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 .
Status of the Claims
Claims 1-4, 6, 8-10, 13-16, 18-19, 22-23, 25, 27, 29, 32, 35, and 42 are currently pending.
Claims 1 and 16 is amended.
Claims 27, 29, and 42 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 5, 7, 11-12, 17, 20-21, 24, 26, 28, 30-31, 33-34, 36-41, and 43-44 remain cancelled.
Claim 1-4, 6, 8-10, 13-16, 18-19, 22-23, 25, 32, and 35 have been considered on the merits.
Withdrawn Rejections
The 112(b) rejection is withdrawn in light of the amendments made onto claim 1 in the reply submitted on 03/04/2026.
The objections made onto claims 4 and 6 are withdrawn in light of the amendments made on 03/04/2026.
Maintained Rejections/Objections
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.
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 1-4, 6, 8-10, 13-16, 18-19, 22, 32, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Berenschot et al (J. Micromech. Microeng., 2013) in view of Borenstein et al (US20020182241A1).
Claim Interpretation: Claim 1 contains the phrase “subtracting at least one geometrical feature from the monocrystalline substrate” regarding step 2, which is being interpreted in light of the specification. The instant specification states that “the subtracting is performed by means of anisotropic etching” (pg. 3, lines 25-27). Therefore, the “subtracting” is being interpreted to be met by anisotropic etching performed on a monocrystalline substrate.
Claim Interpretation: Claim 8 contains the phrase “create one or more apertures in the protective layer”, which is being interpreted in light of the specification. The specification states that the “apertures is created at every apex in the protective layer… various techniques can be used to make an aperture… the apertures are created by means of times isotropic etching. In this technique, the aperture is created by solely removing the protective layer from the apices” (pg. 13, lines 20-35). Therefore, the creating of an aperture is being interpreted to be able to be completed through the steps of isotropic etching an apex in a protective layer.
Regarding claim 1, Berenschot teaches the following steps:
Step 1: Providing a monocrystalline substrate, described by Berenschot as a single crystalline silicone wafer (pg. 2, col. 2, para 2).
Step 2: Subtracting at least one geometrical feature from the monocrystalline substrate, through anisotropic etching, to produce a geometrical cavity in the monocrystalline substrate that renders as the initiation for a three-dimensional (3D) structure (pg. 2, col. 2, para 2).
Step 3: growth/deposition of a base 3D structure material, taught by Berenschot to be silicon dioxide (SiO2) and referred to as “the oxide”, on the surface of the geometrical features in the substrate to form the 3D structure as required by claims 1 and 13 (pg. 2, col. 2, para 2).
Step 4: bonding of the at least one 3D structure to a surface of a support base, in the case of Berenschot the support base is a borofloat glass wafer (pg. 4, col. 2, para 1; and Fig. 3).
Step 5: removal of the bulk-monocrystalline substrate around the 3D structure as required by claims 1 and 13 (pg. 4, col. 2, para 1).
Berenschot teaches wherein the base 3D structure material is silicon nitride and silicon oxide which is deposited through thermal oxidation, and acts as an insulator as required by claims 2, 13, and 22 (pg. 2, co. 2, para 2). Berenschot teaches wherein the 3D structure is a fractal structure as required by claim 3 (pg. 2, col. 2, para 2). Berenschot teaches that the monocrystalline substrate is a monocrystalline silicon substrate as required by claims 4 and 13 (pg. 2, col. 2, para 2). The geometrical cavity is taught to be an octahedral cavity as required by claim 6 (pg. 2, col. 1, para 2).
Berenschot teaches the following steps which are to be performed between steps 2 and 3 in the method described above as required by claim 8:
Step 6: treating the monocrystalline substrate to form a protective layer which is compatible with the next steps as required by claim 8 (pg. 2, col. 2, last para, spanning pg. 3).
Step 7: creating one or more apertures in the protective layer as required by claim 8 (pg. 3, last para spanning pg. 4 first para).
Step 8: subtracting at least one geometrical feature in the monocrystalline substrate through the one or more apertures; followed by stripping the protective layer as required by claim 8 (pg. 3, last para spanning pg. 4 first para).
Berenschot teaches wherein steps 6-8 are performed between step 2 and 3 of the method of claim 1 and optionally repeating steps 6-8 one or more times to create the at least one 3D structure with higher level of complexity as required by claim 8 (pg. 3, last para spanning pg. 4 first para; Fig. 3). Additionally, Berenschot teaches wherein the last round of preparation, step 7 is left out to produce 3D structures having closed apices, as explicitly depicted in Fig. 3, wherein the apices are closed, as required by claim 14 (Fig. 3).
