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 .
Response to Amendment
This is an office action in response to Applicant’s arguments filed on 25 February 2026. Claims 1-3 and 5-20 are currently pending in this application. Claim 4 has been cancelled. Claims 17-20 have been withdrawn. Claims 1-3 and 5-16 are being examined herein.
Status of Objections and Rejections
The rejection of claim 15 under USC § 112(b) is withdrawn in view of amendments.
The rejection of claim 4 under USC § 103 is withdrawn in view of the cancellation.
The rejection of claims 1-8, 11-12, and 14-15 under USC § 103 in view of Nikkah, et. al. (US 20180052151 A1) in view of Parlato, et. al. ("3D Microfluidic Model for Evaluating Immunotherapy Efficacy by Tracking Dendritic Cell Behavior Toward Tumor Cells") are withdrawn in view of amendments.
The rejection of claims 9-10 and 16 under USC § 103 in view of Nikkah, et. al. (US 20180052151 A1) and Parlato, et. al. ("3D Microfluidic Model for Evaluating Immunotherapy Efficacy by Tracking Dendritic Cell Behavior Toward Tumor Cells") in further view of Daojing, et. al. (WO 2019094633 A1) are withdrawn in view of amendments.
The rejection of claims 13 under USC § 103 in view of Nikkah, et. al. (US 20180052151 A1) and Parlato, et. al. ("3D Microfluidic Model for Evaluating Immunotherapy Efficacy by Tracking Dendritic Cell Behavior Toward Tumor Cells") in further view of Chang, et. al. (US 20160059234 A1) are withdrawn in view of amendments.
Response to Arguments
Applicant’s arguments, see Remarks pages 5-8, filed 25 February 2026, with respect to the rejections claims 1-8, 11-12, and 14-15 under USC § 103 in view of Nikkah, et. al. (US 20180052151 A1) in view of Parlato, et. al. ("3D Microfluidic Model for Evaluating Immunotherapy Efficacy by Tracking Dendritic Cell Behavior Toward Tumor Cells") have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Wikswo, et. al. (US 20060154361 A1) in view of Daojing, et. al. (WO 2019094633 A1).
First, Applicant argues the modification of Nikkah in view of Parlato would not disclose, teach, or suggest the claim configuration of the three regions with respect to their functional connection, specifically for the third region (remarks, pg. 6, par. 06 – pg. 7, par. 01; pg. 7, par. 05). While Examiner reminds applicant in apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2173.05(g)), Examiner agrees in light of the amendments, there is no motivation for this specific combination of Nikkah in view of Parlato regarding the structural and functional modification of the three regions. Due to the nature of the analogous art of Nikkah and Parlato, however, Nikkah and Parlato do teach, disclose, or suggest other aspects of the claimed regions such as their individual shape (tapered shape) and the depth of the regions.
Applicant offers no additional argument for the dependent claims outside of their dependence to claim 1 (Remarks, pg. 9, par. 05).
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.
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 1-3, 5-10, 12-13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wikswo, et. al. (US 20060154361 A1) in view of Daojing, et. al. (WO 2019094633 A1; citations made with respect to copies provided with Office Action dated 11 October 2025).
Regarding claim 1, Wikswo teaches a bioreactor for introducing a concentration of an analyte across a chamber holding cells (Abstract). Wikswo teaches the bioreactor serves to study migration of different cell types in response to the environment (par. 0123) (for studying interactions of a first cell type with a second cell type). Wikswo teaches a bioreactor comprising a chamber 732 can be divided into three parts (Fig. 7; par. 0143-0146):
a central chamber 706 for holding a first predetermined cell type, like tumor cells 714 (a first region configured to hold cells of the first cell type)
an intermediate chamber 705 for holding a second predetermined cell type, like tissue cells 713 (a third region configured to collect cells of the second cell type that have not interacted with cells of the first cell type)
an outer chamber 704 for holding a third predetermined cell type, like immune cells (a second region configured to hold cells of the second cell type)
Wikswo teaches first 738 and second 740 barriers disposed between each chamber (Fig. 7; par. 0143-0144) (disposed between the first region and the second region, and disposed between the third region and the second region). It is understood that all chambers are in fluid communication with one another because the setup allows for permeation of a predetermined cell type from the outer chamber to the central chamber (par. 0144) (wherein the first region is in fluid communication with the second region) (wherein the third region is in fluid communication with the first region and the second region).
