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. Drawings The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the limitation “.. .connecting the drug delivery device to an injection system ” in claim 1 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. 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 appl icant regards as his invention. Claims 1-25 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The limitation , i.e., a drug delivery device implanted through a tympanic membrane, and the limitation, i.e., fluidly connecting the drug delivery device to an injection system via an inlet of a flexible catheter of the drug delivery device” in claim 1 is unclear. As shown in Fig. 1A, a flexible catheter 108 is implanted through a tympanic membrane. Therefore, the drug delivery device is equivalent to a flexible catheter 108. However, later on, the claim further requires that: fluid connecting the drug delivery device (the device that being implanted into the tympanic membrane) to injection system via an inlet of a flexible catheter of the drug delivery device. Therefore, it is unclear to Examiner that the drug delivery device is whether same or different element (or separate element) with respect to the flexible catheter . The Fig. 1A shows that the drug delivery device is designated to element 100 which is including a syringe 118, a catheter 108. In other words, the syringe 118, the catheter 108 are parts of the drug delivery device 100. Therefore, it is unclear to Examiner that which element is considered as “an injection system”. In addition, it does not make sense that the part (i.e. flexible catheter 108) of the drug delivery device 100 is being connected to the drug delivery device. Claims 24-25 are being rejected due to their dependency. 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)(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 & 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arenberg et al. (US 6,685,697). Regarding claim 1 , Arenberg discloses a method of administering, to a tympanic cavity 5 , a pharmaceutical composition using a drug delivery device (a whole unit 400 in Fig. 6B or a drug delivery device 10 ) implanted through a tympanic membrane 60 (see similar Fig. 8) , the method comprising: fluidly connecting the drug delivery device to an injection system (reservoir, col. 30, line s 29-32 or including reservoir and catheter 400 ) via an inlet 410 of a flexible catheter 400 of the drug delivery device; and introducing, to the tympanic cavity 5 , a volume of the pharmaceutical composition via the drug delivery device. Note : Examiner only uses Fig. 6B in the references as applied to the claims above for the convenience of the applicant. However, the other Figs. 1-6A, 6C-8 can be used to reject the claimed invention also. Having said that, in the future, if the Examiner uses in certain portion of the other figures beside the Fig. 6B that is not considered as introducing a new ground rejection. Regarding claim 16 , wherein the flexible catheter 400 has an outer diameter of from 0.5-2 mm (which is in the required ranges of 1 Fr to 2 Fr ), col. 29, lines 29, lines 49-50 . Note : the dimension of the elongate member in Fig. 6B is similar to the embodiment in Fig. 6A, see col. 30, lines 12-13 . 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. Claim 1 is rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Decker et al. (US 9,352,084). Regarding claim 1 , Decker discloses a method of administering, to a tympanic cavity, a pharmaceutical composition using a drug delivery device 20 implanted through a tympanic membrane 64 , the method comprising: fluidly connecting the drug delivery device 20 to an injection system 24 via an inlet 32 of a flexible catheter /cannula 24 of the drug delivery device; and introducing, to the tympanic cavity, a volume of the pharmaceutical composition via the drug delivery device , see Fig. 1 . Note : Decker states that the cannula 24 is made of soft cannula. The term “catheter” and “cannula” can be interchangeable. In this case, the soft cannula 24 can be called as “flexible catheter”. Claims 2, 4-12, 14-15, 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084) in view of Lee et al. (US 10,813,947). Regarding claims 2 , 4-9, 23-25 , Decker discloses all the claimed subject matter as required except for limitations as required in claims 2, 4-9, 23-25 Lee discloses a method of administering to a tympanic cavity, col. 7, lines 26-32, a pharmaceutical composition comprises an effective amount of an aqueous solution of a platinum chelator; where in platinum chelator is a thiosulfate salt, see abstract; wherein the chelator is a thiosulfate at a concentration of from 0.1M to 0.4M , see col. 11, lines 25-53; wherein the thiosulfate solution has a pH of from 7.0 to 9.5 , see col. 7, lines 11-13 & lines 36-57, buffered with boric acid , col. 14, line 32-34. In addition, Lee further states that buffering agents are known in the art used to adjust the pH of a pharmaceutical composition, e.g., a pharmaceutical dosage form, a substantially neutral pH level, col. 15, lines 24-28; wherein the platinum chelator is at least one selected from the group consisting of alkali metal thiosulfate salt, an alkaline earth thiosulfate salt, an ammonium thiosulfate salt, and an organoammonium thiosulfate salt , see col. 11, lines 54-56; wherein the platinum chelator is sodium thiosulfate , see claim 2 in Lee; wherein a volume of the administered pharmaceutical composition is in the required ranges of 0.1-0.5 mL, see col. 10, lines 6- col. 11, line 7 and claim 3 in Lee; wherein the effective amount of the aqueous solution of the platinum chelator is introduced to a level at or above a round window membrane in the tympanic cavity , col. 9, lines 55-60 . It would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker with providing the pharmaceutical composition, a concentration of thiosulfate as listed in the claims 2, 4-9, 23-25, as taught by Lee, in order to treat cancers or tumor or to prevent or mitigate hearing