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 .
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed September 17, 2025 is acknowledged. Claims 2-19, 22, 41-56, 58-60 and 62 are canceled. Claims 21 and 61 are amended. Claims 1, 20-21, 23-40, 57 and 61 are pending in this application. Claims 1, 20, 26-27, 29-30, 33-35, 37-38, 40 and 57 are withdrawn without traverse (filed 12/01/2023) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 1, 2023.
3. Claims 21, 23-25, 28, 31-32, 36, 39 and 61 are under examination in this office action.
4. Applicant’s arguments filed on September 17, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
5. The disclosure stands objected to because the recitation of the FSCN2 gene is not italic.
On p. 12 of the response, Applicant argues that the claimed specification is a legal document and thus the recitation of gene abbreviation in italics text is not required.
In response, based on MPEP608.01, the specification is required to be in exact terms as to enable one of skilled in the art or science to understand. Thus, the gene symbol of FSCN2 should be italic as supported in related field and the references: “Scientific Nomenclature: Genes” from the CDC (Centers for Disease Control and Prevention) or the Human Genome Organization (HUGO) Gene Nomenclature Committee (HGNC) and Guidelines for Human Gene Nomenclature, the gene symbol should be italic (see p. 2-3 of the “Scientific Nomenclature: Genes” from the CDC.gov website retrieved on 6/27/2024 or p.469 in Wain et al., Genomics, 2002; 79:464-470 or p.754-755 in Bruford et al., Nat. Genet. 2020; 52:754-758). Appropriate correction is required.
Claim Rejections/Objections Withdrawn
6. The rejection of claim 61 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in response to Applicant’s amendment to the claim.
Claim Rejections/Objections Maintained
In view of the amendment filed on September 17, 2025, the following rejections are maintained.
Claim Rejections - 35 USC § 112
7. 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 21, 23-25, 28, 31-32, 36, 39 and 61 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 21, 23-25, 28, 31-32, 36, 39 and 61 as amended are drawn to a method of treating a subject with a therapeutic agent that treats hearing loss, wherein the subject has hearing loss, the method comprising the steps of:
i) determining whether the subject has a Fascin-2 (FSCN2) predicted loss-of-function (pLOF) variant nucleic acid molecule encoding FSCN2 H138Y by:
a) obtaining or having obtained a biological sample from the subject; and
b) performing or having performed a sequence analysis on the biological sample to determine if the subject has a genotype comprising the FSCN2 pLOF variant nucleic acid molecule; and
ii) administering or continuing to administer to the subject that is heterozygous or homozygous for the FSCN2 pLOF variant nucleic acid molecule the therapeutic agent that treats hearing loss in an amount that is the same as or greater than a standard dosage amount;
wherein the therapeutic agent that treats hearing loss comprises D-methionine, ebselen, N-acetylcysteine, lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents).
The claims encompass methods of treating, preventing and curing all forms of hearing loss in a subject who has hearing loss, comprising steps of determining whether the subject with hearing loss has a genotype comprising a FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y, and then administering or continuing to administer the subject that is heterozygous or homozygous for the FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y the recited therapeutic agent that treats hearing loss in an amount that is the same or greater than a standard dosage amount in view of paragraph [0038] of the published Application.
Response to Arguments
On p. 12-14 of the response, Applicant argues that i) claim 21 has been amended by limiting therapeutic agents to D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol; ii) the term “treat/treating” cannot refer to preventing hearing loss because the subject in claim 21 has hearing loss; iii) based on the definition of “treat/treating” in the specification, curing is not required; iv) all of the compounds recited in amended claim 21 are widely known as having therapeutic effects and protection on the inner ear’s sensory hair cells.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2164, MPEP §§2164.01-2164.06(b) & 2164.08, neither the specification nor the prior art provides sufficient guidance to enable a skilled artisan to practice the claimed invention without undue experimentation because:
i. The instant claims encompass a method of treating, preventing and curing all forms of hearing loss using the recited therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine, lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in an undefined amount that is the same or greater than a standard dosage amount in view of paragraph [0038] of the published specification.
Based on paragraph [0038] of the published specification, the definition of “treat”, “treating” and treatment” encompasses “therapeutic and prophylactic effect…., therapeutic effect comprises……delaying the onset of symptoms……preventing relapse to hearing loss…… A prophylactic effect….a complete….avoidance/inhibition or a delay of hearing loss development/progression….”. The limitation “delaying the onset” means “prevention” and the limitation “a complete…avoidance/inhibition….” means “curing”.
