DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/01/2026 has been entered.
Receipt of Applicants’ Arguments, Remarks and amended claims filed on 04/01/2026 is acknowledged.
Claims 1-4, 6, 7 and 9-19 are pending.
Claims 2, 3, 5 were previously cancelled as filed on 11/07/2025; claims 8, 20 are now cancelled.
Claims 1 and 7 have been amended.
Claims 9, 10 and 19 remains withdrawn per restriction requirement.
Claims 1, 4, 6, 7 and 11-18 are pending and under examination in this application.
Priority
Acknowledgment is made of applicant’s claim for priority under 35 U.S.C. 119 (a)-(d). The current application filed on May 10, 2023 is a 371 of PCT/EP2080108 filed November 19, 2021, which in turn claims priority to patent application EP20208665.8 filed on November 19, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/18/2026, 09/24/2024, 08/07/2024 and 05/10/2023 are in compliance with the provisions of 37 CFR 1.98. Accordingly, the information disclosure statements has been considered by the examiner. Signed copies have been attached to this office action.
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.
Claim 1 is 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.
Amended claim 1 recites (a) “configured to be injectable through a syringe". This phrase is purely functional and does not recite any objective structural or physical property by which a person of ordinary skill in the art can determine the scope of the claim with reasonable certainty (i.e., needle gauge, extrusion force, flow rate). Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 (2014). The claim does not specify needle gauge, extrusion force, flow rate, or any other measurable parameter. A composition that requires a 16-gauge needle and 100 N of force could be considered "injectable," but so could a composition that passes through a 34-gauge needle with 1 N of force. The claim provides no boundary;
(b) the claim further recites "free of polymer". The term is ambiguous because it does not specify: whether it means absolute absence of any polymer molecules (to the limit of detection); Absence of added polymer (allowing trace impurities); or absence of synthetic polymer (allowing natural polymers). Moreover, dependent claims 11 and 12 require "silicon dioxide" as the thickener. Colloidal silicon dioxide (fumed silica) is composed of polymerized silicic acid and is often classified as an inorganic polymer. The claim as written creates internal inconsistency because a composition "free of polymer" could be interpreted to exclude silica, contradicting the dependent claims. Exxon Research & Eng'g Co. v. United States, 265 F.3d 1371 (Fed. Cir. 2001).
Appropriate corrections are required. The Examiner notes that a simple amendment to “free of organic polymer” or “free of synthetic polymer” would not fully resolve the inconsistency unless dependent claims 11 and 12 are also amended to clarify that colloidal silicon dioxide falls outside the intended scope of “polymer” as used in the claim, or unless the specification is amended to provide an explicit definition of “polymer” that excludes inorganic polymerized oxides. Applicant is encouraged to provide a clear definitional statement in the specification or a claim amendment that resolves the ambiguity with reasonable certainty as required under Nautilus.
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) 1, 4, 6, 7 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 and 7, 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 discloses that the formulations are substantially polymer free (¶ 0201) in the hydrophobic solvent “gel” or “semi-solid” composition (¶ 0062). Moreover, Tamarkin explicitly teaches that 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 is waterless (¶ 0074) and substantially non-aqueous (¶ 0076). A safe and effective amount of an anti-oxidant/radical scavenger may be added to the compositions, preferably from about 0.1% to about 10%, more preferably from about 1% to about 5%, of the composition (¶ 0163). 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% (¶ 0235). Therefore, the limitations in the amended claims requiring a polymer-free composition with active agent present in an 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, 7,15, 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.
Regarding claims 13 and 14, 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). Notably, Foster discloses multiple embodiments, including explicitly non-aqueous compositions. The Examiner relies on Foster’s non-aqueous otic gel embodiments, not on Foster’s aqueous or polymer-containing embodiments. A prior art reference may be relied upon for any teaching it discloses, irrespective of whether other embodiments in the same reference differ from the claimed invention. In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012).
Regarding claims 1, 7, 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.