Berenschot teaches wherein the protective layer is silicon oxide and silicon nitride as required by claim 9 (pg. 3, last para spanning pg. 4 first para; Fig. 3). Berenschot teaches an additional step 9 which is to be completed after step 5 of claim 1 and before culturing with cells, comprising providing the 3D structure with an inorganic layer which contacts the base 3D material as required by claim 10 (pg. 3, col. 2, para 1). Berenschot teaches that the 3D structure comprises a surface defining a regular pattern of protrusions, the protrusions are built up from octahedral structures and the octahedral structures are becoming narrower to the outside of the 3 D structure which can all be seen in the diagram of Fig. 3 as required by claim 15 (Fig. 3). Fig. 3 of Berenschot meets the limitations of requiring a pyramid considered G0, a pyramid with an apex on an octahedral considered G1, a pyramid with an apex on an octahedral and on each apex a second level of octahedral structures considered G2, and so on and so forth up to a G5 level of octahedral structures as required by claim 16 (Fig. 3). Berenschot teaches that the 3D structure can contain multiple 3D structures and wherein they are placed on a surface of the support base in a lattice configuration as required by claim 18 (see Fig. 2). Berenschot teaches wherein the bulk-monocrystalline substrate is partially etches away with remaining substrate at least partially covering at least one of the multiple 3D structures to create multiple compartments with one or more 3D structures exposed as required by claim 19 (see Fig. 4).
Berenschot does not teach that after the removal of the bulk-monocrystalline substrate the surface of the at least one 3D structure is provided with cells under growth permitting conditions to produce the cell culture template as required by claim 1. Berenschot does not teach that cells are provided to the at least one 3D structure as required by claim 2. Berenschot does not teach that the 3D structure obtained by the method of claim 1 is provided for culturing cells as required by claim 32. Berenschot does not teach that the method for culturing cells cultures cells which are cancer-associated fibroblasts (CAFs), or stem cells as required by claim 35.
However, Borenstein teaches a method of tissue engineering by culturing cells on substrates comprised of fractal networks ([0088]). Although Berenschot is relied upon to teach the independent claim 1, Borenstein teaches a similar method to that of Berenschot with the only difference in the steps 1-5 of claim 1 is the reversal of the order of steps 4 and 5 (see [0046]-[0048], [0082], [0075-[0077], Fig. 3, [0028]-[0029] and Fig. 15-16). Borenstein teaches that after the removal of the bilk-monocrystalline substrate, the surface of the 3D structure is provided with cells under growth permitting conditions as required by claims 1, 2, and 32 ([0142]-[0144]). Borenstein teaches that the cells which are cultured can be fibroblasts or stem cells as required by claim 35. Additionally, Borenstein teaches that “Advantages of this invention over other methods of tissue engineering include (a) the capability for producing all of the high resolution three-dimensional structures required for complex tissues and vital organs, and (b) the ability of the mechanical (possibly biodegradable) scaffold to provide guidance for cell growth and tissue formation, rather than reliance upon biochemical factors alone.” ([0037]).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the fractal structure protocol taught by Berenschot with the use of a fractal substrate for cell culture taught by Borenstein to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Borenstein teaches that “Advantages of this invention over other methods of tissue engineering include (a) the capability for producing all of the high resolution three-dimensional structures required for complex tissues and vital organs, and (b) the ability of the mechanical (possibly biodegradable) scaffold to provide guidance for cell growth and tissue formation, rather than reliance upon biochemical factors alone.” ([0037]). One of ordinary skill in the art would have a reasonable expectation of success when combining Berenschot with Borenstein because although Berenschot is relied upon to teach the independent claim 1, Borenstein teaches a similar method to that of Berenschot with the only difference in the steps 1-5 of claim 1 is the reversal of the order of steps 4 and 5 (see [0046]-[0048], [0082], [0075-[0077], Fig. 3, [0028]-[0029] and Fig. 15-16).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1, 23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Berenschot et al (J. Micromech. Microeng., 2013), in view of Borenstein et al (US20020182241A1), as applied to claims 1-4, 6, 8-10, 13-16, 18-19, 22, 32, and 35 above, and in further view of Park et al (Scientific Reports, 2018).
Regarding dependent claims 23 and 25, the limitations of the independent claim 1 are taught above.
Berenschot and Borenstein do not teach wherein the cell culture template further comprises at least one metal portion as required by claim 23. Berenschot and Borenstein do not teach wherein electrodes are used for cell stimulation as required by claim 25.
