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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08 January 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 08 January 2026.
CLAIMS UNDER EXAMINATION
Claims 1-3, 5 and 8-20 are pending and have been examined on their merits.
PRIORITY
Provisional Application 62/924111, filed on 21 October 2019, is acknowledged.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
NEW REJECTIONS
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-2 and 12 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3, 6, 11 and 16 of US Patent US12012578B2 (18 June 2024).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claim limitations of the Instant Application encompass claim limitations of the patent.
Claim 1 of the ‘578 Patent teaches a method comprising generating a recirculating flow from a flow confinement device over a substrate. The flow comprises a liquid and cells. A first layer of cells is formed on the substrate. Claim 3 of the ‘578 Patent recites the cells adhere to the substrate. Claim 1 of the ‘578 Patent recites the steps are performed repeatedly using a second liquid containing cells to form a second layer of cells on the first layer of cells. As evidenced by the instant specification, “biological cells” are a cell-attachment agent (see page 11, line 15). Therefore the second layer is interpreted to read on a cell attachment agent. Claim 16 of the ‘578 Patent recites repeating the steps with a further plurality of suspended cells. Claim 6 of the ‘578 Patent recites the substrate is translated in 3D relative to the flow confinement device using an electronically controlled positioning device. Therefore deposition would occur at a new location. The claims do not require detaching the cells from the substrate. A multilayered construct is interpreted to have a predefined thickness. Therefore the limitations in claim 1 of the instant application are rendered obvious. The ‘578 patent teaches the first layer adheres to the substrate. Therefore the cells have been cultured for a period of time to establish cell-substrate attachments as recited in claim 2. Claim 11 of the of the ‘578 Patent recites the liquids have the same composition. Therefore a suspension comprising a single cell type, as recited in instant claim 12 is rendered obvious.
Claims 3, 5, 8-11, 13, 15-16 and 18-19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over US Patent US12012578B2 (18 June 2024) in view of Matsusaki et al.
Claims 1-2 and 12 are rejected in view of the teachings of the ‘578 Patent on the grounds recited above. The claims of the ‘578 Patent does not disclose the limitations recited in claims 3, 5, 8-11, 13, 15-16 and 18-19. The teachings of Matsusaki as set forth below are reiterated.
It would have been obvious to culture cells for about 1 day. Matsusaki teaches 24 hours of incubation after each cell printing to induce stable cell adhesion (see page 537, left column, first paragraph). One would do so to insure cell adhesion. One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 3 are rendered obvious.
It would have been obvious to form a biological structure with a thickness between about 100 µm and about 1mm. One would have been motivated to do so since Matsusaki (Figure 2f) illustrates a thickness of about 200 µm (between about 100 µm and about 1mm). One would have had a reasonable expectation of success since the ‘578 Patent teaches repeated layering. One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 5 is included in this rejection. It would have been obvious to apply the cell-attachment agent globally. One would have been motivated to do so since Matsusaki teaches the fibronectin and gelatin are applied as a nanofilm layer on a substrate. One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 8 is included in this rejection. It would have been obvious to apply the cell-attachment agent in a pattern since Matsusaki deposits cells and fibronectin/gelatin in a pattern (“Osaka”). One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 9 is included in this rejection.
It would have been obvious to apply the cell suspension globally since Matsusaki teaches the cell suspension is applied in a layer (hence, globally). One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 10 is included in this rejection.
It would have been obvious to apply the cell suspension in a pattern since Matsusaki deposits cells in a pattern (“Osaka”). One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 11 is included in this rejection.
It would have been obvious to use different cell types since Figure S5 of Matsusaki (Figure S5) teaches HepG2 cells in layered co-cultures using the disclosed method. One would have had a reasonable expectation of success since the Patent teaches using different solutions. One would have expected similar results since both references are directed to methods of forming cell deposition on a substrate. Therefore claim 13 is included in this rejection. It would have been obvious to deposit a cell blocking agent over the second layer of the suspension. Matsusaki teaches washing and blocking the tissue with 0.2% Trixon-X100 in phosphate buffered saline (PBS) before analysis with antibodies (page 539, left column, fourth paragraph). It is well known in the art that Triton X-100 is a surfactant. One would do so to analyze the construct formed by the method. Therefore claims 15-16 are rejected. It would have been obvious to use a plastic substrate. One would have been motivated to do so since Matsusaki teaches the wells are part of a plastic plate (see page 537, left column, second paragraph). Plastic material reads on claim 18. It would have been obvious to use a substrate with a planar topology. One would have been motivated to do so since Matsusaki illustrates the substrate has flat (planar) wells. Therefore claim 19 is included in this rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5 and 8-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 (c) has been amended to recite depositing a cell attachment agent over the first layer of attached cells without detaching the cells from the substrate. Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims See MPEP 2173.05(i). This limitation is not found in the originally filed specification. The Applicant does not point to the section of the specification that excludes detaching the first layer from the substrate. This is considered new matter. All dependent claims are included in this rejection.
