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 .
Priority
This application, filed 13 October, 2022, is a national stage application of PCT/IT2021/050111, filed 14 April, 2021, which claims foreign benefit of application IT102020000007816, filed 14 April, 2020.
Information Disclosure Statement
Three information disclosure statements (IDS) submitted on 28 November, 2022; 6 June, 2025 and 24 March, 2026 are acknowledged and have been considered.
Election/Restrictions
Applicant’s election without traverse of Group I, which read on Claims 22-32 and 41, in the reply filed on 27 July, 2026 is acknowledged.
Status of the Application
Receipt is acknowledged of Applicant's claimed invention, filed 13 October, 2022, in the matter of Application N° 17/918,733. Said documents have been entered on the record.
Claims 1-6, 8-9, 11, 18-19, 22, 24-27, 29-32, 35, 37, and 39 are amended. Claims 7, 10, 12-17, 20-21, 33-34, 36, 38, and 40 are canceled. Claim 41 is new. No new matter was introduced.
Thus, Claims 1-6, 8-9, 11, 18-19, 22-32, 35, 37, 39 and 41 are pending.
Claims 1-6, 8-9, 11, 18-19, 35, 37 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 27 July, 2026.
Thus, Claims 22-32 and 41 represent all claims currently under consideration.
Claim Objections
Claims 23-29 are objected to because of the following informalities: each claim recites “A medical device according to claim 22.” Since the medical device is previously recited in Claim 22, the indefinite article “A” should be replaced with the definite article “The” in the dependent claims, e.g., “The medical device according to Claim 22.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 26 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.
Regarding claim 26, the phrase “e.g.” (“for example”) renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
For purposes of examination, the exemplary matter following “e.g.” is treated as nonlimiting. Accordingly, claim 26 is construed as requiring that the first component further comprise an anti-inflammatory agent and/or an anti-viral agent.
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 22-32 and 41 is rejected under 35 U.S.C. 103 as being unpatentable over Furukawa et al. (EP 1655292 A1, Patent published 29 April, 2015, cited in IDS and ISR), hereinafter Furukawa, and further in view of Bannert (US 5147648 A, Patent published 15 September, 1992, cited in IDS and ISR), and Benzi (WO 2014/181299 Al, 13 November, 2014, cited in IDS and ISR).
Regarding Claim 22, Furukawa (2015) teaches pharmaceutical compositions for the prevention or treatment of viral infectious diseases, including coronavirus infection, using catechins such as epicatechin (EC), epigallocatechin (EGC), gallocatechin, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), alone or in combination. Furukawa further teaches administration of its catechin-containing pharmaceutical compositions by the intranasal route, including a nasal aerosol or inhalant. In connection with such intranasal administration, Furukawa teaches that the preparation may be provided in the form of a solution, suspension, ointment, or gel, generally contains a large amount of water, and may further contain conventional formulation ingredients including a preservative and a gelling agent. Furukawa additionally teaches administration of the intranasal composition using an atomizer, nebulizer, or medical aerosol. (‘292, Para 0001, 0017, 0026, and 0046-0050).
Bannert (1992) is directed to improving the adhesiveness of gels to mucosae. Bannert explains that gels are useful for protecting and keeping mucosa moist and for applying disinfectants and medications thereto but recognizes insufficient adhesion of conventional gels to mucosa as a disadvantage. Bannert addresses this problem using physically separate components comprising a metal salt and a polysaccharide which, upon application, form a gel having a long-lasting and durable adhesion to the mucosa. Bannert teaches that the gel-forming components should be mucosa-tolerable and non-toxic; identifies alginic acid and its salts among suitable polysaccharides, and sodium alginate as preferred; teaches use of pharmaceutically tolerable aqueous solutions, preferably distilled water containing a pharmaceutically tolerable preservative; and teaches that drugs may be incorporated into the system and that the resulting adhesive gel is particularly suitable as a carrier for localized administration of drugs or disinfectants. Bannert further teaches use of the two-component system on the oral and nasal mucosa, including systems in which aqueous calcium-salt and sodium-alginate components are sprayed into the nose. (‘648, Col 1-4, Examples 1, 8-11 and 13).