loss. Regarding claims 10-12 & 14-15 , Decker discloses all the claimed subject matter as required except for limitations as required in claims 10-12; 14-15. Lee discloses a method of administering to a tympanic cavity, col. 7, lines 26-32, a pharmaceutical composition comprises an effective amount of an aqueous solution of a platinum chelator, i.e., thiosulfate salt; wherein the introducing the pharmaceutical composition to the tympanic cavity occurs at from 1 hour prior to 1 hour after administering one or more platinum-based antineoplastic agents , col. 9,lines 19-35 ; wherein the introducing the pharmaceutical composition to the tympanic cavity occurs at from 30 minutes prior to 30 minutes after administering one or more platinum-based antineoplastic agents , col. 9,lines 19-35 ; wherein the one or more platinum-based antineoplastic agent is cisplatin , see Background, or col. 6, lines 60-61; wherein the pharmaceutical composition is administered multiple times per day , see Figs. 1-3 & 7 in time point (h); wherein the pharmaceutical composition is administered at least once per day for at least two days , see Figs. 1-3 & 7 in time point (h) . It would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker with including a step of i ntroducing the pharmaceutical composition to the tympanic cavity occurs at from 30mins to 1 hour prior to 30mins to 1 hour after administering one or more platinum-based antineoplastic agents , i.e. cisplatin, and the administering multiple times or at least once per day or at least two days, as taught by Lee, in order to treat cancers or tumor or to prevent or mitigate hearing loss. Claim s 3, 17-18 & 22 are rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084). Regarding claim 3 , Decker a ll the claimed subject matter as required. Decker also discloses that forming an incision in the tympanic membrane; inserting the flexible catheter/ cannula 24 through the incision. The catheter/ cannula 24 includes nodules 50 that having diameter larger than an outer diameter of the catheter/ cannula 24 , therefore, a person skilled in the art would recognize that a length/diameter of the incision is being larger than the outer diameter of the catheter/ cannula 24 for preventing rupture tympanic membrane and reducing discomfort to a patient during inserting through the tympanic membrane. Regarding claims 17-18 , Decker discloses all the claimed subject matter as required . Decker also discloses that a tubing/catheter 20 is formed of polyurethan, col. 3, line 60. Since the cannula 24 is formed of soft material. It is well-known in the art that a polyurethan having flexible, soft characteristic. Therefore, a person skilled in the art would recognize that the cannula 24 can be formed of polyurethan material for improving patient comfort during insertion. Note : the limitation “ having a reduced rigidity when exposed to a body temperature of a patient ” is a characteristic of a polyurethane material and therefore it is considered as a functional limitation to performing a function. In this case, the flexible catheter/ cannula 24 in Decker is formed of polyurethane material, and therefore, the flexible polyurethane catheter/cannula in Decker is capable of having a reduced rigidity when exposed to a body temperature of a patient . Regarding claim 22 , Decker discloses claimed subject matter as required. Decker also discloses that the distal end of the catheter/ cannula 24 may be placed adjacent to or in contact with a target location at the membrane wall of the inner ear such that the at least one nodule limit s the insertion depth of the cannula into the wall . The medicine may then be administered to the target location. The at least one nodule may be sized, shaped, arranged and/or otherwise configured to permit passage through one or more membranes, such as the tympanic membrane, while not permitting passage through other membranes, such as the temporal bone lining the inner ear, col. 2, lines 3-15. In other words, the distal end of the catheter just passes through the tympanic membrane and the distal end of the catheter is located in between the tympanic membrane and the temporal bone lining the inner ear. Decker further discloses that a distance 54 of the nodule 50 from the distal end 42 of the cannula/catheter 24 about 0.1 mm to 0.5 mm or any other appropriate distance . The distance 54 is be adjusted in a cannula 24 having a sharpened tip , col. 4, lines 51-57. Although Decker does not disclose that a distance of from 2 mm to 5 mm from the tympanic membrane , a person skilled in the art would recognize that a distance form 2-5 mm from the tympanic membrane that depends on the size structure of the ear in each patient. In addition, inserting into the tympanic cavity about 2-5mm from tympanic membrane is not deeply into the tympanic cavity for less risk to contact with any of structures in the tympanic cavity. Claim s 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084) in view of Lee et al. (US 10,813,947) and further in view of Kadiyala et al. (US 2018/0221503) Regarding claims 13-15, Decker in view of Lee discloses all the claimed subject matter as required except for wherein the composition further comprises PD-1 or PDL-1 inhibitors . Kadiyala discloses pharmaceutical compositions and method for immuno-oncology therapy comprising: a composition comprises PD-1 or PDL-1 inhibitors, paras [0128, 0162]; wherein the composition is administered to multiple target area in a patient that including trans-tympanic (across or through the tympanic cavity), para [0402] on page 50; wherein the pharmaceutical composition is administered multiple times per day or once per day for at least two days, paras [0405-0406]; wherein the dosage(s) is/are injectable via intravenous, para [0407, 0409]. I t would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker in view of Lee with including PD-1 or PDL-1 inhibitor composition(s); wherein the pharmaceutical composition is administered multiple times per day or once per day for at least two days, as taught