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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/03/2024, 08/12/2025, 12/03/2025, 05/26/2026 and 07/07/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 44-49, 51-56, 58, 63-64 and 66-67 are rejected under 35 U.S.C. 103 as being unpatentable over Mellott (US20190241849A1; published Aug 8, 2019; hereinafter “Mellott;” See IDS of Jul 3, 2024).
Regarding claim 44: Mellott was directed to an expandable culture substrate comprising a 3D structure including a coupling point configured for reversible coupling to another 3D structure, wherein the 3D structure includes a void volume configured to accommodate cultured cells. (See Mellott claim 1). Mellott further taught that the 3D structure comprises a porous material having open cavities (See Mellott claim 12). Mellott further taught that the cell culture substrate comprises plurality of coupling points (See Mellott Claim 5), wherein the first coupling point is a male coupling point and the second coupling point is a female coupling point. (See Mellott Claim 8). Mellott taught that the 3D structure may comprise polymeric biomaterials including hyaluronic acid, chitosan alginate, among others (See Mellott claim 15).
Mellott’s 3D polymeric scaffold having open cavities reads on the claimed “continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material.”
The only difference between Mellot and the instant claim is that Mellot does not teach a single embodiment having all the claimed features with sufficient specificity to be anticipatory, however the specific combination of features claimed is disclosed within the teachings of Mellot. Therefore, it would have been obvious for a person of ordinary skill in the art at the time of the invention to provide the porous scaffold of Mellot with an interconnected microporous architecture while retaining Mellott’s male/female coupling points. As such it was known that complementary male/female coupling points and pore architectures were conventionally employed in hydrogel scaffolds to improve biological performance without altering intended modular assembly of the scaffold design principles to obtain the expected benefits of enhanced cell migration, nutrient diffusion and tissue in growth while preserving reversible interlocking functionality taught by Mellott.
Accordingly, it would have been obvious for a person of ordinary skill in the art to arrive at the claimed interlocking hydrogel block comprising a 3D macrostructure having complementary male/female components and a continuous polymeric matrix with interconnected microporous channels.
Regarding claims 45-49, 52 and 64: Mellott taught expandable cell-culture substrate comprising 3 dimensions structures having coupling points configured for coupling additional three-dimensional structures. [0033] of Mellott taught that the coupling points may comprise various interlocking and reversible coupling architectures, including male-female fittings such as “mortise and tenon, tongue-and-groove, dovetails, cross laps, magnetic couplings, and various reactive or chemical couplings.” Further Mellott’s Figure 2 taught the interlocking-male component extending outwardly from the side edge as required by the claim. Further, Figure 5 of Mellott showed three-different interlocking-male component extending outwardly from three different edges, as required by claim 46. Additionally, the cross sectional view clearly showed the female component extending inwardly from the at least one side edge towards an interior portion of the D macrostructure, as required by claim 47. Figure 6 showed various expandable cell culture substrates, comprising various configurations with two sides comprising female components as required by claim 48.
Regarding claim 51: Claim 18 of Mellott taught that “the plurality of coupling points includes a first coupling point and a second coupling point, the first coupling point and the second coupling point are different, the three-dimensional structure includes an x-dimension, a y-dimension, and a z-dimension, each dimension independently between about 0.25 cm and about 1 cm” (See Mellott claim 18). As such the dimensions of the sides in Mellott gives an area between 0.25-25 cm2.
Regarding claim 53-56: Claim 15 of Mellott taught polyurethanes, which are non-degradable as evidenced by Xu (See Xu Abstract). Further hyaluronic acid is biodegradable and swellable and derived from animals or plants (See evidence in Dovedytis, p. 105, col. 1, para 3 and p. 104, col. 1, para 4 and p. 102, col. 1, para 2). Further, as evidenced by Xu, “PUs are soft and elastic polymeric biomaterials with high mechanical strength, which mimics the mechanical properties of soft and elastic tissues.” (See Xu Abstract)
Regarding claim 58: Mellott taught “[s]haping of three-dimensional structure can be performed in various ways.” (See Mellott [0049]) Mellott further taught that “additive manufacturing processes for expandable cell culture substrates include the use of 3D printing, which can include melting and extruding a polymer out of a predefined nozzle, such as a 100 μm diameter nozzle, and layering the polymer in a pre-defined shape.” (See Mellott [0051])
Regarding claim 63: Figure 5 of Mellott taught a scaffolding system comprising a plurality of cell culture scaffolds. Mellott taught that “there can be a plurality of three-dimensional structures, where each of the three-dimensional structures includes a coupling point and a void volume configured to accommodate one or more cultured cells.” (See Mellott [0009])
Regarding claim 66: Mellott taught that when multiple porous blocks are assembled, the interconnected void spaces collectively permit medium flow. (See Mellott [0075]).
