DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 26 June 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, 2, 4, 9 and 10 are rejected under 35 U.S.C. 103 as unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916) and Washington (US 20220040862).
With respect to claims 1 and 4, Ragsdale discloses an electroporation system configured to test for optimal parameters for the electroporation of a sample. The system includes a compartment (Figure 5A:90) configured to removably receive at least one electroporation chamber (Figure 5A:85). A controller (Figure 13:10) is communicatively coupled to the electroporation chamber. Paragraphs [0020]-[0024] indicate that the controller is configured to run a plurality of optimization routines, wherein each optimization routine includes a set of parameters for the electroporation of a particular sample (“intelligence module 10 includes an optimization software module 50 that executes in a microprocessor module 55. According to one embodiment, application module 50 includes instructions for optimizing and controlling electroporation experiments as described herein based in part on user input parameters”). Ragsdale states in paragraphs [0078]-[0088] that the electroporation chambers are arranged around the perimeter of a carousel (Figure 5A:80) to create a queue. The carousel is advanced to sequentially evaluate each electroporation chambers. Those of ordinary skill would have found it obvious to adjust operation of the carousel motor in order to skip predetermined chambers and repeat processing of predetermined chambers as needed. See also paragraph [0078] (“Likewise, at the end of the set of pulses, the operator is given the choice of repeating the set of pulses, any individual pulse(s) or ending the pulse delivery session”).
Ragsdale, however, does not appear to disclose a user interface that displays the queue of predefined optimization routines and receives user input for the selection of a desired optimization routine to run. Ragsdale does not teach that the user interface and controller are configured to display the status of each optimization routine selection and receive user input to repeat, re-order, and/or add an optimization routine to the operation sequence.
Loo discloses a biological analysis system for processing different sample types. Loo indicates that a processing chamber, controller and user interface are provided. The user interface displays a queue of predefined optimization routines based on different parameters relevant to different sample types. The user interface is also configured to receive user input for the selection of an optimization routine from the queue so that the controller may execute the desired routine. See paragraphs [0061]-[0067], [0115] and [0116] (“a controller may control the operation of one or more components of a device according to a protocol. In embodiments, a protocol by which a controller controls the operation of any one or more component or unit of a device may be preprogrammed, e.g., may be resident on the device. In embodiments, a protocol by which a controller controls the operation of any one or more component or unit of a device may be obtained from another device, or from a user, or from a laboratory, or from a network, or from the cloud. In embodiments, a protocol by which a controller controls the operation of any one or more component or unit of a device may be updated, or may be updatable, according to information or instructions from another device, or from a user, or from a laboratory, or from a network, or from the cloud. In embodiments, a device may receive information, or instructions, or updates, or protocols, via a user interface”).
Washington discloses a user interface and controller for operating a biological analysis system. Washington teaches that a queue of predefined routines defined by different parameters is displayed on a user interface (see Figs. 4-7), and that optimum parameters are obtained using a simulation model (“the parameters may describe a desired protocol location for performing the protocol, a desired proximity to the protocol location, equipment preferences, reagent preferences, and the like. The simulation module 340 may select one or more variants to simulate for the protocol to optimize satisfying the parameters”). Paragraphs [0077]-[0079] state that the status of a routine is displayed using the user interface, and the user interface allows a user to receive other information and submit input for a selected routine. The input may involve typical commands, such as an action to repeat a predefined routine, skip a predefined routine, and/or re-order a selection of routines. For example, when the controller cannot find a solution to an identified problem, the user will be asked (see Figure 8:820) to resolve the error. This is described in paragraphs [0041] and [0079].
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Ragsdale system includes a user interface and controller configured to display and perform a plurality of predefined optimization routines that may be selected, repeated, skipped and/or re-ordered by a user based on the particulars of a specific sample type. Loo and Washington show that it is beneficial to allow a user to select from a plurality of given predefined routines in order to permit adaptation to the varying conditions and requirements of different sample types. This would have been particularly useful for implementation in the Ragsdale system since Ragsdale describes in paragraphs [0003]-[0005] how it is important to account for changes to different sample parameters when determining optimum transfection conditions (“Such an optimization experiment is generally run manually and typically includes performing electroporation on aliquots of the sample at slightly different settings of the electroporation instrument parameters”). Ragsdale is interested in considering multiple possible optimization routines in order to evaluate different parameter sets, and Loo and Washington recommend that these available routines should be displayed on a user interface as choices for a skilled operator, which would allow for both automation and expert input.
