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 ACTION
Election/Restriction
Applicant’s election, without traverse, of Group I, claims 1-7, drawn to a bladder cancer mimic and a lab-on-a-chip thereof, in the reply filed on 12/08/2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Status
Claims 1-8 are pending. Claim 8 is withdrawn. Claims 1-7 are considered on the merits.
Priority
This application is a 371 of PCT/KR2021/017186 (filed on 11/22/2021), which claims benefit from foreign application KR10-2021-0016235 (filed on 02/04/2021). The priority claim of the instant application has been granted and the earliest benefit date is 02/04/2021 from the application KR10-2021-0016235.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/15/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Claim Rejections - 35 USC § 103
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 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al,. (PLoS ONE. 2019; 14(10): e0223689. p. 1-15. Cited in IDS 05/15/2023) in view of Datta et al., (npj Precision Oncology. 2020; 4:18, p. 1-13. Cited in IDS 05/15/2023) and Cho et al., (Adv. Healthcare Mater. 2019, 8, 1801019, p. 1-11).
With respect to claim 1, Kim teaches a three-dimensional (3D) cell culture printing model for bladder cancer made by bioprinting bladder cancer cells into a 3D structure (see e.g., abstract and Fig 1 for the 3D cancer cell construct), thus teaches a bladder cancer mimic comprising a structure including bladder cancer cells.
However, Kim is silent on the 3D cancer mimic including endothelial cells and fibroblasts.
Nevertheless, Kim teaches almost all cells in the in vivo environment are surrounded by extracellular matrix (ECM) and other cells, and 3D bioprinting techniques with scaffold bioink made up of cellular materials have been utilized to provide major ECM elements of the tumor microenvironment (p. 2, “Introduction”). Kim further teaches that this 3D printing technique can be used to create a cancer cell-like environment for a drug screening platform (e.g., abstract).
Datta summarizes 3D bioprinting in mimicking cancer microenvironment (e.g., abstract). Datta teaches, e.g., for reconstructing the tumor microenvironment, individual 3D bioprinted components can be assembled from droplets of tumor cells obtained from primary tumor site, microchannels comprising endothelial cells, fibroblast containing hydrogel acting as tumor stroma (e.g., p. 2, left col, last part, also see Table 1 for a list of 3D bioprinted cancer models comprising cancer cells, endothelial cells and fibroblasts), thus suggests endothelial cells and fibroblasts can be incorporated into the 3D bioprinted cancer models in mimicking cancer microenvironment.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the 3D bioprinted bladder cancer mimic disclosed by Kim, by combining endothelial cells and fibroblasts in the cancer mimic as suggested by Datta with a reasonable expectation of success. Since Kim aims to use 3D bioprinting technique with scaffold bioink made up of cellular materials to create a cancer cell-like environment for a drug screening platform (e.g., abstract and p. 2, “Introduction”), and since Datta suggests individual 3D bioprinted components comprising tumor cells, endothelial cells and fibroblasts can be assembled for reconstructing the tumor microenvironment (e.g., p. 2, left col, last part, also see Table 1), one of ordinary skill in the art would have had a reason to combine endothelial cells and fibroblasts in Kim’s 3D bioprinted bladder cancer mimic as suggested by Datta in order to create a cancer cell-like environment for drug screening (Kim, abstract).
However, Kim and Datta are silent on the 3D bioprinted cancer mimic comprising a stacked structure including layers of each cell type.
Nevertheless, Kim reduces to practice a method for bioprinting a cell layer to form a 3D model (see e.g., Fig 1 for bioprinting a bladder cancer cell layer) and contemplates stacking layers with many cells into 3D structure (see p. 5, para 1).
As stated supra, Datta teaches for reconstructing the tumor microenvironment, individual 3D bioprinted components can be assembled (e.g., p. 2, left col, last part, also see e.g., Fig 1B-1C for assembling individually bioprinted cancer cell layer and endothelial cell layer).
Cho teaches 3D cell printing of a human skin equivalent that better reflects the actual complexity of native human skin (e.g., abstract). Cho teaches the skin model is made by 3D cell printing of individual layers of bioinks each comprising a different cell type (see Fig 1 for the step-by-step process, especially see the bottom-right panel of Fig 1(A) for the diagram of the final stacked structure including an endothelial cell layer, a fibroblast layer and a keratinocyte layer). Cho teaches the compartments (i.e., layers) provide a more realistic microenvironment and the model offers better predictive and reliable in vitro platform for investigation of mechanisms of pathological research and skin disease modeling (e.g., abstract).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the 3D bioprinted bladder cancer mimic comprising bladder cancer cells, endothelial cells and fibroblasts as suggested by Kim in view of Datta, by combining bioprinting individual layer of each cell type so as to prepare a stacked structure as suggested by Datta and Cho with a reasonable expectation of success. Since Kim contemplates stacking layers with many cells into 3D structure and reduces to practice a method for bioprinting a cell layer (see p. 5, para 1 and Fig 1), since Datta teaches individual 3D bioprinted components of cancer cells, endothelial cells and fibroblasts can be assembled for reconstructing the tumor microenvironment (e.g., p. 2, left col, last part, and Fig 1), and since Cho teaches 3D cell printing of individual layers of endothelial cells, fibroblasts and keratinocytes to form a stacked structure (see Fig 1A) that provides a more realistic microenvironment and offers better predictive and reliable in vitro platform for disease modeling (e.g., abstract), one of ordinary skill in the art would have had a reason to combining the layer-by-layer 3D bioprinting to obtain a stacked structure in order to better mimic the bladder cancer microenvironment for a drug screening platform (Kim, abstract).
