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 Application
Receipt of Applicants’ Remarks is acknowledged.
Claims 1, 4, and 6-20 are pending.
Claims (9,10 withdrawn-amended), and claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 2-3 and 5 are cancelled.
Claims 1, 7, and 8 are amended.
Claims 1, 4, 6-8, and 11-18 are pending and under examination in this application.
New Rejections Necessitated by Amendments
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.
Claims 1, 4, 6, 7, 8, and 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Tamarkin (WO 2011/039637 A2) in view Bös (WO 2018/158256 A2), Foster et al. (US2019/0374606 A1) hereinafter the reference is referred as Foster, and further in view of Mattern (US 20180296472 A1).
Tamarkin teaches oleaginous foamable formulations and foams and uses comprising hydrophobic solvents with active agent, and surprisingly, the formulations and foam are without surfactants; and/or without surfactants and polymeric agents, and in further application, in semi solid gel compositions what liquefy on application of mild shear force such as gentle rubbing (¶ 0008). In one or more embodiments the active pharmaceutical ingredients are formulated for use on sensitive target areas such as sensitive or damaged skin areas, wounds, bums, mucosal membranes, and body cavities (¶ 0017).
Regarding claims 1, 7 and 8, Tamarkin explicitly teaches pharmaceutical compositions with hydrophobic solvents (a) without surfactants; and/or (b) without polymeric agents and/or (c) without water (¶ 0010), and explicitly disclose that the formulations are substantially polymer free (¶ 0201) in the hydrophobic solvent “gel” or “semi-solid” composition (¶ 0062). Moreover, Tamarkin explicitly teaches the foamable composition is suitable for administration to various body areas, including a body cavity, e.g., the ear as the target site (¶ 0073), can be applied to a wide range of body cavities, including aural (¶ 0234), and waterless (¶ 0074) and substantially non-aqueous (¶ 0076), and a safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions of the subject invention, preferably from about 0.1% to about 10%, more preferably from about 1 % to about 5%, of the composition (¶ 0163). Notably, Tamarkin discloses whether delivered as a foam, gel, ointment or suspension the active pharmaceutical tetracycline can be present by weight in the range of about 0.2% to about 20%, or at about 0.2%, at about 0.3%, at about 0.4%, at about 0.5%, at about 0.6%, at about 0.7%, at about 0.8%, at about 0.9%, at about 1 %, at about 1.5%, at about 2%, at about 2.5%, at about 3%, at about 3.5% at about 4%, at about 4.5%, at about 5%, at about 6%,at about 7%, at about 8%, at about 9%, at about 10%, at about 12%, or at about 14%, at about 16%, at about 18%, or at about 20% (¶ 0235). Therefore, the limitations in the amended claims to require polymer free and active agent present is the amount from 0.05 % to about 10 % by weight, based on the total weight of the composition are explicitly taught.
Bös teaches novel compounds which are useful as potassium channel openers directed to the Kv7.4 potassium channel, wherein the novel compounds are compounds according to formula (I), wherein-n = 0 or I, -RL is a substituent selected from the group consisting of unsubstituted or substituted cycloalkyl groups, in particular bicycloalkyl groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted thienyl groups or cyclopentathienyl groups, and unsubstituted or substituted indanyl groups, which optionally contain heteroatoms, and - RR is a substituent selected from the group consisting of unsubstituted or substituted phenyl groups or unsubstituted or substituted benzyl groups, which optionally contain heteroatoms, - or a stereoisomer, a tautomer, a pro drug or a salt, preferably pharmaceutically acceptable salt thereof (abstract). Notably, Bös discloses that the potassium channel openers of the Kv7.4 potassium channel relates to highly expressed in sensory outer hair cells (OHCs) in the organ of Corti, suggests that Kv.7.4 is a promising target for the prophylaxis and the treatment of hearing loss (page 1, lines 21-26), and the general formula (I) is
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and compound ACOU001
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(page 16, line 27).