With respect to claim 2, Ragsdale, Loo and Washington disclose the combination as described above. Ragsdale further teaches in paragraph [0007] that voltage, pulse width, pulse number, pulse type and pulse interval are parameters that are varied between optimization routines.
With respect to claims 9 and 10, Ragsdale, Loo and Washington disclose the combination as described above. Ragsdale further teaches that a display (Figure 13:20) is provided to convey information to a user. Paragraphs [0020] and [0021] indicate that a step-by-step guide is created based in part on user input parameters. The user is allowed to select an auto-optimization mode and may input as many or as little instructions as desired. Instances in which reduced user input is required are understood to read on a “quick start” option, as are instances in which “the user is repeated the published protocol of some other researcher”.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916) and Washington (US 20220040862) as applied to claim 2, and further in view of Garcia Dominguez (US 20190136224).
Ragsdale, Loo and Washington disclose the combination as described above, however do not expressly state that the optimization routines are configured to evaluate the effect of alternating pulse polarity.
Garcia Dominguez discloses a system for optimizing electroporation conditions within at least one chamber. Garcia Dominguez teaches in paragraphs [0147] and [0156] that testing is performed to determine how changes in the applied electric field (“The ability to modulate the exposure duration and specific waveform that the cells experience in a flow-through manner allows for further optimization of electroporation protocols”), flow rate and cartridge geometry affect electroporation efficiency. Paragraph [0167] and Fig. 37 teach that pulses were delivered from electrodes with alternating polarity.
Before the effective filing date of the claimed invention, it would have been obvious to use the Ragsdale system to evaluate the effects of alternating positive and negative polarity on electroporation optimization. Garcia Dominguez teaches that switching the polarity of an electric field may improve efficiency of an electroporation processes, and that it is important to consider this parameter when determining optimum poration conditions for any given sample. Garcia Dominguez shows how polarity may be alternated by switching the electrodes from negative to positive and reversing the direction of the applied electric field.
Claims 11-13, 15, 20, 21 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916) and Washington (US 20220040862) as applied to claim 1, and further in view of Chen (US 20170335269).
Ragsdale, Loo and Washington disclose the combination as described above, however Ragsdale does not state that the electroporation chambers include at least one electrode in communication with a resealable cap and at least one fluid overfill reservoir.
Chen discloses an electroporation system comprising an electroporation chamber disposed within an electroporation cartridge (Figure 2:1) having an elongate body. A first electrode (Figure 2:3) is provided in communication with a resealable cap (Figure 2:4). A second electrode (Figure 2:2) is arranged at an opposite end of the elongate body. The electroporation cartridge additionally includes at least one fluid overfill reservoir (Figure 2:1f). This is taught in paragraphs [0104]-[0111]. Paragraph [0055] teaches that the cartridge is made from non-conductive plastic materials.
Before the effective filing date of the claimed invention, it would have been obvious to use the Ragsdale system to an perform an optimization protocol using essentially any electroporation cartridge suitable for automation. Chen shows how elongate shock tubes may be configured to electroporate cells using a strong electric field produced with a high degree of reliability and minimal user input. Chen further teaches that the tubes are manipulated by a programmable microcomputer and optically evaluated using an automated detection system.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916), Washington (US 20220040862) and Chen (US 20170335269) as applied to claim 11, and further in view of Gamelin (US 20070128708).
Ragsdale, Loo, Washington and Chen disclose the combination as described above, however do not expressly state that the electroporation chamber includes a volume reducing sleeve.
Gamelin discloses an electroporation cartridge comprising a volume reducing sleeve (Figure 1:10) comprising a plunger (Figure 1:12). This is taught in paragraph [0031].
