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
The instant application is a national stage entry under 35 USC 371 of PCT/JP2022/021748, filed
27 May 2022. Acknowledgement is made of Applicant’s claim for foreign priority under 35 USC 119(a)-(d) to Japanese Application No. JP2021-092013, filed 01 June 2021. Receipt is acknowledged of certified copies of papers, in a non-English language, required by 37 CFR 1.55.
Status of the Claims
Applicant’s preliminary submission filed 29 November 2023 has been entered. Claims 13-20 are pending. Claims 1-12 have been cancelled without prejudice or disclaimer and claims 13-20 have been newly added. Therefore, prosecution on the merits commences for claims 13-20.
Specification
The preliminary amendments to the Specification filed 29 November 2023 are acknowledged and entered into the application file.
However, the abstract of the disclosure is objected to because it exceeds the 150 word count limit. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
In addition, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code within Page 2 of the Specification filed 29 November 2023. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Furthermore, the disclosure is objected to for referencing colors within the figures, when colored drawings have not submitted in the application. More specifically, the Specification references colors at least within Page 46 in reference to Figure 13A. Applicant is requested to review the Specification to identify any additional references to colors within the drawings and delete as appropriate since black and white drawings are submitted. The Specification must be amended to delete reference to specific colors within the text of the Specification.
Appropriate correction is required.
Claim Objections
Claims 14, 16-17, and 19-20 are objected to because of the following informalities:
Regarding claim 14: The instant claim is objected to for reciting “wherein the cell is an intestinal epithelial cell or an epithelial cell of another tissue or organ or the cell is of epidermis cell, and wherein the tissue is an intestinal epithelial tissue or another epithelial tissue or the tissue is an epidermis tissue” instead of “wherein the cell is an intestinal epithelial cell or an epithelial cell of another tissue or organ, or the cell is an epidermis cell[[,]]; and wherein the tissue is an intestinal epithelial tissue or another epithelial tissue, or the tissue is an epidermis tissue”, or the like. The Examiner notes that the additional punctuation is necessary to clarify and separate the claim limitations.
Appropriate correction is required.
Regarding claims 16 and 19: The instant claims are each objected to for reciting “wherein the cell is an intestinal epithelial cell or an epithelial cell of another tissue or organ or the cell is of epidermis cell, wherein the tissue is an intestinal epithelial tissue or another epithelial tissue or the tissue is an epidermis tissue, and wherein the biological tissue model is selected from an intestinal epithelial tissue model, an epithelial tissue model of another epithelial tissue and an epidermis tissue model” instead of “wherein the cell is an intestinal epithelial cell or an epithelial cell of another tissue or organ, or the cell is an epidermis cell[[,]]; wherein the tissue is an intestinal epithelial tissue or another epithelial tissue, or the tissue is an epidermis tissue[[,]]; and wherein the biological tissue model is selected from an intestinal epithelial tissue model, an epithelial tissue model of another epithelial tissue, and an epidermis tissue model”, or the like. The Examiner notes that the additional punctuation is necessary to clarify and separate the claim limitations.
Appropriate correction is required.
Regarding claims 17 and 20: The instant claims are each objected to for reciting “wherein the intestinal epithelial tissue model expresses intestinal villus structure, microvillus structure, digestive enzyme activity, drug-metabolizing enzyme activity, mucus production capacity, barrier function and/or alkaline phosphatase (ALP)” instead of “wherein the intestinal epithelial tissue model expresses an intestinal villus structure, a microvillus structure, digestive enzyme activity, drug-metabolizing enzyme activity, mucus production capacity, barrier function, and/or alkaline phosphatase (ALP)”, or the like.
Appropriate correction is required.