Examiner notes "configured to collect cells of the second cell type that have not interacted with cells of the first cell type" and "configured to selectively allow movement of cells of the second cell type from the second region to an interaction zone that is at least partially disposed within the first region for interaction with cells of the first cell type in the interaction zone" contains functional language (ex: "configured to "). However, functional language does not add any further structure to an apparatus beyond a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2173.05(g)). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims. Because the device for studying cell migration with predetermine physical barriers to influence cell migration (par. 0123) it is entirely capable of allowing the predetermined cell type of the outer chamber 704 (a second region configured to hold cells of the second cell type) to migrate through the intermediate chamber 705 (a third region) to central chamber 706 (par. 0158) (a first region configured to hold cells of the first cell type), wherein cells that do not completely migrate to the central chamber 706 from the outer chamber 704 remain in the intermediate chamber 705 and do not react with the first cell type in the central chamber 706 (configured to collect cells of the second cell type that have not interacted with cells of the first cell type) (configured to selectively allow movement of cells of the second cell type from the second region to an interaction zone that is at least partially disposed within the first region for interaction with cells of the first cell type in the interaction zone).
Wikswo is silent to the barriers between each chamber specifically being an array of microstructures.
Daojing teaches a microfluidic device with obstacles disposed within the microfluidic channel to separate particles from a fluid flow (Abstract). Daojing teaches the physical attributes of the obstacles (microstructures) influences the movement of particles throughout the channel/microfluidic space (par. 0011-0013) (an array of microstructures). Daojing teaches controlled separation and sorting of biological particles (types of cells) through the use of a microfluidic spaces with an array of obstacles provides diagnostic and therapeutic information because the array of obstacles is driving the particle separation (par. 0004, 0009-0010).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to substitute the generic physical barriers of Wikswo with the microstructures of Daojing. One would be motivated to do so because microstructures within microfluidic space influence the movement of particles through the microfluidic space providing diagnostic information and this involves the simple substitution of a generic barrier for the microstructures to obtain predictable results. MPEP 2143(I)(B).
Regarding claim 2, modified Wikswo teaches a highly symmetrical device with multiple lines of symmetry (wherein the first and second regions are symmetrical about a same line of symmetry). Provided below is Figure 7 (Wikswo) with two examples of lines of symmetry added to show the symmetry of each chamber with respect to one another.
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Regarding claim 3, modified Wikswo teaches the barriers 738, 740 (interpreted to be microstructures in view of Daojing, see claim 1) separate each chamber from one another, meaning a particle cannot move from one chamber to another without passing through at least one set of barriers/microstructures (Wikswo, Fig. 7)
Regarding claim 5, modified Wikswo teaches the central chamber 706 is radially surrounded by the intermediate chamber 705 (Wikswo, Fig. 7) (wherein the third region substantially surrounds the first region).
Regarding claim 6, modified Wikswo teaches a highly symmetrical device with multiple lines of symmetry (wherein the first, second and third regions are symmetrical about a same line of symmetry). Provided above is Figure 7 (Wikswo) with two examples of lines of symmetry added to show the symmetry of each chamber with respect to one another.
Regarding claim 7, modified Wikswo teaches the barriers (interpreted to be microstructures in view of Daojing, see claim 1) are arranged in a radial manner separating each chamber from one another (Wikswo, Fig. 7) (wherein the array of microstructures comprises microstructures organised in a radial manner).
Regarding claim 8, modified Wikswo teaches the barriers 738, 740 (interpreted to be microstructures in view of Daojing, see claim 1) are arranged in concentric rows separating each chamber from one another (Wikswo, Fig. 7) (wherein the array of microstructures comprises microstructures organised as substantially concentric rows of microstructures).
Regarding claim 9, modified Wikswo in view of Daojing teaches barriers in the form of microstructures (see claim 1).
Modified Wikswo is silent to wherein the distance between the microstructures in the row closest to the first region is smaller than the distance between the microstructures in the row furthest from the first region.
