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 .
Applicants' arguments, filed 09/09/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103--Previous
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.
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.
Claim(s) 1-2, 4-6, 8-13, 21-22 remain rejected under 35 U.S.C. 103 as being unpatentable over Rolland et al., (Journal of Otolaryngology-Head and Neck surgery, 2019, cited in IDS).
Rolland et al. teaches a method of preventing cisplatin-induced ototoxicity in patients by way of trans-tympanic injection of a sodium thiosulfate gel (Title).
Rolland et al. states, “Antioxidants such as sodium thiosulfate (STS) can neutralize the effects of cisplatin. The objective of the trial was to test the efficacy of trans-tympanic injections of a STS gel to prevent cisplatin-induced ototoxicity” (Abstract).
“On the eve of each cisplatin treatment, a pharmacist prepared the gel for the injection by mixing 0.55 ml hyaluronate gel (Healon 10 mg, Abbott Medical Optics Inc) and 0.55 ml of a 25% solution of sodium thiosulfate pentahydrate (Seacalphyx, Ceaford Pharmaceuticals Inc). The sodium thiosulfate solution (STS) concentration in the resulting gel was 0.5M” (p. 2, right column last para. through p. 3, left column 1st para.).
“Since no previous clinical study used a thiosulfate sodium gel, the concentration of our gel was in part determined with the results of Berglin et al. [18]. In this study, a 0.1 M sodium thiosulfate-hyaluronan gel was injected in the guinea pigs’ middle ears and was found in the Scala tympani’s perilymph 1 hour after injection. We decided to maximize the concentration of sodium thiosulfate in the hyaluronan gel and to inject a quantity of gel sufficient only to fil the round window area. This was chosen in order to prevent a conductive hearing loss with a full middle ear packing. The highest sodium thiosulfate concentration that could be achieved in order to obtain a stable and homogenous gel was 0.5 M” (p. 3, left column. 2nd paragraph).
“After a local anesthesia of the tympanic membrane, the otologist performed a formal otoscopy with a microscope to localize the round window niche, and then deposited 0.1 ml of the gel exactly on it” (Id. 3rd paragraph).
“Also, the trans-tympanic injections were done the day before the patients received their cisplatin treatment, allowing some time to the gel to get through the inner ear. The average elapsed time between the injection and the cisplatin treatment was 20.5H” (p. 7, right column, 2nd paragraph). It was noted that his time was chosen solely for convenience of the of the patient stating, “We chose this timing because it was easier for the patients, according to their treatment’s schedule” (Id.).
Earlier times for injection were possible insofar as the prior art teaches, “In the study of Riga et al. [21], the trans-tympanic N-acetylcysteine injections were performed during the hydration procedure preceeding intravenous effusion of cisplatin” (Id.), where the Examiner understands the hydration procedure takes place a few hours before cisplatin therapy (see Technological Background below).
Rolland et al. admits, “Our study could not demonstrate statistically significant efficacy of a trans-tympanic injection of a viscous sodium thiosulfate-hyaluronate gel prior to cisplatin therapy to prevent its induced ototoxicity in patients with advanced HNSCC” (p. 6, right column, 3rd para.)
Nevertheless, the prior art encouraged further study, stating, “This trial showed that a trans-tympanic injection of a sodium thiosulfate-hyaluronate gel is feasible and innocuous for the middle and inner ears and that further investigations of this innovative gel could be conducted safely” (p. 7, last para.).
The trial demonstrated outcomes such as, “For all frequencies between 3 and 10 kHz the hearing loss was less pronounced for the treated ear than for the control” (p. 5, left column, last para.) and “Although not significant these differences pointed to less severe hearing loss in the treated ears: 22,2% (p = 0.99)” (Id, right column, last para.).
Accordingly, it would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to administer a sodium thiosulfate-hyaluronate gel to the round window of the middle ear of a human subject prior to cisplatin treatment to prevent cisplatin-ototoxicity.
