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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 208-231, in the reply filed on 08/11/2025 is acknowledged.
Accordingly, claims 232-236 are withdrawn as being directed to a non-elected invention. Claims 1-207 are canceled. Claims 208-231 are examined on the merits herein.
Priority
The instant application filed 03/07/2023, is a continuation of PCT/US21/49449, filed 09/08/2021, which claims priority to Provisional Application No. 63/075,803, filed 09/08/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/26/2023, 10/18/2024, and 08/11/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
The terms “scaffolding agents” and “blowing agents” are not explicitly defined by the instant claims or specification. According to claim 217, the scaffolding agents may comprise powdered cellulose, microcrystalline cellulose, saponins, or quillaja extract. However, the instant specification teaches that pore-creating excipients include but are not limited to, scaffolding agents (e.g., powdered cellulose), and blowing agents (e.g., saponin, quillaja extract powder, etc.) ([0036]). Thus, there is a discrepancy between what is designated as a the “scaffolding agents” and “blowing agents” in the claims versus the specification. Furthermore, the specification teaches wherein citric acid plus bicarbonate is an example of a blowing agent ([0036]), which reads on the acid/base pair of claims 218 and 219. It is also taught by the instant specification that the plurality of pores form during the manufacturing process, e.g., as a result of blowing agents, which promote pore formation and help create structure in the matrix. Prior to curing, the blowing agents incorporate or trap air (or other gas, e.g., CO2), e.g., create a froth, from a liquid composition comprising the active agents and excipients ([0076]). As such, the Examiner is interpreting the one or more blowing agents of claims 208 and 211 as any agent capable of incorporating or trapping air bubbles in the matrix, whether that be by generating CO2 gas chemically, by bubbling air into the mixture, or by increasing the foaming capabilities of a mixed solution (i.e., a foaming agent). The scaffolding agent will be interpreted as any agent used to support, stabilize, or provide structure to the dissolvable sheet and the acid/base pair which generates a gas will be interpreted as different than the blowing agent of claims 208 and 211.
Claim Objections
Claims 220, 223, and 225 are objected to because of the following informalities:
Claim 220 recites “when the sheet is treated is having a flat external surface for the purpose determining surface area”. This is assumed to be a typographical error which should recite: “when the sheet is treated as having a flat external surface for the purpose of determining surface area”;
Claim 223 contains several capitalized words. Please remove capitalization;
Claim 225 recites “glycerine”, which is assumed to be a typographical error which should recite glycerin.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 217, 219, 220, 226, and 230 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.
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 217 recites the broad recitation of “powdered cellulose” and “saponins”. The claim also recites “microcrystalline cellulose” and “quillaja extract” which are narrower statements of the respective limitations. The claim is 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 219 recites “wherein the acid/base pair comprises citric acid, carbonate, calcium bicarbonate, or calcium citrate”. Citric acid and citrate are known in the art as a conjugate acid base pair. Similarly, bicarbonate and carbonate are known as a conjugate acid base pair. As such, it is unclear if the acid/base pair of claim 219 contains only one component from the list which interconverts between the acid and base form, or multiple components from the list, one of which is an acid and the other which is a base.
Claim 220 recites a specific surface area “when the sheet is treated is having a flat external surface for the purpose of determining surface area”. This limitation is unclear as it is not known what is meant by treating the sheet as having a flat surface. For instance, is total surface area including or excluding the surface area occupied by surface pores? For the sake of compact prosecution the claim will be interpreted as the total “external” surface area including the pores (i.e., as if the pores were not present).
Claim 226 recites “4% water (w/w)” without reciting the basis for the percent. Is the percent based on the total weight of the dissolvable sheet or the weight of a single component?
Claim 230 recites “a cross-sectional area”, while claims 209 and 212 recite “average cross-sectional area”. As such, it is unclear to the examiner if this is a typographical error or if Applicant is actually referring to total cross-sectional area. For the sake of compact prosecution the Examiner is interpreting the claim as average cross-sectional area rather than total cross-sectional area.
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.