Regarding claims 1, 4, 6, 7, 8,15, and 16, as noted above, Bös teaches transtympanic administration (page 11, lines 19-20) of formula (I), comprising active ingredient (1 R,2 R,4S )-rel-N-(3-(pentafluorosulfanyl)benzyl)bicyclo[2 .2.1 ]heptane-2-carboxamide (page 17, line 30; claim 13); and (1 S,2S,4R)-N-(3-(pentafluorosulfanyl) benzyl)bicyclo[2.2.1 ]heptane-2-carboxamide (page 18, top of page; claim 13). Therefore, the API is explicitly taught and the feature of solubility in water at room temperature of < 1 mg/mL would reasonably exist due to the same pharmaceutically active agent. Furthermore, the feature of the API having mean particle size of 5 to 80 µm would also be reasonably exist because of the intended target of administration into the inner ear. Therefore, the structural features of at least one pharmaceutically active agent is explicitly taught.
Regarding claim 13, Bös teaches in the treatment of an inner ear hearing loss after damage or loss of sensory hair cells in an organ of Corti, the dosage can be related to the "number of inner ears treated" and/or to the "number of administration", and the reason is, that a repeated administration of the compound/pharmaceutical composition over a time period, e.g., between a number of days and a number of weeks/months, preferably at intervals of some days (1 to 7 days), is appropriate, and in these cases, the amount of active compound employed, preferably directly to the
Cochlea, e.g., via infusion, should be in the range of from 0,5 μg to 1.0 mg
per inner ear and administration (page 12, lines 18-25). Therefore, the feature of at least one pharmaceutically active agent is present in an amount from 0.05 – 10% would reasonably exist and taught in the composition.
Bös fails to specifically teach a non-aqueous gel composition comprising castor oil, oleoyl polyoxyl-6 glyceride, colloidal silicon dioxide (thickener), with a viscosity between 2,000 and 10.000 mPas-sec.
Foster teaches compositions and methods for the treatment of otic disease or conditions with a non-natural neurotrophic agent compositions and formulations administered through direct application onto or via perfusion into the targeted auris structure(s) of the ear (abstract).
Regarding claims 1, 7, 8, 11, and 12, Foster teaches an otic pharmaceutic composition comprising a therapeutically active agent and an auris-acceptable vehicle (claim 37) comprising: wherein the active pharmaceutical ingredient comprises a non-natural Trk receptor agonist, with a concentration from about 0.0001% to about 60% of the API by weight of the formulation, from about 1 µg/ml to about 500 µg/ml by volume of the formulation (¶ 0242); and in one embodiment the viscosity is designed to provide a suitable rate of release from an auris compatible gel… the concentration of a thickening agent (e.g., gelling components) (¶ 0243 to ¶ 0247)…allows for a tunable mean dissolution time; and the composition is a non-aqueous media such as … synthetic oils and natural oils and optionally a surfactant added to the continuous phase to prevent the microparticles from agglomerating and to control the size of the solvent microdroplets in the emulsion (¶ 0310). Furthermore, Foster teaches triglycerides comprising medium chain fatty acids and/or long chain fatty acids to include castor oil from about 80 % to about 99.9 % (¶ 0005, ¶ 0371); wherein the pharmaceutically acceptable vehicle is PEG-6 glyceryl mono oleate (Labrafil ® 1944 CS) (¶ 0340) in an amount ranging from about 0.1 % to about 20 %, from about 0.5 % to about 20 % (¶ 0341), (it is noted that Labrafil ® 1944 CS is an oleoyl polyoxy-6-glyceride – Specification, page 7, ¶ 6); wherein the auris-acceptable viscosity agent includes silicon dioxide (¶ 0279), if present, is from about 3% to about 15%, by weight of the composition, wherein silicon dioxide, if present, includes fumed silicon dioxide, precipitated silicon dioxide, coacervated silicon dioxide, gel silicon dioxide, and mixtures thereof (¶ 0297), corresponding to “at least one thickener is colloidal silicon dioxide in an amount from 1% to 6%”; and a viscosity from about 2,000 to about 100,000 centipoise, 3,000 to about 50,000 centipoise (¶ 0528) (equivalent to 2,000 to 100,000 mPas-sec).
