DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of species A, the sliding window size is selected automatically by a processor based on the level of noise, in the reply filed on 15 August 2025 is acknowledged.
Claim 5 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 15 August 2025.
Claim Status
3. Claims 1-20 are currently pending.
Claim 5 is withdrawn, as discussed above.
Claims 1-4 and 6-20 are under examination herein.
Claims 1-4 and 6-20 is/are rejected.
Priority
4. The instant application is a 35 U.S.C. 371 filing of international application PCT/US2020/039599, filed 25 June 2020, which claims benefit to U.S. provisional application No. 62/866,524 filed 25 June 2019. Domestic benefit is acknowledged. At this point in examination, the effective filing date of claims 1-4 and 6-20 is 25 June 2019.
Information Disclosure Statement
5. The Information Disclosure Statements filed on 22 December 2021, 7 July 2023, and 26 January 2024 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of the list of references cited from each IDS is included with this Office Action.
Drawings
6. The Drawings filed on 22 December 2021 are accepted.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
7. Claims 1-4 and 6-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 2A, Prong 1
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1 recites calculating a series of slopes for the oscillation pattern; and identifying peaks of the oscillation pattern using the series of slopes.
Claim 2 recites calculating uses a sliding window to define subsets of the series of data points from which the series of slopes are calculated.
Claim 3 recites selecting a size of the sliding window from a plurality of permitted sizes, wherein the size of the sliding window corresponds to a number of data points from the series of data points that are encompassed by the sliding window.
Claim 4 recites wherein the size of the sliding window is assigned based on a level of noise in the oscillation pattern and/or a sampling interval for the series of data points.
Claim 6 recites wherein the series of data points is not filtered to reduce noise prior to calculating a series of slopes.
Claim 7 recites wherein the peaks include a series of primary peaks, wherein the oscillation pattern comprises a series of events each including only one of the primary peaks, the method further comprising determining at least one aspect of secondary peaks of the identified peaks, each secondary peak following one of the primary peaks within an event.
Claim 8 recites wherein the at least one aspect of secondary peaks relates to a number, frequency, or period of the secondary peaks within the oscillation pattern.
Claim 9 recites wherein the oscillation pattern crosses a predefined trigger level twice for each event, and wherein the trigger level is set relative to a baseline of the oscillation pattern.
Claim 10 recites wherein identifying peaks includes searching for transitions from positive to negative, or from negative to positive, for slopes within the series of slopes.
Claim 11 recites wherein identifying peaks includes filtering peaks associated with the transitions to obtain a set of peaks deemed to be valid.
Claim 12 recites determining values of peak-related parameters for the set of peaks deemed to be valid.
Claim 15 recites wherein the oscillation pattern includes a series of events each including a single primary peak, and wherein the oscillation pattern includes one or more secondary peaks each included in an event of the series of events, the method further comprising determining at least one value for one or more parameters related to the one or more secondary peaks.
Claim 16 recites identifying primary peaks and secondary peaks in the oscillation pattern, and determining an aspect of the secondary peaks.
Claim 17 recites wherein determining an aspect of the secondary peaks includes determining a number, frequency, or period of the secondary peaks.
Claim 18 recites determining a spacing regularity/irregularity of the primary peaks and/or, an amplitude regularity/irregularity of the primary peaks.
Claim 19 recites comparing an amplitude of each primary peak to a predefined threshold to enumerate smaller peaks, if any, of the primary peaks.
Claim 20 recites calculate a series of slopes for the oscillation pattern, using a sliding window to define subsets of the series of data points from which the series of slopes are calculated, and identify peaks of the oscillation pattern using the series of slopes.
The limitations regarding the calculation a series of slopes or determining a number , frequency or period of secondary peaks are verbal equivalents that describe a mathematical calculation that is performed as the limitation and are so simple that they could be performed with pen and paper. Therefore, these limitations fall under the “Mathematical concepts” and “Mental processes” groupings of abstract ideas. The remaining limitations for identifying peaks, selecting window sizes, filtering data, analyzing the peak data, and comparing data to thresholds are generically recited data analysis steps that can be practically performed in the human mind because the human mind is capable of identifying relevant information, comparing values, and determining information from other values.
While claims 4 and 20 recite performing some aspects of the analysis with a processor, there are no additional limitations that indicate that this processor requires anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claims 1-4 and 6-20 recite an abstract idea (Step 2A, Prong 1: YES).
Step 2A, Prong 2
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception in some other meaningful way. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or insignificant extra-solution activity. Specifically, the claims recite the following additional elements:
Claims 1 and 16 recite detecting fluorescence representing an oscillating ion flux associated with one or more biological cells, to produce a series of data points describing an oscillation pattern.
Claim 4 recites performing the abstract steps with a processor.
Claim 13 recites labeling the one or more biological cells with a calcium indicator, wherein the fluorescence is emitted by the calcium indicator.
Claim 14 recites wherein the one or more biological cells include one or more cardiomyocytes or neurons.
Claim 20 recites an optical sensor configured to detect fluorescence representing an oscillating ion flux associated with one or more biological cells, to produce a series of data points describing an oscillation pattern; and performing the judicial exceptions with a processor.
The limitations for detecting fluorescence, an optical sensor for detecting fluorescence, and the types of cells and indicators utilized in the detection merely serve to gather data that is used an input for the judicial exception. Therefore, these limitations are mere data gathering activities. As set forth in MPEP 2106.05(g), mere data gathering activity has been identified by the courts as insignificant extra-solution activity that does not provide a practical application.
