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. DETAILED ACTION Election/Restrictions Acknowledge is made of Applicant’s election with traverse in the reply filed 10 / 28 /202 5 : Group I, claims 27-45, drawn to a method for the treatment of an inner ear disorder in a subject in need thereof comprising administration of a therapeutically effective dose of a pharmaceutical composition compris ing at least one active agent ; and a pharmaceutically acceptable vehicle comprising: at least one solubilizing agent selected from the group consisting of vegetable oils, oil/water serum bases, glycerine, alcohols, and a mixture thereof, and at least one diffusing agent selected from the group consisting of terpenes and derivatives thereof. Species election without traverse : Inner ear disorder species: tinnitus ; active agent: 7,8-dihydroxyflavone (7,8-DHF) ; solubilizing agent in the pharmaceutically acceptable vehicle: apricot oil [a vegetable oil], and diffusing agent in the pharmaceutically acceptable vehicle: u-(-)-bisabolol [a terpene]. Applicant’s traversal is on the ground that the inventions relate to category (4) a process (i.e., a method of inner ear treatment) and apparatus specifically designed for carrying out the said process (i.e., device for inner ear treatment). Please note Restriction Requirement is NOT full examination. Applicant’s argument is NOT found persuasive because as set forth in the election/restriction requirement mailed on 08/28/2025, Group II (claim 46) recites a device for the local administration of a pharmaceutical composition comprising a reservoir comprising a pharmaceutical composition, wherein the pharmaceutical composition does not refer back to the pharmaceutical composition recited in Group I invention as Applicant argues . Thus, the unity of invention is said to be lacking “a priori” between the groups. The administration of pharmaceutical composition comprising one active agent could be carried out without the device comprising pump or reservoir as descripted in claim 46. Yoshpe teaches pharmaceutical composition comprising one active agent and a pharmaceutically acceptable vehicle comprising solubilizing agent and diffusing agent for treating inner ear disorder . T he common matter shared by groups of inventions and species listed above is not novel, does not make contribution over the prior art and therefore cannot be considered as "special technical features” . As such, t he requirement is still deemed proper and therefore made FINAL. Claim 46 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Instant specification (See page 3) disclosed the elected 7,8-dihydroxyflavone (7,8-DHF) as Tropomyosin Receptor Kinase (TRK) agonist . As such, c laims 27-45 are considered as read on the elected invention/species. Status of Claims Claims 24-46 are pending and under examination in this office action . Claim 46 is withdrawn . Claims 27-45 are currently under examination in this office action . Priority This application 18/034,960 filed on is a 371 of PCT/EP2021/083195 filed on 11/26/2021 , and claims priority of foreign Application No. EP 20306455.5 filed on 11/26/2020 . Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of foreign Application No. EP 20306455.5 in English is filed on 05/02/2023 . Information Disclosure Statement The information disclosure statement (IDS) dated 08/24/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner . However, t he copy for non-patent literature , Cederroth (2018), Liu(2019), Meltser (2014), and M urillo- C uesta (2010) are NOT legible. Applicant is required to provide a legible copy for non-patent literatures . Claim Objections Claim 41 is objected to because of the following informalities. The semicolon between different inner ear disorder in claim 41 should be comma. Claim Rejections - 35 USC § 112 / Improper Markush Grouping Claims 27- 31 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch , 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi , 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117. The Markush grouping of “ active agent ” is improper because the alternatives defined by the Markush grouping do not share a single structural similarity and /or a common use for the following reasons: Claim 27 does not specify what ‘ active agent ” could be used for treating inner ear disorders. C laim 28 recite s the active agent s elected from the group consisting of repair agents , ionic channels antagonists, glutamate receptors antagonists, dopamine agonists or precursors , psychotropic drugs, antioxidant compounds, myorelaxant agents, vasodilators, diuretic compounds, other agents blocking signal transmission , nutritional supplements , anti-edema compounds, and a mixture thereof. It’s noted the alternative active agent s recited in claim 28 are directed to subgenus of agents that do NOT share structural similarity and there is NO common use for the recited alternative active agent s on the record . For example, d opamine agonists or precursors are