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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7, in the reply filed on 03/13/2026 is acknowledged.
Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/13/2026.
Claims 1-7 (claims set filed 07/27/2023) are examined on the merits herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) based on application Japan 2022-121195 filed 07/29/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/27/2023 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is 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 1, 2, 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Iwashita (JP 2019017255 A on record in IDS) as evidenced by Wellplate (Wellplate, 96-Well Plate Dimensions [retrieved on 06/15/2026]. Retrieved from the Internet: <https://www.wellplate.com/96-well-plate-dimensions/>).
Iwashita teaches a method of manufacturing a cell culture substrate including step of “applying solution containing fixative A to the substrate, and a step of applying a suspension containing fixative and cells that can be mixed with fixative A, wherein at least a portion of fixative A and fixative B are
mixed to form a hydrogel, and the cells are fixed to the substrate via the hydrogel” (paragraph 0008). Solution containing fixative A in Iwashita teaching corresponds to instant first liquid and solution containing fixative B and cells corresponds to instant second liquid. Iwashita provides example of the aqueous first solution with fixative which is fibrinogen aqueous solution (fixative A solution) (paragraph 0085). Iwashita mentions that other ingredients can be used in solutions such as culture media and provides examples of liquid culture media such as DMEM which contains water (paragraphs 0028, 0074). Iwashita discloses that the suspension of fixative B and cells is applied by droplet dispensing with inkjet method (paragraph 0030) and for inkjet method pressure application is preferred (paragraph 0031) that corresponds to ejecting droplets of the second liquid onto the film of the first liquid. Iwashita provides example of application of fibrinogen solution (fixative A) to wells of 96-well plate (paragraph 0087, Figure 9A) and wells of which correspond to a recess in the substrate interior of which is filled with the film of the first solution. Iwashita describes that the area surrounding the cells only needs to be a hydrogel formed by mixing/reacting at least a portion of fixative A and fixative B (paragraph 0067) indicating encapsulation of cells. Iwashita discloses that the developed method provides adherence of cells to the cell culture substrate in short time which can be used for in vitro toxicity and efficacy evaluation (paragraphs 0002, 0009). Iwashita described that the cells immobilized in hydrogel by the disclosed method and cells seeded in the DMEM medium have the same trend in toxic reactions, viability, cell membrane damage rate and secretion of inflammatory substances indicating that the cell culture substrate prepared by the described method is effective for toxic reactions (paragraph 0100).
Iwashita does not explicitly teach the particles of hydrogel to correspond to a size of the droplets in the ejecting.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Iwashita teaching and prepare a cell culture substrate by method of ejecting the droplets of the suspension of fixative B with cells to the plate containing the first fixative that will provide fixing of cells on the surface of the substrate via hydrogel. One would have been motivated to do that since Iwashita describes the method providing adherence of cells to the cell culture substrate in short time. Additionally, the developed method which can be used for in vitro toxicity and efficacy evaluation as was confirmed by working examples described above. A skilled artisan would have reasonably expected success in manufacturing the cell culture substrate with cells immobilized via a hydrogel following the description of Iwashita.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that formation of hydrogel on the surface of droplets results in cell encapsulation and that the size of the obtained particles will depend on the size of droplets at ejecting. One would have been motivated to suggest that with reasonably expected success since Iwashita describes reacting of only a portion of fixative A and fixative B to form hydrogel surrounding cells indicating formation of particles the size of which will be determined by the size of cells droplets which were ejected. Additionally, since Iwashita method includes all the steps of the instant method of claim 1, the formed particles are expected to correspond to a size of droplets in the ejecting.
Thus, Iwashita teaching renders claim 1 obvious.
Regarding claim 2, Iwashita teaches the diameter of the nozzle dispensing droplets from 10 µm to 200 µm (paragraph 0056) and hence droplets can be envisioned to have diameter of 10-200 µm. Iwashita describes 96-well flat bottom plates as a substrate for application of the first solution of fixative A (paragraph 0087). The diameter of well of standard 96-well flat bottom plates is 6.94 mm and the depth of recess is 10.65 mm as evidenced by Wellplate (p. 4). Therefore, the diameter of droplets is less than a film thickness of the first liquid defined by the depth of the recess. Thus, Iwashita teaching as evidenced by Wellplate renders claim 2 obvious.
Regarding claim 6, Iwashita teaches the substrate to be a 96-well plate in Example 1 (paragraph 0087) with the recess at a bottom of the wells as shown on Figure 9A. Thus, Iwashita teaching renders claim 6 obvious.
Regarding claim 7, Iwashita teaches that the second liquid containing suspension of the second fixative and cells is applied by inkjet bioprinter (paragraph 0088). Thus, Iwashita teaching renders claim 7 obvious.
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Iwashita (JP 2019017255 A) in view of as applied to claim 1 above, and further in view of Lawman (US 4039247).
The teachings of Iwashita and have been set forth above.
Iwashita does not teach recess surrounded by a convex strip on the substrate.
Regarding claims 3-5, Lawman teaches a device for testing in which fluid samples are disposed on a microscopic slide. The device can be used for cell culturing (column 1, lines 5-10). The device includes silicone rubber gasket attached to slides and readily removable from the slides (column 1, lines 64-68). Lawman describes that device is composed of the slide support with holes through which the content of wells can be examined by the inverted microscope, slides, silicone rubber gasket on top of the slides that have ten rows of well-forming apertures arranged in pairs and a plate with plurality of well-forming apertures aligned with well in the gasket (column 2, lines 23-51). The wells in silicone rubber gasket have a ring shape as can be seen from the Figure. Lawman mentions that the wells are provided by the surface of the slide and walls of the gasket and the plate (column 2, lines 55-58). The cells are grown in the wells and inspected with microscope. After the growth is complete cells can be fixed, subjected to immunofluorescent testing and stained. After that the device is dismantled by removing the silicone rubber gasket and the plate and slides are examined under microscope (column 2, lines 59-62, 65-67, column 3, lines 1-2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Iwashita and Lawman teachings and use device with the removable silicone rubber strip described by Lawman for the cell culture substrate on microscopic slide in which cells are fixed on the substrate via hydrogel as described by Iwashita. One would have been motivated to do that since Lawman describes device allowing to monitor cell growth and perform cell tests with microscope. A skilled artisan would have reasonably expected success in the combination because Iwashita and Lawman teach cell culturing with cell attachment to the surface, Iwashita provides method of cell attachment in a short time via hydrogel and Lawman teaches device for controlling cell growth and analyzing cells by microscopy.
Alternatively, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add silicone rubber strip from Lawman teaching to cell culture substrate of Iwashita teaching. One would have been motivated to do that with reasonably expected success since addition of the silicone rubber strip to the cell culture substrate will increase the well volume and prevent evaporation.
Thus, Iwashita and Lawman teachings render claims 3-5 obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (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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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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