Claim Interpretation
Instant claim 13 defines the transparent dual-layer substrate as being “manufactured by a method comprising the steps of:
1) dissolving a cellulose derivative in an organic solvent to prepare an organic solvent solution of the cellulose derivative;
2) coating a substrate with the organic solvent solution of the cellulose derivative and drying it to prepare a cellulose derivative membrane;
3) drying the cellulose derivative membrane for a prescribed period of time, immersing the membrane in hot water for a prescribed period of time, immersing the membrane in cold water for another prescribed period of time, and then peeling the membrane from the substrate to prepare a porous cellulose derivative membrane; and
4) spinning polymer microfibers on the porous cellulose derivative membrane by electrospinning to laminate the porous cellulose derivative membrane with the polymer microfibers,
wherein coating thickness in the step 2) is from 150 to 200 μm, and an upper half of the membrane has an average porous diameter of 0.306 μm while a lower half of the membrane has an average porous diameter of 0.515 μm.
This is a product-by-process limitation. Product-by-process limitations are only considered in so far as the method of production affects the structure of the final product. In the instant case, there is no evidence that the transparent dual-layer substrate derived from recited production method imparts any
particular structure or significance to the dual-layer substrate other than requiring the thickness of the cellulose derivative membrane to be 150 to 200 μm, and have an average porous diameter of 0.306 μm in the upper half of the membrane while the lower half of the membrane has an average porous diameter of 0.515 μm. Therefore, instant claim 1 will be interpreted as if a transparent dual-layer substrate comprising a porous cellulose derivative membrane having a thickness of 150 to 200 μm and an average porous diameter of 0.306 μm in the upper half of the membrane while the lower half of the membrane has an average porous diameter of 0.515 μm fulfills the limitation detailed in the instant claim.
Furthermore, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure or composition, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See MPEP § 2111.02 (II) and In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976); Kropa v. Robie, 88 USPQ 478, 481 (CCPA 1951). Therefore, the transparent dual-substrate of instant claim 13 is being interpreted as being drawn to the specific structural limitations recited in the claim, wherein the transparent dual-layer substrate comprises a porous cellulose derivative membrane on which polymer microfibers are spun and laminated, wherein the porous cellulose derivative membrane is light permeable under a wet condition, and wherein the porous cellulose derivative membrane has a thickness of 150 to 200 μm and an average porous diameter of 0.306 μm in the upper half of the membrane while the lower half of the membrane has an average porous diameter of 0.515 μm.
On the contrary, in regards to the “biological tissue model involving air-liquid interface culture of a cell and/or tissue” recited within the preamble of instant claim 15, the involvement of the air-liquid interface culture of a cell and/or tissue is necessary to give life, meaning, and vitality to the claim. Therefore, the preamble is afforded patentable weight and thereby limits the scope of the claim. See MPEP § 2111.02.
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 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al (CN110373378A, translation provided by Espacenet) in view of Baca et al (US 2008/0187996 A1, of record on IDS filed 29 November 2023) and Kaminaga et al (US 2020/0138014 A1).
Hu et al is considered prior art under 35 USC 102(a)(1), with a publication date of 25 October 2019. Baca et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Kaminaga et al is
considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 13-14: Independent claim 13 comprises a product-by-process limitation as well as an intended use limitation that are each interpreted as set forth in the Claim Interpretation section above.
Hu et al disclose an in vitro intestinal model based on primary intestinal cells and its construction method and application (Abstract).
As such, Hu et al disclose the culture of primary intestinal epithelial cells on a patterned electrospun nanofiber scaffold that is situated within a transwell insert, wherein the intestinal epithelial cell layer forms intestinal microvilli that are capable of being differentiated to obtain an in vitro intestinal model with complete biological activity and physiological functions (Pages 1-4, 6; Figures 1, 3-5, 8).
Hu et al further disclose that the electrospun nanofibers are 50 nm to 5000 nm in size, and are comprised of cellulose acetate (Pages 3-4, 6). Hu et al further disclose that the electrospun nanofiber scaffold can be adhered to the surface of a porous material, wherein the porous material is a porous film or membrane (Pages 3-4).
Hu et al do not disclose that the porous membrane is comprised of a cellulose derivative, nor that the porous membrane has a thickness of 150 to 200 μm and an average pore diameter of 0.306 μm in the upper half of the membrane while the lower half of the membrane has an average pore diameter of 0.515 μm, as required by instant claim 13.