used for treating neurological /neurodegenerative disorders, e.g. Parkinson’s. T here is nothing common between nutritional supplements and repair agents, psychotropic drugs , dopamine agonists or precursors , etc. Claims 29 and 30 are also directed to subgenus of agents that do NOT share structural similarity and there is NO common use for the recited alternative active agent s on the record. Claim 31 recite specific active agent s from different recognized class . However, the active agent s species lidocaine, amitriptyline and cannabidiol ( psychotropic drugs ), dextromethorphan ( glutamate receptor antagonist ), levodopa (L- DOPA), pramipexole, and ropinirole ( dopamine agonists or precursors ), 7,8-dihydroxyflavone (7,8-DHF) and neurotrophin-3 (NT3) ( repair agents ) , etc. belong to different reco gnized class , have different chemical structures, different physical properties and different mechanism of action. To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. Claim Rejections - 35 USC § 112 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. Claims 27-45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for treating certain inner ear disorder (e.g. ear infection, hearing loss , etc. ) with certain active agent (e.g. dextromethorphan, 7,8-dihydroxyflavone DHF , etc. ) in light of prior art, does not reasonably provide enablement for treating any inner ear disorder with any instantly claimed vast variety of active agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright , 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation" would have been needed to practice the claimed invention in full scope is not a single, simple factual determination. As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands , 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons: The Breadth of The Claims/ Nature of The Invention Instant claim 27 recites a method for the treatment of an inner ear disorder in a subject in need thereof , wherein said pharmaceutical composition comprises: at least one active agent ; and a pharmaceutically acceptable vehicle comprising: at least one solubilizing agent selected from the group consisting of vegetable oils, oil/water serum bases, glycerine, alcohols, and a mixture thereof, and at least one diffusing agent selected from the group consisting of terpenes and derivatives thereof. The scope of “ active agent s” in claim 27 is extremely broad. Although claim 28 further recite the active agent s elected from the group consisting of repair agents , ionic channels antagonists, glutamate receptors antagonists, dopamine agonists or precursors , psychotropic drugs, antioxidant compounds , myorelaxant agents, vasodilators, diuretic compounds, other agents blocking signal transmission , nutritional supplements , anti-edema compounds, and a mixture thereof. However, each subgenus class comprises vast variety of active agent s having different chemical structure, different physical properties and different pharmaceutical activities , for example, the nutritional supplements and antioxidant compounds are extremely broad . As disclosed by instant specification (See page 4, lines 1-14) and recited in instant claim 41, inner ear disorder are directed to variety of disorder/conditions having different etiology, symptoms, different treatment mechanism and targeted outcome , for example, tinnitus, hearing loss, etc. For example, Ménière's disease is a disorder of the inner ear wherein fluid buildup causes severe dizziness (vertigo), ringing in the ears (tinnitus), hearing loss, and a feeling of fullness, which is different from ear infection or ototoxicity. The nature of the invention is method of treating a variety of inner ear disorders with vast variety of active agents. The scope of instant claims are extremely broad compared with instantly disclosed working examples that are only directed to pharmacokinetic study of pharmaceutical compositions comprising 11 “ active agents ” without efficacy data of treating inner ear disorders. The State of the Prior Art and the Predictability or Lack Thereof in the Art Instant claims are directed to a method of treating inner ear disorder with variety of active agent s having different structures, different properties and different mechanism of action, wherein different inner ear disorder has different etiology, symptoms, different treatment mechanism and targeted outcome, etc. The efficacies of treating inner ear disorder vary greatly due to a lot factors including the structures/ physical properties of the agents , mechanism of action, delivery route, dosage regimen, etc. Activity by in-vitro experiment does not necessarily translate into efficacy in animals and/or humans. Szeto ( 20 20 ) reviews the challenge of inner ear drug delivery for treating inner ear and states: “ Despite the assortment of treatment options, current approaches have been associated with inconsistent efficacy and safety. Systemic therapy—often the first-line approach for treating sudden