Claim 208 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park, M.R., et al. (US 20160279071 A1, 09/29/2016, PTO-892), hereinafter Park.
Park discloses an orally disintegrating porous film which reads on a pore-containing dissolvable sheet as recited in claim 208. Regarding the recitation of “for delivery of one or more active agents into an aqueous medium”, this is a recitation of intended use. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). However, in the instant case the orally disintegrating porous film of Park would fulfill the intended use since it is a dissolving film for delivering active ingredients to the user (abstract).
The orally disintegrating porous film includes a foaming agent, a foam stabilizer, a plasticizer, and a pharmacologically active ingredient (abstract). The foaming agent may be selected from the group consisting of a surfactant, an animal-based foaming agent, a polymer foaming agent, and a mineral-based foaming agent. Preferably the foaming agent is a surfactant. The addition of the surfactant facilitates the generation of microfoam in the preparation of a film solution ([0021]). Given the claim interpretation above, the foaming agent reads on the one or more blowing agents of claim 208.
The foam stabilizer may be a thickener, a gelling agent, an aqueous polymer, a non-aqueous polymer, or a combination thereof ([0024]). Given the claim interpretation above, the foaming stabilizer reads on the one or more scaffolding agents of claim 208.
The pharmacologically active ingredient, which is incorporated in the orally disintegrating porous film, may contain a drug without limitation so long as the drug may be prepared as an oral formulation ([0039]). The pharmacologically active ingredient reads on the one or more active agents of claim 208.
Regarding the moisture absorption and fracture profile of the pore-containing dissolvable sheet of claim 208, such properties are inherent to the film of Park since it is identical to the sheet as defined in instant claim 208. When the composition anticipated by the prior art is identical to the composition claimed, the composition must necessarily have the characteristics claimed as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Claim Rejections - 35 USC § 102/103
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.
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.
Claims 208-216, 221, 225, and 227-230 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Park, M.R., et al. (US 20160279071 A1, 09/29/2016, PTO-892), hereinafter Park as evidenced by Porometer – pore size distribution and capillary flow porometry measurement Glossary. Retrieved 10/16/2025, (PTO-892), hereinafter Porometer and IKA, T-25 digital ULTRA-TURRAX® technical data sheet. Retrieved 10/16/2025. (PTO-892), hereinafter IKA.
Park discloses an orally disintegrating porous film which reads on a pore-containing dissolvable sheet as recited in claims 208 and 211. Regarding the recitation of “for delivery of one or more active agents into an aqueous medium”, this is a recitation of intended use. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). However, in the instant case the orally disintegrating porous film of Park would fulfill the intended use since it is a dissolving film for delivering active ingredients to the user (abstract).
The orally disintegrating porous film includes a foaming agent, a foam stabilizer, a plasticizer, and a pharmacologically active ingredient (abstract). The foaming agent may be selected from the group consisting of a surfactant, an animal-based foaming agent, a polymer foaming agent, and a mineral-based foaming agent. Preferably the foaming agent is a surfactant. The addition of the surfactant facilitates the generation of microfoam in the preparation of a film solution ([0021]). Given the claim interpretation above, the foaming agent reads on the one or more blowing agents of claims 208 and 211.
The foam stabilizer may be a thickener, a gelling agent, an aqueous polymer, a non-aqueous polymer, or a combination thereof ([0024]). Given the claim interpretation above, the foaming stabilizer reads on the one or more scaffolding agents of claims 208 and 211.
The pharmacologically active ingredient, which is incorporated in the orally disintegrating porous film, may contain a drug without limitation so long as the drug may be prepared as an oral formulation ([0039]). The pharmacologically active ingredient reads on the one or more active agents of claims 208 and 211.