Daojing teaches the physical attributes of the obstacles influences the movement of particles throughout the channel (par. 0011-0013). One such physical attribute is spacing between the obstacles (par. 0017, 0052, 0057). Daojing teaches additional separation of particles can be realized when one or more of the obstacles is altered and therefore altering the space between said obstacles to create different cross-sections, dimensions, and geometries to allow for different thresholds of separation (par. 0069, 0071, 0081). Daojing teaches a wide range of spacing between the obstacles dependent on the type of cell being separated (par. 0017, 0069, 0071) including variable spacing between the obstacles in an array (par. 0069), while also preventing clogging issues (par. 0030).
Further, Daojing teaches wherein the spacing between obstacles is a result-effective variable. Specifically, Daojing teaches that the spacing between obstacles is dependent on the type of particle (cell) that will be moving through the obstacles while preventing clogging (par. 0069, 0030). Daojing teaches obstacles having variable space from the average changes the allowable threshold value and therefore changes the size/type of particle that will be able to pass the array of obstacles, specifically through modifying one or more obstacles in an array (adding obstacles to make spacing smaller, removing to make spacing larger, or changing obstacle shape) (par. 0081). The use of different spacing on different rows allows for a continuous flow (prevent clogging issues with wider spacing) while only target particles (cells) make it through the entirety of the obstacles (narrower spacing). Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the distance between the microstructures in the row closest to the first region is smaller than the distance between the microstructures in the row furthest from the first region as taught by Daojing because doing so would allow separation of particles of multiple sizes based on the particle size with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 10, modified Wikswo in view of Daojing teaches barriers in the form of microstructures (see claim 1).
Modified Wikswo is silent to wherein the size of the microstructures in the row closest to the first region is smaller than the size of the microstructures in the row furthest from the first region.
Daojing teaches the physical attributes of the obstacles influences the movement of particles throughout the channel (par. 0011-0013). One such physical attribute is the size of the obstacles (par. 0045-0047). Daojing teaches a plurality of sizes of the obstacles (par. 0045-0047) and that the sizing of the obstacles within an array can vary/be irregular (par. 0039). Daojing further teaches the location of the obstacle array can vary based on location in the microchannel (par. 0053) meaning in region the size of the obstacles can be different than the size of the obstacles in another region of the same microchannel because doing so impacts the sorting of particles based on size (par. 0053).
Further, Daojing teaches wherein the size of the obstacles is a result-effective variable. Specifically, Daojing teaches that the size of the obstacles is dependent on the type of particle (cell) that will be moving through the obstacles while preventing clogging. Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). The use of different sizing on different rows allows for a continuous flow while only target particles (cells) make it through the entirety of the obstacles. Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the size of the microstructures in the row closest to the first region is smaller than the size of the microstructures in the row furthest from the first region based on the type of particle being separated as taught by Daojing through routine optimization. MPEP 2144.05 (II)(A).
Regarding claim 12, modified Wikswo teaches a series of inlet and outlet ports each corresponding to a specific chamber (further comprising ports corresponding to each of said regions for providing access to each of the regions). Ports 701 are connected to outer chamber 704 (par. 0148). Ports 702 are connected to central chamber 706 (par. 0149). Ports 703 are connected to intermediate chamber 705 (par. 0150).
Regarding claim 13, modified Wikswo teaches the bioreactor is formed with a first substrate and second substrate wherein the cavities (chambers) are formed between the first surface of the first substrate and second surface of the second substrate (support layer) and a biocompatible coating is applied to the second (bottom) surface of the second substrate (seeding layer). Ports are additionally formed in the second substrate (par. 0021-0025) (wherein the device comprises a seeding layer and a support layer, wherein the ports are disposed on the seeding layer and the corresponding regions are disposed on the support layer).
Regarding claim 16, modified Wikswo teaches the limitation as applied to claim 1 (see above).
Modified Wikswo is silent to the use of a plurality of the microfluidic device (of claim 1) being used with a chip.
Daojing teaches the microfluidic platform can be used as a part of a multiunit microfluidic chip through stacking of the individual channels (Fig. 6A-6E; par. 0034, 0118). Daojing teaches combining multiple channels on a single chip allows for ultrahigh throughput and parallel processing (par. 0011, 0068).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the microfluidic device of modified Wikswo to be multiple microfluidic devices combined as taught by Daojing because doing so would increase throughput by parallel processing across multiple devices on a singular chip (par. 0011) with reasonable expectation of success. MPEP 2143(I)(G).
