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 .
Election/Restrictions
Applicant’s election of group I with claims 16-22, 31, 32 and (species 1 for the stimulation of cell growth and species 4 for flow cytometry) with traverse in the reply filed on 04/03/2026 is acknowledged.
Applicant traversal argument regarding the prior Kniep US 20140017758 A1 is acknowledged and considered.
New prior arts were found to teach or suggest the teaching of claims of this application. Please see claim rejections.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on -12/14/2023, 12/26/2024- is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 16, 18, 31, 32 objected to because of the following informalities:
Claim 16 and 18 recite word “analysing”, please amend the recited word as “analyzing”.
Claim 31 and 32 missing a comma. Please amend the claims as
31. The method according to claim 19, …
32. The method according to calm 19, …
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 31 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim Clam 31. “a) comprises treating samples comprising cellular material with two or more different conditions” is unclear applicant is suggested to add the intended cellular material conditions in the claim language.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 16-19, 21, 22, 31 is/are rejected under 35 U.S.C. 102 (a)(1)/ (a)(2) as being anticipated by Burnett et al US 20040115614 A1.
Regarding claim 16, Burnett teaches a method for identification of optimized conditions for treating cells with electric pulses for stimulation of cell growth or cellular compounds or both (abstract: The present invention provides a system that is capable of supplying electric field stimulation to a cell and optically monitoring a physiological response of the stimulated cell. Para [0077] The electrical stimulation must be optimized to elicit a desired physiological response in the stimulated cell and to avoid killing or over heating of the cell.), the method comprising the steps of:
treating samples comprising cellular material with at least one condition (para [0073] According to the present invention, cells used in the assays of the present invention are subjected to repetitive electric pulses supplied by the transparent electrode and a second electrode of opposing polarity, wherein said repetitive electric pulses are of about 250-1000 .mu.s duration at about 1-100 pulses/s and 2-120 V amplitude, and produce a controlled change in the physiological response of said cell.);
Examiner views the cell samples are introduced or treated with electrical pluses (i.e., at least one condition).
analysing the results of the treatment in step a) for the applied condition(s) (Fig. 3. para [0082] In a preferred embodiment, a microscope-based detection system, such as Pathway-HT (Atto Bioscience, Rockville, Md.) can be used for optical recording. The microscope-based detection system has the advantage of recording changes in fluorescence both temporally (changes in membrane potential over time) and spatially (movement of cells, reorganization of plasma membrane or cell death).
Examiner views the cell samples response are recorded and analyzed in fig. 3 after the cell are introduced or treated with electrical pluses.
and c) identifying suitable conditions from the analysis of step b) (para [0120] The use of an electrical stimulus that evoked a half maximal response under normal conditions would give an acceptable "dynamic range" in which decreases or increases in the response could be observed. It was found that the optimal stimulation parameters for SK-N-SH cells to be a series of square-wave voltage pulses (750 .mu.s pulses at 8 pulses/s for 3 s), wherein the voltage was stepped from 0 to a positive voltage, preferably less than 120 V.)
From fig. 3 and above paragraph examiner viewed the paragraph discusses or identifies a favorable or optimized configuration for cell treatment with series of electrical pulses (i.e, conditions) from the response observation.
Regarding claim 17, Burnett teaches the method according to claim 16, wherein suitable conditions from the analysis of step c) are stored in a database and used to determine an initial condition or set of conditions used in a subsequent treatment of cells (para [0011] The method further comprises comparing the optical signal with an optical signal measured from a cell that is not exposed to the repetitive electric pulses. Preferably, the physiological response in a cell comprises a change in the activity of an ion channel, a change in the secretion or absorption of a biological molecule by the cell, plasma membrane rearrangement, intracellular rearrangement, a change in cellular metabolism, apoptosis, or gene transcription.).
Examiner views the favorable condition using optical signal (i.e., of electrical signal or pulses) are recorded. The recorded condition is compared with the cell data that is not exposed to the electrical pulses (i.e., use as an initial condition) for subsequent cell treatment.
Regarding claim 18, Burnett teaches the method according to claim 16, wherein step a) is performed in a system where the samples flow through a treatment area to which varying treatment conditions are applied, and for each of the applied treatment condition a probe is analysed in step b) (para [0080] In another embodiment, repetitive pulses of electric stimuli are supplied to the cell with an amplitude of about 2-120 V. When high voltage, often greater than 120 V, was used, cells detached from the surface of the electrode (often due to cell death) resulting in lower detectable optical signal. When low voltage, often less than 2 V, was used, no activation of any physiological response could be observed. Preferably, repetitive pulses of electric stimuli are supplied to the cell with an amplitude of about 20-100 V.
Para [0082] In a preferred embodiment, a microscope-based detection system, such as Pathway-HT (Atto Bioscience, Rockville, Md.) can be used for optical recording. The microscope-based detection system has the advantage of recording changes in fluorescence both temporally (changes in membrane potential over time) and spatially (movement of cells, reorganization of plasma membrane or cell death).
[0106] Loading of cells with optically detectable marker: Changes in cellular parameters in response to stimuli, such as ions (Ca.sup.2+, Na.sup.+, K.sup.+), pH, membrane potential, metabolites (cAMP, IP.sub.3) or proteins can be monitored by the selection of an appropriate reporter system (probe and detection apparatus).).
Examiner views the cell samples movement or flow through a treatment area due varying electrical stimulation conditions applied are detected and monitored by probe apparatus.