[0038] The terms “treat”, “treating”, and “treatment” and “prevent”, “preventing”, and “prevention” as used herein, refer to eliciting the desired biological response, such as a therapeutic and prophylactic effect, respectively…..a therapeutic effect comprises one or more of a decrease/reduction in hearing loss, … delaying the onset of symptoms and hearing loss-related effects…. preventing relapse to hearing loss, ………. A prophylactic effect may comprise a complete or partial avoidance/inhibition or a delay of hearing loss development/progression (such as, for example, a complete or partial avoidance/inhibition or a delay), following administration of a therapeutic protocol. Treatment of hearing loss encompasses …. the delay of the onset … and/or preventing and/or reducing the severity of hearing loss.
ii. Applicant is not enabled for a method of treating all forms of hearing loss including preventing and curing all forms of hearing loss by the claimed therapeutic agent that comprises D-methionine, ebselen, N-acetylcysteine, lipoic acid, allopurinol and resveratrol because currently, hearing loss cannot be prevented or cured in any given agent as evidenced by the factsheet of hearing loss (see the factsheet retrieved from the CDC website), Muller et al. (see p. 346, abstract; Nature Rev. Drug Discov., 2015; 14: 346-365, cited previously) and Ostrowski et al. ( see p.5; Types of hearing loss from the healthy hearing website: www.healthyhearing.com/help/hearing-loss/types retrieved on 6/14/2025, cited previously). Muller teaches that currently there is no drug-based therapy for hearing loss (see p. 346, abstract) and Ostrowski teaches that “there is no medical or surgical method to reverse SNHL. However, it can be treated with hearing aids or cochlear implants, depending on how severe your hearing problems are" (see p. 5).
Neither the specification nor the prior art provides guidance as to how to cure hearing loss caused by all possible mechanisms or prevent a person who has hearing loss from having hearing loss caused by all possible mechanisms by any given agents. Thus, it is unpredictable whether the therapeutic agent comprises can be used for treating, preventing or curing hearing loss. Thus, a skilled artisan cannot contemplate how to use the claimed invention without undue experimentation.
iii. Neither the specification nor the prior art provides a well-established correlation between treatment of all forms of hearing loss with the FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y by the recited therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine, lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) using an undefined amount that is the same or greater than the standard dosage amount and the treatment of a specific form of hearing loss using a specific agent in a specific amount.
The sole working example in the specification, as originally filed, pertains to detecting a missense variant in FSCN2 that is associated with increased risk of hearing loss based on a genome-wide and exome-wide association analysis of risk of hearing loss, wherein the missense variant is His138Tyr (Figure 1, Example 1) and some other missense variants in FSCN2.
Hearing loss can be due to multiple mechanisms including genetic and environmental factors. For example, genetic forms due to functional null alleles of USH1C, MYO7A, CDH23; targets of genetic damages, noise-induced hearing loss, chemically induced hearing loss, age-related hearing loss, which each has its own mechanisms and genes involved (see p.348-353; Muller et al., Nature Rev. Drug Discov., 2015; 14: 346-365. doi.10.1038/nrd4533, cited previously). Sensorineural hearing loss (SNHL), a type of hearing loss, occurs due to damage to the hair cells (HCs) in the cochlea and/or damage to the auditory neural pathway. Mitochondrial dysfunction is associated with the etiologies of SNHL, such as age-related hearing loss (ARHL), noise-induced hearing loss (NIHL) and ototoxic drugs (Ototoxic hearing loss), as well as hearing loss due to mitochondrial gene mutation. Different gene mutations have also been identified to be associated with hearing loss based on a genome-wide association meta-analysis. For example, mutations in several genes including COL9A3, TMPRSS3, EYA4, CDH23, TRIOBP, GJB2, SLC26A5, KLHDC7B, FSCN2, and SYNJ2 have been identified to be associated with hearing loss based on a genome-wide association meta-analysis (see p. 1 abstract; p.2-4, tables 1-2; Praveen et al. Commun. Biol. 2022; 5:540. Doi.org/10.1038/s42003-022-03408-7, cited previously). Further, based on Applicant’s own admission, other missense variants in FSCN2 including Gly5Ser, Arg199His, Phe367Ser, Asp225Asn, Arg269Cys, Pro156Leu, Ala220Asp, Tyr184*, Val271Ile, Glu479Asp, Tyr23Cys may also increase the risk of hearing loss (See Example 1).
Neither the specification nor the prior art provides a well-established structural and functional correlation between treatment of all forms of hearing loss having the FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y using the recited therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in an undefined amount that is the same or greater than a standard dosage amount and the treatment of a specific form hearing loss using a specific therapeutic agent that is D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol or resveratrol in an effective amount for each specific agent. The specification also provides no guidance as to what the relationship or correlation between a specific amount that is the same or greater than a standard dosage amount for a mixture of 6 recited agents and the amount of oral administration of N-acetyl-L-cysteine (NAC) or other agents that showed no otoprotection in human suffering from noise-induced hearing loss (NIHL).