Regarding the limitation that “the non-aqueous gel composition is a thermoreversible gel,” this property is an inherent or predictable consequence of the claimed composition. Castor oil-based non-aqueous gel systems thickened with colloidal silicon dioxide are known in the art to exhibit thermoreversible rheological behavior, wherein viscosity decreases at elevated temperature (37°C, body temperature) relative to room temperature (25°C). This is consistent with the viscosity values recited in claim 1 itself — 1400–2400 mPas at 25°C decreasing to 500–1200 mPas at 37°C — which directly reflects thermoreversible behavior. Mattern explicitly discloses a castor oil/silica/Labrafil composition with a viscosity of 2,000–10,000 mPas (¶ 0071), and Foster similarly discloses temperature-dependent viscosity in non-aqueous otic gels designed to provide a suitable rate of release upon administration to body-temperature tissue (¶¶ 0243–0247). A person of ordinary skill in the art formulating a castor oil/silica gel for administration at body temperature would have recognized and expected thermoreversible behavior as a natural consequence of the composition’s rheological profile. Where a claimed property is an inherent result of following the prior art’s teachings, that property does not confer patentability. In re Dillon, 919 F.2d 688, 693 (Fed. Cir. 1990) (en banc). To the extent applicant contends that thermoreversibility is an unexpected result, applicant bears the burden of providing comparative data demonstrating that this property is not merely the predictable consequence of the known composition. In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984).
Motivation to Combine
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 formula (I) of Bös and incorporate a transtympanic non-aqueous gel composition comprising castor oil, oleoyl polyoxyl-6 glyceride, and at least one thickener (silicon dioxide), with a viscosity between 1400 and 2400 mPas at 25°C and between 500 and 1200 mPas at 37°C, and further to incorporate a polymer-free formulation with API in the range of 0.05% to about 10% by weight, as taught by Tamarkin, Foster, and Mattern. One would have been motivated to do so because the combined teachings of Tamarkin, Bös, Foster, and Mattern disclose a non-aqueous gel composition for transtympanic administration for the treatment and prophylaxis of diseases of the inner ear. Moreover, Bös discloses novel compounds useful as potassium channel openers directed to the Kv7.4 potassium channel, for which existing literature identifies as a promising target for treating 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. The combined 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. 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 recitation of polymer-free composition with 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 rendering little patentable weight to a composition claim.
The narrowed viscosity ranges recited in amended claim 1 (1400–2400 mPas at 25°C; 500–1200 mPas at 37°C) represent routine optimization within the broader ranges taught by Mattern (2,000–10,000 mPas) and Foster (2,000–100,000 mPas). No unexpected results have been demonstrated for this specific sub-range. In re Aller, 220 F.2d 454, 456 (CCPA 1955) (where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art). 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's arguments filed 04/01/2026 have been fully considered but they are not persuasive. Applicant argues:
"Tamarkin teaches away because it is surfactant-free, while claim 1 requires a surfactant (oleoyl polyoxyl-6-glyceride)."
This argument is not persuasive for the following reasons:
First, Tamarkin does not teach away. A reference teaches away only when it "criticizes, discredits, or otherwise discourages" the claimed feature. DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009). Tamarkin discloses that its formulations can be substantially surfactant-free (¶ [0010]), but it does not state that surfactants cannot be used, nor does it criticize their use. Disclosing an alternative embodiment does not constitute teaching away. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) ("A reference does not teach away merely because it discloses an alternative.").
Second, even if Tamarkin preferred surfactant-free formulations, Mattern and Foster positively teach the use of oleoyl polyoxyl-6-glyceride (Labrafil) in similar non-aqueous gels. Mattern explicitly includes Labrafil at 4 wt% (¶ [0087]). Foster teaches Labrafil for otic compositions (¶ [0340]). When some references favor a feature and others do not, the Examiner may properly rely on those that do. In re Ethicon, Inc., 844 F.3d 1344, 1351 (Fed. Cir. 2017) ("The fact that certain prior art references may be directed to different features does not negate a motivation to combine.").
Third, Applicant's own specification confirms that Labrafil provides a specific advantage (wettability). That advantage would have been predictable to a person of ordinary skill, who would have been motivated to include a surfactant to improve particle wetting in a non-aqueous gel.