Regarding the moisture absorption and fracture profile of the pore-containing dissolvable sheet of claim 208, such properties are inherent to the film of Park since it is identical to the sheet as defined in instant claim 208. When the composition anticipated by the prior art is identical to the composition claimed, the composition must necessarily have the characteristics claimed as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Regarding the pore structure of the instantly claim invention, Park further teaches that the orally disintegrating porous film contains micropores with a size of 10 to 150, preferably 20 to 120, and more preferably 30 to 100 microns ([0038]; claim 9). The orally disintegrating porous film has a porosity of 8% to 40%, preferably 10% to 35%, and more preferably 15% to 30% ([0038]). In the case where the orally disintegrating film has micropores having a size of greater than 150 and an excessively high porosity, the properties of the film may deteriorate. On the other hand, in the case where the size of the micropores is less than 10 and the porosity is excessively low, dissolution of the pharmacologically active ingredient in the film may be impeded ([0038]).
Pore size is defined in the art as the width between two opposite walls of a pore and is often represented as the pore diameter or pore radius, as evidenced by Porometer. As such, the pore size of Park which is preferably 30 to 100 microns, reads on the instantly claimed “longest cross-sectional length” of claims 209 and 211 (i.e., 10 to 200 microns).
Regarding the void volume of the dissolvable sheet as recited in claims 210 and 213, Park teaches a porosity of preferably 15 to 30%, which falls within the instantly claimed void volume range. In the instant case, void volume is not defined by the specification. However, based on the description of void volume in the instant specification ([0076]) the examiner concludes that it is the same as porosity and is being interpreted as such.
Regarding the pore structure elements which Park does not explicitly teach such as the pore density, average cross-sectional area and its standard deviation as defined in claims 209, 211-212, and 230, the Examiner has reason to believe that the porous sheet of Park would inherently possess such characteristics given the similarities between the instant disclosure and that of Park as outlined below.
First, Park teaches that the film solution used to provide the porous film has a viscosity of 5,000 to 20,000 cps ([0047]), specifically the examples teach a viscosity of 12,000 (Examples 1.1-1.4; table 3). If the viscosity of the film solution is too low, foam stability may decrease, thus making it impossible to prepare an orally disintegrating porous film. On the other hand, if the viscosity thereof is too high, it is impossible to mold a film. Viscosity can be adjusted by varying the amounts of film forming agent and foam stabilizer ([0047]). The instant specification teaches mixing ingredients until a cP within the range of 5,000-12,000 cP is achieved ([0149] of instant spec.). As such, both Park and the instant invention teach a preferred viscosity of 12,000 cP.
Park further teaches optimal rpms for the homogenizer and stirrer used in the method of generating the porous films (Examples 1.1-1.4; table 2). Specifically, Park discloses that when the rates of the homogenizer and the stirrer were increased to 6000 rpm and 900 rpm, respectively, foam was generated in the film solution, and the porosity of the resulting film was increased at least about 3 to 4 times, compared to examples which used lower rpms ([0078]; tables 2-3). The cross-section of the film of Example 1 (increased rpms) and the porosity thereof were observed using a microscope ([0079]). As shown in FIG. 2, pores were observed on the surface of the film, indicating that the generation of foam (i.e., pores) was promoted by increasing the rpm of the homogenizer and the rpm of the stirrer ([0080]). Alternatively, as seen in the microscopic results of FIG. 1, pores were not clearly observed on the surface of the film of Comparative Example 1 (lower rpms), and the porosity thereof was merely 7% ([0077]). While not explicitly defined, the microscope images also demonstrate that the film of Park possesses a given number of pores per unit of area (i.e., density) and each pore has a cross-sectional area from which an average and standard deviation could be determined.
The homogenizer used in Park is an IKAT25 digital UTRA-TURRAX ([0064]), which has an extension arm diameter of 13 mm as evidenced by IKA. Thus, at an rpm of 6000 (i.e., as taught by Park), the fpm would be approximately 800 (FPM = RPM × π × D), thereby falling within the optimal mixing speed as defined in the instant specification (i.e., 1-1500 FPM) ([0149] of instant spec.).
Lastly, Park teaches molding the film solution using a continuous film molding machine and then slitting and cutting, thereby preparing a film. The molding step includes drying the film solution at a temperature of 50 to 160 degrees C ([0044]; [0050]). The instant invention teaches using a 2D screen printer and stencil to give sheets of a specific weight and thickness (i.e., a mold). The substrates were set to cure at a temperature of 45-110 degrees C ([0149] of instant spec.) which overlaps with the temperature taught by Park.