The prior art does not recommend a time frame or concentration range for administering the sodium thiosulfate gel to the patient. In the study, the average time between injection and the cisplatin treatment was 20.5 hours, but only as a convenience factor for the patient, as opposed to effect. The reference also taught administration during the hydration period, i.e. moments before cisplatin injections stating “Additional studies are required to further determine the optimal dosage and protocol of the sodium thiosulfate-hyaluronate gel” (p. 7, last para). Further, since the reference teaches administering 0.1 M sodium thiosulfate to a patient, it would have been obvious to administer amounts falling within the claimed range of 0.025M and 0.2M. Accordingly, it would have been obvious to optimize when, as well as, how much, of the gel is administered prior to cisplatin injection. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" (see MPEP 2144.05 IIA quoting In re Aller, 220 F.2d 454, 456 (105 USPQ 233)).
The adjustment of particular conventional working conditions of thiosulfate gel treatment prior to cisplatin (e.g., determining result effective amounts and times for when the injections take place, especially within the broad ranges instantly claimed), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
Concerning claims 5-6, Rolland et al. teaches, “The planed treatment included cisplatin 100 mg/m2 at days 1, 22 and 43” (Abstract).
Concerning claims 9-10, the artisan would have expected the gel to have a viscosity conducive to administering to the inner ear. Again, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" (see MPEP 2144.05 IIA quoting In re Aller, 220 F.2d 454, 456 (105 USPQ 233)).
Concerning claims 1 and 11, the normal tympanic (inner ear) temperature is in the range of 35.8ºC to 37.9ºC. It would behoove the artisan to administer the gel within this range for the sake of the patient’s comfort. Rolland et al. remarked that “dizziness and transient mild vertigo could be explained by the gel that could have been colder than the inner ear temperature” (p. 6, right column, last paragraph).
Technological Background
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure ChemoExperts (chemoexperts.com, 2017). ChemoExperts is pertinent for teaching, “Typically, I.V. hydration is given both before and after cisplatin and can add up to two hours to infuse” (1st page, 3rd bullet point under “Estimated total infusion time for this treatment”).
Response to Arguments
The declaration of Charlotte Louise Zuur, filed 09/09/2026, is acknowledged. Affiant opined, “Rolland did not establish that the timing of STS administration affected the prevention or reduction of cisplatin-induced hearing loss” (¶ 7); “the Riga study would not have provided a person of ordinary skill in the art with a reason to change Rolland’s approximately 20-hour timing for STS administration or with a reasonable expectation that administering STS within 3 hours before cisplatin would prevent or reduce hearing loss” (¶ 8). Affiant describes a clinical trial where patients were administered STS 3 hours before cisplatin administration and found that this proved successful in reducing hearing loss. Affiant admits the results of the trial “were not statistically significant. Nevertheless, the results provided preliminary evidence of clinical protection in individual patients using 0.1M STS gel administered 3 hours before cisplatin” (¶ 12).
i) Applicant argument echoes the sentiment of affiant, i.e. that Rolland fails to provide an optimal time for administering STS to patients for reduction in hearing loss.
Applicant adds, the person having ordinary skill in the art would not view time of administration as routine optimization since Rolland “did not recognize the timing of STS administration as a result-effective variable” (p. 7).
However, the amended 3-hour administration window does not go beyond the scope of the prior art insofar as it does not change the patient population, the drug, nor the expected result of administering said drug to said patient population. See In re Huang, 100 F.3d 135, 139 [40 USPQ2d 1685] (Fed. Cir. 1996) (holding that claimed ranges must “produce a new and unexpected result which is different in kind and not merely in degree from results of the prior art”) [emphasis added].
When Rolland stated, “Additional studies are required to further determine the optimal dosage and protocol of the sodium thiosulfate-hyaluronate gel” (p. 7, last para), this was an admission that the procedure had not been mastered, and further research was necessary. The artisan would not have been reasonably expected to rest on the 20-hour time frame, since it was not justified scientifically. Timing would have reasonably been included in determining optimal dosage and protocol for the STS gel. Thus, timing would have been a result-effective variable.
It must be remembered, "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 82 USPQ2d at 1397.
Again, "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
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.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb
/WALTER E WEBB/Primary Examiner, Art Unit 1612
