants have provided no accepted, conventional models for AMD treatment. The high degree of unpredictability associated with the claimed method underscores the need to provide teachings in the specification that would provide the skilled artisan with specific treatment regimens that achieve a therapeutic benefit by in vivo or ex vivo therapy with regard to treatment of AMD at least in a mouse model or xenograft.
(5) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification discloses no data demonstrating the inhibiting of drusen formation in an ocular tissue in a subject who is in drusen stage, even in an animal models. There is a description of the pathologies of rodTsc1/S6K1 knock-out (rodTsc1-/- S6K-/-) mice (Fig. 23-26, 0038-0041, Example 1). The rodTsc1/S6K1 knock-out mouse is a mouse model of AMD, which has increased expression of mTORC1 by deleting the tuberous sclerosis complex (TSC1) (0093). In addition, there is a description of p-S6 staining in retinal cross sections of non-diseased and diseased individuals with AMD which shows increased expression of p-S6 in the retinas of AMD patients (Fig. 27 and 0042). There are also general directions on potential pharmaceutical compositions, expression vectors, and methods of delivery of a S6K1 inhibitor (0066-0091). However, the specification does not provide any guidance for the inhibiting of drusen formation in an ocular tissue in a subject who is in the drusen stage by administering an inhibitory nucleic acid that binds to a nucleic acid encoding S6K1 protein and reduces or prevents expression of the S6K1 protein.
Claims drawn to pharmaceuticals and methods of treatment generally require supporting data because of the unpredictability in biological responses to therapeutic treatments. The efficacy of a drug treatment faces numerable unfavorable obstacles in vivo. As such, in vivo utility necessarily involves unpredictability with respect to physiological activity of an asserted process in a subject. See discussion in Ex parte Kranz, 19 USPQ 2d 1216, 1218-1219 (6/90). For example, the delivery of a drug across necessary cell surfaces in amounts needed to be efficacious, but not lethal to the subject, necessitates sensitive testing in order to adequately determine the proper dosage.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the claimed invention within the broad scope as instantly claimed.
Claim Rejections - 35 USC § 112(b)
The claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ), are withdrawn due to amendment.
Claim Rejections - 35 USC § 102
The claim rejections under 35 USC § 102 are withdrawn due to amendment.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are withdrawn due to amendment.
Double Patenting
The nonstatutory double patenting rejection are withdrawn due to amendment.
Response to Arguments
Applicant's arguments filed Jan. 27, 2026 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that the references do not teach administering an inhibitory nucleic acid that binds to a nucleic acid encoding a S6K1 protein and reduces or prevents expression of the S6K1 protein to a subject who is in drusen stage thereby preventing drusen formation (Remarks pg. 16-17 bridging para.). The Applicant’s amendments limiting claim 1 to a subject that is in the drusen stage necessitated the withdrawal of 35 U.S.C. § 103 rejection. Applicant’s arguments are drawn to the references failing to teach this new limitation. The claims are presently being rejected under 35 U.S.C. § 112(a).
Further with respect to the rejections under 35 U.S.C. § 103, Applicant argues that there is no motivation to combine Li and Hayashi, since Li is not directed to ocular tissues or drusen and only lists AMD among many disease and Hayashi is directed to an acute NMDA excitotoxicity rat model and rats do not have a macula analogous to the human macula. Applicant argues that AMD drusen are chronic extracellular deposits at the RPE/Bruch’s membrane interface and the rat eye does not contain macula tissue as stated by the Examiner to have (Remarks pg. 17 para. 2). Applicant argues that no reason was provided to why a skilled person would look to an NMDA ganglion cell death rat model to expected that silencing S6K1 would prevent ocular damage, since Hayashi is related to acute neurotoxicity and microglial activation and not drusen biogenesis (Remarks pg. 17 para. 3). Applicant argues that the blanket statement that “once administered…the inhibitor would treat whatever condition present is a conclusory statement that is forbidden (Remarks pg. 17 para. 3). Additionally, Applicant argues that Zhang does not remedy the deficiencies of Hayashi (Remarks pg. 18 para. 1). Applicant’s arguments with respect to the rejections under 35 U.S.C. § 103 rejection have been considered but are moot, since the rejections have been withdrawn due to amendment.
Applicant argues that it premature to file a terminal disclaimer, since neither 17/966,711 or 18/375,235 are allowed (Remarks pg. 18 para. 2). The nonstatutory double patenting rejection has been withdrawn due to the claim amendments.
Conclusion
No claims are 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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