As such, the methods of producing the porous films of Park and the porous sheets of the instant invention seem remarkably similar. Furthermore, other parameters relating to pore structure (i.e., pore size and porosity) appear to be the same, as discussed above. Also discussed above, Park teaches each necessary component of the instantly claimed porous sheet (i.e., scaffolding, blowing, and active agent). Thus, the Examiner has reason to believe that the porous films of Park, which are produced by substantially the same method, comprise substantially the same components, and display the same porous structure based on other parameters, would inherently possess the same pore density, average cross sectional area, and standard deviation as instantly claimed.
Assuming for the sake of argument that the porous film of Park does not possess the same pore structure as defined in the instant claims, Park differs from the instant invention in that Park does not explicitly teach the pore structure as defined in claims 209, 211-212, and 230.
However, it would have been obvious to one of ordinary skill in the art to optimize parameters such as longest cross sectional length, pore density, average cross-sectional area and standard deviation to arrive at the instantly claimed invention since pore structure is a results effective parameter as taught by Park. The optimization of a result effective parameter is considered within the skill of the artisan. See, In re Boesch and Slaney (CCPA) 204 USPQ 215. This is what research chemists do, optimization of result-effective variables through routine experimentation (MPEP 2144.05 IIA and B). One of ordinary skill in the art would have a reasonable expectation of success since Park teaches that pore structure can be optimized by varying elements of the production method such as viscosity and mixing speed.
Regarding claims 214-216 and 227, the moisture absorption, water activity, dissolution, and fracture profiles of the pore-containing dissolvable sheet of claim 211 are inherent to the film of Park since it is identical to the sheet as defined in instant claim 211. When the composition anticipated by or made obvious by the prior art is identical to the composition claimed, the composition must necessarily have the characteristics claimed as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Example 1 of Park specifically comprises polysorbate 80 as the foaming agent (i.e., blowing agent), pullulan as the foam stabilizer (i.e., scaffolding agent), and Aripiprazole as the main ingredient (i.e., active agent) (Table 1). The Aripiprazole reads on the pharmaceutical composition of claim 221. Example 1 also comprises glycerin (Table 1), which reads on the humectant of claim 225.
Regarding claim 228, the foam stabilizer (i.e., scaffolding agent) is preferably contained in an amount of 20 wt % to 90 wt % based on the total weight of the orally disintegrating porous film ([0026]). Specifically, Example 1 teaches 31 g of Pullulan as the foam stabilizer (Table 1). By the Examiner’s calculations the film comprises ~34% by weight of the foam stabilizer (i.e., scaffolding agent), which falls within the instantly claimed range.
The active ingredient of Example 1 (i.e., Aripiprazole) is added at an amount of 10 g (Table 1), which by Examiner’s calculations is ~11% by weight in the film formulation thereby falling within the range of claim 229.
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 208-216, 220-221, 225, and 227-231 are rejected under 35 U.S.C. 103 as being unpatentable over Park, M.R., et al. (US 20160279071 A1, 09/29/2016, PTO-892), hereinafter Park.
The teachings of Park are discussed above.
Park further teaches that the thickness of the film of Example 1 was measured to be 90 μm ([0080]), which falls within the range of claim 220.
The teachings of Park differ from the instantly claimed invention in that Park does not explicitly teach the surface area of claim 220 nor the weight ration of claim 231.
