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 .
DETAILED ACTION
Election/Restriction
Applicant’s election, without traverse, of Group I, claims 1-4 and 10-14, drawn to a method of culturing cells, in the reply filed on 08/14/2026 is acknowledged.
Claims 5-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Status
Claims 1-14 are pending.
Claims 5-9 are withdrawn.
Claims 1-4 and 10-14 are considered on the merits.
Priority
This application is a 371 of PCT/GB2023/050284 (filed on 02/08/2023), which claims benefit from foreign application GB2201609.1 (filed on 02/08/2022). The priority claim of the instant application has been granted and the earliest benefit date is 02/08/2022 from the application GB2201609.1.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/11/2024 and 07/09/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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 10-14 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.
Claims 10, 11 and 14 recite the limitation “wherein the first substrate, second substrate when present, third substrate when present, and the at least one additional pair of substrates when present”. There is insufficient antecedent basis for this limitation in the claims because base claim 1 only recites a first substrate but is silent on a second, third or at least one additional pair of substrates. This limitation is being examined as “wherein the first substrate”. Claims 12-13 are rejected as being dependent on claim 10 but not resolving the ambiguity.
Claim Rejections - 35 USC § 102
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.
Claims 1-4 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Wilhelm (US Patent No. 5,190,878. Cited in IDS 07/09/2025).
With respect to claim 1, Wilhelm teaches a technique that permits the cultivation of highly differentiated cells on a cell support in bioreactors (col. 1, lines 50-54, see e.g., Figs 3-6 for a bioreactor) and teaches in Fig 1, Fig 3 and Fig 4 that cells (#8) are seeded and cultured on a surface of a cell substrate (#1), thus teaches a method of culturing cells wherein the method comprises introducing seed cells onto a first surface of a first substrate (see e.g., Fig 4 attached below), and culturing cells on the first surface of the first substrate within a bioreactor. Wilhelm teaches cell culture medium is introduced via an inflow port (#13) (e.g., abstract and Figs 3-4). Wilhelm teaches an apparatus for cultivation of biological cells comprising “a penetrable flat cell substrate (#1) with a cell culture thereon … and the cell treatment medium can come into contact with said cell substrate (#1) from both the apical and basal sides” (see reference claim 1 in col. 5) and “As a result of this construction a separate apical and basal perfusion of the cells (#8) is made possible concurrently” (col. 3, lines 18-20), thus teaches the culture medium is introduced over a second surface of the first substrate (i.e., the basal side of the substrate) and permeates through the substrate to the first surface (i.e., resulting in basal perfusion of the cells), and the second surface is on the opposite side of the substrate to the first surface (see annotated Fig 4 attached below).
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With respect to claim 2, Wilhelm teaches a second substrate that has a first surface and a second surface that are on the opposite sides to each other, the second substrate is arranged in the bioreactor such that the second surface of the second substrate opposes the second surface of the first substrate to bound a perfusion region (see Fig 4 above). As stated supra, Wilhelm teaches the cell substrates are penetrable (see e.g., reference claim 1) and a separate apical and basal perfusion of the cells (#8) is made possible concurrently (col. 3, lines 18-20), thus teaches the culture medium is introduced into the perfusion region (see top “culture medium” on the left of the panel above) so as to introduce the culture medium over the second surface of the first substrate and the second surface of the second substrate so as to permeate through the first substrate to the first surface of the first substrate and permeate through the second substrate to the first surface of the second substrate.
With respect to claim 3, Wilhelm teaches a third substrate that has a first surface and a second surface that are on the opposite sides to each other, the third substrate is arranged in the bioreactor such that the first surface of the third substrate opposes the first surface of the second substrate to bound a cell region (see Fig 4 above, see the cells seeded on the first surface of the third substrate). As stated supra, Wilhelm teaches the cell substrates are penetrable (see e.g., reference claim 1) and a separate apical and basal perfusion of the cells (#8) is made possible concurrently (col. 3, lines 18-20), thus teaches the culture medium is additionally introduced over the second surface of the third substrate and permeates through the third substrate to its first surface (see bottom “culture medium” on the left of the panel above).
With respect to claim 4 directed to an additional pair of substrates, Wilhelm teaches a plurality of holding devices (#2), each supporting a cell substrate (#1), is successively arranged in said internal space (#19) (see e.g., reference claim 6 and Figs 4-6. It is noted that Fig 4 exemplifies 3 cell substrates, Fig 5 exemplifies 12 holding devices and cell substrates and Fig 6 exemplifies 4 holding devices and cell substrates), thus teaches additional pairs of substrates (e.g., 6 pairs of substrates in Fig 5). A modified Fig 4, with the addition of a fourth cell substrate (thus exemplifying an additional pair of substrates in addition to the pair of the first and second substrates) is attached below for addressing instant claim 4.
