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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/4/2026 has been entered.
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.
Claims 1, 3-5, 7-8, 10-13, and 75-76 are rejected under 35 U.S.C. 103 as being unpatentable over Borenstein et al. (US 2017/0349912) as applied to claims above, and further in view of Maguire (WO 2016/065341).3
Regarding claim 1 Borenstein discloses a method comprising:filling a chamber of a cell engineering platform with a mixture of cells and a first medium;and discharging the first medium from the chamber through a filter, leaving the cells deposited on the filter,wherein the cell engineering platform includes: (See Borenstrin Fig. 1A-2, [0059]-[0062] wherein a chamber is filled with cells and first medium, and said first medium is discharged through a filter and cells are deposited on the filter.)
a chamber;a lid disposed at a first end of the chamber;a base disposed at a second end of the chamber; and a filter holder disposed within the chamber. See Borenstrin Fig. 1A-3E wherein a chamber 102 has a lid, i.e. top substrate 108, a base, i.e. bottom substrate 104, and a filter holder, i.e. second substrate 106, is housed therein.)
Borenstein discloses all the claim limitations as set forth above as well as applying a delivery solution which contains a payload to cells deposited on the filter but does not specifically disclose applying said solution by spraying.
Maguire et al. discloses a method of delivering a delivery solution comprising a payload to cells wherein the solution is sprayed onto the cells in order to delivery said payload to cells and that such spraying is preferred to submersion in such delivery solutions. (See Maguire Abstract, [0004]-[0005], and [00021])
It would have been obvious to one of ordinary skill in the art at the time of invention to spray the deliver solution on the cells on the filter in the method of Borenstein as described by Maguire et al. because such a spray is known to more efficiently deliver a payload to cells as would be desirable in the method of Borenstein and is a known preferred alternative to submersion of cells in a solution
Borenstein discloses all the claim limitations as set forth above as well as the method further comprising culturing the cells within the chamber. (See Borenstein [0049]and [0059]-[0062] wherein cells in medium are placed and maintained in a viable state in the chamber along with a media ,i.e. they are cultured.)
Regarding claim 3 Borenstein discloses all the claim limitations as set forth above as well as the method further comprising applying a stop solution in the chamber. (See Borenstein [0065] wherein a stop solution is used to wash cells in the chamber.)
Regarding claim 4 Borenstein discloses all the claim limitations as set forth above as well as the method further comprising filling the chamber with a second medium to resuspend the cells from the filter. (See Borenstein [0066]-[0068] wherein the chamber is filled in a reverse direction with a second medium to resuspend the cells from the filter for removal.)
Regarding claim 5 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the discharged first medium is reused as the second medium. (See Borenstrin Fig. 1A wherein the first medium is stored in the fluid reservoir 126 and said second medium is reused from said fluid reservoir 126 and thus the second medium is reused first medium.)
Regarding claim 7 Borenstein discloses all the claim limitations as set forth above as well as the method further comprising extracting the resuspended cells from the chamber. (See Borenstein [0068] and [0079] wherein the cells are removed, i.e. extracted, from the chamber after resuspension.)
Regarding claim 8 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the filling the chamber is performed automatically with a pump and a controller. (See Borenstein [0053] wherein a controller and pump automatically provide the solutions to the chamber.)
Regarding claim 10 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the discharging the first medium from the chamber is performed by supplying a positive pressure into the chamber. (See Borenstein Fig. 1A-1B wherein the first medium is supplied via positive pressure from a pump and thus is discharged by supplying a positive pressure from said pump.)
Regarding claim 11 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the discharging the first medium from the chamber is performed by gravity. (See Borenstein Fig. 1A-1B wherein the first medium flows from top to bottom of the chamber and thus is discharged by gravitational force. )
Regarding claim 12 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the applying the stop solution is performed to wash the cells. (See Borenstein [0065] wherein the stop solution washes the cells.)
Regarding claim 13 Borenstein discloses all the claim limitations as set forth above as well as the method, wherein the filling the chamber with the second medium is performed as at least one of a cell wash process, a cell concentration change process, and a cell medium change process. (See Borenstein wherein the second medium is provided in a cell wash process.)
