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 .
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/1/25 has been entered.
Claims 2, 4-11 have been cancelled. Claim 12 has been added. Claims 1, 3, 12 are pending and examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and modified due to the claim amendments.
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 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zuo et al. (WO 2018/204226 A1, of record).
Zuo et al. teach a method for the treatment or prevention of hearing loss by administering to an animal in need thereof an inhibitor of epidermal growth factor receptor (EGFR) signaling (paragraph 0005). Preferred EGFR inhibitors are afatinib and AZD3759 (paragraphs 0032, 0054, 00151). Hearing loss may be from damage caused by cisplatin, antibiotics, noise, aging, ototoxic insults, medicines, such as antibiotics, and some cancer treatments, for example chemotherapy and radiation therapy (paragraphs 0010, 0064, 0069, 0072). Hearing impairment may also be drug-induced, such as from the chemotherapeutic agent, cisplatin (paragraph 0073). In various aspects, the disclosed molecules can be used in combination with one or more other drugs in the treatment, prevention, control, amelioration, or reduction of risk of hearing impairments and disorders for which disclosed molecules or the other drugs can have utility, where the combination of the drugs together are safer or more effective than either drug alone. Figure 4 shows that a EGFR inhibitor protects against cisplatin induced hair cell loss (paragraph 0009). Kits may include active agents as well as instructions for use (paragraph 00138). The dose of the drug should be sufficient to affect the desired response over a reasonable time frame. One skilled in the art will recognize that dosage will depend upon a variety of factors, including age, species, location of damaged sensory epithelia, the pathology, and condition or disease state. Dosage also depends on the EGFR inhibitor, the route, timing, and frequency of administration, as well as the existence, nature, and extent of any side effects (paragraph 00129).
Response to Arguments
It is noted that Applicant’s arguments are essentially the same as before, therefore the same response will apply.
Applicant argues that St. Jude teaches away from afatinib as a preferred EGFR inhibitor in preventing cisplatin induced hair cell loss. St. Jude lists afatinib as one tyrosine kinase inhibitor in a list of 30 compounds. In Example 4, 75 kinase inhibitors were screened for compounds that were protective against cisplatin-induced hair cell loss, and only 4 compounds (mubritinib, dabrafenib, GSK2118436A, and crenolanib) were identified as having the desired effect. Furthermore, there was no data on the efficacy of drugs that function to protect ear cells from death from noise.
This is not persuasive because the essence of St. Jude is to teach that, in general, EGFR inhibitors are useful for treating hearing loss from a variety of sources. St. Jude goes on further to identify that afatinib is a preferred embodiment of a EGFR inhibitor. While Example 4 identified only 4 compounds in a study of 75 kinase inhibitors for treating hearing loss, it remains to be seen how many of the 75 compounds were EGFR inhibitors, let alone afatinib specifically. Without that information, it is impossible to state that afatinib was not effective in treating hearing loss.
Applicant also argues that the particular result of “prevent ear cell loss caused by noise exposure” is not shown in the cited art. Applicant argues that the Chen review article notes that different drugs are efficacious on different types of hearing loss. The present application provides in vivo data in an animal model and data from mice. Claim 1 requires a particular result that is not shown in the cited art. St. Jude does not enable one of ordinary skill in the art to practice the claimed invention. This is because one skilled in the art would know that EGFR inhibitors can induce ototoxicity as taught by Aylin et al.
This is not persuasive because since the same claimed active agent (afatinib) is being administered to the same claimed patient population (anyone that is need of prevention of hearing loss), it is inherent that prevention of hearing loss will necessarily occur. Regardless, Applicant is reminded that the prior art need not teach enablement of every embodiment as long as there is sufficient teaching of every limitation of the claims. Finally, the arguments directed to unpredictability in the art or no reasonable expectation of success is irrelevant because the rejection of record is not a 103 obviousness rejection, but a 102 anticipatory rejection.
Applicant argues that it is known that EGFR inhibitors that are used in medical treatments have a side effect of loss of hearing and tinnitus as shown in Alexeeva et al. Thus, one skill in the art cannot reasonably infer from the prior art that afatinib is effective to prevent ear cell loss caused by noise.
This is not persuasive because the Alexeeva reference was not used in the making the prior art rejection, nor is the Alexeeva reference sufficient to establish the state of the art. Furthermore, the teachings of Alexeeva refer to medical treatment that have nothing to do with treating hearing loss.
Applicant also argues that certain EGFR inhibitors that are used in medical treatments have a known side effect of loss of hearing and tinnitus, such as axitinib and ruxolitinib, as shown by Alexeeva. Therefore, one skilled in the art cannot reasonably infer that afatinib is effective in preventing ear cell loss caused by noise.
This is not persuasive because no where in Alexeeva does it mention afatinib, therefore no conclusions can be made regarding not preventing ear cell loss.
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.
Claim 3 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (“Histone deacetylases in hearing loss: Current perspectives for therapy,” Journal of Otology, 2017, 12, 47-54, of record).
Chen et al. teach that histone deacetylases (HDAC) are associated with the development and progression of hearing loss (abstract). Hair cells of organ of Corti (inner ear) are susceptible to acoustic trauma, ototoxic drugs, infections or aging, thus resulting in permanent hearing loss (page 48, left column, first paragraph). Ototoxic deafness is severe and permanent hearing loss and/or vestibular dysfunction caused by ototoxic drugs, such as aminoglycoside antibiotics, loop diuretics, antimalarials and platinum chemotherapy. Accumulating evidence have suggested that the aminoglycoside antibiotics-induced ototoxicity is associated with the generation of reactive oxygen species and nuclear factor-kB misregulation in outer hair cells (page 50, right column, last paragraph). HDAC inhibitors can block the activity of HDACs and thus act as therapy options for hearing loss (page 51, left column, last paragraph). Table 2 on page 49 identifies SAHA (vorinostat) as a preferred HDAC inhibitor. For example, SAHA showed protective effects on gentamicin-induced hair loss. In another example, pre-treatment with SAHA markedly reduced noise-induced outer hair cell (OHC) loss and threshold shifts in noise-induced hair loss (NIHL) mice. Similarly, SAHA could protect guinea pigs against cisplatin ototoxicity. Therefore, there is good correlation between HDAC inhibitors and treatment of hearing loss (page 51, right column, first full paragraph).
Response to Arguments
Applicant argues that Chen teaches HDACs in ototoxic hearing loss involved antibiotics, whereas the present claim is directed to cisplatin. Applicant also argues that the art teaches away from use of vorinostat as an otoprotective agent in vivo. Furthermore, the Yang reference teaches that HDAC inhibitors are protective in acute but not in chronic models of ototoxicity.
This is not persuasive because since the same claimed active agent (vorinostat) is being administered to the same claimed patient population (anyone that is need of prevention of ear cell loss from an ototoxic event), it is inherent that prevention of ear cell loss will necessarily occur no matter whether the ear cell loss is caused by cisplatin treatment or not. With regard to the Yang argument, it is noted that the instant claims do not recite any difference between acute or chronic oxtotoxicity, therefore this argument is irrelevant.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623