For example, based on clinical trials of N-acetyl-L-cysteine (NAC) in patients with noise-induced hearing loss (NIHL), oral administration of NAC in an amount of 1800 mg/day showed no otoprotection in the patients with NIHL compared to placebo (see p. P.130-131; Lynch et al. Chapter 5 Development of Drugs for Noise-Induced Hearing Loss, Book: Translational Research in Audiology, Neurology, and the Hearing Science, edited by Le Prell et al., ASA Press, Springer Handbook of Auditory Research. DOI 10.1007/978-3-319-40848-4). Thus, it is unknown what the claimed amount that is the same or greater than the standard dosage amount for the claimed therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) is. It is also not known what the specific effective standard dosage amount for NAC is. Thus, it is unpredictable whether the use of the claimed therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in the claimed undefined amount that is the same or greater than the undefined standard dosage amount can treat or even prevent or cure all forms of hearing loss because there is no drug-based therapy for hearing loss and other approaches are still uncertain in view of Muller et al. and Lynch et al.. Therefore, a skilled artisan cannot contemplate how to make and use the claimed invention without undue experimentation.
Note that a patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100,(CAFC 1997), the court held that:
“[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure”. The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art”, “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement”.
The instant specification is not enabling for the full scope of the claimed subject matter because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, no working example, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform while practicing the claimed invention as it pertains to a method for treating all forms of hearing loss in a subject having the hearing loss by administering to the subject with all forms of hearing loss and a heterozygous or homozygous FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y using the claimed therapeutic agent in an undefined amount that is the same as or greater than a standard dosage amount.
Accordingly, the rejection of claims 21, 23-25, 28, 31-32, 36, 39 and 61 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is maintained.
Claim Rejections - 35 USC § 112
8. Claims 21, 23-25, 28, 31-32, 36, 39 and 61 stand 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 21, 23-25, 28, 31-32, 36, 39 and 61 as amended encompass using a therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in a genus of an amount that is the same or greater than a genus of a standard dosage amount for treating hearing loss in a subject with hearing loss and having a heterozygous or homozygous FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y.
The specification only describes detecting a missense variant in FSCN2 associated with increased risk of hearing loss based on a genome-wide and exome-wide association analysis of risk of hearing loss, wherein the missense variant is His138Tyr (Figure 1, Example 1), and other missense variants in FSCN2 including Gly5Ser, Arg199His, Phe367Ser, Asp225Asn, Arg269Cys, Pro156Leu, Ala220Asp, Tyr184*, Val271Ile, Glu479Asp, Tyr23Cys that may also increase the risk of hearing loss (See Example 1).
However, the claims are directed to a method of treating hearing loss in a subject with hearing loss and a heterozygous or homozygous FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y using the claimed therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in an undefined amount that is the same or greater than an unknown standard dosage amount.
Response to Arguments
On p. 14 of the response, Applicant argues that the rejection has been overcome in view of amendment to claim 21 and for the reasons set forth above.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of using the therapeutic agent in a genus of an undefined amount that is the same or greater than a genus of an undefined standard dosage amount for treating hearing loss in a subject with hearing loss and having a heterozygous or homozygous FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y because:
i. The specification provides no well-established structural and functional relationship or correlation between treatment of all forms of hearing loss with the claimed FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y using the claimed therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in an undefined amount that is the same or greater than an unknown standard dosage amount and the treatment of a specific form hearing loss using a specific therapeutic agent that is D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol or resveratrol in an effective amount for each specific agent. The specification also provides no sufficient information as to what the relationship or correlation between a specific amount that is the same or greater than a standard dosage amount for a mixture of 6 recited agents and the amount of oral administration of N-acetyl-L-cysteine (NAC) or other agents that showed no otoprotection in human suffering from noise-induced hearing loss (NIHL) because the effective standard dosage amount for NAC for treating NIHL is unknown.
For example, based on clinical trials of N-acetyl-L-cysteine (NAC) in patients with noise-induced hearing loss (NIHL), oral administration of NAC in an amount of 1800 mg/day showed no otoprotection in the patients with NIHL compared to placebo (see p. P.130-131; Lynch et al. Chapter 5 Development of Drugs for Noise-Induced Hearing Loss, Book: Translational Research in Audiology, Neurology, and the Hearing Science, edited by Le Prell et al., ASA Press, Springer Handbook of Auditory Research. DOI 10.1007/978-3-319-40848-4). Thus, it is not known what the claimed amount that is the same or greater than the standard dosage amount for the claimed therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) is and thus can be used for treating or even preventing or curing all forms of hearing loss.