Fourth, Applicant further argues that Tamarkin’s semi-solid gel “liquefies on application of mild shear force such as gentle rubbing” and is therefore incompatible with transtympanic syringe administration. This argument is not persuasive. Shear-thinning behavior — wherein a composition’s viscosity decreases under applied shear force — is a well-recognized and desirable property for injectable gel formulations precisely because it facilitates extrusion through a syringe needle. The application of mild shear during injection is the mechanism by which such gels are administered. Tamarkin’s disclosure of shear-dependent liquefaction does not criticize, discourage, or teach away from syringe injectability; if anything, it is consistent with it. Moreover, the Examiner does not rely on Tamarkin as the structural template for the gel vehicle. Mattern and Foster are the primary references for the non-aqueous castor oil/Labrafil/silica composition; Tamarkin is relied upon only for the teachings of polymer-free formulation and the API concentration range. Any incompatibility between Tamarkin’s foam/semi-solid embodiments and syringe injection is therefore irrelevant to the combination as articulated. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
"Mattern is for nasal administration, not transtympanic administration."
This argument is not persuasive for the following reasons:
First, the claims at issue are composition claims, not method claims. The recitation "for transtympanic administration" is a statement of intended use, which does not structurally distinguish the composition from prior art compositions. In re Schreiber, 128 F.3d 1473, 1478 (Fed. Cir. 1997) ("The mere recitation of a new intended use for an otherwise old composition does not render the composition novel or nonobvious."). Mattern teaches a non-aqueous gel composition with the same structural components (castor oil, Labrafil, silica, similar viscosity, polymer-free). That composition is prima facie obvious regardless of the intended use. To the extent Applicant argues that a skilled artisan would not consult Mattern because its stated purpose is binding air pollutants in the nasal cavity, the Examiner notes that a reference may be relied upon for any teaching it discloses regardless of its primary stated use. In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012). The structural disclosure of a non-aqueous castor oil/Labrafil/silica gel with defined viscosity properties is fully applicable to the formulation problem at hand, independent of Mattern’s therapeutic purpose.
Second, Mattern's nasal composition is structurally and functionally analogous to a transtympanic gel. Both are administered to moist mucosal/serosal surfaces via a syringe or dropper. Both require bioadhesion, syringeability, and sustained release. One of ordinary skill in the art would recognize that a gel suitable for nasal administration is also physically suitable for transtympanic injection. The fields are analogous. In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004) (prior art is analogous if it is from the same field or reasonably pertinent to the problem).
Third, Bös explicitly teaches transtympanic administration of the same active agent (Bös, page 11, lines 19-20). The Examiner is not required to find a single reference that teaches all limitations. The combination of Mattern (carrier) + Bös (active agent + route of administration) provides the full claimed invention.
"The combination provides unexpected results (wettability, sustained release, homogeneity)."
This argument is not persuasive for the following reasons:
First, Applicant bears the burden of providing factual evidence when alleging unexpected results. In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) ("Mere argument and speculation as to unexpected results, without evidence in the form of comparative data, is insufficient to rebut a prima facie case of obviousness."). Applicant has not submitted any declaration under 37 CFR 1.132, any comparative data, or any side-by-side testing against the closest prior art (Mattern's formulation). Attorney argument is not evidence.
Second, the specification pages cited by Applicant (pages 25-26, Tables 11a-11b) describe viscosity measurements of certain formulations. However, the Examiner has reviewed these pages and finds that they do not provide a comparison between the claimed composition and Mattern's formulation. Tables 11a and 11b report viscosities of formulations with varying thickener concentrations but do not identify Mattern's composition (56-92% castor oil, 4% Labrafil, 4% silica) as a control. Without a direct comparison to the closest prior art, no conclusion of "unexpectedness" can be drawn. In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) ("To establish unexpected results, the evidence must show that the claimed composition exhibits properties that were not expected in light of the prior art.").
Third, the alleged improvements are predictable consequences of the claimed features: (a) Improved viscosity properties: Adjusting thickener (silica) concentration to achieve a target viscosity is routine optimization. Mattern teaches silica at 4% yielding 2,000-10,000 mPas. Reducing silica to 2-3% predictably lowers viscosity into the claimed 1400-2400 mPas range. (b) Improved wettability/homogeneous distribution: Labrafil is a known nonionic surfactant and wetting agent. One of ordinary skill would expect that adding a surfactant to a non-aqueous gel improves wetting of hydrophobic particles. This is not unexpected result; it is the predictable function of the ingredient.