An amendment to the claims or the addition of a new claim must be supported by the description of the invention in the application as filed. In re Wright, 866 F.2d 422, 9 USPQ2d 1649 (Fed. Cir. 1989). Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Rejections - 35 USC § 102
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 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 1-3, 5, 8-13 and 15-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Matsusaki et al. (Three-Dimensional Human Tissue Chips Fabricated by Rapid and Automatic Inkjet Cell Printing. Adv. Healthcare Mater. 2013, 2, 534-539).
Matsusaki et al. fabricate human 3D-tissue structures, micrometer-sized multilayers with different layer numbers and cell types, using a technique combining hierarchical cell manipulation and inkjet printing (page 534, right column, second paragraph).
Matsusaki teaches a layer-by-layer printing method (LBL) (see page 535, left column; Figure 1). In Figure 1, a first layer of “Cell 1” is printed in a well of a substrate using the inkjet printer. The cells are in a buffer (see left column, second paragraph, page 539). Figure 1(a) illustrates the cells are attached to the bottom of the well.
A nanofilm of fibronectin and gelatin is printed on the first layer of cells in the first well. (see Figure 1A; see page 537, left column, first paragraph). This is interpreted to read on a cell-attachment layer. Figure 1 illustrates a second layer comprising “Cell 2” is printed by the inkjet printer over the cell-attachment layer in the first well. Figure 1 discloses the process is repeated to form a three-layered structure in the well. Figure 1 illustrates the process is repeated in a second well (hence, a new location) of the substrate. Figure 1 illustrates the process creates a 3D micro-tissue chip (hence, a three-dimensional predefined biological structure).
Figure 2 discloses a 4-layered construct using C2C12 cells printed in 50-well plates (see Figure 2, text d-f). Matsusaki teaches it is constructed as shown in Figure 1a. A suspension of C2C12 cells is used to prepare each layer in Figure 2.
Printing is performed four times in 50-micro-wells as shown in Figure 1a, (see page 537, left column, first paragraph). A 50-well plate is a substrate. Matsusaki teaches the process is repeated in 50 wells. Therefore the art teaches the process is repeated at a new location (i.e., another well).
The specification as filed does not provide an explicit definition for a “flow-confinement device”. The art teaches “drops” of cells are printed to fabricate a multilayered structure in each well (see page 539, left column, third paragraph). As evidenced by Merriam Webster, a drop is “a quantity of fluid that falls in one spherical mass”. A buffer is interpreted to be a liquid that flows. A spherical mass of a “drop” of cells/buffer on a substrate is interpreted to be a liquid confined to a localized regio of a substrate. Matsusaki teaches the inkjet printer releases a specific volume of fluid (see page 535, left column). Therefore the printer taught by Matsusaki reads on a flow-confinement device. As illustrated in Figure 2, the art does not teach the first layer is detached from the substrate. Figure 2 illustrates a construct that is 4 layers thick. Therefore a predefined desired thickness is generated. Therefore this experiment (Figure 2f) anticipates claim 1.
The art teaches the tissues made by the method reproduced cell-cell interactions in three-dimensions similar to actual tissues or organs (page 538, left column, second paragraph). The art illustrates cells are attached to the substrate and each other to make a layer Therefore the cells are cultured for a period of time to establish cell-cell interactions (see Figure 1 and 2). Therefore claim 2 is included in this rejection.
Matsusaki teaches 24 hours of incubation after each cell printing to induce stable cell adhesion (see page 537, left column, first paragraph). 24 hours reads on “from about 1 day to about 3 days”. Therefore claim 3 is included in this rejection.
Figure 2f illustrates a thickness of about 200 µm (between about 100 µm and about 1mm). Therefore claim 5 is included in this rejection.