sensorineural hearing loss and Ménière's disease—is noninvasive, but it is also linked to subtherapeutic inner ear drug concentrations and adverse effects ” (See Introduction). Szeto further explains c hallenges with systemic delivery stem primarily from the blood-labyrinth barrier (BLB), whereas challenges with local delivery (e . g . intratympanic injection) result from barriers such as the round window membrane (RWM), the oval window and stapes, and the loss of intratympanic drug solution through the eustachian tube ( See Introduction, Figure 1). With respect to treatment for the elected t innitus as recited in instant claim 42-44. McFerran (2019) reviews treatment options for tinnitus and states “ there are few treatment options and those that are available are aimed at reducing the impact rather than specifically addressing the tinnitus percept. In particular, there is no drug recommended specifically for the management of tinnitus. Whilst some of the currently available interventions are effective at improving quality of life and reducing tinnitus-associated psychological distress, most show little if any effect on the primary symptom of subjective tinnitus loudness ”(See page 2, Introduction). Regarding the elected species dihydroxyflavone, a selective tropomyosin receptor kinase B (TrkB) agonist for treating tinnitus, McFerran (2019) states “ By experimentally activating tropomyosin receptor kinase type B (TrkB) using a selective agonist, 7,8-dihydroxyflavone (DHF), the mice could be protected against nocturnally induced hearing loss; DHF made no difference to the temporary hearing loss produced by diurnal noise exposure. The relevance of these findings to humans, to tinnitus and to human drug administration remains to be established ” (See page 802, right column, 2nd para). Cederroth (2018 , Applicant’s IDS dated 08/24/2023 ) reviews emerging drugs for tinnitus (See whole article). Cederroth (2018) states “I n spite of the high clinical demand, attempts to treat tinnitus by various means have failed … Currently no drug is approved for the treatment of tinnitus by the FDA or the EMA ” (See page 251, Existing treatment) and “ I n spite of huge advances in pathophysiologic knowledge and research methodology in the last decades, pharmaceutical research in tinnitus still represents a high-risk field. Important research directions include the identification of potential therapeutic targets and the development of objective outcome measurements to facilitate translational research ” (See Expert Opinion , Conclusion ) . Regarding the elected species dihydroxyflavone, a selective tropomyosin receptor kinase B (TrkB) agonist for treating tinnitus, Cederroth (2018) teaches systemic treatment of dihydroxyflavone protected from noise trauma at nighttime but not at daytime , which might not correlate with treatment of humans in day time( See page 256, left column, last para). More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity (e.g., cancer prevention) is generally considered an unpredictable factor. See In re Fisher , 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The Amount of Direction Present and Presence or Absence of Working Examples The specification does not provide sufficient guidance/protocols for a skilled artisan to practice the claimed method of treating vast variety of inner ear disorders that have different etiology/mechanisms, symptoms/signs, etc. with any instantly claimed “ active agent ” , e.g. any repair agent, any ionic channels antagonist, any glutamate receptors antagonist , dopamine agonists or precursors, psychotropic drug, antioxidant compound, myorelaxant agent, vasodilato r , diuretic compounds, other agents blocking signal transmission, nutritional supplements, anti-edema compounds, and a mixture thereof. Instant specification disclosed formulation comprising different active agent s (e.g. lidocaine , 7, 8-dihydroxyflavone, etc. ), pharmacokinetics study of different active agents ( See Examples 1-3, Table 7) . Instant specification disclosed composition of active agent s comprising solubilizing agent could be delivered to inner ear/perilymph after administration onto the tympanic membrane of subject . Instant specification does not disclose how the treatment outcome of treating inner ear disorder, e.g. tinnitus and other inner ear disorders are measured after the “ active agent ” was administered and does not disclose the efficacy of the active agent s for the treatment of any inner ear disorder. Please note the presence of active agent in the inner ear does NOT mean the active agent is effective for treating the alleged inner ear disorder. It’s also noted the subject of assay is HEALTHY subject(See bridging page 40 and 41 , Selection of Animals) . In absence of any efficacy data to support the alleged method of treating inner ear disorder in a subject suffering inner ear disorder with any active agent , an ordinary skilled in the art would not know if any instantly claimed “ active agent ” , e.g. nutritional