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
This Office Action is a response to Applicant’s Amendment and Remarks filed February 2, 2026.
Claims 6 and 33 have been canceled. New claims 58 and 59 are acknowledged. Claims 1, 3, 8, 24, 28, 29, 35, 53-55 and 57 have been amended.
Claims 1, 3, 8-11, 14, 24, 28, 29, 35, and 51-59 are pending in the instant application.
Accordingly, claims 1, 3, 8-11, 14, 24, 28, 29, 35, and 51-59 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed February 2, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
In the previous Office Action mailed August 1, 2025, the Drawings were objected to because some Drawings referenced the colors, "red" and "green" without an accompanying petition. This objection is withdrawn in view of Applicant’s Amendment to the Specification to remove any reference to color Drawings.
Claim Rejections - 35 USC § 112
In the previous Office Action mailed August 1, 2025, claims 1, 3, 6, 8-11, 14, 24, 28, 29, 33, 35, and 51-57 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. This rejection is moot against claims 6 and 33 in view of Applicant’s Amendment filed February 2, 2026 to cancel these claims. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims to spell out the terms, “CaMKKb” and “AMPKa”.
In the previous Office Action mailed August 1, 2025, claims 3, 29 and 35 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. This rejection is withdrawn in view of Applicant’s Amendment to the claims to remove the indefinite term, “optionally”.
In the previous Office Action mailed August 1, 2025, claims 3 and 29 were 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. This rejection is withdrawn in view of Applicant’s Amendment to the claims to remove the phrase, “50-100 percent”.
Claim Rejections - 35 USC § 102
In the previous Office Action mailed August 1, 2025, claims 1, 24, 28, 33, 35, 54 and 55 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20080108583 A1 (to Feinstein). This rejection is moot against claim 33 in view of Applicant’s Amendment filed February 2, 2026 to cancel this claim. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims to limit the scope of AMPKa to isoform 1.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed August 1, 2025, claims 1, 8-11, 14, 24, 28, 33, 35, and 51-57 were rejected under 35 U.S.C. 103 as being unpatentable over US 20080108583 A1 (to Feinstein) This rejection is moot against claim 33 in view of Applicant’s Amendment filed February 2, 2026 to cancel this claim. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims to limit the scope of AMPKa to isoform 1.
Applicant’s Amendment filed February 2, 2026 necessitated the new ground of rejection(s) presented below:
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 51 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 51 is dependent on claim 33. Claim 33 was canceled in Applicant’s Amendment to the claims filed February 2, 2026. Because claim 51 is dependent on a canceled claim, the metes and bounds of claim 51 cannot be determined. See MPEP 608.01(n), for further explanation. Claim 51 has not been further considered on the merits.
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.
Claim Rejections - 35 USC § 102
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, 8, 9, 24, 28, 35, 54, 58 and 59 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hill et al. (Journal of Neuroscience, July 13, 2016 Vol. 36(28):7497-7510) (submitted and made of record on the IDS filed June 3, 2022).
The claims are drawn a method of treating or preventing an acquired (i) hearing loss, (ii) ototoxicity, (iii) outer hair cell damage or death, (iv) loss of an outer hair cell function, or a combination thereof comprising: a. administering an amount of an AMP-activated protein kinase (AMPK) AMPK alpha isoform 1 targeting RNAi molecule to the subject in need thereof, wherein the AMPK alpha isoform 1 targeting RNAi molecule is capable of specifically binding a target sequence in an AMPK alpha isoform 1 gene product; b. administering an amount of a calcium/calmodulin-dependent protein kinase beta (CaMKKb) targeting RNAi molecule to the subject in need thereof, wherein the CaMKKb targeting RNAi molecule is capable of specifically binding a CaMKKb gene product; or c. a combination thereof.
Hill et al. disclose the inhibition of AMPK alpha via siRNA (siAMPKa1) attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. See Figure 3, for example. Hill et al. also disclose the inhibition of AMPK alpha via siRNA (siAMPKa1) reduced AMPK alpha isoform gene product. See Figure 3.
Hill et al. disclose that siAMPKa1 was administered via Intratympanic delivery as a naked siRNA. See page 7498, second column. Hill teach that a customized sterile micro medical tube was inserted into the hole just above the round window to slowly deliver the single siRNA type via syringe.
NOTE: The present Specification identifies an anesthetic as an ototoxic agent. See claim 9, for example.
Hill et al. disclose that siAMPKa1 was administered after exposure to the anesthetic agent, xylazine. See page 7498, second column.
NOTE: Hill et al. disclose AMPK a1 siRNA (siAMPKa1; catalog #s98535; Invitrogen) was used in their studies. However, the Examiner cannot find more information on the exact sequence of the siRNA.
Therefore, claims 1, 8, 9, 24, 28, 35, 54, 58 and 59 are anticipated by Hill et al.
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 53 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Hill et al. (Journal of Neuroscience, July 13, 2016 Vol. 36(28):7497-7510) (submitted and made of record on the IDS filed June 3, 2022).
The claims are as described above.
Hill et al. is relied upon as described above.
Hill et al. teach that siAMPKa1 is administered after exposure to the ototoxic anesthetic agent, xylazine, but does not teach wherein administering the siAMPKa1 prior to exposure of the subject to an ototoxic agent. Applicant is reminded that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See In re Aller, 105 USPQ 233. Also see MPEP 2144.05. In other words, it is not inventive to discover the optimum or workable ranges by routine experimentation and optimization.