Regarding the total surface area of the sheet as recited in claim 220, Park teaches that that the film is molded and aged for about 1 to 10 days to prepare it for slitting or cutting. The aged roll is slit into small rolls, cut to an appropriate size, and placed in an aluminum package. The packaged aluminum product is further packaged in a small box, yielding the orally disintegrating porous film ([0055]). As such, Park teaches that the films may be adjusted to any size that is desirable for packaging and use. The total surface area of the film is therefore an optimizable parameter that one of ordinary skill could adjust with no trouble at all. Thus, one of ordinary skill in the art would have arrived at the instantly claimed range of total surface area through no more than routine experimentation. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 231, the weight ratio of the foaming stabilizer (i.e., scaffolding agent) to the active ingredient in Example 1 is 3.1 to 1 (Table 1), which does not fall within the instantly claimed range but is very close. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art by are merely close. See MPEP 2144.05. Example 7 further teaches a ratio of 1.24 to 1 with a different active (Table 5), which falls within the range of claim 231. It can be observed from Table 5, which discloses various main (i.e., active) ingredients, that the amount of active added is different for each active. Thus, one of ordinary skill in the art would have had to optimize both the amount of active ingredient and ratio of scaffolding agent to active, depending on the active ingredient used and its desired pharmacological effects. As such, one of ordinary skill in the art would have arrived at the instantly claimed ranges of claim 231 through no more than routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 208-217, 220-223, 225, and 227-231 are rejected under 35 U.S.C. 103 as being unpatentable over Park, M.R., et al. (US 20160279071 A1, 09/29/2016, PTO-892), hereinafter Park as applied to claims 208-216, 220-221, 225, and 227-231 above, and further in view of Bernardo, J., (US 20200383962 A1, 12/10/2020, PTO-892), hereinafter Bernardo.
The teachings of Park are discussed above.
Park further teaches that the foam stabilizer is a thickener, a gelling agent, an aqueous polymer, a non-aqueous polymer, or a combination thereof, and preferably is at least one selected from the group consisting of pullulan, hydroxypropyl methylcellulose, polyvinylacetate, polyethylene oxide, xanthan gum, guar gum, locust bean gum, starch and starch derivatives, pectin and pectin hydrolyzates, alginic acid and alginic acid hydrolyzates ([0024]; claim 6). The active ingredient preferably includes at least one selected from the group consisting of a therapeutic agent for insomnia, a vitamin, a nutrient, and more ([0039]).
The teachings of Park differ from the instantly claimed invention in that Park does not teach specific embodiments wherein the foam stabilizer (i.e., the scaffolding agent) is one of those selected from instant claim 217 nor wherein the active ingredient is one of those selected form instant claims 222 and 223.
Bernardo discloses compositions suitable for oral use (e.g., oral thin film) containing various excipients and a combination of melatonin, caryophyllene, GABA, L-theanine, and vitamin B6 as active ingredients. Methods of using the composition, e.g., in the treatment of a sleeping disorder, as well as methods of manufacturing the composition (abstract). An “Oral thin film,” also known as an “oral dissolving film,” refers to a product used to administer active ingredients via absorption in the mouth (buccally or sublingually), the stomach (gastrically), and/or via the small intestines (enterically). The OTF is edible and pharmaceutically acceptable. A film is prepared typically using hydrophilic polymers that rapidly dissolve on the tongue, palatine tissue, or buccal cavity, delivering the active ingredient to the systemic circulation via dissolution when contact with liquid is made ([0056]). The composition of Bernardo specifically includes: (i) melatonin, (ii) caryophyllene, (iii) GABA, (iv) L-theanine, (v) vitamin B6, (vi) at least one of a binder, thickening agent, and gelling agent, (vii) plasticizer, (viii) lipid, (iv) optionally a flavoring agent, and (v) optionally a sweetener ([0005]). Specifically, component (vi) is a combination of pectin and microcrystalline cellulose ([0009]; [0285]). Pullulan, hydroxypropyl methylcellulose, xanthan gum and other polymers are also listed as examples of the binder, thickening agent, and/or gelling agent ([0147]). Additives may also be included in the films. Examples of classes of additives include blowing agents and more ([0108]).