With respect to claim 2 directed to cells used in each layer, Kim teaches the bladder cancer cell layer includes bladder cancer cell line T24 and 5637 (e.g. abstract and Fig 3). Both Datta and Cho teaches the endothelial cell layer includes a HUVEC line (Datta, e.g., Fig 1 and Table 1; and Cho, e.g., Fig 1). Datta further teaches the fibroblast cell layer includes MRC5 (Datta, e.g., Table 1 and p. 6, last para.).
Accordingly, it would have been obvious for one of ordinary skill in the art to have chosen the claimed cell lines as suggested by Kim, Datta and Cho with a reasonable expectation of success. Since the cited art reduce to practice the claimed cell lines in making a 3D disease model, one of ordinary skill in the art would have had a reason to choose the taught cell lines in making the bladder cancer mimic.
With respect to claim 3 directed to the mimic having a cylindrical shape, Kim teaches user-created constructs design is loaded into the computer and is controlled by a computer program design model (p. 3, para 2). Datta summarizes multiple 3D bioprinted cancer models including models that have a cylindrical shape (see e.g., Fig 1 a GBM model and Fig 5 an ovarian cancer model that have a cylindrical shape).
Accordingly, it would have been obvious for one of ordinary skill in the art to have chosen the 3D cancer mimic having a cylindrical shape as suggested by Datta with a reasonable expectation of success. Since Kim teaches the shape of the constructs can be designed and controlled by a computer program design model (p. 3, para 2), and since Datta summarizes and thus reduces to practice 3D bioprinted cancer models that have a cylindrical shape (see e.g., Fig 1 and Fig 5), one of ordinary skill in the art would have had a reason to choose to design and make the bladder cancer mimic having a cylindrical shape.
With respect to claim 4 directed to the layers being obtained by 3D printing, as stated supra, Kim, Datta and Cho all teach the layers of each cell type are obtained by 3D printing (see above).
With respect to claim 5 directed to layers each having a filling rate of 5 to 25%, Kim teaches the bladder cancer cell layer has a porous platform of the scaffold (see e.g., Fig 1 and legend, also see microscopic view of the porous structure in Fig 2E). From the microscopic view in Fig 2E, the porous cell layer likely has a filling rate of 5% to 25% (i.e., the percentage of the bioprinting area in one layer to the total stacked area, see definition in specification [0031]). Accordingly, it would have been obvious for one of ordinary skill in the art to have chosen the filling rate suggested by Kim with a reasonable expectation of success. Since Kim has reduced to practice a bladder cancer cell layer that likely has a filling rate of 5% to 25%, one of ordinary skill in the art would have had a reason to choose the suggested filling rate in bioprinting the cell layers. Furthermore, since one of ordinary skill in the art would have immediately expected that the filling rate of the cell layers (i.e., the porosity) would affect the circulation of culture medium in the cancer mimic, and thus is a result effective variable, it would have been obvious to one having ordinary skill in the art to choose the claimed filling rate, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
With respect to claim 6 directed to a permeate flow rate through the bladder cancer mimic being 10 to 30 µl/min, it is noted that there is no clear structural limitation given to the bladder cancer mimic by the claimed limitation of providing a permeate flow at the claimed rate. Therefore, the wherein clause does not provide any patentable weight in determining patentability of the claimed product. Thus, claim 6 is rejected in the same way as its base claim 4.
With respect to claim 7 directed to a lab-on-a-chip comprising the mimic, Kim suggests that further research on organs-on-chips systems would improve the treatment of cancer and other diseases (p. 13, para 2). Datta teaches cancer-on-a-chip devices have allowed more physiologically relevant three-dimensional (3D) in vitro cancer models (e.g., abstract, and see Fig 1 and Fig 7 for integration of microfluidic devices with 3D bioprinted organ-on-a-chip models). Cho teaches combined with a microfluidic device, in vitro 3D skin models, termed as a skin-on-a-chip or skin integrated vascular channel-on-a-chip, could improve tissue-tissue interfaces (p. 2, para 1).
Accordingly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined a microfluidic device with the bladder cancer mimic so as to make a lab-on-a-chip as suggested by Kim, Datta and Cho with a reasonable expectation of success. Since Kim, Datta and Cho all suggest a lab-on-a-chip device comprising the 3D bioprinted model, one of ordinary skill in the art would have had a reason to make a lab-on-a-chip device comprising the bladder cancer mimic in order to build more physiologically relevant 3D in vitro cancer models to improve the treatment of cancer (Datta, abstract and Kim, p. 13, para 2).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631