Before the effective filing date of the claimed invention, a method of treating or preventing an acquired (i) hearing loss, (ii) ototoxicity, (iii) outer hair cell damage or death, (iv) loss of an outer hair cell function, or a combination thereof comprising administering an amount of an AMP-activated protein kinase (AMPK) AMPK alpha isoform 1 targeting RNAi molecule to the subject in need thereof, wherein the AMPK alpha isoform 1 targeting RNAi molecule is capable of specifically binding a target sequence in an AMPK alpha isoform 1 gene product was known in the art as taught and suggested by Hill et al.
A person of ordinary skill in the art would have been motivated to modify the teachings of Hill et al. to administer the AMPK alpha isoform 1 targeting RNAi molecule prior to exposure of the subject to an ototoxic agent for the purpose of protecting hearing loss potentially caused by the ototoxic agent.
One of ordinary skill in the art would have been motivated and expected reasonable success to devise the methods of the claimed invention since the prior art of Hill et al. represents an exact blueprint of how to successfully carry out such methods.
Accordingly, claims 53 and 57 taken as a whole would have been prima facie obvious before the effective filing date of the claimed invention.
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Claims 10, 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Hill et al. (Journal of Neuroscience, July 13, 2016 Vol. 36(28):7497-7510) (submitted and made of record on the IDS filed June 3, 2022) in view of Cannizarro et al. (Hearing, Balance and Communication, 2014; Vol.12:166-175).
The claims are as described above.
Hill et al. is relied upon as described above.
Hill et al. teach that to induce noise exposure, a broadband noise was used to induce severe permanent threshold shifts with a loss of both outer hair cells and inner hair cells.
Hill et al. do not teach an ototoxic agent.
Cannizarro et al. teach noise exposure and many drugs or chemical compounds and agents frequently share the same ototoxic mechanisms.
Before the effective filing date of the claimed invention, a method of treating or preventing an acquired (i) hearing loss, (ii) ototoxicity, (iii) outer hair cell damage or death, (iv) loss of an outer hair cell function, or a combination thereof comprising administering an amount of an AMP-activated protein kinase (AMPK) AMPK alpha isoform 1 targeting RNAi molecule to the subject in need thereof, wherein the AMPK alpha isoform 1 targeting RNAi molecule is capable of specifically binding a target sequence in an AMPK alpha isoform 1 gene product was known in the art as taught and suggested by Hill et al.
A person of ordinary skill in the art would have been motivated to modify the teachings of Hill et al. and substitute the noise exposure with the ototoxic agent/chemical of Cannizarro et al. since they are functional equivalents of each other, and it is obvious to substitute one functional equivalent for another, particularly when they are to be used for the same purpose. See MPEP 2144.06.
One of ordinary skill in the art would have been motivated and expected reasonable success to devise the methods of the claimed invention since the prior art of Hill et al. represents an exact blueprint of how to successfully carry out such methods.
Accordingly, claims 10, 11 and 14 taken as a whole would have been prima facie obvious before the effective filing date of the claimed invention.
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Claims 52 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Hill et al. (Journal of Neuroscience, July 13, 2016 Vol. 36(28):7497-7510) (submitted and made of record on the IDS filed June 3, 2022) in view of Hastings et al. (Neurotherapeutics (2019), published online 10 April 2019, Vol.16:348-359).
The claims are as described above.
Hill et al. is relied upon as described above.
Hill et al. teach that siAMPKa1 was administered via Intratympanic delivery, but does not teach wherein the delivery is posterior semicircular canal delivery.
Hastings et al. teach that local delivery of therapeutic molecules could be advantageous in that it would provide drug presentation directly and exclusively to the target organ, thereby maximizing local concentration and minimizing systemic effects while also bypassing many of the physical barriers present following systemic delivery. Hastings et al. describe that local delivery routes that have been explored include (1) intratympanic administration via injection through the tympanic membrane and into the middle ear, (2) intracochlear through the round window or cochleostomy, and (3) intralabyrinthine to the posterior semi-circular canal via canalostomy.
Hastings et al. also teach intratympanic administration application is limited by passage through the middle ear epithelium, which covers the round window and the oval window, and elimination through the Eustachian tube. Intratympanic administration of therapeutic molecules in hydrogel systems, in some cases, has been shown to address some of these problems.
Before the effective filing date of the claimed invention, a method of treating or preventing an acquired (i) hearing loss, (ii) ototoxicity, (iii) outer hair cell damage or death, (iv) loss of an outer hair cell function, or a combination thereof comprising administering an amount of an AMP-activated protein kinase (AMPK) AMPK alpha isoform 1 targeting RNAi molecule to the subject in need thereof, wherein the AMPK alpha isoform 1 targeting RNAi molecule is capable of specifically binding a target sequence in an AMPK alpha isoform 1 gene product was known in the art as taught and suggested by Hill et al.
A person of ordinary skill in the art would have been motivated to modify the teachings of Hill et al. and substitute the Intratympanic delivery with the posterior semicircular canal delivery of Hastings et al. since they are functional equivalents of each other, and it is obvious to substitute one functional equivalent for another, particularly when they are to be used for the same purpose. See MPEP 2144.06.
One of ordinary skill in the art would have been motivated and expected reasonable success to devise the methods of the claimed invention since the prior art of Hill et al. represents an exact blueprint of how to successfully carry out such methods.
Accordingly, claims 52 and 55 taken as a whole would have been prima facie obvious before the effective filing date of the claimed invention.
Conclusion
Claims 3, 29 and 56 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Art Made of Record but not Relied Upon
Art made of record but not relied upon: Wu et al. (Cellular and Molecular Life Sciences (2022) 79:249, pages 1-20) teach and disclose traumatic-noise-induced hair cell death and hearing loss is mediated by activation of CaMKKb. More specifically, Wu et al. teach targeting CaMKKb with a short hairpin RNA or siRNA via intra-tympanic delivery is a key strategy for prevention of noise-induced hearing loss.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635