Regarding claim 67: Mellott taught that “cells from various cultures and/or sources can therefore be combined by coupling of expandable cell culture substrates.” (See Mellott [0054]). As such it would have been obvious to a person of ordinary skill in the art that cells from different sources or cultures may be different primary cell types. Accordingly it would have been obvious to seed a first expandable cell-culture substrate with a first primary cell and second expandable cell-culture substrate with a second primary cell, and coupling the substrates together in order to combine different cell populations in a single modular scaffold system as contemplated by Mellott.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Mellott (US20190241849A1; published Aug 8, 2019; hereinafter “Mellott;” See IDS of Jul 3, 2024) and Li et al (Bioanalysis. 2012 Jun; hereinafter “Li;” See PTO-892).
Regarding claim 50: The teachings of Mellott are set forth above. It is noted that Mellott did not teach the claimed differences in textures. Li taught that structural projections and micropillars are conventionally used in 3D cell culture systems to optimize cell-culture medium flow, oxygen perfusion, nutrient transport and removal of metabolic waste. Li explained that micropillars create flow paths for culture medium through gaps between adjacent structural projections, thereby reducing medium-starved regions and improving the culture environment.
It would have been obvious to a person of ordinary skill in the art to modify the bottom surface of Mellott’s 3D cell-culture substrate to include a plurality of minor protrusions functions as structural spacers in order to facilitate the flow of culture medium beneath the substrate. Li taught that micropillars are “designed to optimize medium flow and oxygen perfusion throughout the cell culture and diminish the effect of medium-starved necrotic regions. The ease of design and fabrication of micro-scale features such as microfluidic channels and micropillars through the use of PDMS injection-molding has allowed the harnessing of these features for dynamically-perfused 3D culture” (See Li p. 3, last para to p. 4, 1st para). Particular geometry of minor protrusions such as configuring the projections as nubs, ridges or other protruding spacer features would have been an obvious matter of routine engineering design choice.
Claims 57, and 59-62 are rejected under 35 U.S.C. 103 as being unpatentable over Mellott (US20190241849A1; published Aug 8, 2019; hereinafter “Mellott;” See IDS of Jul 3, 2024) and Ebrahimi et al (Front. Mater. Sci., 2021; hereinafter “Ebrahimi;” See PTO-892).
Regarding claims 57, 59-61: The teachings of Mellott are set forth above. Mellott did not teach varying the pore size according to the morphology of a natural tissue of interest as required by the claim.
However, Ebrahimi taught that tissue engineering should be designed according to a biomimetic approach, in which scaffold architecture, including pore geometry, pore size, pore distribution and porosity is tailored to mimic the morphology and heterogenous architecture of the target natural tissue. For example, Ebrahimi taught that “The scaffold should ideally possess varying porosity parameters in different regions to support the ingrowth and functions of different cells and tissues. Literature has shown that different cells and tissue regeneration are supported by different pore sizes, for example, 100–400 μm for bone cells, 70–120 μm for chondrocyte, and 5–15 μm for fibroblast cell ingrowth” (See Ebrahimi p. 357, col. 1, para 2).
It would have been obvious to a person of ordinary skill in the art to modify the porous network of Mellott so that the geometry and dimensions of its microporous channels and/or chambers mimic morphology of desired natural tissue as taught by Ebrahimi, because doing so represents a known biomimetic design strategy for improving scaffold performance, promoting appropriate cellular interactions and facilitating tissue regeneration.