Before the effective filing date of the claimed invention, it would have been obvious to provide at least one electroporation chamber of Ragsdale with a volume reducing sleeve. Gamelin shows that this allows an operator to easily adjust sample fluid volume, sample fluid conductivity and cell density, which are known parameters that affect electroporation efficiency. This would have allowed he Ragsdale optimization routine to more thoroughly evaluate electroporation conditions and determine how changes in these specific variables affect cell transfection.
Claims 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916), Washington (US 20220040862) and Chen (US 20170335269) as applied to claim 11, and further in view of Eberhart (US 20150024436).
Ragsdale, Loo, Washington and Chen disclose the combination as described above, however do not expressly disclose an electroporation cartridge comprising an authentication chip.
Eberhart discloses an automated sample preparation, processing and analysis system for biological samples disclosed in a plurality of sample cartridges. See paragraph [0011]. Paragraphs [0411]-[0417] teach that the sample cartridges are labeled using known authentication chips, such as RFID, EEPROM and EPROM tags.
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the sample cartridges taught by Ragsdale are labelled using available prior art authentication chips. Eberhart teaches that this allows for automated tracking and analysis of individual samples (“such identifying information enables a controller of the system to identify the cartridge and configure the system for an appropriate processing and/or analysis routine. Accordingly, each fluidic circuit in the cassette can be labeled with information about the sample being loaded. For example, information taken, e.g., at a collection site can be associated with the cassette in a fluidic circuit corresponding to the sample. Such information can include, for example, time of collection, place of collection, and information about a subject from whom a sample is taken”).
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Ragsdale (US 20060246572), Loo (US 20160069916), Washington (US 20220040862), Chen (US 20170335269) and Eberhart (US 20150024436) as applied to claim 19, and further in view of Garcia Dominguez (US 20190136224).
Ragsdale, Loo, Washington, Chen and Eberhart disclose the combination as described above, however do not expressly state that the electroporation chamber is tapered.
Garcia Dominguez discloses a system for optimizing electroporation conditions within at least one chamber. Garcia Dominguez teaches in paragraphs [0147] and [0156] that testing is performed to determine how changes in the applied electric field (“The ability to modulate the exposure duration and specific waveform that the cells experience in a flow-through manner allows for further optimization of electroporation protocols”), flow rate and cartridge geometry affect electroporation efficiency. For example, Garcia Dominguez investigates how electroporation chambers that are tapered in one or more directions impact cell transformation. See Figs.23A-C.
Before the effective filing date of the claimed invention, it would have been obvious to use conduct the optimization routines of Ragsdale using cuvettes that are tapered. Garcia Dominguez teaches in paragraph [0146] that converging and diverging geometries affect electric field distribution and therefore transformation efficiency. Garcia Dominguez states that it is important to consider tapered (e.g., converging, bilaterally converging) designs when determining optimum electroporation conditions for a given cell sample.
Claims 54-56 are rejected under 35 U.S.C. 103 as unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916), Washington (US 20220040862) and Neal (US 20180071014).
Ragsdale discloses an electroporation system configured to test for optimal parameters for the electroporation of a sample. The system includes a compartment (Figure 5A:90) configured to removably receive at least one electroporation chamber (Figure 5A:85). A controller (Figure 13:10) is communicatively coupled to the electroporation chamber. Paragraphs [0020]-[0024] indicate that the controller is configured to run a plurality of optimization routines, wherein each optimization routine includes a set of parameters for the electroporation of a particular sample (“intelligence module 10 includes an optimization software module 50 that executes in a microprocessor module 55. According to one embodiment, application module 50 includes instructions for optimizing and controlling electroporation experiments as described herein based in part on user input parameters”). Ragsdale, however, does not appear to disclose a user interface that displays a queue of predefined optimization routines and receives user input for the selection of a desired optimization routine to run. Ragsdale teach that the user interface and controller are configured to display the status of each optimization routine selection and receive user input to repeat, re-order, and/or add an optimization routine to the operation sequence.