Regarding claim 217, it would have been obvious to combine the compositions of Park and Bernardo before the effective filing date of the claimed invention by substituting the foam stabilizer of Park with the pectin and microcrystalline cellulose of Bernardo to yield the instantly claimed invention. Both Park and Bernardo teach oral dissolving films for delivering active ingredients to the user. The foam stabilizer (i.e., scaffolding agent) of Park is chosen from thickeners, gelling agents, and various polymers while component (vi) of Bernardo is defined as at least one of a binder, thickening agent, and gelling agent. It would have been obvious to use the pectin and microcrystalline cellulose of Bernardo as the foam stabilizer (i.e., scaffolding agent) in the dissolvable film of Park, since pectin and MCC are known and effective thickening/gelling agents for dissolvable films as taught by Bernardo and the foam stabilizer of Park is selected from similar thickening/gelling agents. Simple substitution of one known element for another (i.e., thickening/gelling agents) to obtain predictable results is considered prima facie obvious. See MPEP 2143. One of ordinary skill in the art would have had a reasonable expectation of success in making such a substitution since both Park and Bernardo teach oral dissolving films that comprise thickening/gelling agents, active ingredients, and blowing agents.
Regarding claims 222-223, it would have been further obvious to substitute the active ingredients of Park with those of Bernardo to arrive at the instantly claimed invention. As discussed above, both Park and Bernardo teach oral dissolving films for delivering active ingredients to the user. It would have been obvious to use the actives of Bernardo, specifically melatonin, caryophyllene, GABA, L-theanine, and vitamin B6, as the active ingredients in the dissolvable film of Park since these actives are known and effective actives for use in an oral dissolving film that delivers active agents to the user. It would have been obvious to use the actives of Bernardo since they treat sleeping disorders as taught by Bernardo and the actives of Park may be therapeutic agents for insomnia. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In this case, the actives of Bernardo are suitable for their use in treating insomnia as well as their use in oral dissolving films. The actives of Bernardo read on the active agents of claims 222 and 223. One of ordinary skill in the art would have had a reasonable expectation of success in using the active of Bernardo in the film of Park since both Bernardo and Park teach oral dissolving films that integrate various active ingredients into a matrix comprising thickening/gelling agents and blowing agents.
Claims 208-216, 218-221, 224-225, and 227-231 are rejected under 35 U.S.C. 103 as being unpatentable over Park, M.R., et al. (US 20160279071 A1, 09/29/2016, PTO-892), hereinafter Park as applied to claims 208-216, 220-221, 225, and 227-231 above, and further in view of Rademacher, T., et al. (US 20050163830 A1, 07/28/2005, PTO-892), hereinafter Rademacher as evidenced by Afrooz, H., et al. (2021). Salt Engineering of Aripiprazole with Polycarboxylic Acids to Improve Physicochemical Properties. AAPS PharmSciTech. 22(1):31, (PTO-892), hereinafter Afrooz.
The teachings of Park are discussed above.
Park further teaches that the orally disintegrating porous film may further include a pH controller in addition to the foaming agent, the foam stabilizer, the plasticizer, and the pharmacologically active ingredient ([0029]). The pH controller may include potassium dihydrogen phosphate, sodium hydroxide, sodium bicarbonate, sodium phosphate, ammonium hydroxide, sodium stannate, triethanolamine, citric acid, hydrochloric acid, sodium citrate, and combinations thereof ([0031]). Also, as discussed above Example 1 of Park specifically comprises Aripiprazole as the main ingredient (i.e., active agent) (Table 1). Aripiprazole is known to have a bitter tase as evidenced by Afrooz (abstract).
The teachings of Park differ from that of the instantly claimed invention in that Park does not explicitly disclose an acid/base pair that, when combined, results in the evolution of a gas, as defined in claims 218-219.