Regarding claim 75 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the cell engineering platform further includes at least one of a pump, a valve, a heating element, a cooling element, and an agitation device. (See Borenstein Figs. 1A wherein the device comprises valves 124,136 and pumps 122,134)
Regarding claim 75 Borenstein discloses all the claim limitations as set forth above as well as the method wherein the cell engineering platform is configured to treat at least 10^7 cells in a single transfection. (See Borenstein [0039] wherein the second substrate which holds cells for a single transfection in cavities therein includes up to 10,00,000 cavities and each cavity may hold from 1 cell to a million cells and thus the device is fully configured to treat at least 10^7 cells in a single transfection.)
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Borenstein et al. (US 2017/0349912) in view of Maguire (WO 2016/065341) as applied to claims above, and further in view of Plasson (US 5,654,185)
Regarding claim 6 Borenstein discloses all the claim limitations as set forth above but does not disclose agitating the chamber.
Plasson discloses a method of cell engineering wherein a device housing cells is agitated to increase contact between a delivery solution and the cells.
It would have been obvious to one of ordinary skill in the art at the time of invention to agitate the chamber in the method of Borenstein as described by Plasson because such an agitation allows increase in contact between cells and delivery solution as would be desirable in the method of Borenstein.
Response to Arguments
Applicant's arguments filed 9/24/2025 have been fully considered but they are not persuasive.
Applicant argues that “As explained in the Response to Non-Final Office Action filed on March 24, 2025, Borenstein relates to systems and methods for use in transducing, activating and treating cells using a multi- layered stack with a flow chamber and a plurality of cell entrainment regions. See Borenstein at Abstract. The whole system in Borenstein is defined by reversible flow across the chambers within each layer. See Borenstein at [0031]. Borenstein relies on control and perfusing solutions vertically and/or horizontally through membranes (e.g., closed-loop, directional flow) for cell modification. A person skilled in the art would not have resulted in claim 1 by combining Borenstein and Maguire because modifying Borenstein to include spraying a delivery solution on to the cells would result in a fundamental change in how Borenstein operates: the directional flow (horizonal and vertical) is what gives Borenstein its "confer[red] significant advantages over existing systems and methods." See Borenstein at [0089].”
The examiner notes that Borenstein discloses improving efficiency/effectiveness of cell culture, transfection, and cell capture by circulating materials to cells by pumping materials such that they circulate and flow vertically through the system. Borenstein traps cells on a filter and thereafter applies a genetic information introduction agents. (See Borenstein [0012])
As described in the rejection above Borenstein does not require a specific method by which genetic information introduction agents are originally made to contact the cells and thus does not disclose spraying the cells with said agents.
Maguire discloses that a payload, i.e. genetic information introduction agents, are preferably sprayed onto cells because such a spray provides for greater contact and effectiveness of payload introduction into cells over other flow and submersion methods. Maguire also discloses that after spraying the cells with the payload other materials, including those which also include payload, are made to flow over the cells. (See Maguire [00130])
Thus contrary to applicant’s arguments such a combination of references does not result in any replacement of flow systems or change in principle operation as described by Borenstein but merely provides the addition of a spraying step as described by Maguire. The examiner maintains that one of ordinary skill in the art at the time of invention would have recognized the desirability of providing such a spraying step in Borenstein as described by Maguire because doing so provides the discussed benefits over other methods of applying genetic material to cells and such a combination requires no replacement or significant change in the fundamental operation of Borenstein.
Applicant also argues “Applicant respectfully submits that contrary to the Office's assertion that Borenstein discloses the method further comprising culturing the cells within the chamber, Borenstein teaches away from said culturing of the cells within the chamber.
MPEP §2141.02 notes that "a prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention. W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984)."
Borenstein at [0064] states:
"As shown in FIG. 3B, the cells 302 and genetic information introduction agents 304 remain entrained in the cell entrainment cavities for a dwell time sufficient to allow the genetic information carried by the genetic information introduction agents 304 to be introduced into the cells 302, but not so long as to endanger the viability of the cells 302. Accordingly, in some implementations, the dwell time is between about 5 minutes to about 7 hours."
In addition, Borenstein at [0087] states: "Following treatment with the GFP+ lentiviral vector, cells were removed from the device (in the case of experimental samples) or the spinoculation tubes (in the case of control samples). The cells were re-suspended in fresh RPMI media and cultured for
four days under standard cell culture conditions."
[Emphasis added]
Therefore, a skilled artisan, reading Borenstein as a whole, would understand that the Borenstein fluidic system is NOT intended for culturing the transfected cells. Rather, the cells are to be removed from the fluidic system after treating the cells, to prevent endangering the viability of the cells.”
