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 .
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, 7-13, and 75 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).
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
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 ina 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 9 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] wherein cells in medium are placed and maintained container in the chamber ,i.e. they are cultured.)
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)
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 “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.
At issue is (i) whether the cited art teaches each and every element of the claimed invention, and (ii) whether a person having ordinary skill in the art at the time of filing the application would have been motivated to arrive at the claimed invention with a reasonable expectation of success. As discussed below, the cited art does not teach or suggest each and every element of the claimed invention, and the combined art provides no basis for a motivation to arrive at the particular solution recited in the claims.
The cited art simply does not teach the claimed combination of elements. Borenstein relies heavily on the directional flow of the fluid through the system for cell modification. The fluidics in the system include a vertical flow system (used to release cells from the cell entertainment cavities) and a horizontal flow system (configured to introduce cells and genetic information introduction agents). See para. [0031], [0046] and [0047]. Both the vertical and horizontal flow systems are required for the apparatus and methods of Borenstein to work. There is no teaching of "... discharging the first medium from the chamber through a filter, leaving the cells deposited on the filter, and spraying a delivery solution that contains a payload to the cells deposited on the filter..." as claimed.
The Office states that Borenstein "does not specifically disclose applying said solution by spraying." See Office Action at page 5. Instead, the Office relied on Maguire for disclosing "a method for delivering a delivery solution comprising a payload to cells wherein the solution is sprayed onto the cells..." Id. The Office further states that "it would have been obvious to one of ordinary skill in the art at the time of filing the invention to spray the deliver[y] 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." Id.
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].
It is respectfully submitted that a person skilled in the art would not have resulted in amended 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. As discussed above, the directional flow (horizonal and vertical) is what gives Borenstein its "confer[red] significant advantages over existing systems and methods." See Borenstein at [0089]. See MPEP § 2143.01 (VI) (If the proposed modification or combination of the prior art would change the principle operation of the prior art invention being modified, then the teachings of the references are not sufficient to render the claims prima facie obvious. In re Ratti, 270 F.2d 810, 813, 123 USPQ 349, 352 (CCPA 1959)).
The examples of Borenstein further state that the "devices of the disclosure confer significant advantages over existing systems and methods for gene delivery into target cells. It should be further noted that the devices of the disclosure improve transduction efficiency without compromising cell viability." Thus, there would be no motivation to modify the teachings of Borenstein, much less using a spray, as described by Maguire.
Accordingly, the proposed modification is not obvious because one skilled in the art would not have been motivated to make the modification and such a modification would change the principle operation of Borenstein. Furthermore, the person skilled in the art would not only not be motivated to replace the flow-mechanism described in Borenstein with the spray, but would also not have any reasonable expectation of success that such a spray would work.”
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.
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 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.
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/JONATHAN M HURST/Primary Examiner, Art Unit 1799