supplement, antioxidant , etc. , could be enabled for treating any of the instantly claimed inner ear disorder, e.g. tinnitus i n a subject in need thereof . The level of one of ordinary skill in the art The level of skill required to make and/or use the instant invention would likely require many years of professional experience conducting research in the art (e.g., medicine, pharmaceutical science, biology, biochemistry, etc.) as well as an advanced educational degree (e.g., M.D. and/or Ph.D.) commensurate in level with the advanced techniques involved in the preparation and/or use of the instant invention. The quantity of experimentation needed An unduly extensive amount of experimentation would be required for one of ordinary skill in the art to develop protocols for the claimed method of treating vast variety of inner ear disorders that have different etiology/mechanisms, symptoms/signs, etc. with any instantly claimed “ active agent ” . Working examples would be needed to determine the therapeutically effective dose for different type of inner ear disorder with different active agent . The therapeutically effective amount may vary depending on many factors, such as the structure, property(chemical, physical, toxicological, etc.), mechanism of action, efficacy of the agent , subjects being treated, the disease condition and intended treatment income , etc. T he specific dosage may vary depending on the compound selected, the dosing regimen to be followed , administration route, the toxicological profile, etc. Therefore, it would be a great burden for one of ordinary skill in the art to carry out undue experimentation to use the claimed invention for claimed method of t reating a variety of i nner ear disorder s with vast variety of agents, in full scope . Conclusion MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright , 999 F.2d 1557,1562,27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here with respect to the claimed method of t reating variety of inner ear disorders with vast variety of improper Markush group of “ active agent ” , in view of the analysis above pursuant to In re Wands . In other words, one skilled in the art could not practice the claimed invention without undue experimentation. 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. Claim 27- 30, 32-42 and 44 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. Instant claim 27 recites a method for the treatment of an inner ear disorder in a subject in need thereof; wherein the method comprises a step of administration of a therapeutically effective dose of a pharmaceutical composition into the ear canal or onto the tympanic membrane of the subject; and wherein said pharmaceutical composition comprises: at least one active agent ; and a pharmaceutically acceptable vehicle comprising: at least one solubilizing agent selected from the group consisting of vegetable oils, oil/water serum bases, glycerine, alcohols, and a mixture thereof , and at least one diffusing agent selected from the group consisting of terpenes and derivatives thereof. Although claim 28 further recite the active agent s elected from the group consisting of repair agents , ionic channels antagonists, glutamate receptors antagonists, dopamine agonists or precursors , psychotropic drugs, antioxidant compounds, myorelaxant agents, vasodilators, diuretic compounds, other agents blocking signal transmission , nutritional supplements , anti-edema compounds, and a mixture thereof. However, the term “ active agent ” , “repair agent” , “other agents blocking signal transmission” are vague and indefinite. The “repair agent” is not commonly used term for pharmaceutical active agent s. Instant specification(See page 10, line 21-) defines “ Repair agents are agents that are able to at least partially repair or restore the structure and/or functionality of body elements, especially ear elements, which dysfunction or alteration may contribute to at least one ear or neurological disease, such as cells, in particular ciliated cells, nerves, synapses and/or myelin. Repair agents may be selected from the group consisting of growth factors, such as neurotrophin-3 (NT3)… gene therapy agents , such as Atohl;p271P1 inhibitors; stem cells regenerating agents such as lithium, valproic acid or a salt thereof, for instance sodium valproate (Depakine®); and any mixture thereof ” . However, the “repair agents” defined by the function of repair ing or restor ing the structure and/or functionality of body elements might encompass other agents that are not disclosed by instant specification and/or not known. As such , the scope of “repair agent” is indefinite. Further, the term “other agents blocking signal transmission” also renders claim 28 indefinite, I t ’s not clear what signal transmission is blocked by instantly recited “ other agents blocking signal transmission ” ? The limitation of “ nutritional supplements ” as active agent s is also indefinite. It’s not clear what nutritional supplements