The examiner notes that contrary to applicant’s assertion Borenstein does not “teach away” from culturing cells within the chamber. Borenstein specifically discloses maintaining cells in a cell medium, both with and without transfecting materials, in a viable condition in the chamber. One of ordinary skill in the art would understand such a procedure to be cell culture.
As applicant notes Borenstein may disclose methods wherein cells are removed from the chamber and subjected to additional culturing.
MPEP 2123 states “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." Id. at 554, 31 USPQ2d at 1132.). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).”
Thus the fact that Borenstein provides examples where cells are cultured outside of the chamber in additional to performing culture within the chamber, i.e. alternative culture steps, does not constitute teaching away. Borenstein makes no disclosure which criticizes or discourages culturing within the chamber but merely gives examples where additional culture steps are performed outside of the chamber.
Applicant also argues “The Office alleges Borenstein discloses the method further comprising culturing the cells within the chamber, referring to Borenstein [0049] and [0059]. See Office Action at page 5.
Applicant respectfully disagrees and submits that those paragraphs do not disclose or teach a method that further comprises culturing the cells within the chamber. [0049] teaches recirculating the fluid to allow more of the cells and genetic information introduction agents to become entrained. [0059] describes an example method of transducing genetic information into cells and describes certain components such as a pump and a valve for introducing cells into the Borenstein fluidic system. Applicant respectfully submits that those paragraphs do not suggest "cells in medium are placed and maintained container in the chamber, i.e. they are cultured" as asserted by the Office
Maguire relates to methods for delivering a payload across a plasma membrane of a cell. See Maguire at Abstract. Maguire also relates to contacting a population of cells in the form of a spray. Id. at [0011]. Nowhere does Maguire teach or suggest culturing of cells in the same chamber as where the cells are sprayed with the delivery solution. Plasson teaches localizing particles (e.g. viral particles) on a cell growth support and directing target cells to contact the particle-loaded cell growth support to increase the transfection efficiency. See Plasson at column 4, lines 19-24. Plasson also does not teach or suggest culturing the cells in the same chamber as where the cells are treated with the delivery solution. Therefore, neither Maguire nor Plasson cures the deficiencies of Borenstein.
Nor would a person of ordinary skill in the art find it obvious to modify Borenstein, Maguire, and Plasson to culture cells within the chamber because of added complexities to allow transfecting cells and culturing them in the same system, let alone in the same chamber of the system. Furthermore, as described above, a skilled artisan reading Borenstein would have no motivation to modify the Borenstein fluidic system to culture cells within the chamber because Borenstein expressly teaches not to leave the cells in the system for too long to avoid endangering the viability of the cells, and to remove the cells from the system and culture them under standard culturing conditions. Plasson teaches localizing particles on a cell growth support and directing target cells to contact the particle- loaded cell growth support to increase the transfection efficiency. A skilled artisan would be motivated to remove the particles from the cells after transfection and therefore would not culture the cells in the same chamber.”
The examiner notes that applicant appears to have a narrow view of culture steps and processes and asserts that Borenstein does not disclose culturing cells within the chamber according to a narrow definition of cell culture. The examiner notes that in Borenstein cells are added to the device along with a cell medium, i.e. a solution that allows growth and maintenance of cells, both with and without transfection agents and kept viable for some amount of time. The examiner maintains that one of ordinary skill in the art at the time of invention would understand such maintenance of cells in a medium to be a cell culture. This is evidenced by the previously cited Plason reference which notes “transfection occurs by culturing target cells with viral particles suspended in the cell culture medium” (See Plason Col. 2 Lines 12-27). Thus one of ordinary skill in the art would fully understand that when Borenstein describes maintaining cells and viral particles in a cell medium so that they remain viable within the chamber to read on “culturing the cells within the chamber” as is so broadly claimed.
If applicant envisions specific cell culture steps or materials to be used it is suggested that applicant amend to claims to include such features rather than rely on broad “culturing” the cells” as is presently claimed and which is taught by Borenstein.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONATHAN M HURST whose telephone number is (571)270-7065. The examiner can normally be reached on M-F 7AM-4PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached on 571-272-1374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JONATHAN M HURST/Primary Examiner, Art Unit 1799
Prosecution Insights