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 .
Application Status Summary
This action is written in response to applicant's correspondence received May 26, 2026.
Claims 1, 4- 11 are pending.
Claims 1, 4- 10 are considered on the merits.
Claim 11 is withdrawn.
Claims 1, 4- 10 are rejected.
No Claims are allowed.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant's amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Withdrawn Claim Objections
Applicant’s amendments filed May 26, 2026 (also see applicant comments page 6 line 15- page 7 line 2), with respect to claims 5- 7 have been fully considered. The informalities leading to objections of claims 5- 7 have been corrected by the amendment and the objections therefore withdrawn.
Withdrawn Claim Rejections - 35 USC § 112
Applicant’s arguments, see page 7, lines 9- 14, 18- 27 and page 8 lines 1- 9 filed May 26, 2026, with respect to claim 1 have been fully considered and are persuasive. The 112(a) rejection of claim 1 and its dependent claims 4-10 have been withdrawn. In particular, the applicant’s highlight of “the "immediately after noise exposure" and "24 hours after exposure"” treatment in combination with “the intervention of the drug possesses a therapeutic effect in blocking the disease progression” was persuasive.
The applicant is reminded the original 112(a) rejection of claim 1 dated March 9, 2026 was a 112(a) scope of enablement rejection, not a 112(a) written description enablement as recited by the applicant in their comments on page 7, line 5.
Applicant’s amendments filed May 26, 2026 (also see applicant comments page 8 line 15- 21), to claim 8 and its dependent claims 9 and 10 have been fully considered. The applicant’s amendment removed the tradename ODN 2088 to overcome the 112(b) rejection. Therefore the corresponding 112(b) rejection is withdrawn
Claim Interpretation
In response to the 112(a) rejection issued toward claim 1, the applicant successfully argued “the present specification demonstrates that the decrease in ABR threshold shift data 24 hours after injury represents "partial recovery" of function or "cessation of deterioration," which Applicant respectfully asserts meets the clinical criteria for "treating" or "mitigation.” The Applicant concomitantly amended claim 1 preamble from “A method for treating and/or preventing hearing loss,” to “A method for mitigating or preventing hearing loss.” This examiner will carry this argument in the broadest reasonable interpretation of the claim language.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4- 7 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nedergaard (US 20250049957 A1, effectively filed December 23, 2021), as evidenced by Warchol (Warchol et al. 2021. Front. Cell. Neurosci. 14:613246) and Karper (Karper et al. Arterioscler Thromb Vase Biol. 2012 Aug;32(8):e72-80).
Regarding Claim 1: Nedergaard teaches A method for treating and/or preventing hearing loss ([0012], [0069]), comprising administering to a subject in need thereof [0012] a pharmaceutical composition ([0061]) comprising an effective amount [0012] of a ... Toll-like receptor antagonist and/or Toll-like receptor 9 antagonist (TLR9 antagonist) [0007]. Whereas Nedergaard does not teach a TLR7 antagonist, the specification in the instant application teaches TLR7 and TLR9 are interchangeable [0006], [0010], [0011] ... [0037], [0038], [0039]. Furthermore, the instant application uses lnvivogen's ODN2088 as a TLR7 /9 antagonist [0039]. However, the specification sheet provided by lnvivogen does not indicate ODN2088 is a TLR7 antagonist (lnvivogen. ODN2088 spec sheet. Version 18J26-MM_tds). Therefore, since the instant application treats TLR7 and TLR9 as interchangeable, Nedergaard therefore teaches a TLR7 /9 antagonist. Nedergaard further teaches ... wherein the hearing loss is acute sensorineural hearing loss and wherein the acute sensorineural hearing loss includes noise-induced hearing loss, “a human patient suffering from sensorineural hearing loss” [0061] [0072] (noise-induced hearing loss is a species of the genus acute sensorineural hearing loss and the species anticipates the genus).
Regarding Claim 4: Nedergaard further teaches ... wherein the noise-induced hearing loss is noise-induced outer hair cell loss [0065], [0084].