Mattern teaches a nasal composition that is non-aqueous or water-free, and the specific form of the nasal composition is not limited (0036). Mattern discloses in some embodiments (Compositions 1-6 of ¶ 0087), a composition comprising silicon dioxide (4%), castor oil (56-92%), oleoyl polyoxyl-6 glyceride (4%) and 0.5-50 % colloidal silicon dioxide (¶ 0087, claim 9), with a viscosity of the composition between 2,000 and 10.000 mPas (¶ 0071).
Regarding claims 1, 11, 12, 17, 18, as noted above, Mattern teaches non-aqueous or water-free composition comprising castor oil, oleoyl polyoxyl-6 glyceride, colloidal silicon dioxide (thickener), with a viscosity between 2,000 and 10.000 mPas-sec. Therefore these limitations are taught and all the ranges overlaps with instant range. Claim 1 is directed to a composition for preventing or treating inner ear diseases and the composition must be suitable for this intended use via transtympanic administration in order for the composition to reach into the inner ear. The claims are limited to the structure implied by the composition, and thus the claim has been met because the composition is a non-aqueous or water-free composition comprising castor oil, oleoyl polyoxyl-6 glyceride, colloidal silicon dioxide (thickener), with a viscosity between 2,000 and 10.000 mPas-sec and an active ingredient. Treating the inner ear disease by administering the non-aqueous composition in need thereof (Withdrawn-currently amended claim 10) is regarded as intended use of the composition and does not impart patentability to the product claim. Therefore, the recitation in the preamble “for transtympanic administration” is considered an intended use because the composition is intended to treat the inner ear disease via transtympanic route of administration and thus renders little patentable weight to a composition claim.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to improve the delivery of the pharmaceutically active agent having the formula (I) of Bös and incorporate the transtympanic administration comprising castor oil, oleoyl polyoxyl-6 glyceride , as least one thickener (silicon dioxide), and with a viscosity between 1400 and 2400 mPas and further incorporate the polymer free with API in the range of 0.05 % to about 10 % by weight as taught by Tamarkin, in view Foster and further in view of Mattern. One would have been motivated to do so because the combined teaching of Tamarkin, Bös, Foster in view of Matter discloses a non-aqueous gel composition for transtympanic administration for the treatment and prophylaxis diseases of the inner ear. Moreover, Bös discloses novel compounds which are useful as potassium channel openers directed to the Kv7.4 potassium channel, which there are existing literature to target for promising target to treat hearing loss.
One of ordinary skill in the art would have been motivated to replace the API Trk receptor agonist of Foster with the novel compound comprising the active ingredient (1 R,2 R,4S )-rel-N-(3-(pentafluorosulfanyl)benzyl)bicyclo[2 .2.1 ]heptane-2-carboxamide or (1 S,2S,4R)-N-(3-(pentafluorosulfanyl) benzyl)bicyclo[2.2.1 ]heptane-2-carboxamide of Bös because both references are drawn to compositions and methods for transtympanic administration to target the inner ear, and thus the combine teachings of the references and its components would render one of ordinary skill in the art to have found it obvious to apply the different methods to formulate and to improve the composition for delivery into the inner ear as taught by Tamarkin, Bös in view of Foster. Mattern is relied upon for the teachings of castor oil, oleoyl polyoxyl-6 glyceride, colloidal silicon dioxide (thickener), with a viscosity between 2,000 and 10.000 mPas. The amended claim 1 to recite polymer free and API in an amount from 0.05 % to 10 % by weight is explicitly taught by Tamarkin and the recitation “for transtympanic administration” is considered an intended use as noted in the rejections above, and thus renders little patentable weight to a composition claim. From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Response to Arguments
Applicant traverse filed 11/07/2025 have been fully considered, however is found not persuasive.
Applicant argues that cited references, alone or in combination, do not teach or suggest the features of amended claim 1 as a whole.
The amended claim 1 now requires the non-aqueous gel composition to contain at least one pharmaceutically active agent is present in an amount from 0.05 % to 10 % by weight, based on the total weight of the composition, and wherein the non-aqueous gel composition is free of polymer and for transtympanic administration.
As noted above in New Rejections Necessitated by Amendments, addition of Tamarkin explicitly teaches API amounts that overlaps instant range of 0.05 % to 10 % by weight explicitly disclose that the formulations are substantially polymer free. Thus, the combined references teach and suggest all the limitations and features of the claimed invention.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615