Rademacher teaches a thin film-shaped or wafer-shaped pharmaceutical preparations for oral administration of active substances. The preparations contain at least one matrix-forming polymer which has at least one active substance and at least one carbon dioxide-forming substance dissolved or dispersed therein (abstract). The pharmaceutical preparations are in the form of thin, solid foams. Wafers in the form of thin foams are advantageous since they quickly adhere to the mucosa due to their large specific surface, and since they also disintegrate quickly ([0045]; claim 18). The object of Rademacher was to provide thin, sheet-like pharmaceutical preparations for administration of active substances via the oral mucosa which no longer exhibit the disadvantages of a problematic taste sensation, or otherwise have such a disadvantage significantly reduced ([0012]). Such a problem is especially prevalent with mucoadhesive and/or rapidly disintegrating flat administration forms where the active substance is to be released and absorbed by the oral mucosa as quickly as possible ([0011]). A solution was achieved by including a gas-forming component which comprises at least one carbon dioxide-forming substance for reducing or suppressing the unpleasant taste of the active substance ([0013]). Carbon dioxide-forming substances suitable for the pharmaceutical preparations according to the invention are pharmaceutically applicable monobasic to dibasic salts of carbonic acid, e.g. alkali metal hydrogen carbonates or alkali metal carbonates, alkali earth metal carbonates or ammonium carbonates and mixtures thereof. Preferred carbon dioxide-releasing substances are sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate or potassium carbonate ([0016]; claim 3).
Rademacher also teaches that with the preparations according to the invention, the active substance release takes place by way of permeation through the oral mucosa. As a prerequisite for this, the flat preparation must be in close contact with the mucosa during the period of application, i.e. if possible until the dissolution or disintegration of the preparation has taken place. By choosing suitable auxiliary substances, it is possible to produce improved contact between the pharmaceutical preparation and the oral mucosa. For this reason, the pharmaceutical preparation contains an adhesion-imparting auxiliary substance or auxiliary substance mixture imparting bio-adhesive or mucoadhesive properties to the preparation. Certain orally applicable auxiliary substances which are usual in pharmaceutics are known to possess mucoadhesive properties. Examples for such mucoadhesive substances are carboxymethyl cellulose and more ([0039]; claim 12).
First, it would have been obvious to combine the teachings of Park and Rademacher before the effective filing date of the claimed invention by adding a carbon dioxide-forming substance as taught by Rademacher into the oral disintegrating film of Park to yield the instantly claimed invention. Both Park and Rademacher teach orally disintegrating films used to deliver an active agent through the oral mucosa. Rademacher teaches that preparations of that type are known to exhibit the disadvantages of a problematic taste sensation, a problem which is solved by the addition of a carbon dioxide-forming substance. Furthermore, the active ingredient of Park is known to have a bitter taste. Thus, one of ordinary skill in the art would have been motivated to include the carbon dioxide-forming substance of Rademacher in the oral film of Park, in order to mask the bitter taste of the active ingredient present in the oral film of Park. It would have been further obvious to use any of the preferred carbon dioxide-releasing substances of Rademacher (i.e., various carbonates), since the selection of a known material for incorporation into a composition, based on its recognized suitability for its intended use is prima facie obvious. See MPEP 2144.07. One of ordinary skill in the art would have had a reasonable expectation of success in incorporating the carbonates of Rademacher into the oral film of Park since both Rademacher and Park teach oral films which disintegrate to deliver active ingredients to the oral mucosa.
Second it would have been obvious to combine the teachings of Park and Rademacher before the effective filing date of the claimed invention by adding an auxiliary substances with mucoadhesive properties as taught by Rademacher into the oral disintegrating film of Park to yield the instantly claimed invention. The auxiliary substances of Rademacher, specifically carboxymethyl cellulose, are known and effective for increasing the mucoadhesive properties of an orally disintegrating film for delivering pharmaceuticals. The increase in mucoadhesion improves the contact between the film and the oral mucosa to improve drug delivery as reasonably suggested by Rademacher. Thus, one of ordinary skill in the art would have been motivated to add the auxiliary substance of Rademacher in order to increase the mucoadhesive properties of the film and therefore improve the delivery of the active ingredient. It would have been further obvious to select carboxymethyl cellulose as the auxiliary substance to be incorporated since carboxymethyl cellulose is a known and effective auxiliary substance with mucoadhesive properties as taught by Rademacher. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07.
The combined composition of Park and Rademacher therefore comprises a carbon dioxide-releasing substance in the form of a carbonate, which reads on the acid/base pair of claims 218 and 219, as well as an auxiliary substance in the form of carboxymethyl cellulose, which reads on the hygroscopicity modifier of claim 224.