Regarding claim 62: Ebrahimi taught that “several modifications have been implemented using different peptide or protein sequences to optimize substrate surfaces for better cellular responses. Application of peptide sequence “Arg-Gly-Asp (RGD)” as cell-adhesion moieties is such a method suggested to improve initial cellular attachment.” (See Ebrahimi p. 354, col. 2, 1st para). It would have been obvious to a person of ordinary skill in the art to modify the porous network of Mellott to incorporate cell-adhesion moieties to enhance cell adhesion. Doing so represents a known biomimetic design strategy for improving scaffold performance, promoting appropriate cellular interactions and facilitating tissue regeneration.
Claims 65 is rejected under 35 U.S.C. 103 as being unpatentable over Mellott (US20190241849A1; published Aug 8, 2019; hereinafter “Mellott;” See IDS of Jul 3, 2024) and Park et al (ACS Macro Lett. 2017; hereinafter “Park;” See PTO-892).
Regarding claim 65: The teachings of Mellott are set forth above. Mellott did not teach providing the first and second IPHB in a swollen state as required by the claim to improve interlocking. However, it would have been obvious to a person of ordinary skill in the art to form Mellott’s interlocking hydrogel cell culture substrate from swellable hydrogel materials, such that, upon absorbing culture medium, the interlocking members swell and thereby increase the mechanical engagement between complementary coupling members. Such interlocking systems were well known in the art. For example, Park taught “wet-responsive, shape-reconfigurable, and flexible hydrogel adhesives that exhibit strong adhesion under wet environments based on reversible interlocking between reconfigurable microhook arrays” (See Park Abstract). Park further taught that “The adhesion between the interlocked microhook arrays is greatly enhanced under wet conditions because of the hydration triggered shape reconfiguration of the hydrogel microstructures. Furthermore, wet adhesion monotonically increases with water exposure time. A maximum adhesion force of 79.9 N cm−2 in the shear direction is obtained with the hydrogel microhook array after 20 h of swelling, which is 732.3% greater than that under dry conditions (i.e., 9.6 N cm−2).” (See Park Abstract).
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 50, 54 and 57 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 50: The claim required “minor protrusions.” However, it is pointed out that the relative term “minor” is not defined in the specification. The specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Regarding claim 54: The claim requires the matrix to be selectably degradable. It is not clear what material or properties are considered selectably degradable. As such the metes and bounds of this term are unclear.
Regarding claim 57: The claim requires that the matrix material have softness or tension within about 20% of natural tissue of interest. It is unclear, what tissue the property of matrix material is being compared. Further, it is unclear how a person of ordinary skill in the art can measure softness.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 44-49, 51-57, 63-64 and 66-67 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-43 of copending Application No. 18/726,671 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons listed below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 44-47: Claim1 of the reference application is directed to interlocking porous hydrogel block (IPHB), wherein the first IPHB comprises a three-dimensional (3D) macrostructure defined by a continuous polymeric matrix material and a network of microporous channels and/or chambers extending throughout the continuous polymeric matrix material, and wherein the 3D macrostructure comprises a top surface, a bottom surface, and a thickness defined by at least one side edge extending from the top surface to the bottom surface, and wherein the 3D macrostructure structure includes at least one interlocking-male component and at least one interlocking-female component. This reads on the claims of the instant application. It is further noted that [0056] of the reference application taught that the interlocking-male component extending outwardly from the first side edge and the second side edge may include the at least one interlocking-female component extending inwardly from the second side edge towards an interior portion of the 3D macrostructure. This reads on claim 46 and 47 of the instant application.
Claims 48-49, 51-57, 63-64 and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-43 of copending Application No. 18/726,671 (reference application) in view of Mellott (US20190241849A1; published Aug 8, 2019; hereinafter “Mellott;” See IDS of Jul 3, 2024).
The teachings of Mellot are set forth above. Further, the teachings of the copending reference application are set forth above. A person or ordinary skill in the art would have been able to arrive at the dependent claims as set forth in the indicated claims in view of the teachings of the claims of reference application further in view of Mellott due to the reasons set forth above.
Conclusion
No claims are free of art.
No claims are allowed.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633
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