by Kadiyala , in order to treat cancers or tumor or to prevent or mitigate hearing loss. Claim 1 6 is rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084) in view of Arenberg et al. (US 6,685,697). Decker discloses all claimed subject matter as required except for the limitation that the flexible catheter has an outer diameter of 1-2Fr. Arenberg discloses a method of administering, to a tympanic cavity 5 , a pharmaceutical composition using a drug delivery device and a flexible catheter 200 has an outer diameter of from 0.5-2 mm (which is in the required ranges of 1 Fr to 2 Fr ), col. 29, lines 29, lines 49-50. I t would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker with obtaining a size of outer diameter of the catheter in ranges from 1-2Fr , as taught by Arenberg , in order to allow a comfort to a patient during inserting the catheter into the tympanic cavity/membrane Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084) in view of Lobl et al. (US 2006/0264897). Regarding claim 19 , Decker discloses all claimed sub ject matter as required . Decker further discloses that a syringe or other primary drug container may be utilized to initially store the treatment and dispense it for delivery to the targeted location, col. 4, lines 8-10. In other words, a person skilled in the art would recognize that a syringe can be located at a proximal end 32 of the flexible cannula/catheter 40. Alternatively, a syringe can be replaced to the infusion pump 20; and person skilled in the art would recognize that the catheter tubing 28 and the soft cannula 24 can be formed in one unitary unit; wherein the syringe is being connected to an inlet end 30 of the catheter 28. Decker does not disclose that the inlet of the flexible catheter is connector of the injection system having a Luerlock, the inlet having a complementary lock to the Luer lock configured to twistable receive the connector. Lobl discloses a drug delivery device system comprising: a syringe (or an injection system) 14 having a Luerlock 15/16, see Figs. 2-6; an inlet 33 of a flexible catheter 21 is a complementary lock 33 to the Luer lock 16 configured to twistable receive the connector 15/16. I t would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker with providing a luer lock in the injection system (or syringe) and complementary lock of the inlet of the catheter , as taught by Lobl , in order to improve a securing in between the injection system (syringe) and the catheter. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084) in view of Krolikowski et al. (US 4,642,101). Regarding claim 20 , Decker discloses all claimed subject matter as required except for the limitation that attaching the inlet of the flexible catheter, via a suture, to a surface exterior to an ear canal. Krolikowski discloses a catheter device 10 and a method of securing the catheter device to a patient comprising: a catheter 10; a hub 26; the method comprising: attaching the inlet of the catheter 18 , via a suture 34 (& via tabs 22) , to a surface exterior of a skin . I t would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker with including a method of attaching the inlet of the flexible catheter, via a suture, to a surface exterior of a skin, as taught by Krolikowski, for securing the catheter to the skin of a patient such as to a surface exterior to an ear canal. Note : although Krolikowski shows that the catheter is secured at an exterior surface of a patient’s arm; however, a person skilled in the art would recognize that the method of attaching the catheter to a patient’s skin can be applied in different exterior location of skin such as outside of ear canal, such as ear’s skin and that considered as rearrangement purpose or intended use purpose. Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Decker et al. (US 9,352,084) in view of Stypulkowski et al. (US 4,706,682). Regarding claim 21 , Decker discloses all claimed sub ject matter as required except for the limitation that attaching the inlet of the flexible catheter, via an adhesive tape, to a surface exterior to an ear canal. Stypulkowski discloses a method and device comprising: an elongated device 10 being inserted into an ear canal 46; wherein a method comprising attaching an inlet of the flexible catheter 24 via an adhesive tape 26, to a surface exterior to an ear canal for providing some mechanical stability to the elongate member when it is in place, see Figs. 1 & 4. I t would have been obvious to one of ordinary skill in the art, prior to the effective filling date of the claimed invention to modify the method of Decker with including a method of attaching the inlet of the flexible catheter, via an adhesive tape, to a surface exterior to an ear canal , as taught by Stypukowski, for the benefits of providing some mechanical stability to the elongate member when it is in place. Examiner Notes Examiner cites particular columns and line numbers in the references as applied to the claims above for the convenience of the applicant. Although the specified citations are representative of the teachings in the art and are applied to the specific limitations within the individual claim, other passages and figures may apply as well. It is respectfully requested that, in preparing responses, the applicant fully consider the references in entirety as potentially teaching all or part of the claimed invention, as well as the context of the passage as taught by the prior art or disclosed by the examiner. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT QUYNH-NHU HOANG VU whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-3228 . The examiner can normally be reached on FILLIN "Work schedule?" \* MERGEFORMAT M-F 7:30 am-4:00 pm . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration t ool. To schedule an interview, a pplicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Tsai can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-5246 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Quynh-Nhu H. Vu/ Quynh-Nhu H Vu Primary Examiner, Art Unit 3783