Accordingly, 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 employ Bannert’s two-component mucosa-adherent gel system for Furukawa’s catechin-containing intranasal pharmaceutical composition. Furukawa expressly contemplates delivering its antiviral catechin composition to the nasal mucosa in the form of an aqueous gel and further teaches that such intranasal preparations may contain conventional formulation ingredients including a preservative and gelling agent. Bannert, in turn, identifies insufficient mucosal adhesion as a known problem associated with gels used for localized mucosal administration and provides a two-component aqueous gel-forming system specifically designed to address that problem. One of ordinary skill therefore would have been motivated to employ Bannert’s gel-forming system for Furukawa’s catechin-containing intranasal preparation in order to provide improved adhesion and retention of the pharmaceutical composition at the nasal mucosa and thereby facilitate localized delivery of Furukawa’s antiviral catechin composition. The resulting system would comprise a first aqueous component containing Furukawa’s catechin-containing pharmaceutical composition, and preservative, together with Bannert’s gel-forming polysaccharide, including sodium alginate as expressly preferred by Bannert, and a physically separate aqueous component comprising a Bannert’s multivalent metal salt.
In considering known formulations and advantageous variations of such two-component aqueous gel-forming systems for localized pharmaceutical delivery, one of ordinary skill in the art would also have had reason to consider the teachings of Benzi (2014). Furukawa itself contemplates localized administration of its catechin-containing compositions by both the intranasal route and as oral mouthwash or gargle preparations, while Bannert expressly teaches use of its drug-carrying adhesive gel systems on mucosae, including both oral and nasal mucosa. Benzi is likewise directed to localized pharmaceutical treatment in the oral environment and teaches a closely analogous two-component aqueous gel-forming system comprising an alginate-containing first component and a physically separate aqueous second component containing a divalent, trivalent, or multivalent cation that serves as a crosslinker. Benzi further teaches a formulation in which the first aqueous component contains both polyvinyl alcohol (PVA) and alginate, preferably sodium alginate, and is preferably in the form of an aqueous gel. Benzi further exemplifies PVA and sodium alginate together in the first aqueous component with a separate aqueous calcium-chloride crosslinking component. Importantly, Benzi teaches that PVA provides the resulting material with adhesive properties that permit sealing and protection of the application site and expressly attributes a mucoadhesive sealing effect to the PVA-containing formulation, as well as anti-inflammatory properties to PVA (‘299, Abstract, Pg 2 Para 3, Pg 4 Para 3, and Example 1).
Thus, having been led by Bannert to employ a two-component aqueous alginate/multivalent-cation gel-forming system to improve localized mucosal delivery of Furukawa’s catechin composition, one of ordinary skill seeking known formulations and improvements of that system would have had a reason to employ Benzi’s PVA-containing formulation. Benzi teaches PVA as an additional component of the alginate-containing aqueous gel and expressly identifies adhesive and mucoadhesive properties imparted by PVA to the resulting material. Accordingly, incorporation of PVA into the alginate-containing first component of the Furukawa/Bannert system would have represented the use of a known formulation variation of a closely analogous two-component gel-forming system to obtain the known adhesive/mucoadhesive properties associated with PVA. Although Benzi exemplifies its system in periodontal applications, Benzi is pertinent for its teaching concerning the formulation and properties of the same basic two-component aqueous alginate/multivalent-cation gel-forming architecture, rather than for the particular anatomical site of administration.
One of ordinary skill in the art would have had a reasonable expectation of success in making the proposed combination. Furukawa expressly contemplates catechin-containing aqueous intranasal gels containing conventional gelling agents and preservatives; Bannert demonstrates that physically separate aqueous polysaccharide and metal-salt components, including sodium-alginate-containing systems, form long lasting adherent drug-carrying gels upon application to mucosa; and Benzi expressly demonstrates that PVA and sodium alginate are compatible in the same aqueous first component and that the PVA/alginate-containing component remains capable of crosslinking upon application of a physically separate aqueous multivalent-cation component. Benzi’s Example 1, for example, prepares the base gel by dissolving PVA in water and subsequently adding sodium alginate, followed by use of a second crosslinking component, calcium chloride. Moreover, Benzi expressly teaches the adhesive and mucoadhesive properties associated with the resulting PVA-containing material. Thus, the proposed combination would have involved the predictable use of known formulation components in a closely analogous gel-forming system, with the respective components performing their previously recognized functions.
Regarding Claim 23, Benzi further teaches the polyvinyl alcohol (PVA) has a molecular weight in the range from 100 to 1,000,000 and is present in the first component at a concentration within the range of 1-30% w/w (‘299, Pg 2, Para 2). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). See MPEP §2144.05(I).