(c) Advantageous uptake requiring lesser API: A smaller particle size (0.01-100 µm) increases surface area and dissolution rate. This is a fundamental principle of pharmaceutical science. No unexpected result arises from applying this principle.
Fourth, even if Applicant had submitted comparative data, any such data would need to be "commensurate in scope" with the full breadth of the claimed invention. In re Chupp, 816 F.3d 770, 779 (Fed. Cir. 2016). The claim covers a broad range of thickener concentrations (1-6 wt%), API concentrations (0.05-10 wt%), and particle sizes (0.01-100 µm). Applicant has not provided data showing unexpected results across this entire range.
Fifth, and independently dispositive, Applicant’s alleged unexpected result regarding Labrafil’s improvement of wettability is not a property of the claimed invention over the prior art — it is a property of Labrafil itself, which is expressly present in both Mattern (at 4 wt%, ¶ 0087) and Foster (¶¶ 0340–0341). Any wettability benefit attributable to Labrafil as a nonionic surfactant is thus a benefit already residing in the prior art combination. A result that flows from a component that is itself taught by the prior art cannot constitute an unexpected result distinguishing the claimed invention from that prior art. In re Merck & Co., 800 F.2d 1091, 1099 (Fed. Cir. 1986).
Conclusion: Applicant has failed to rebut the prima facie case of obviousness with factual evidence of unexpected results. The rejections under 35 U.S.C. § 103 are maintained.
"There is no motivation to combine because the references are directed to different fields."
This argument is not persuasive for the following reasons:
First, all four references are directed to pharmaceutical compositions for administration to mucosal or serosal surfaces. Mattern (nasal mucosa), Bös (transtympanic/inner ear), Foster (otic), and Tamarkin (body cavities, including aural). These are analogous arts because they address the same core problems: formulating hydrophobic or poorly soluble drugs, achieving sustained release, ensuring syringeability or sprayability, and providing bioadhesion. In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004) (prior art is analogous if it is "reasonably pertinent to the particular problem with which the inventor is involved").
Second, the specific problem the inventor sought to solve (as stated in Applicant's Remarks at page 6) was "to allow a good administration of a pharmaceutically active agent with a low solubility in water, in the middle ear behind the transtympanic membrane while also enabling an advantageous release profile." A person of ordinary skill addressing this problem would naturally look to: Bös for the active agent and the route of administration; Mattern for a non-aqueous gel vehicle with the required excipients and viscosity; Foster for confirmation that castor oil, Labrafil, and silica are standard in otic gels; Tamarkin for confirmation that polymer-free compositions and the claimed API concentration ranges are routine.
Third, the combination is not the product of impermissible hindsight. It is a simple substitution of one known active agent for another in a known carrier, with routine optimization of thickener concentration to achieve a desired viscosity. This is precisely the type of predictable variation held obvious in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). ("When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one.").
Fourth, Applicant characterizes Foster as disclosing “water and polymer in combination with a non-natural neurotrophic agent,” arguing that Foster is therefore directed to a fundamentally different composition than the claimed invention. This characterization is incomplete. Foster discloses multiple embodiments, including explicitly non-aqueous compositions comprising triglycerides (including castor oil, ¶ 0371), oleoyl polyoxyl-6-glyceride/Labrafil (¶¶ 0340–0341), and silicon dioxide thickener (¶¶ 0279, 0297) — precisely the excipient combination at issue. The Examiner relies on Foster’s non-aqueous otic gel embodiments, not on Foster’s aqueous or polymer-containing embodiments. A prior art reference may be relied upon for any teaching it discloses, irrespective of whether other embodiments in the same reference differ from the claimed invention. In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012).
Fifth, Applicant’s argument that “there would have been no reason to combine Mattern because Mattern is for binding air pollutants” is factually incomplete. While Mattern’s primary disclosed use is for binding air pollutants, Mattern also discloses the structural composition of a non-aqueous gel that is physically suitable for administration to mucosal surfaces. The Examiner is entitled to rely on a reference for what it discloses, not only for its stated preferred use. In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012).
Applicant has failed to rebut the prima facie case of obviousness. The rejections under 35 U.S.C. § 103(a) are maintained.
Conclusion
No claims are allowed.
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
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