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 OFFICE ACTION
This Office Action is in response to the papers filed on 10 May 2026.
CLAIMS UNDER EXAMINATION
Claims 1-3, 5 and 8-20 are pending and have been examined on their merits.
PRIORITY
Provisional Application 62/924,111, filed on 21 October 2019, are acknowledged.
WITHDRAWN REJECTIONS
The Terminal Disclaimer filed on 10 May 2026 has been approved. The rejection of claims 1-2 and 12 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 6, 11 and 16 of US Patent US12012578B2 is withdrawn. The rejection of claims 1-3, 5 and 8-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, has been withdrawn due to claim amendment. The rejections made under 35 USC 102 and 103 have been withdrawn due to claim amendment.
NEW REJECTIONS
Claim 1 has been amended to recite a flow-confinement device that generates a hydrodynamically confined liquid volume outside of the flow-confinement device. This limitation was not previously presented. New grounds of rejection have been necessitated by claim amendment.
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 1-3, 5 and 8-20 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.
Regarding claim 1: steps (a), (b), (c) and (e) recite “…the substrate”. There is a lack of antecedent basis for a substrate in the amended claim because “a substrate” has been deleted in step (a). It is unclear what substrate the steps are referring to. Appropriate correction is required. All dependent claims are included in this rejection.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 5, 8-14 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Beyer et al. (System For Additive Manufacturing Of Three-Dimensional Structures And Method For Same. 2016/0136895) in view of Akashi et al. (previously cited; Method of Producing Three-Dimensional Tissue And Method Of Producing Extracellular Matrix Used In The Same. Patent 8137964 2012).
Beyer teaches a method and system of making a three-dimensional structure ([0010]). The system comprises at least one printhead and microfluidic channels ([0010]). The printhead comprises a tip with an orifice for dispensing materials from the print head ([0086]). The microfluidic channels regulate the flow of materials to be printed ([0062]).
Claim 1 has been amended to recite a flow-confinement device that generates a hydrodynamically confined liquid volume outside of the flow-confinement device. The specification does not explicitly define a flow-confinement device. At [0016] the specification discloses a “fluidic printhead tip, demonstrating the hydrodynamically confined flow”. Because Bayer anticipates the disclosed structure, it would generate a hydrodynamically confined liquid as claimed.
Beyer teaches a “receiving surface” for receiving a first layer of the materials dispensed from an orifice of the printhead ([0010][0059]). The receiving surface is interpreted to be a substrate. A hydrogel with the capacity to support growth and/or proliferation of one or more cell types is printed ([0056]). As evidenced by the specification, a hydrogel is a cell attachment agent ([0012] of PG Pub). The art teaches the cells can be dispersed in the hydrogel or added to the hydrogel after it has been printed ([0056]). A hydrogel upon which cells can be printed is also interpreted to read on a substrate.
Bayer teaches “depositing a first layer of the dispensed materials on the receiving surface; repeating the depositing step by depositing subsequent dispensed material on the first and any subsequent layers of deposited material, thereby depositing layer upon layer of dispensed materials in a geometric arrangement according to the 3D structure” ([0037]). Because the layers are based on a desired 3D shape, the art is interpreted to teach repeating the process until a 3D shape with a predefined thickness is generated.
Bayer teaches “it is possible…to assign a specific material type to different geometrical locations…FIG. 2 shows three 3D structures printed…: a cube, a hollow cylinder and a hollow coaxial cylinder” ([0073]). Therefore the art teaches different structures can be made at new locations.
While Beyer teaches cells can be added on a substrate, the art does not do so with sufficient specificity to anticipate the claim.
Akashi teaches a method of producing a three-dimensional tissue using cell lamination (Abstract). The art teaches a “Layer-by-Layer (LBL) method (column 7, lines 50-55).
A cell layer is formed on a substrate (i.e., cells are attached). An extracellular matrix (ECM) is formed on the cell layer. Cells are cultured on the ECM to form a further cell layer (see column 2, line 60 bridging line 1 of column 3; See Example 2). The ECM is for adhering cell layers (column 3, line 22). Therefore it is interpreted to read on a cell attachment layer. Akashi teaches the substrate is not limited and can be an artificial organ (column 1, line 18). The art teaches the steps are repeated to produce multiple layers (see column 3, lines 25-32; see column 13, lines 62-65).
Akashi does not require separating the first layer. Akash teaches “the method of bringing the substrate into contact with the respective solutions is not particularly limited” (column 9, lines 46-47).
It would have been obvious to combine the teachings of the prior art by depositing cells on a substrate followed by adding a cell-attachment layer. Bayer manufactures 3D cell-laden structures using “layer upon layer” deposition and Akashi teaches first depositing cells on a substrate for “layer by layer” manufacturing. One would have had a reasonable expectation of success since Akashi teaches 3D structures can be manufactured by first depositing a layer of cells, and then adding additional layers. One would have expected similar results since both references are directed to layer-by-layer 3D manufacturing. Therefore claim 1 is rendered obvious.
Akashi teaches a cell layer is formed on a substrate. This is interpreted to read on a culturing for a period of time to establish cell-substrate attachment. Claim 2 is included in this rejection.
Example 2 of Akashi teaches cells are cultured for 6 hours (column 13, line 46). 6 hours reads on about 1 to about 12 hours. Therefore claim 3 is included in this rejection.