Regarding Claim 24, Benzi further teaches the alginate is sodium alginate and is present in the first component at a concentration within the range of 0.1 to 10% w/w (‘299, Pg 2, Para 3). See MPEP §2144.05(I).
Regarding Claim 25, Furukawa further teaches varying the concentration of catechin in its pharmaceutical preparations and expressly provides preferred catechin concentrations for intranasal administration (‘292, Pg 8, Para 0049). Furukawa further exemplifies an intranasal catechin spray prepared by dissolving 3 mg of catechin in 1 mL of physiological saline (‘292, Pg 11, Para 0104, Example 1), corresponding to a catechin concentration of 3 mg/mL (0.3% w/v). Thus, Furukawa expressly recognizes the amount of catechin in the intranasal pharmaceutical composition as a formulation variable and teaches an exemplary aqueous intranasal formulation having a catechin concentration closely corresponding to the claimed concentration. See MPEP §2144.05.
Regarding Claim 26, Furukawa further teaches the use of glutathione as an antiviral therapeutic agent. Furukawa explains that glutathione was known to have an effect in preventing or treating infectious disease caused by influenza virus (‘292, Pg 3, Para 0009) and is itself directed to pharmaceutical compositions comprising glutathione and/or catechin for preventing or treating viral infectious diseases, including Coronavirus and Flavivirus infections. Significantly, Furukawa expressly teaches compositions comprising glutathione in combination with catechin and exemplifies an intranasal spray containing both glutathione and catechin in physiological saline (‘292, Pg 11, Para 0105, Example 1).
Bannert further teaches that its mucosa-adherent gel-forming system is particularly suitable as a carrier for drugs for localized administration to the mucosa and expressly teaches preferred formulations in which at least one of the two gel-forming components contains additional drugs (‘648, Col 3, Lines 27-30). Benzi likewise demonstrates incorporation of an additional therapeutic agent directly into the PVA-alginate-containing aqueous first component of its two-component gel-forming system, specifically teaching a first aqueous component comprising PVA, alginate, and an antibiotic (‘299, Pg 1, Final Para – Pg 2, First Para).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to include Furukawa’s glutathione as an additional antiviral agent in the first aqueous component of the Furukawa/Bannert/Benzi system. Furukawa itself provides express reason to administer glutathione together with catechin for the prevention or treatment of viral infectious disease and demonstrates their combined administration in an intranasal pharmaceutical preparation. Bannert teaches that additional drugs may be incorporated into the components of its mucosa-adherent gel system for localized drug delivery, while Benzi confirms that an additional therapeutic agent may be incorporated directly into the PVA-alginate-containing first aqueous component of the two-component gel-forming system. One of ordinary skill therefore would have reasonably expected Furukawa’s glutathione to be incorporated into the first aqueous component while retaining its known antiviral therapeutic function.
Regarding Claim 27, Benzi further teaches the salt is preferably selected from the group consisting of calcium chloride, magnesium chloride and zinc chloride (‘299, Pg 2, Para 5).
Regarding Claim 28, Benzi further teaches the salt is present in the aqueous solution at a concentration comprised between 0.001 molar and the saturation concentration of the solution (‘299, Pg 2, Para 5).
Regarding Claim 29, Furukawa teaches intranasal administration preparation can be prepared in the intranasal dosage form such as drops, a spray agent or aerosol (‘292, Pg 8, Para 0049), while Bannert further teaches it is preferable that the two components be sprayed onto the mucosa (‘648, Col 1, Lines 67-68).
Regarding Claim 30, the claim is directed to a bioadhesive film situated at the oral and/or nasal mucous membranes and defines the film, at least in part, by the process by which it is obtainable, namely, by applying the first and second components recited in claim 22 to the oral and/or nasal mucous membranes. Thus, claim 30 is construed as a product-by-process claim. See MPEP §2113. In determining the patentability of a product-by-process claim, patentability is based on the product rather than the particular process by which the product is produced. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). However, any structure or characteristics imparted to the product by the recited process are considered in determining patentability.
As discussed above with respect to claim 22, Furukawa in view of Bannert and Benzi renders obvious the recited first and second components. Bannert further teaches applying its physically separate aqueous gel-forming components directly to mucosa, including oral and nasal mucosa, whereby the separately applied components interact to form a long-lasting, adherent gel on the mucosal surface. Bannert expressly teaches that lower concentrations of the components produce thin gel films suitable for application in the mouth and throat and as an artificial nasal secretion, and further describes gel films that adhere to and cover the mucosal surface (‘648, Col 3, Lines 40-47).