could be considered as active agent s for method of treating inner ear disorder. The “growth factors” recited in claims 30 and 44 as active agents is also indefinite. It’s not clear what growth factors are considered as active agents for method of treating inner ear disorder. An ordinary skilled in the art would not be appraised of the scope of active agent that are directed to vast variety of improper Markush groups , e.g. repair agents, other agents blocking signal transmission , nutritional supplements , etc. that do not share structural similarity and/or a common use. The limitation “terpenes and derivatives ” also renders the scope of claim 27 indefinite , since terpenes derivatives include compounds that have different functional groups/different structures and different properties, including compounds which are structurally remote from terpenes , etc. Dependent claims 28-30, 32-42 and 44 are rejected due to dependency on claim 27. Claim 41 recites variety of inner ear disorder selected from the group consisting of otosclerosis; non-obliterative and obliterative otosclerosis involving oval window; cochlear otosclerosis ; acoustic neuroma; bilateral and unilateral sensorineural hearing loss; noise-induced hearing loss; aged-induced hearing loss; bilateral and unilateral conductive hearing loss; bilateral and unilateral mixed conductive and sensorineural hearing loss; sudden idiopathic hearing loss; drug-induced hearing loss; single sided deafness; ear infection; ototoxicity; drug-induced ototoxicity ; herpes zoster oticus; labyrinthitis; purulent labyrinthitis ; labyrinthine fistula; Labyrinthine dysfunction; vestibular neuronitis; excitotoxicity; autoimmune inner ear disease; acute unilateral vestibulopathy; vestibular neuronitis; benign paroxysmal positional vertigo; vertigo of central origin; Meniere's disease; Meniere's syndrome; and tinnitus. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 41 recites the broad recitation otosclerosis , and the claim also recites non-obliterative and obliterative otosclerosis involving oval window; cochlear otosclerosis that are the narrower statement of the range/limitation. C laim 41 recites the broad recitation ototoxicity and also recites drug-induced ototoxicity which is the narrower statement of the range/limitation. Labyrinthitis is the broad recitation while purulent labyrinthitis is the narrower statement of the limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. 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. (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 27-29, 32 and 36-38 are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) and (a)(2) as being anticipated by Yoshpe et al. (US 8758836 B2, Applicant’s IDS dated 08/24/2023). Yoshpe teaches a method of treating diseases and conditions associated with inflammation of the inner ear of a mammal, comprising applying to the ear canal of said mammal, a pharmaceutical composition comprising anti-inflammatory, anti-irritant , active agent ( hydrocortisone , also anti-edema ) and polyhydroxy solvent (See abstract ; Col 1. lines 10-15; claims 1-14). Regarding the solubilizing agent, Yoshp teaches polyhydroxy liquid solvent further comprises a lipid and glycol lubricating hydrophilic base formulation including combinations of glyco l, glycerin , s ugar alcohols (See claim s 7 and 14) . Yoshpe teaches composition embodiments comprising at least one active agent (hydrocortisone), 1,3-butylene glycol (solubilizing agent) and alpha-bisabolol (terpene and derivatives as diffusing agent ) (See Col. 8, lines 15-30; Col. 9, lines 1-18 ; Example ). Regarding claim 32 and 36-37 , Yoshpe teaches concentration of active agent (hydrocortisone) at 0.2375% to about 0.2625% by weight (See Col. 7, lines 40-42) and variety of embodiments comprising 0.25% of hydrocortisone and alpha- b isabolol (See Col 8, lines 9, 32). Regarding claim 38, Yoshpe teaches the ear drop formulation ( See Col. 5, lines 11, 58, 61) and the ear drop is applied to the ear canal of the human(See claim 13). Yoshpe collectively teaches a method of treating diseases and conditions associated with inflammation of the inner ear of a mammal, comprising applying to the ear canal of said mammal, a pharmaceutical composition comprising anti-inflammatory, anti-irritant active agent ( hydrocortisone) , at least one solubilizing agent ( 3-butylene glycol ) and at least one diffusing agent selected from terpene and derivatives , e.g. alpha-bisabolol . Thus, Yoshpe anticipates instantly claimed invention. Claim s 27 , 32 -33 , 3 5 - 39 and 41 are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) and (a)(2) as being anticipated by Simons et al. ( US 8,822,410 B2 ) . Simons teaches a method of treating ear disease (e.g. ear infections, otosclerosis, vertigo, Meniere's disease , etc.) comprising administering composition comprising active agent and penetration enhancer across tympanic membrane (See abstract, Col. 2, lines 55-65; Col. 14, lines 49-65 ; Examples 1-4 ; claim 11 ). Regarding the active agent, Simons teaches therapeutic agent can be any agent used to treat ear disease, or symptom of an ear disease , e.g. antibiotics (e.g. ciprofloxacin , etc.) , anesthetics (e.g. lidocaine, bupivacaine, etc.) , anti-inflammatory, anti-fibrotic, anti- s clerotics, anticoagulants, etc. ( See Col. 12, line 21-25; Col. 13, line s 1-55; Examples 1-4 ) . Simons teaches various concentration of the active agent, e.g. between about 0.01 to about 10 percent , between about 0.01 to about 1 percent of the composition of the composition , etc.