Regarding Claim 5, 6, and 7: Nedergaard further teaches Claim 5 ... wherein the TLR7 /9 antagonist attenuates noise-induced increased gene expression of cytokines and chemokines in cochlea; Claim 6 .... wherein the TLR7 /9 antagonist attenuates noise-induced increase of nuclear factor kappa-B (NF-KB) expression in cochlea; and Claim 7 ... wherein the TLR7 /9 antagonist decreases noise-induced macrophage infiltration into cochlea. The instant claims simply state scientific truisms. TLR7 /9 activation induces an inflammatory response that includes macrophage recruitment and increased expression of inflammatory cytokines and chemokines including interleukin-1~ (11-lB), tumor necrosis factor-a (Tnf-a), Interferon regulatory factor 7 (lrf-7), C-C motif chemokine ligand 2 (Ccl2), C-C motif chemokine ligand 4 (Cc14), and C-C motif chemokine ligand 12 (Ccl12) (Figs. 3-6). This inflammatory recruitment and response leads to death of OHCs (Fig. 3). This truism is supported by Warchol, and Karper. "Macrophages ... are recruited to sites of cellular injury" in the inner ear leading to OHC loss (Warchol). Additionally, macrophage induction via TLR7 /9 is well known according to Karper, "Activation of endosomal TLRs like TLR7 and TLR9 may lead to upregulation of interferon-a (IFN-a), interleukin-6 (IL-6), IL-12, or tumor necrosis factor-a (TNF-a) by innate immune cells (e.g., macrophages) (Karper)."
A TLR7 /9 antagonist will inherently inhibit the downstream effects, including downstream gene expression of cytokines, chemokines, and nuclear factor kappa-B (NF-kB) and macrophage infiltration in the cochlea. Therefore, Nedergaard anticipates the invention.
Response to Arguments
Regarding response to 102(a)(2) rejection of claims 1, 4-7: Applicant’s arguments/amendments, see page 10 lines 7- 19, filed May 26, 2026 have been fully considered but they are not persuasive. Claim 1 was amended to add the limitations “wherein the hearing loss is acute sensorineural hearing loss, and wherein the acute sensorineural hearing loss includes noise-induced hearing loss.” Applicant notes this amendment incorporates the limitations from claim 2, “wherein the hearing loss is acute sensorineural hearing loss” and a portion of claim 3, “wherein the acute sensorineural hearing loss includes noise-induced hearing loss.” Applicant further notes that the limitation of 3 was not subject to a novelty rejection.
The applicant further argues that each of the cited references fail to anticipate the claimed invention. However, the applicant fails to provide any evidence or even further statement supporting this argument and therefore fails to specifically address the merits of the rejection.
Furthermore, the applicant argues (page 10 lines 25- 27) that their amendment of claim 1 places claims 4-7 in condition for allowance.
Claim 1 and claim 2 were anticipated by Nedergard in the 102(a)(2) rejection dated March 9, 2026. In the same office action, the full limitation (scope) of claim 3 stated “wherein the acute sensorineural hearing loss includes noise-induced hearing loss and idiopathic sudden sensorineural hearing loss.” Claim 3 was rejected for 112(a) enablement for the portion of the limitation directed toward “idiopathic sudden sensorineural hearing loss.” However as written, the full scope of claim 3 required multiple modes of hearing loss, and therefore, this examiner did not find prior art that read on the claim. The amendment of claim 3 removing the “idiopathic sudden sensorineural hearing loss” changed the scope of claim 3, necessitating new grounds of rejection of claim 3. However, the amendment to claim 1, with the recited amended portion of claim 3, necessitates a new rejection, based on the scope-changing amendment (see 102(a)(2) below). Furthermore, since claim 1 is rejected under 102(a)(2), its dependent claims 4- 7 remain similarly rejected, and dependent claims 8- 10 remain similarly rejected.
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.
Regarding Claims 8 and 9: Claim 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Nedergaard as applied to claim 1 above, and further in view of Sun (Sun et al. TLR7 /9 Antagonists as Therapeutics for Immune-Mediated Inflammatory Disorders, Inflammation & Allergy - Drug Targets; Volume 6, Issue 4, Year 2007.).
The applicant is reminded that the oligonucleotide of claim 8 was subject to election of species requirement included in the non-final office action dated 2026 March 9. The applicant elected the species “quinine drug” and therefore the oligonucleotide is withdrawn from consideration.
Regarding claims 8 and 9, Nedergaard teaches all of the elements of claim 1 as described above.
However, Nedergaard does not teach that the TLR9 antagonist that was administered to the subject was a quinine drug, or chloroquine or hydroxychloroquine.