Accordingly, Bannert teaches formation in situ on oral and/or nasal mucosa of the same type of bioadhesive film recited in claim 30 by application of the separately maintained gel-forming components. One of ordinary skill in the art applying the first and second components of the Furukawa/Bannert/Benzi combination to the oral or nasal mucosa as taught by Bannert would therefore have reasonably expected the components to interact and form the corresponding adherent gel film on the mucosal surface. The resulting bioadhesive film would have been the predictable product of applying the previously discussed first and second components according to Bannert’s expressly taught mucosal application technique. Therefore, the bioadhesive film of claim 30 would have been obvious over Furukawa in view of Bannert and Benzi.
Regarding Claim 31, Bannert teaches that the two aqueous components of its gel-forming system are maintained physically separate from one another prior to administration and are thereafter applied to the same mucosal area, preferably sequentially (‘648, Col 6, Claim 4). Benzi likewise teaches maintaining its first gel component and second aqueous crosslinking component using a syringe followed by administration of the calcium-chloride crosslinking component using a second syringe (‘299, Pg 6, Example 2).
It would have been prima facie obvious to one of ordinary skill in the art to provide the physically separate first and second components of the Furukawa/Bannert/Benzi system in respective first and second containers as a kit. Because the components are expressly taught to be maintained separately until administration, providing each component in its own container would have constituted a predictable arrangement of the known components according to their established manner of use, permitting storage and subsequent separate administration of the respective components without altering their functions. See MPEP §2143(I)(A).
Regarding Claim 32, Bannert further teaches administration of its physically separate first and second aqueous components by spraying the respective components onto the mucosa. Bannert specifically teaches formation of this gel film suitable for nasal administration by applying the same volumes of a calcium-salt solution and the alginate solution onto the mucosa (‘648, Col 3, Lines 47-51).
Furukawa further teaches administration of an intranasal pharmaceutical preparation using a spray or aerosol and expressly teaches use of a unit administration system in which a predetermined volume of solutions or suspension is administered as a unit dose, preferably 5-400 μL and more preferably 50-150 μL (‘292, Pg 8, Para 0049). Furukawa teaches that suitable administration devices include an atomizer, nebulizer, or medical aerosol and expressly contemplates unit-dose and plural-dose packages (‘292, Pg 8, Para 0050).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to provide each of the respective containers of claim 31 with a spray or nebulizer administration system configured to deliver a metered volume of the respective component. Bannert already teaches separate spray administration of the two components, including administration of predetermined corresponding volumes thereof, while Furukawa teaches known intranasal spray/nebulizer systems for administering predetermined unit volumes of pharmaceutical preparations. Applying Furukawa’s known unit-dose spray/nebulizer administration technique to Bannert’s separately administered aqueous components would have predictably permitted controlled delivery of the desired volume of each component to the mucosal surface. A system intended to administer Furukawa’s predetermined unit volume necessarily would require control of the quantity discharged for each administration; configuring the spray/nebulizer system to meter that predetermined volume would therefore have been a predictable implementation of the Furukawa’s expressly taught unit-dose administration. See MPEP §2143(I)(C-D).
Regarding Claim 41, Furukawa teaches catechin-containing pharmaceutical compositions comprising catechins including epicatechin (EC), epigallocatechin (EGC), gallocatechin, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), alone or in combination. Furukawa further teaches aqueous intranasal pharmaceutical preparations that may be formulated as gels and expressly teaches inclusion of preservatives and gelling agents in such preparations.
Bannert teaches aqueous gel-forming pharmaceutical compositions for application to mucosa and expressly teaches polysaccharides including alginic acid and salts thereof, with sodium alginate being preferred. Bannert further teaches that its aqueous polysaccharide solutions may contain preservatives and may serve as carriers for drugs.
Benzi further teaches an aqueous gel-forming first component comprising both PVA and alginate, preferably sodium alginate.
Accordingly, for substantially the same reasons set forth above with respect to claim 22, it would have been prima facie obvious to one of ordinary skill in the art to formulate Furukawa’s catechin-containing aqueous pharmaceutical gel using the alginate-containing gel system taught by Bannert and the PVA/alginate formulation taught by Benzi, thereby providing an aqueous gel comprising PVA as the biocompatible polymer, sodium alginate as the polyacid salt, a preservative, and Furukawa’s catechin-containing composition. The rationale for combining the references and reasonable expectation of success are as discussed above with respect to claim 22 and are incorporated herein.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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/D.M.N./Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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