(See Col. 12, line 25-40)(which also reads on instant claim 32). Regarding the administration route/step, Simons teaches applying the composition into a s ubject’s ear canal or on the surface of the tympanic membrane wherein the therapeutic agent penetrates the tympanic membrane for treating inner ear disease (See Col. 14, lines 47-65; Col. 15, lines 11-27, Examples 1). Regarding the inner ear disorder limitation, Simons teaches methods can be used to treat ear diseases, e.g. ear infections, otosclerosis , vertigo, Meniere's disease , mastoiditis, labryrinthitis, etc. (See Col. lines 55-59). Regarding the solubilizing agent, Simons teaches dosage form comprising active compounds and commonly excipients used in the ar t , e.g. water or other s olvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol , ethyl carbonate, ethyl acetate, benzyl alcohol , benzyl benzoate, propylene glycol. 1,3-butylene glycol, dimethylformamide, oils (in particular, cotton seed, groundnut, corn, germ, olive, castor, and sesame oils ), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof … solubilizing agents s uch an Cremophor, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and combinations thereof (See Col. 14, lines 15-30) (which also reads on instant claims 33 and 35). Simons also teaches alcohol as penetration enhancers methanol, ethanol, propanol, isopropanol, butanol, isobutyl alcohol, etc. (See Col. 10,lines 65-67). Regarding the diffusing agent, Simons teaches pharmaceutical composition comprising penetration enhancer (e.g., a surfactant, terpene ) , wherein t he penetration enhancer that alters the stratum corneum of the tympanic membrane to increase the flux of the therapeutic agent across the tympanic membrane and facilitates delivery of the therapeutic agent into the middle and/or inner ear (See abstract, Col. 7, lines 37-44 ). Simons teaches variety of t erpene penetration enhancers e.g. limonene, cymene, pinene, camphor, menthol, comphone, phellandrine, Sabinene, terpinene, borneol, cineole, geraniol, linalol, pipertone, terpineol, eugenol, eugenolacetate, Safrole, benzyl benzoate, humulene, beta-caryophylene, eucakytol, etc or terpenoid (See Col.10, lines 50-64)(which also read on claims 36 and 37) . Regarding claim 38, Simons teaches tympanic membrane permeating ear drops(See title, Example 4). Simons collectively teaches a method of treating ear disease (e.g. ear infections, otosclerosis, vertigo, Meniere's disease , etc.) comprising administering composition comprising active agent ( ciprofloxacin, bupivacaine, etc.), solubilizing agent (alcohol, vegetable oils, etc.), and penetration enhancer ( terpene and derivatives , e.g. limonene , linalool, etc . ) across tympanic membrane . Thus, Simons anticipates instantly claimed invention. Claim s 27 - 2 9, 31, 33 and 38 are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) as being anticipated by Liu et al. ( CN111568950A , Applicant’s IDS dated 08/24/2023). Liu teaches cannabidiol ear drops comprising solubilizing agent ( glycerin , propylene glycol , etc.) for treating otitis in pet (See abstract, [0006]). Liu teaches otitis media is mostly an inflammation of the tympanic mucosa caused by the spread of infection of the ear canal and otitis in pets refers to inflammation of the inner ear(See [0003]). L iu teaches embodiments comprising 0.05-0.5 parts of cannabidiol (CBD), 15-40 parts of medical glycerin, 25-50 parts of medical propylene glycol, and 0.1-1 parts of tea tree essential oil, 0.1 to 1 part of camphor essential oil, 0.01 to 0.2 part of pyrethrin, 0.2 to 0.5 part of borneol, 0.1 to 0.3 part of benzalkonium chloride, 15 to 30 parts of purified water (See abstract, [0008], claim 1). L iu teaches pet clinical trial wherein the cannabidiol ear drop was administered to a subject diagnosed with otitis media and cannabidiol ear drop has good cure rate and effect (See [0058]-[0067]). Liu collectively teaches a method of treating otitis comprising administering a composition comprising active agent (CBD), solubilizing agent (glycerin, propylene glycol ) and terpene and derivative (borneol). As such, L iu anticipates instantly claimed invention. 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. 