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The modified Fig 4 above demonstrates one additional pair of substrates (i.e., the pair of the third and the fourth substrates), the pair of substrates being arranged and configured in the same manner as the first and second substrates (see above), and wherein the additional pair is arranged such that it is arranged over the first and second substrate such that the first substrate, the second substrate and the additional pair of substrates form a stacked arrangement comprising further perfusion regions within each of the at least one additional pair of substrates (see the perfusion region between the third and the fourth substrates) and cell regions between the at least one additional pair of substrates and the second substrate (see the cell region between the second and the third substrates) and between any further additional pairs of substrates (implicitly taught when additional pairs of substrates are added and arranged in the same manner).
Accordingly, Wilhelm anticipates instant claims.
Claims 1, 10-12 and 14 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Garrison et al., (J Biomed Mater Res. 2021;109:733-744).
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With respect to claim 1, Garrison generates a multilayered scaffold with distinct fiber organizations - aligned to unaligned, by electrospinning and performs cell culture on aligned and unaligned sides of this scaffold to demonstrate the differently-oriented scaffold fibers direct cell and extracellular matrix organization (see e.g., abstract and p. 737, section 3.2). Garrison teaches culturing cells on this scaffold in a transwell design and teaches the scaffold has permeability such that proteins freely diffuse across the multilayered scaffold populated with cells (see e.g., p. 738, left col, section 3.3 “Scaffold permeability” and see Fig 3 attached). Thus, Garrison teaches a method of culturing cells, wherein the method comprises introducing seed cells onto a first surface of a first substrate (see e.g., SMCs on the surface of the scaffold); culturing cells on the first surface of the first substrate within a bioreactor (e.g., in a cell culture well), wherein culture medium is introduced over a second surface of the first substrate (i.e., the DMEM medium outside the transwell) and permeates through the substrate to the first surface (since the scaffold is permeable); and the second surface is on the opposite side of the substrate to the first surface.
With respect to claim 10, Garrison teaches the multilayered scaffold is formed from a plurality of fibres (see e.g., abstract and see e.g., Fig 1 for fibers).
With respect to claim 11 directed to aligned and randomly oriented fibers on the surfaces, as stated supra, Garrison teaches the multilayered scaffold with distinct fiber organizations - aligned to unaligned, yielding densely-packed, aligned fibers that transition into randomly-oriented fibers (e.g., abstract and p. 736, section 3.1, also see e.g., Fig 1 “Aligned side” and “Unaligned side”). Thus, Garrison teaches the multilayered scaffold has aligned fibres on the first surface and randomly oriented fibres on the second surface.
With respect to claim 12 directed to electrospun fibers, Garrison teaches the multilayered scaffold is generated by electrospinning a polymer (see e.g., abstract and p. 736, section 3.1).
With respect to claim 14 directed to planar substrate, Garrison teaches the scaffolds are electrospun as flat sheets (e.g., p. 734, right col, para 2).
Accordingly, Garrison anticipates instant claims.
Claims 1, 10 and 12-14 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Bischel et al., (J Biomed Mater Res Part A. 2016; 104A: 901-909).
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With respect to claim 1, Bischel teaches producing electrospun gelatin biopapers as a substrate for co-culturing cells (e.g., abstract and p. 903, left col, section “Cell culture”, also see Fig 1C attached). Bischel teaches astrocytes and endothelial cells are seeded and cultured on either side of the gelatin biopaper (as a bilayer BBB model) and teaches the permeability of the bilayer model is similar to blank gelatin biopaper at Day 4 to FITC-labeled dextrans and is roughly 100 times more permeable than bilayers grown on PET membranes (see Table I and p. 907, right col, para 2), indicating the gelatin biopapers are permeable. Thus, Bischel teaches a method of culturing cells, comprising introducing seed cells onto a first surface of a first substrate (e.g., endothelial cells on the upper surface of the biopaper); culturing cells on the first surface of the first substrate within a bioreactor (e.g., in a cell culture well), wherein culture medium is introduced over a second surface of the first substrate (i.e., the cell culture medium outside the transwell) and permeates through the substrate to the first surface (since the biopaper is permeable); and the second surface is on the opposite side of the substrate to the first surface.
With respect to claim 10, Bischel teaches the electrospun gelatin biopapers are formed from a plurality of fibers (see e.g., Fig 2 for fibers).
With respect to claim 12, Bischel teaches the biopapers are formed by electrospun gelatin fibers (see e.g., Fig 2 for electrospun fibers).
With respect to claim 13, Bischel teaches the biopapers are formed by gelatin (e.g., abstract), which is well-known to be used as food supplement or food additive, thus teaches the plurality of gelatin fibers are edible fibers.
With respect to claim 14, as stated supra, Bischel teaches the biopapers in a cell culture insert (see Fig 1C above), thus teaches the biopaper is a planar substrate.
Accordingly, Bischel anticipates instant claims.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