However, Park teaches a method of fractal-shaped platinum microelectrodes as required by claims 23 and 25 (abstract). Park teaches that these electrodes are used for neural stimulation and that fractal shaped microelectrodes, despite having smaller perimeter than other designs, demonstrated superior charge injection capacity (abstract). Additionally, Park teaches that the smaller electrodes can potentially reduce tissue damage and allow better spatial resolution for neural stimulation (abstract).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the fractal structure used for cell culture taught by Berenschot and Borenstein with the platinum microelectrodes taught by Park to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Park teaches that the platinum electrodes are used for neural stimulation and that fractal shaped microelectrodes, despite having smaller perimeter than other designs, demonstrated superior charge injection capacity (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Berenschot with Borenstein because Park teaches that the smaller electrodes can potentially reduce tissue damage and allow better spatial resolution for neural stimulation (abstract).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 03/04/2026 have been fully considered but they are not persuasive.
Applicant argues (Remarks, pg. 11-13) that in the instant invention the cells are provided to the base three-dimensional structure at the side that was originally in contact with the monocrystalline structure and that Borenstein is distinguishable from the claimed method because Borenstein “merely describes the preparation of three-dimensional templates or scaffolds that mimic blood vessels and serve as template for cell adhesion and growth… however these paragraphs for not detail on which surface the cells are seeded” (pg. 12).
In response, this argument is not found persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the specific side of the three-dimensional structure which cells are seeded on) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Additionally, the claim requires that the at least one three-dimensional structure is bonded to a surface of a support base and then subsequently the bulk-monocrystalline substrate is removed. These steps imply that there is a base containing a single side with the three-dimensional structure which has had the bulk-monocrystalline substrate removed. One of ordinary skill in the art would understand that the culturing of cells is not intended to happen on the ”back side” of the support base. This is supported in Borenstein. Borenstein teaches Example 1 which details silicon wafer etching with various chemistries ([0188]) and the formation of various channels which “resulted in excellent adhesion and enhanced lifting of living tissue” ([0191]). Thus, a person of ordinary skill in the art would read Borenstein and understand that the cells are being seeded on the side of the three-dimensional structure which is being manipulated and not the back off the silicon wafer base material. Thus, the argument is not found persuasive.
Applicant argues (Remarks, pg. 13) that Borenstein does not perform the steps of the instant method in the order presented in claim 1.
In response, this argument is not found persuasive. Borenstein is not relied upon as an anticipatory reference, rather Borenstein is only relied upon to teach the use of the three-dimensional structure in cell culture. It is stated in the rejection of record that the instant steps and the steps of Borenstein are similar but not identical, however as described in the rejection, Berenschot is relied upon to teach the limitations including the order of steps of independent claim 1. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues (Remarks, pg. 14-15) that step 3 and step 5 of the instant claim 1 is not described in Borenstein.
In response, this argument is not found persuasive. Borenstein is not relied upon to teach these steps. Steps 1-5 are outlined in the rejection as being taught by Berenschot. It is stated in the rejection of record that the instant steps and the steps of Borenstein are similar but not identical, however as described in the rejection, Berenschot is relied upon to teach the limitations including the order of steps of independent claim 1. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that Berenschot does not teach the use of the claimed method to make structures for cell culture and that Borenstein does not use a method identical to the instantly claimed method and thus there is no motivation to combine Berenschot and Borenstein to arrive at the instant invention.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the fractal structure protocol taught by Berenschot with the use of a fractal substrate for cell culture taught by Borenstein to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Borenstein teaches that “Advantages of this invention over other methods of tissue engineering include (a) the capability for producing all of the high resolution three-dimensional structures required for complex tissues and vital organs, and (b) the ability of the mechanical (possibly biodegradable) scaffold to provide guidance for cell growth and tissue formation, rather than reliance upon biochemical factors alone.” ([0037]). One of ordinary skill in the art would have a reasonable expectation of success when combining Berenschot with Borenstein because although Berenschot is relied upon to teach the independent claim 1, Borenstein teaches a similar method to that of Berenschot with the only difference in the steps 1-5 of claim 1 is the reversal of the order of steps 4 and 5 (see [0046]-[0048], [0082], [0075-[0077], Fig. 3, [0028]-[0029] and Fig. 15-16). Thus, the argument is not found persuasive.
Applicant argues (pg. 17) that Park does not remedy the alleged deficiencies of Berenschot and Borenstein.
In response, the alleged deficiencies of Berenschot and Borenstein are addressed at points 23-26 above and thus the argument is not found persuasive.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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