DETAILED 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.
Claims 1, 2, 4, 6-10 and 24 are rejected under 35 U.S.C. 103 as unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916).
With respect to claim 1, 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.
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”).
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 by a user based on the particulars of a specific sample type. Loo shows 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 recommends 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 and Loo 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 4 and 6-8, Ragsdale and Loo disclose the combination as described above. 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”).
With respect to claims 9 and 10, Ragsdale and Loo 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”.
With respect to claim 24, Ragsdale and Loo disclose the combination as described above. As previously described, it would have been obvious to skip and/or repeat an optimization protocol when evaluating samples in the queue.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Ragsdale (US 20060246572) in view of Loo (US 20160069916) as applied to claim 2, and further in view of Garcia Dominguez (US 20190136224).
Ragsdale and Loo 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) as applied to claim 1, and further in view of Chen (US 20170335269).
Ragsdale and Loo 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) and Chen (US 20170335269) as applied to claim 11, and further in view of Gamelin (US 20070128708).
Ragsdale, Loo 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) and Chen (US 20170335269) as applied to claim 11, and further in view of Eberhart (US 20150024436).
Ragsdale, Loo 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), Chen (US 20170335269) and Eberhart (US 20150024436) as applied to claim 19, and further in view of Garcia Dominguez (US 20190136224).
Ragsdale, Loo, 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.
Response to Arguments
In response to Applicant’s amendment filed 05 March 2026, the previous rejections have been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the combination of Ragsdale with Loo.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Tomono (US 20250094158) reference discloses the state of the art regarding a user interface that displays a protocol queue list.
THIS ACTION IS MADE FINAL. 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 NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm.
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/NATHAN A BOWERS/ Primary Examiner, Art Unit 1799