Applicant cannot use the recited therapeutic agent in an unknown amount to treat hearing loss based on another unknown standard dosage amount for NAC or other agents that showed no otoprotective effect. Neither the specification nor the prior art provides sufficient support to demonstrate that that Applicant is in possession of using the recited therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in a genus of undefined amount that is the same or greater than a genus of undefined standard dosage amount for treating hearing loss in a subject with hearing loss and the FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y because there is no drug-based therapy for hearing loss and other approaches are still uncertain in view of Muller et al. and Lynch et al..
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of using the claimed therapeutic agent comprising D-methionine, ebselen, N-acetylcysteine (NAC), lipoic acid, allopurinol and resveratrol (i.e. a mixture of 6 agents) in a genus of an undefined amount that is the same or greater than a genus of undefined standard dosage amount for treating hearing loss in a subject with hearing loss and the FSCN2 pLOF variant nucleic acid molecule encoding FSCN2 H138Y, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation.
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed method has not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 21, 23-25, 28, 31-32, 36, 39 and 61 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 is maintained.
Conclusion
9. NO CLAIM IS ALLOWED.
10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lichter et al. (US9132087) teach a method of treating otic disorders including hearing loss in a subject, comprising administering to the subject in need thereof a pharmaceutical intratympanic formulation comprising a multiparticulate immunomodulating agent or pharmaceutically acceptable salt thereof, wherein the immunomodulating agent is an anti-TNF agent, a calcineurin inhibitor, an IKK inhibitor, an interleukin inhibitor, a TNF-a converting enzyme (TACE) inhibitor or a toll-like receptor inhibitor (claims 1-6).
Fujimoto et al. (Antioxidants, 2019; 109; doi:10.3390/antiox8040109) teach treatment effect of antioxidants on hearing loss including D-methionine (which protects against cisplatin-induced hearing loss), ebselen (showed effective in Meniere's disease and acute noise-induced hearing loss), N-acetylcysteine (NAC) (which some showed effective to attenuate NIHL some showed no otoprotection), lipoic acid, allopurinol and resveratrol (protects cisplatin-induced hair cell damage) (p. 5-8).
Liu et al. (G3, doi.org/10.w1534/g3.118.200405, as in IDS) teaches a null mutation of FSCN2 gene in C57BL/6 mice result in progressive hearing loss and retinal degeneration
Gamundi et al. (Mol. Vis. 2005; 11:922-8. Published Nov 2, 2005) teaches detecting 16 nucleotide substitutions in FSCN2 gene in Spanish patients with autosomal dominant retinitis pigmentosa and macular dystrophy, and 9 of them are missense mutations including His7Tyr, Ala122Thr, Ser126Phe, His138Tyr, Arg149Gln, Ala240Thr, Ala323Thr, Asn331His and Phe367Leu (p. 922, abstract).
Shin et al. (J. Neurosci. 2010; 30:9683-9694, as in IDS) teaches that DBA/2J mice with early-onset, age-related hearing loss have a mutation, R109H, in FSCN2 (p. 9686, col. 2).
Yang et al. (Hearing Res. 2015; 327:109-116) teaches that DBA/2J mice displayed progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) after 2 weeks of age, and that the mRNA level of Caspase-3 in the inner ears was much higher at 2 weeks of age than that at 4 or 8 weeks of age. The transcriptional levels of Caspase-3 and Caspase-9 in the inner ears of DBA/2J mice were significantly higher than those of C57BL/6J mice at 2 or 8 weeks of age. Yang teaches intraperitoneally administering a pan-caspase inhibitor Z-VAD-FMK to DBA/J2 mice over an 8-week period starting at one week of age can preserve hearing in the mice by more than 10 dB (dB) sound pressure level (SPL) of the ABR thresholds and significantly reduced outer hair cell loss at the basal turns of the cochleae (see p. 109, abstract; p. 110-114).
JP7036723 (filed Dec 14, 2016) teaches that “The most common form of retinitis pigmentosa in the syndrome is Usher's syndrome, which is characterized by a combination of anopsia and hearing loss that occurs at an early age. Retinitis pigmentosa is also a function of several other genetic syndromes, including Bardet-Biedle syndrome; Refsum disease; and neuropathy, ataxia, and retinitis pigmentosa (NARP)” (p. 13) and deletion of FSCN2 gene affect ocular function (p.2).
11. THIS ACTION IS MADE FINAL. 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.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
January 12, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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