However, Sun teaches "TLR7 /9 antagonists, such as ... chloroquine, hydroxychloroquine and quinacrine, have been used since the 1950s (abstract)." Furthermore, the specifications of the instant application recognizes quinine drugs include chloroquine and hydroxychloroquine [0014]. Therefore, according to Sun, quinine drugs, specifically chloroquine and hydroxychloroquine, have long been known in the art to be TLR7 /9 antagonists. Therefore, Sun teaches ... wherein the TLR7 /9 antagonist is a quinine drug.
Therefore, regarding claims 8 and 9, it would have been obvious to one of ordinary skill in the art to have modified the method of Nedergaard by specifically administering chloroquine or hydroxychloroquine because it would have merely amounted to a simple substitution of one known TLR9 antagonist for another to yield predictable results. A person having ordinary skill in the art (PHOSITA) at the time of the filed instant invention using the method of Nedergaard's embodiment envisioned by a TLR9 antagonist would necessarily look to a specific antagonist. Motivated by this necessity, a PHOSITA would have found and used the quinine drug taught by Sun because they were known to have this common function of TLR7 /9 antagonist activity.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Nedergaard and Sun as applied to claim 9 above, and further in view of Youle (Youle. US 2002/0016335 Al. 2002).
Claim 10 depends from Claim 9 and is therefore rejected for all of the reasons inherited from Claim 9 as taught by Nedergaard and Sun. In particular, a method for treating and/or preventing hearing loss, by administering a chloroquine TLR7 /9 antagonist.
Nedergaard and Sun do not teach the 40-60mg/kg chloroquine dose of the instant claim.
However, Nedergaard contemplates a dosing regimen of "an effective amount" and further teaches delivering a pharmaceutical agent" ... at dosages ... necessary ... ([0101])."
Youle teaches administering a therapeutic chloroquine dose of 45mg/kg ([0102]). Youle is in the same field of endeavor, medical health research, as Nedergaard and Sun. Furthermore, the specific 45mg/kg dose of Youle teaches the 40-60 mg/kg range of the instant application. Therefore, Youle teaches ... wherein the effective amount of the chloroquine is 40-60 mg/kg of the subject.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the dosage of Youle with the method and teachings of Nedergaard and Sun because a PHOSITA using the combined methods of Nedergaard's TLR7 /9 antagonist lacking a specific effective dosing amount and Sun's chloroquine would necessarily look to a specific chloroquine dose. Motivated by this necessity, a PHOSITA would have found and used the chloroquine dose taught by Youle. This amounts to simply "applying a known technique (Youle's chloroquine dose of 45mg/kg) to a known method (Nedergard and Sun's treating hearing loss with an effective amount of chloroquine) ready for improvement to yield predictable results.
Therefore, it would have been obvious for a PHO SITA at the time of filing to combine the dosage of Youle with the method and teachings of Nedergaard and Sun to arrive at the same instant invention.
Response to Arguments
Regarding response to 103 rejection of claims 8-10: Applicant argues “Amended claim 1 now includes technical features of original claim 3 where no novelty or non-obviousness rejections were levied.” Applicant’s arguments have been fully considered but they are not persuasive as described above.
Applicant further argues “the macrophage mechanism discovered in the "vascular system" (as taught by Karper) could not have expected the same therapeutic effect in the spiral ligament of the cochlea.” Applicant’s arguments have been fully considered but they are not persuasive because this is simply an inherent effect as recited in the original statement of rejection. Additionally, the applicant is reminded that this examiner cited Warhol’s teaching "Macrophages ... are recruited to sites of cellular injury" in the inner ear leading to OHC loss.” Therefore, the prior art shows an expectation of success of therapeutic effect in the cochlea.
The applicant further argues unexpected results of “from nearly total death" to "significant survival" of OHCs in referring to Fig. 3. Applicant’s arguments have been fully considered but they are not persuasive because the applicant interprets survival rate data against a control instead of against a therapeutic known in the prior art as indicated in MPEP 716.02. Therefore, the applicant has failed to show “unexpected superior effect” due to the absence of comparable evidence against the prior art.
Conclusion
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 AARON DUREL WARD whose telephone number is (571)272-8495. The examiner can normally be reached Monday to Thursday 8:00AM 6:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 15712705919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AARON DUREL WARD/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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