Regarding claim 19, Burnett teach the method according to claim 18, wherein step b) is either performed directly after step a) or is performed after the treated sample has been cultivated in a cultivation system, wherein the cultivation system comprises at least one cultivation container (para [0065] Cells can be cultivated in a well of an EFS device for a relatively long period of incubation time, or transferred to the well of the EFS device shortly prior to the assay.
Para [0095] A voltage applied between these two electrodes created a vertical electric field capable of stimulating cells cultured inside these wells.).
For the steps a and b see above in claim 1, where step a is performed before step b. Above paragraphs discuss the stimulation is applied to the cultured cell with cultivation container or well.
Regarding claim 21, Burnett teach the method according to claim 16, wherein step a) is performed in a high-throughput system comprising a treatment area with a plurality of varying treatment conditions, wherein said plurality of varying treatment conditions are provided in wells of a well-plate (para [0062] According to the present invention, cells of interest are first placed in a liquid medium into one or more wells of an EFS device…. For HTS, the transparent electrode can also be fabricated across the entire bottom of a multi-well plate, such as a 96 well plate, a 384 well plate, or a 1536 well plate.
para [0073] According to the present invention, cells used in the assays of the present invention are subjected to repetitive electric pulses supplied by the transparent electrode and a second electrode of opposing polarity, wherein said repetitive electric pulses are of about 250-1000 .mu.s duration at about 1-100 pulses/s and 2-120 V amplitude, and produce a controlled change in the physiological response of said cell.);
Examiner views the cell samples in wells are introduced or treated with different or varying electrical pulses of about 250-1000 .mu.s duration at about 1-100 pulses/s and 2-120 V amplitude.
Regarding claim 22, Burnett teach the method according to claim 21, wherein step b) is performed directly in the wells of said well-plate ([0083] In another preferred embodiment, a multi-well plate reader, preferable a specialized kinetic plate reader can be used for optical recording. Examples of multi-well plate readers include, but are not limited to, the TopCount plate reader (Packard) for luminescent recording or scintillation counting, the Fluorimetric Imaging Plate Reader (FLIPR; Molecular Devices, Sunnyvale, Calif.) for fluorescent recording, and the Fusion plate reader (Packard) for recording luminescent, fluorescent, or radiation signals. These readers can be equipped with integrated liquid handlers to introduce compounds or other reagents into the assay wells in order to initiate and observe effects on biological activity.).
Examiner view the optical readers and imaging are used for cell activities in wells analysis in the well plate.
Regarding claim 31, Burnett teach the method according to claim 16 wherein step a) comprises treating samples comprising cellular material with two or more different conditions (para [0066] In one embodiment, the cells used in the assay are cell lines containing an endogenous voltage-gated ion channel, such as a pulmonary artery smooth muscle cells (PASMC), mammalian cardiac cells, or human neuroblastoma cells. Examples of such cell lines include, but are not limited to, SK-N-SH, HEK-293 cells, RBL cells, F11 cells, or HL5 cells. Para [0067] Preferably, the cell or cells used can be a cell line that has no or very low detectable endogenous expression of other ion channels, such as CHO-K1, CHL, or LTK(-) cell lines. These cells inherently have a resting potential above the activation and inactivation thresholds of most voltage-gated channels.)
Examiner views the sample cells like muscle cell, cardiac cell has two or more different conditions and behave differently with electrical treatments (like pulses, voltages, amplitudes as mentioned in claim 1).
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.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Burnett in view of Mandal et al US 20100211364 A1 herein after “Mandal”.
Regarding claim 20, Burnett teach the method according to claim 16, wherein in step a) the samples comprising cellular material are treated with one condition (see in claim 1 the step a is performed with electrical pulse of about 250-1000 .mu.s duration at about 1-100 pulses/s and 2-120 V amplitude which includes a condition ), and
Burnett does not teach the analysis in step b) is performed with a machine-learning module.
Mandal et al teaches the analysis in step b) is performed with a machine-learning module. (para [0167] Therefore, a system and method for modeling chemical reactions is provided that utilizes exponential current-voltage devices to simulate chemical reaction events… For example, machine-learning techniques, such as stochastic gradient descent, regression, and gradient descent analysis, may be to analyze and configure the reaction simulation chips such that they optimize fits to experimental data, are consistent with known constraints, and maximize objective functions known to be of biological importance such as cell growth).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing of the invention to have incorporated Mandal into Burnett for the purpose of analyzing the cell treatment result using a machine learning so that the future patterns and also errors the process can be effectively analyzed for larger data.
Claim(s) 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Burnett in view of Oldham et al US 7428047 B2 herein after “Oldham”
Regarding claim 32, Burnett teach the method according to claim 19 Burnett does not teach wherein step b) includes flow cytometry.
Oldham teaches wherein step b) includes flow cytometry (abstract: An apparatus for detecting analytes in a sample is provided. The apparatus can include: a flow cytometry system including one or more detection zones).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing of the invention to have incorporated Oldham into Burnett for the purpose of analyzing the cell treatment result using a flow cytometer so that the properties of the cell can be accurately measured.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bhatia US 20060160066 A1 discusses cell conditioning system using electrical signals in the cells.
Simpson et al US 20040037813 A1 discusses cell processing using electrical pulses.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARAD TIMILSINA whose telephone number is (571)272-7104. The examiner can normally be reached Monday-Friday 9:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Catherine Rastovski can be reached at 571-270-0349. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHARAD TIMILSINA/Examiner, Art Unit 2857
/Catherine T. Rastovski/Supervisory Primary Examiner, Art Unit 2857
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