Matsusaki teaches the fibronectin and gelatin are applied as a nanofilm layer. A film is interpreted to read on global application. Therefore claim 8 is included in this rejection.
Matsusaki teaches the fibronectin and gelatin are applied as a layer of drops (supra). The specification does not define the term “pattern”. Therefore deposition of drops in a layer is interpreted to read on a pattern. Therefore claim 9 is included in this rejection.
Matsusaki teaches the cell suspension is applied in a layer (hence, globally). Therefore claim 10 is included in this rejection.
Matsusaki deposits cells as drops in a layer. The specification does not define the term “pattern”. Therefore deposition of drops in a layer is interpreted to read on a pattern. Therefore claim 11 is included in this rejection.
The suspension in Figure 2 contains a single cell type (C2C12 cells). Therefore claim 12 is included in this rejection.
Figure S5 of Matsusaki teaches HepG2 cells in layered co-cultures using the disclosed method. Therefore claim 13 is included in this rejection.
Matsusaki teaches washing and blocking the tissue with 0.2% Trixon-X100 in phosphate buffered saline (PBS) before analysis with antibodies (page 539, left column, fourth paragraph). It is well known in the art that Triton X-100 is a surfactant. Therefore claims 15-16 are rejected.
The art teaches a nanofilm of fibronectin and gelatin (supra). Therefore claim 17 is included in this rejection.
The art teaches the wells are part of a plastic plate (see page 537, left column, second paragraph). Plastic material reads on claim 18.
The art illustrates the substrate has flat (planar) wells. Therefore claim 19 is included in this rejection.
Therefore Applicant’s Invention is anticipated as claimed.
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 14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Matsusaki 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).
Claim 1 is rejected on the grounds set forth above. The teachings of Matsusaki et al. are reiterated.
Matsusaki is silent regarding the use of an organ or tissue as a substrate.
Akashi teaches a method of producing a three-dimensional tissue using cell lamination (Abstract). A cell layer is formed on a substrate. An extracellular matrix 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 art teaches the ECM adheres cell layers (column 3, line 22). Therefore it is broadly interpreted to read on a cell attachment layer. The art 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. Matsusaki 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.
Matsusaki does not teach the substrate comprises adjacent sections of different materials.
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 Matsusaki. 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.
RESPSONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 08 January 2026 are acknowledged. New grounds of rejection have been made to address the amended claims.
Argument 1: The Applicant argues Matsusaki does not teach depositing a cell-attachment agent onto an already attached layer of living cells, followed by deposition of a further cell suspension in the manner required by claim 1.
Response to argument 1: Claim 1 does not recite “living cells”. Therefore this argument is not commensurate with the scope of the claim. However, it is noted the art teaches “live/dead staining clearly showed considerably high cell viability” (see page 536, left column, first paragraph). Therefore the cells printed by Matsusaki are live. Figures 1 and 2 show a first layer of cells attached to the substrate. This reads on the claim limitation. The art explicitly teaches printing is performed four times in 50-micro-wells as shown in Figure 1a, accompanied by 24 hours of incubation after each cell printing to induce stable cell adhesion (see page 537, left column, first paragraph). Adhesion is attachment. Therefore this argument is not persuasive.
Argument 2: The Applicant argues Matsusaki does not teach steps a-d are performed at a new location on the substrate.
Response to argument 2: Matsusaki teaches a four layers of C2C12 cells are printed in “50-well plates”. A plate is a substrate. The art teaches the constructs are formed in “the wells”. The art teaches printing is performed four times in 50-micro-wells as shown in Figure 1a, (see page 537, left column, first paragraph). Matsusaki teaches the process is repeated in multiple wells. Therefore the art teaches the process is repeated at a new location (i.e., another well). Therefore this argument is not persuasive.
Argument 3: The Applicant argues Matsusaki does not teach a flow-containment device.
Response to argument 3: The specification as filed does not define a “flow-confinement device”. Matsusaki teaches “drops” of cells are printed to fabricate a multilayered structure in each well (see page 539, left column, third paragraph). A drop is “a quantity of fluid that falls in one spherical mass”. A spherical mass of a “drop” of cells/buffer on a substrate is interpreted to be a liquid confined to a localized region of a substrate. Therefore the printer taught by Matsusaki reads on a flow-confinement device. Therefore the argument is not persuasive.
Conclusion
No claims are allowed.
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) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653