Baca et al, however, disclose the culture of epithelial cells on a substrate, wherein the substrate comprises a network of nanofibers that is deposited on a base porous membrane (Paragraphs [0102]-[0103], [0114]-[0116], [0139]). Baca et al further disclose that the base porous membrane is comprised of the same material as the nanofibers, which includes cellulose derivatives (Paragraphs [0056], [0099], [0115], [0117]). Baca et al further disclose that the pore size of the porous membrane is greater than 0.2 microns and less than 1 micron (Paragraph [0116]).
With that, Kaminaga et al disclose that porous cellulose acetate membranes for the culture of intestinal epithelial cells can have a thickness between 35 μm to 200 μm and an average pore diameter that increases in the thickness direction, indicating that an average pore diameter in the upper half of the membrane will be smaller than the average pore diameter in the lower half of the membrane (Paragraphs [0064]-[0066], [0076]-[0089], [0101]-[0106], [0110], [0117], [0149], [0161]-[0170]). Kaminaga et al further disclose that the average pore diameter distribution can range from 0.15 μm to 100 μm (Paragraph [0088]).
Therefore, it would have been prima facie obvious to have modified the in vitro intestinal model of Hu et al such that the porous membrane is comprised of the same material as the electrospun nanofiber scaffold – or cellulose acetate – and has a thickness of 200 μm and an average pore diameter that increases when moving towards the lower half of the membrane, wherein the average pore diameter within the membrane ranges from 0.2 μm to 1 μm, as detailed in Baca et al and Kaminaga et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to adhere the electrospun nanofiber scaffold to a porous membrane that is known in the art for the culture of intestinal epithelial cells, and would have had a reasonable expectation of success given that the disclosures of Hu et al, Baca et al, and Kaminaga et al are each concerned with the culturing of epithelial cells on porous membranes. Furthermore, the ordinary artisan would have understood that since Hu et al disclose the adherence of electrospun nanofiber scaffolds to porous membranes for the culture of intestinal epithelial cells, there would have been minimal adaptation required when incorporating the teachings of Baca et al and Kaminaga et al. See MPEP § 2143(I)(G).
Consequently, Hu et al as modified by Baca et al and Kaminaga et al render obvious an in vitro intestinal model comprising primary intestinal epithelial cells (claim 14) cultured on a patterned electrospun nanofiber scaffold that is adhered to the surface of a cellulose acetate porous membrane, wherein the porous membrane has a thickness of 200 μm and an average pore diameter that increases when moving towards the lower half of the membrane. Since the average pore diameter within the membrane ranges from 0.2 μm to 1 μm, and cellulose acetate is inherently light-permeable when wet, this therefore renders obvious the transparent dual-layer substrate of instant claim 13. See MPEP § 2131.03 and 2144.05 in regards to the membrane thickness and associated pore diameter distribution, as well as Pages 4-5, 12, 16 of the instant Specification filed 29 November 2023 in regards to the inherent feature of the cellulose acetate.
Claims 13-20 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al (CN110373378A, translation provided by Espacenet) in view of Hayden et al (US 2018/0100142 A1) and Kaminaga et al (US 2020/0138014 A1).
Hu et al is considered prior art under 35 USC 102(a)(1), with a publication date of 25 October 2019. Hayden et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Kaminaga et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claims 13-16 and 18-19: Independent claim 13 comprises a product-by-process limitation that is interpreted as set forth in the Claim Interpretation section above.
Hu et al disclose an in vitro intestinal model based on primary intestinal cells and its construction method and application (Abstract).
As such, Hu et al disclose the culture of primary intestinal epithelial cells on a patterned electrospun nanofiber scaffold that is situated within a transwell insert, wherein the intestinal epithelial cell layer forms intestinal microvilli that are capable of being differentiated to obtain an in vitro intestinal model with complete biological activity and physiological functions (Pages 1-4, 6; Figures 1, 3-5, 8).
Hu et al further disclose that the electrospun nanofibers are 50 nm to 5000 nm in size, and are comprised of cellulose acetate (Pages 3-4, 6). Hu et al further disclose that the electrospun nanofiber scaffold can be adhered to the surface of a porous material, wherein the porous material is a porous film or membrane (Pages 3-4).