Akashi teaches the number of times the steps are performed is not limited, and can be determined as appropriate depending on the desired size (thickness) of the three-dimensional tissue to be formed (column 11, lines 43-49). The art discloses four ECM layers (column 14, line 1). Each layer can be 1000 nm (1µm) (column 11, line 30). It would have been obvious to produce a structure with a predefined thickness between 100 um and 1mm. The skilled artisan would do so based on the desired size of the 3D tissue. Therefore claim 5 is included in this rejection.
Bayer teaches the final 3D geometry is determined by 3D design software ([0073]). Bayer teaches different shapes can be produced using the disclosed system (Figure 2). Bayer teaches the printhead can print across the x, y and z axis (Figure 1). The art does not explicitly teach applying the materials globally (everywhere). In Figure 9, Akashi teaches a first layer of cells covering a substrate. Additional layers are stacked on top. Therefore the materials are applied globally. It would have been obvious to apply the cell-attachment and suspension globally. One would have been motivated to do so to manufacture a sheet shaped structure on the substrate. One would have had a reasonable expectation of success since Bayer teaches the 3D geometry can be pre-determined. Claims 8 and 10 are included in this rejection.
Bayer teaches a specific material type can be assigned to different geometrical locations. The art teaches FIG. 2 shows three 3D structures, each design comprising two different types of materials (dyed alginate), which were dyed different colors to provide visual clarity of the materials used to generate the printed cube and hollow cylinder ([0073]). Therefore applying the cell-attachment agent and cell suspension in a pattern is rendered obvious. Claims 9 and 11 are included in this rejection.
Beyer teaches living cells are dispensed ([0015]). Therefore claim 12 is included in this rejection. The art teaches more than one cell type can be used ([0110]). Therefore claim 13 is included in this rejection.
Beyer is silent regarding the use of an organ or tissue as a substrate. Akashi teaches the substrate is not limited and can be an artificial organ (column 1, line 18).
It would have been obvious to use an organ as a substrate. Beyer teaches a layer-by-layer method to prepare a tissue on a substrate and Akashi teaches an artificial organ can be used as a substrate. One would have been motivated to do so to make an artificial organ. One would have had a reasonable expectation of success since Akashi teaches an artificial organ can be used as a substrate. One would have expected similar results since both references are directed to methods of making a layered tissue. Therefore claim 14 is included in this rejection.
Beyer teaches natural hydrogels including collagen and gelatin ([0056]). Therefore claim 17 is included in this rejection.
Beyer teaches cells can be deposited on a hydrogel (hence, a substrate). Therefore claim 18 is included in this rejection.
Beyer teaches “the receiving surface is substantially planar, thereby providing a flat surface upon which a first layer of dispensed material can be deposited” ([0059]). Therefore claim 19 is included in this rejection.
Akashi teaches a glass slide with half coated in an ECM (see column 13, lines 31-42).
This is interpreted to read on a substrate comprising adjacent sections of different
substrate materials (glass and ECM). The art teaches doing so to obtain a three-dimensional tissue with a hollow shape to form a blood vessel (same cited section).
It would have been obvious to use a substrate with adjacent sections of different materials in the method taught by Beyer One would have been motivated to do so to form a tissue, such as a vessel, as taught by Akashi. One would have had a reasonable expectation of success since Akashi teaches a substrate can comprise different materials. One would have expected similar results since both references are directed to methods of making a layered tissue. Therefore claim 20 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Beyer in view of Akashi as applied to claim 1 above, and further in view of Kowalczynska et al. (Albumin adsorption on unmodified and sulfonated polystyrene surfaces, in relation to cell–substratum adhesion. Colloids and Surfaces B: Biointerfaces 84 (2011) 536–544).
Claim 1 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. Beyer teaches a three-dimensional tissue comprising multiple cell-layers.
Beyer teaches structures generated using the system and method can be used to determine cellular responses to various chemical compounds and compositions are of interest. Fabricated 3D cell cultures may provide experimental conditions that more closely resemble in vivo cellular and tissue conditions ([0117]).
Beyer is silent regarding the use of a blocking agent.
Kowalczynska teaches albumin is commonly applied to prevent the nonspecific adhesion of cells to diverse artificial substrate (first sentence of Abstract).
When an artificial material comes into contact with a biological environment, diverse proteins adsorb over it. Proteins adsorbed on such substrata create bio logically active layers important for cell adhesion, proliferation and migration under in vivo and in vitro conditions. These adsorption phenomena are crucial for mediating cell functions on tissue implants and for in solid-phase immunology test systems (see first paragraph on page 536).
It would have been obvious to deposit albumin over the second cell suspension layer taught by Bayer. Bayer teaches a 3D tissue used to resemble in vivo cellular and tissue conditions. One would have been motivated to block cells with albumin to prevent non-specific binding to the cells in the 3D tissue. One would have had a reasonable expectation of success since Kowalczynska teaches albumin is commonly applied to prevent non-specific adhesion to cells. One would have expected similar results since both references are directed to cell adhesion. Therefore claims 15-16 are rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
RESPSONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 10 May 2026 are acknowledged.
Argument 1: Claim 1 has been amended to recite a device which “generates a hydrodynamically confined liquid volume…”. The Applicant argues neither Matsusaki
or Akashi teach this limitation.
Response to argument 1: The arguments directed to the amended limitation are persuasive. New grounds of rejection have been made to address the amended claims.
CONCLUSION
No Claims Are Allowed
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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