There are no limitations that indicate that the processor requires anything other than a generic computing system. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
The above recited additional elements do not provide a practical application of the recited judicial exception. As such, claims 1-4 and 6-20 are directed to an abstract idea (Step 2A, Prong 2: NO).
Step 2B
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic computing environment or well-understood, routine and conventional activity.
As discussed above, there are no additional limitations to indicate that the claimed processor requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
Furthermore, the additional elements recited in the claims amount to well-understood, routine and conventional activity, as evidenced by Herron et al (Circulation Research 2012, Vol 110, No 4, pgs. 609-623). Herron et al. discloses that fluorescence techniques are widely used in cardiac research, including the use of calcium sensitive fluorescence probes with cardiomyocytes (pg. 609, col. 2, para. 2). Herron et al. also discloses that optical detection of ion concentrations in cells is done with a system that includes optical sensors for measuring fluorescence that is connected to a computer interface for analysis of the data (Fig. 1; pg. 610, col. 2, para. 1). As such, the combination of additional elements recited in the claims is well-understood, routine and conventional.
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-4 and 6-20 are not patent eligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
8. Claims 1-4, 6, 10-14, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Sirenko et al. (Journal of Biomolecular Screening 2013, 18(I), pgs. 39-53; 22 Dec 2021 IDS Document) in view of Lorimer et al (US 2007/0276611 A1; 22 Dec 2021 IDS Document).
With respect to claims 1, 14 and 20, Sirenko et al. discloses monitoring changes in Ca2+ fluxes in cardiomyocyte cells via fluorescence imaging with a CCD camera sensor and that these changes are monitored during cell beating, presenting oscillating signals (pg. 40, col. 2, para. 3 to pg. 41, col. 1, para. 3; pg. 41, col. 2, para. 3; Fig. 2). Sirenko et al. then discloses detecting signal peaks using dynamic thresholding and derivative analysis using the ScreenWorks Peak Pro software (pg. 41, col. 1, para. 3). While Sirenko et al. does not explicitly describe carrying out the peak detection and analysis with a processor, it is inherent that software requires a processor to be carried out.
Regarding claim 6, Sirenko et al. does not disclose filtering the signal to reduce noise prior to analysis (pg. 41, col. 1, para. 3).
Concerning claim 12, Sirenko et al. discloses calculating the peak amplitude, temporal position, count and full width (pg. 41, col. 1, para. 3).
Pertaining to claim 13, Sirenko et al. discloses labeling the cells with a FLIPR Calcium 5 assay kit and measuring the fluorescence emitted by the FLIPR system (pg. 41, col. 1, paras. 2-3).
Sirenko et al. is silent to calculating a series of slopes for the oscillation patterns and identifying the peaks using the slopes in claims 1 and 20; calculating uses a sliding window to define subsets of the series of data points from which the series of slopes are calculated in claim 2; selecting a size of the sliding window from a plurality of permitted sizes, wherein the size of the sliding window corresponds to a number of data points from the series of data points that are encompassed by the sliding window in claim 3; wherein the size of the sliding window is assigned automatically by a processor based on a level of noise in the oscillation pattern and/or a sampling interval for the series of data points, and wherein the processor also calculates the series of slopes and identifies the peaks in claim 4; wherein identifying peaks includes searching for transitions from positive to negative, or from negative to positive, for slopes within the series of slopes in claim 10; and wherein identifying peaks includes filtering peaks associated with the transitions to obtain a set of peaks deemed to be valid in claim 11. However, these limitations were known in the art at the time of the effective filing date of the invention, as taught by Lorimer et al.
As to claims 1-2 and 20, Lorimer et al. discloses a method of detecting peaks in a signal (abstract). Lorimer et al. discloses that the method divides the data into groups via windowing and calculates the slope of each group (para. [0011]). The slope changes are then used to identify locations of peaks in the data (para. [0011]).
With respect to claims 3-4, Lorimer et al. discloses that the data points are taken and divided into windows covering the range set by the user and the number of data points in each window is related to the number of measurements (paras. [0022] and [0025]). Lorimer et al. also discloses that the number of data points in each window can be varied according to the species to be detected and the experimental conditions (para. [0026]). While Lorimer et al. does not explicitly disclose that this size selection is assigned automatically by a processor, it is obvious to one of ordinary skill in the art to automate a manual activity (see MPEP 2144.04.III).
Regarding claims 10-11, Lorimer et al. discloses that slope changes in successive groups from positive to negative or vice versa indicate that a peak occurs within the groups (para. [0011]). Lorimer et al. also discloses that the data points can than be measured or fitted with a model to identify the peaks (para. [0011]).
An invention would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention if one of ordinary skill in the art could have substituted one known element for another and the results of the substitution would have been predictable. Sirenko et al. discloses detecting peaks using dynamic thresholding and derivative analysis (pg. 41, col. 1, para. 3). Lorimer et al. discloses a method for detecting peaks in signals using windowing and slopes (para. [0011]). Therefore, one of ordinary skill in the art would have recognized that the peak detection method of Lorimer et al. could be substituted for the peak detection method in Sirenko et al. because both methods perform the same function. Furthermore, one of ordinary skill in the art would be able to predict that the outcome for the substitution of the peak detection methods because both methods are applicable on the same type of signal. The invention is therefore prima facie obvious.
Conclusion
9. No claims are allowed.
E-mail Communications Authorization
10. Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300):
“Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.”
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Inquiries
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/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685