Claims 11 is rejected under 35 U.S.C. 103 as being unpatentable over Wikswo, et. al. (US 20060154361 A1) and Daojing, et. al. (WO 2019094633 A1 as applied to claim 1 above, and further in view of Parlato, et. al. ("3D Microfluidic Model for Evaluating Immunotherapy Efficacy by Tracking Dendritic Cell Behavior Toward Tumor Cells"; citations made with respect to the copy provided with IDS dated 19 Oct. 2022).
Regarding claim 11, modified Wikswo teaches the limitations as applied to claim 1 (see above). Modified Wikswo teaches the embodiment of the bioreactor as seen in Figure 7 wherein a port area is connected to its respective wider chamber via a narrow channel (Fig. 7, par. 0148-0150).
Modified Wikswo is silent to the shape of this transition, specifically, wherein each of said regions comprises a shape defined by tapering of a bigger area to a smaller area.
Parlato teaches a microfluidic platform for testing the immunotherapy of dendritic cells against cancer cells. Parlato teaches tumor chambers (a first region) and an immune chamber (a second region) along with their associated loading reservoirs (Fig. 2a, 2c, 2d). Parlato teaches each of the three chambers, tumor, immune, and media chambers, have larger terminal ends serving as reservoirs that taper into narrower channels (Fig. 2a). Parlato teaches this design of the microfluidic device to have loading reservoirs that lead to narrower channels is to best recreate 3D tumor spaces (pg. 04, Fig. 2a description) (each of said regions comprises a shape defined by tapering of a bigger area to a smaller area). Parlato teaches the tapering design of the microfluidic device is done in order to best mimic the complex 3D space to recreate physical and biochemical cues in the in vivo environment to specifically monitor how immune cells interact with tumor cells (pg. 02, par. 02).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the shape the chambers/regions of Wikswo to be wider at one area and taper to a smaller areas as taught by Parlato because doing so would more closely recreate a 3D tumor space to study the migration of immune cells (pg. 02, par. 02) with reasonable expectation of success. MPEP 2143(I)(G).
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Wikswo, et. al. (US 20060154361 A1) and Daojing, et. al. (WO 2019094633 A1 as applied to claim 1 above, and further in view of Nikkah, et. al. (US 20180052151 A1).
Regarding claim 14, modified Wikswo teaches the limitations as applied to claim 1 (see above).
Modified Wikswo is silent to wherein the first region has a larger depth than the second region.
Nikkah teaches a microfluidic device for modeling a cancerous environment (Abstract). Nikkah teaches a microfluidic device comprising a tumor region and channels connected to cell filing ports and leading into a stromal region that hold immune cells (Fig. 2A, 3; par. 0076). Nikkah teaches the tumor (first) region and the stomal (second) region are of different dimensions as seen in Figure 2B. Modified Nikkah teaches a dimension of 0.5 mm of the tumor region leading to the respective port and a dimension of 0.4250 mm of the stromal region leading to the respective ports (the first region has a larger depth than the second region). Nikkah teaches the design of the device, including the depth of each region, is done in order to best recreate a native tumor stroma to best create a physiologically relevant model in vitro microenvironments (par. 0010).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the central and outer chamber depths of modified Wikswo to have a deeper central chamber compared to the outer chamber as taught by Nikkah because doing so would best recreate native tumor stroma to create a physiologically relevant model (par. 0010) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 15, Modified Wikswo teaches the limitations as applied to claim 1 (see above).
Modified Wikswo is silent to wherein the second region has substantially the same depth as the third region.
Nikkah further teaches height of all regions are the same, meaning the stromal (second) and vascular/media (third) region have the same depth (par. 0119) (the second region has substantially the same depth as the third region). Nikkah teaches the design of the device, including the depth of each region, is done in order to best recreate a native tumor stroma to best create a physiologically relevant model in vitro microenvironments (par. 0010).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the intermediate and outer chamber depths of modified Wikswo to have the same depth as taught by Nikkah because doing so would best recreate native tumor stroma to create a physiologically relevant model with (par. 0010) reasonable expectation of success. MPEP 2143(I)(G).
Conclusion
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADISON T HERBERT whose telephone number is (571)270-1448. The examiner can normally be reached Monday-Friday 8:30a-5:00p.
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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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