Loo discloses a biological analysis system for processing different sample types. Loo indicates that a processing chamber, controller and user interface are provided. The user interface displays a queue of predefined optimization routines based on different parameters relevant to different sample types. The user interface is also configured to receive user input for the selection of an optimization routine from the queue so that the controller may execute the desired routine. See paragraphs [0061]-[0067], [0115] and [0116] (“a controller may control the operation of one or more components of a device according to a protocol. In embodiments, a protocol by which a controller controls the operation of any one or more component or unit of a device may be preprogrammed, e.g., may be resident on the device. In embodiments, a protocol by which a controller controls the operation of any one or more component or unit of a device may be obtained from another device, or from a user, or from a laboratory, or from a network, or from the cloud. In embodiments, a protocol by which a controller controls the operation of any one or more component or unit of a device may be updated, or may be updatable, according to information or instructions from another device, or from a user, or from a laboratory, or from a network, or from the cloud. In embodiments, a device may receive information, or instructions, or updates, or protocols, via a user interface”).
Washington discloses a user interface and controller for operating a biological analysis system. Washington teaches that a queue of predefined routines defined by different parameters is displayed on a user interface (see Figs. 4-7), and that optimum parameters are obtained using a simulation model (“the parameters may describe a desired protocol location for performing the protocol, a desired proximity to the protocol location, equipment preferences, reagent preferences, and the like. The simulation module 340 may select one or more variants to simulate for the protocol to optimize satisfying the parameters”). Paragraphs [0077]-[0079] state that the status of a routine is displayed using the user interface, and the user interface allows a user to receive other information and submit input for a selected routine. The input may involve typical commands, such as an action to repeat a predefined routine, skip a predefined routine, and/or re-order a selection of routines. For example, when the controller cannot find a solution to an identified problem, the user will be asked (see Figure 8:820) to resolve the error. This is described in paragraphs [0041] and [0079].
Before the effective filing date of the claimed invention, it would have been obvious to ensure that the Ragsdale system includes a user interface and controller configured to display and perform a plurality of predefined optimization routines that may be selected, repeated, skipped and/or re-ordered by a user based on the particulars of a specific sample type. Loo and Washington show that it is beneficial to allow a user to select from a plurality of given predefined routines in order to permit adaptation to the varying conditions and requirements of different sample types. This would have been particularly useful for implementation in the Ragsdale system since Ragsdale describes in paragraphs [0003]-[0005] how it is important to account for changes to different sample parameters when determining optimum transfection conditions (“Such an optimization experiment is generally run manually and typically includes performing electroporation on aliquots of the sample at slightly different settings of the electroporation instrument parameters”). Ragsdale is interested in considering multiple possible optimization routines in order to evaluate different parameter sets, and Loo and Washington recommend that these available routines should be displayed on a user interface as choices for a skilled operator, which would allow for both automation and expert input.
The modified Ragsdale system still differs from the claimed invention because Ragsdale does not specifically state that optimization of each routine involves assessing a risk of arcing.
Neal discloses an electroporation system comprising a controller. See Fig. 1. Neal states that an overall risk of arcing is determined prior to the commencement of an electroporation method. Paragraphs [0073], [0074], [0087], [0093], [0094] and [0104] indicate that the risk assessment is based on a number of factors, such as temperature, tissue conductivity, the presence of air pockets/bubbles, and the magnitude of the applied current.
Before the effective filing date of the claimed invention, it would have been obvious to consider a risk of arcing when optimizing each of Ragsdale’s predetermined routines. Neal indicates that arcing is a common problem in electroporation, and that variables such as the nature of the applied current, temperature and cell/tissue type must be taken into account when modeling an optimum electroporation process (“Advantages…include mitigating the extent of unintended tissue thermal damage when delivering IRE pulses and preventing arcing between electrodes and the resultant generator faulting”).
Response to Arguments
In response to Applicant’s amendment filed 26 June 2026, a new ground of rejection is made in view of Washington and Neal. It would have been obvious to implement the laboratory management techniques described by these references to improve essentially any specialized sample processing protocol, including the electroporation control method of Ragsdale.
Conclusion
This is a non-final rejection.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached at (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 published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799
Prosecution Insights