Claims 208-216, 220-221, 225-231 are rejected under 35 U.S.C. 103 as being unpatentable over Park, M.R., et al. (US 20160279071 A1, 09/29/2016, PTO-892), hereinafter Park as applied to claims 208-216, 220-221, 225, and 227-231 above, and further in view of Borges, A.F., et al. (2015). Oral films: Current status and future perspectives: I — Galenical development and quality attributes, Journal of Controlled Release, Volume 206, Pages 1-19 (PTO-892), hereinafter Borges and Nair, A.B., et al. (2013). In vitro techniques to evaluate buccal films, Journal of Controlled Release, Volume 166, Issue 1, Pages 10-21 (PTO-892), hereinafter Nair.
The teachings of Park are discussed above.
Park further teaches a step (d) of drying the film solution to mold a film ([0013]). The prepared film solution is filtered and then placed in a molding machine wherein the temperature of the molding machine is preferably 50 to 150 (oC), and the solution is applied on a PET film and prepared in roll form using a belt dryer, thus obtaining a film ([0054]). Park also teaches that the molded film is aged for about 1 to 10 days at a relative humidity of 50 to 70%, so that it has moisture content is suitable for slitting or cutting ([0055]).
The teachings of Park differ from the instantly claimed invention in that Park does not teach wherein the dissolvable sheet comprises no more than 4% water (w/w) as recited in claim 226.
Borges teaches that the residual water content of orodispersible films is critical and should be strictly defined for each specific formulation, since it may significantly influence various properties. It is also crucial to monitor and control the room conditions during production (temperature and relative humidity), and an appropriate primary packaging material should be provided to avoid water transferences between the product and the surrounding room. An excess or deficit of water content may affect the mechanical properties of the polymeric matrix. The water molecules may interpose in the polymer chains functioning as a plasticizer, so the loss of water content, may contribute for brittle polymeric matrices. In turn, an excess of water absorption by the polymeric matrix may originate sticky films that may adhere to the patient's fingers and/or packaging material. Moreover, the interposition of the water molecules in the polymeric chains may also influence the disintegration/dissolution of the films. The loss of water molecules would contribute to tighten the polymeric chain links, making the water penetration difficult and therefore the disintegration time. Furthermore, the free water in the film may also interfere with the stability of the drug substance incorporated and/or with the excipients (section 7.5).
Nair discloses an overview on the various parameters that are considered and assessed as a part of formulation development for buccal films to ensure quality product with desired characteristics (abstract). Specifically, Nair discusses moisture content stating that the amount of moisture affects the brittleness and friability of buccal films. Typically, a specific size of preweighed film is heated to 100–120 °C until it attains constant weight and the difference in weight gives the amount or degree of moisture present in the film. The moisture content in an ideal buccal film should be < 5% according to Nair (section 2.8).
It would have been obvious to combine the teachings of Park, Borges, and Nair before the effective filing date of the claimed invention by modifying the oral disintegrating film of Park according to the teachings of Borges and Nair to give the instantly claimed invention. Park, Borges, and Nair all teach oral films for the delivery of active agents to a user. As taught by Park, the films undergo a drying and aging step that controls the final moisture content of the film. Borges and Nair both discuss the influence of moisture content on the properties of oral films. Specifically, Borges teaches how moisture content affects the mechanical properties, texture, disintegration, and stability of oral films. Nair also provides a teaching that an ideal buccal film should have a moisture content of < 5%. Thus, one of ordinary skill in the art would have been motivated to adjust the moisture content of the oral film of Park to be below 5% since this is a desirable moisture content for oral films as taught by Nair and moisture content affects various results effective parameters of the final product. One of ordinary skill in the art would have had a reasonable expectation of success in adjusting the moisture content in the oral film of Park since the water content can be adjusted by the time and temperature of the drying step as well as the time and humidity of the aging step as reasonably suggested by Park, Borges, and Nair. While a water content of <5% does not fall completely within the instantly claimed range of <4%, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05.
Conclusion
No claims are allowed.
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616