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 27 - 31, 3 3 , 35-3 9 , 41-42 and 44-45 are rejected under 35 U.S.C. 103 as unpatentable over Meltser et al. ( Current Biology, February 27, 2014, Vol. 24, No. 6, pages 658-663 , Applicant’s IDS dated 08/24/2023, "TrkB-Mediated Protection Against Circadian Sensitivity to Noise Trauma in the Murine Cochlea" ), in view of Simons et al. ( US 8,822,410 B2) and Yoshpe et al. (US 8758836 B2, Applicant’s IDS dated 08/24/2023). Meltser teaches a dministration of selective BDNF receptor, tropomyosin related kinase type B (TrkB), protected the inner hair cell’s synaptic ribbons and subsequent full recovery of hearing thresholds . Meltser teaches TrkB a ctivation p rotects from n oise-induced hearing loss (NIHL) wherein TrkB antagonist (e.g. 7,8-dihydroxyflavone ) boosted the amplitude of circadian rhythms in the isolated cochlea (See Summary, whole article). Meltser explicitly teaches evaluation of 7,8-dihydroxyflavone (DHF) wherein DHF modulates PER2 oscillations in the cochlea via TrkB and preserves cochlear synaptic integrity after noise overexposure (See page 660; Figure 2 and 3) . Meltser also teaches l ocal delivery of DHF in the ear has been shown to rescue auditory neuronal loss and function in a mouse model of auditory neuropathy (cCx26 null mice) and suggested DHF may (1) protect immediately, presumably by decreasing glutamate release during noise overexposure and subsequent excitotoxicity, (2) act on the recovery processes after noise overexposure by facilitating synaptogenesis (See page 661). Meltser is silent about the solubilizing agent and terpen diffusing agent. The collective teachings of Simons and Yoshpe are elaborated in preceding 102 rejection and applied as before. The collective teachings of as elaborated in preceding 102 rejection are applied as before . Simons collectively teaches a method of treating ear disease comprising administering composition comprising active agent , solubilizing agent (alcohol, vegetable oils, etc.) and penetration enhancer (terpene and derivatives, e.g. limonene, linalool, etc.) across tympanic membrane. Simons teaches tympanic membrane permeating ear drops. Please note the bisabolol is considered as functional equivalent of limonene , linalool and other terpene taught by Simons as diffusing agent in absence of evidence to the contrary. The apricot oil recited in claim 34 is considered as functional equivalent of sesame oil, and other vegetable oil as solubilizing agent taught by Simons. Yoshpe collectively teach es an otic pharmaceutical composition comprising active agent , at least one solubilizing agent (3-butylene glycol ) and at least one diffusing agent selected from terpene and derivatives e.g. alpha-bisabolol. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of instantly claimed invention, to formulate TrkB antagonist (e.g. 7,8-dihydroxyflavone) taught by Meltser with solubilizing agent and terpene taught by Simons and Yoshpe , together with experimentation/optimization based on general knowledge of pharmaceutical composition for treating ear disease/disorder . A skilled artisan would reasonably expect the pharmaceutical composition comprising active agent (e.g. TrkB or TrkC agonist , 7,8-dihydroxyflavone (DHF) , solubilizing agent (alcohol, vegetable oils, etc.) and terpene ( limonene, linalool, alpha-bisabolol) would provide a method for treating inner ear disorder (e.g. hearing loss) with enhanced penetration /delivery of active agent (e.g. TrkB or TrkC agonist). Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Claims 27-31, 33, 35 -39, 41-42 and 44-45 are rejected under 35 U.S.C. 103 as unpatentable over Kujawa et al. (WO 2017120465 A1, Applicant’s IDS dated 08/24/2023) in view of Simons et al. ( US 8,822,410 B2 ) . Kujawa teaches a method of treating or reducing the risk of developing hidden hearing loss by administering a small molecule Trk agonists (e.g., 7, 8-dihydroxyflavone (DHF), amitriptyline, imipramine, , 7,8,3'-Trihydroxyflavone (THF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4) (See abstract, page 2, lines 30-34; page 3, lines 1-32; page 11, lines 29-33; Examples1-4; Figures 1-6; claims 1-14). Regarding the solubilizing agent, Kujawa teaches pharmaceutically acceptable carrier , e.g. oils, polyethylene glycols, glycerine, propylene glycol , benzyl alcohol (See page 12, lines 15-22). Kujawa is silent about the terpene as diffusing agent. The collective teachings of Simons as elaborated in preceding 102 rejection are applied as before . Simons collectively teaches a method of treating ear disease comprising administering composition comprising active agent , solubilizing agent (alcohol, vegetable oils, etc.) and penetration enhancer (terpene and derivatives, e.g. limonene , linalool, etc. ) across tympanic membrane. Simons teaches tympanic membrane permeating ear drops. It would have been prima facie obvious to one of ordinary skill ed in the art before the effective filing date of instantly claimed invention to incorporate the terpene penetration enhancer taught by Simmons into Kujawa ’s composition comprising TrkB or TrkC agonist for treating inner ear disorder (e.g. tinnitus, hearing loss ), together with experimentation/optimization