Hu et al do not disclose that the primary epithelial cells are cultured at an air-liquid interface, nor that the porous membrane is comprised of a cellulose derivative, has a thickness of 150 to 200 μm, and an average pore diameter of 0.306 μm in the upper half of the membrane while the lower half of the membrane has an average pore diameter of 0.515 μm, as required by instant claims 13, 15, and 18.
Hayden et al, however, disclose the culture of intestinal epithelial cells at an air-liquid interface on a porous cellulose nitrate membrane that is situated within a transwell insert, wherein the porous membrane can be overlain with an extracellular matrix material or artificial scaffold (Paragraphs [0007], [0009], [0015]-[0017], [0020]-[0021], [0040], [0047], [0050]-[0056]). Hayden et al further disclose that the average pore size of the porous membrane ranges from 0.1 μm to about 10 μm (Paragraph [0050]).
With that, Kaminaga et al disclose that porous cellulose derivative membranes for the culture of intestinal epithelial cells can have a thickness between 35 μm to 200 μm and an average pore diameter that increases in the thickness direction, indicating that an average pore diameter in the upper half of the membrane will be smaller than the average pore diameter in the lower half of the membrane (Paragraphs [0064]-[0066], [0076]-[0089], [0101]-[0106], [0110], [0117], [0149], [0161]-[0170]). Kaminaga et al further disclose that the average pore diameter distribution can range from 0.15 μm to 100 μm (Paragraph [0088]).
Therefore, it would have been prima facie obvious to have modified the in vitro intestinal model of Hu et al such that the intestinal epithelial cells are cultured at an air-liquid interface and the porous membrane is comprised of cellulose nitrate, has a thickness of 200 μm, and an average pore diameter that increases when moving towards the lower half of the membrane, wherein the average pore diameter within the membrane ranges from 0.1 μm to about 10 μm, as detailed in Hayden et al and Kaminaga et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to adhere the electrospun nanofiber scaffold to a porous membrane that is known in the art for the culture of intestinal epithelial cells, and would have had a reasonable expectation of success given that the disclosures of Hu et al, Hayden et al, and Kaminaga et al are each concerned with the culturing of intestinal epithelial cells on porous membranes. Furthermore, the ordinary artisan would have understood that since Hu et al disclose the adherence of electrospun nanofiber scaffolds to porous membranes for the culture of intestinal epithelial cells within a transwell insert, there would have been minimal adaptation required when incorporating the teachings of Hayden et al and Kaminaga et al – particularly in regards to the culture and differentiation of the intestinal epithelial cells at an air-liquid interface within a transwell insert. See MPEP § 2143(I)(G).
Consequently, Hu et al as modified by Hayden et al and Kaminaga et al render obvious an in vitro intestinal model comprising primary intestinal epithelial cells (claims 14, 16, 19) cultured at an air-liquid interface on a patterned electrospun nanofiber scaffold that is adhered to the surface of a cellulose nitrate porous membrane, wherein the porous membrane has a thickness of 200 μm and an average pore diameter that increases when moving towards the lower half of the membrane. Since the average pore diameter within the membrane ranges from 0.1 μm to 10 μm, and cellulose nitrate is inherently light-permeable when wet, this therefore renders obvious the transparent dual-layer substrate of instant claim 13, the biological tissue model of instant claim 15, and the method of instant claim 18. See MPEP § 2131.03 and 2144.05 in regards to the membrane thickness and associated pore diameter distribution, as well as Pages 4-5, 12, 16 of the instant Specification filed 29 November 2023 in regards to the inherent feature of the cellulose nitrate.
Regarding claims 17 and 20: Following the discussion of claims 16 and 18, Hu et al further disclose that the intestinal epithelial cell layer forms intestinal microvilli that are capable of being differentiated to obtain an in vitro intestinal model with complete biological activity and physiological functions (Pages 1-6; Figures 5, 8). This therefore reads on the biological tissue model of instant claim 17 and the method of instant claim 20.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633