based on general knowledge of pharmaceutical composition for treating ear disease/disorder, and arrive at the instant invention with reasonable expectation of success . A skilled artisan would be motivated to combine the teachings of Kujawa and Simons because both teachings are directed to treating ear disease and Simons teaches penetration enhancer across tympanic membrane . The combined teaching of prior art, together with experimentation/optimization based on general knowledge of pharmaceutical composition for treating ear disease/disorder, would provide a method for treating inner ear disorder (e.g. hearing loss ) with enhanced penetration /delivery of active agent (e.g. TrkB or TrkC agonist ). One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of pharmaceutical composition for treating ear disease(e.g. inner ear disorder, etc.) . Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Claims 27-45 are rejected under 35 U.S.C. 103 as unpatentable over Saragovi et al. ( US 2017/0029511 A1 ), in view of Simons et al. ( US 8,822,410 B2 ) . Saragovi teaches a method for treating otic diseases or conditions comprising administering an otic composition comprising a therapeutically effective amount of TrkB or TrkC agonist to an individual in need thereof , through direct application of aforementioned compositions onto or via perfusion into the targeted auris structure( See abstract, [0005], [0059], Examples 1-11, claims 1, 7, 16-23). Regarding the active agent recited in claims 27-31 and 43-45 , Saragovi teaches TrkB or TrkC agonist selected from a group consisting of 7.8-dihydroxy flavone , 7.8.3'-Trihydroxyflavone … N-acetylserotonin, and a mitryptiline (See [0021] ,[0042], [0177] ). Saragovi also teaches embodiments wherein the TrkB or TrkC agonist is a chemically modified analog of a neurotrophic agent, wherein the neurotrophic agent is brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF), neurotrophin-3 , neurotrophin-4, fibrobla st growth factor(FGF)(See [0023] , [0157] ). Regarding the inner ear disorder recited in claims 41-44, Saragovi teaches the otic disease is ototoxicity, chemotherapy induced hearing loss, excitotoxicity, sensorineural hearing loss, noise induced hearing loss, Meniere's Disease/Syndrome, labyrinthitis, Ramsay Hunt's Syndrome, a ge-related hearing loss (presbycusis) , vestibular neuronitis, tinnitus , etc. (See [0059] -[0061] , [0115] -[0149] , Examples 3-9 ). Saragovi teaches embodiments wherein a TrkB or TrkC agonist reduces or inhibits auris sensory cell damage and/or death associated with tinnitus , and other treatmen t options for tinnitus , e.g. l idocaine, selective neurotransmitter reuptake inhibitors , b en z odiazepines , etc. ( See [0122]). Regarding the administration limitation recited in claim 27 and 39, Saragovi teaches i ntratympanic injecting a therapeutic agent behind the tympanic membrane into the middle and/or inner ear. Saragovi teaches embodiment wherein TrkB or TrkC agonist formulations are administered directly onto the round window membrane via transtympanic injection and another embodiment, the TrkB or TrkC agonist auris-acceptable formulations are administered onto the round window membrane via a non-transtympanic approach to the inner ear (See [0416]) . Saragovi also teaches delivery system (e.g. syringe and needle apparatus ) that is capable of piercing the tympanic membrane and directly accessing the round window m embrane( See [0417]-[0419]) . Saragovi explicitly teaches embodiments wherein the pharmacokinetic profile of active agent (e.g. BDNF and NT3) is evaluated/ measured after intratympanic injection (See [0052], Example 3, FIG. 2A and FIG. 2B ) . Regarding the solubilizing agent, Saragovi teaches commonly used solvents/carrier for administration to the ear, e.g. alcohols, p ropylene glycol, etc.(See [0064], [0358] ). Saragovi teaches solubilizer that a ssist or increase the solubility of the TrkB or TrkC agonist s, e.g. ethanol, n-butanol, isopropyl alcohol, polyethylene glycol, glycofurol, transcutol, propylene glycol and the like(See [0097]) (which also reads on instant claim 35). Saragovi also teaches auris-acceptable s urfactants , e.g. p olyoxyethylene fatty acid glycerides , vegetable oils , e.g., polyoxyethylene (60) hydrogenated castor oil; . (See [0387], [0389]) (which reads on castor oil recited in claim 33). . Saragovi teaches embodiments of lipid nano capsules comprising emulsifying capric and caprylic acid triglycerides (See [0369])(which reads on MCT recited in claim 33). Please note the apricot oil recited in claim 34 is considered as functional equivalent of castor oil and other vegetable oil as solubilizing agent in absence of evidence to the contrary. Regarding the diffusing agent, Saragovi teaches r ound w indow m embrane p enetration e nhancers , e.g. s urfactants, Tween 80 , fatty acids and derivatives , etc. alcohols (ethanol, isopropanol, glycerol, propanediol and the like) also function as round window membrane penetration enhancers