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 Objections
Claim 12 is objected to because of the following informalities:
Claim 12 recites the limitation " all cells" in line 3. There is insufficient antecedent basis for this limitation in the claim. Appropriate correction is required.
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.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (abstract idea) without significantly more.
Under Step 1 of the 2019 Revised Patent Subject Matter Eligibility Guidance, the claims are directed to a process (claim 1, a method) which are statutory category.
However, evaluating claim 1, under Step 2A, Prong One, the claim is
directed to the judicial exception of an abstract idea using the grouping of a mathematical relationship/mental process. The limitations include:
III) analyzing the collected data and calculating the gate position of QC beads based on the collected data; and VI) adjusting the acquisition parameters of the equipment based on the calculated gate position.
The examiner notes that this is a classic data acquisition [Wingdings font/0xE0] analysis [Wingdings font/0xE0] decision/control workflow, which courts hold to be abstract, see Electric Power Group.
Although the claim is applied in the context of QC for an instrument, it does not change the character of the claim, which remains focused on information processing and decision-making.
Next, Step 2A, Prong Two evaluates whether additional elements of the claim “integrate the abstract idea into a practical application” in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception. The claim does not recite additional elements that integrate the judicial exception into a practical application.
The claim recites a generic technical environment (QC beads, equipment, acquisition parameters). No improvement to the functionality of the equipment itself. It does not specify how acquisition parameters are adjusted in a technically specific way. It only treats the instrument as a black box that merely receives inputs and settings. Merely applying an abstract data analysis to a field of use (quality control of equipment) is insufficient to elevate the claim to a practical application.
Therefore, the claims are directed to an abstract idea.
At Step 2B, consideration is given to additional elements that may make the abstract idea significantly more. Under Step 2B, there are no additional elements that make the claim significantly more than the abstract idea.
The additional elements of “I) providing QC beads used for testing the performance index of an equipment of interest” and “II) setting the equipment to collect the data of the QC beads” are considered insignificant extra-solution activity of collecting data that is not sufficient to integrate the claim into a particular practical application. The act of data gathering is considered insufficient to elevate the claim to a practical application.
The additional elements “QC beads”, “equipment” and “acquisition parameters” are generic and conventional in flow cytometry and measurement instruments.
The claim does not require a specific sensor architecture, require a specific signal-processing pipeline, required a specific control loop structure, or recite unconventional hardware interactions. The steps are performed by generic instrumentation and generic control logic, which courts consistently find insufficient to supply an inventive concept or amount to “significantly more”.
The limitations have been considered individually and as a whole and do not amount to significantly more than the abstract idea itself.
Dependent claims 2-20 do not add anything which would render the claimed invention a patent eligible application of the abstract idea. The claim merely extends (or narrow) the abstract idea which do not amount for "significant more" because it merely adds details to the algorithm which forms the abstract idea as discussed above.
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.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al.
(Pub. No. US 2015/0140577) (hereinafter Li) in view of Ortyn et al. (Pub. No. US 2003/0142289) (hereinafter Ortyn).
As per claim 1, Li teaches I) providing QC beads used for testing the performance index of an equipment of interest (see ¶ [0048], i.e., providing beads of known characteristics to verify and assess system detection performance); II) setting the equipment to collect the data of the QC beads (see ¶¶ [0013]-[0014], [0017], i.e., describes a flow cytometry system including detectors and processor configured to acquire and analyze data from particles passing through the flow cell); III) analyzing the collected data and calculating the gate position of QC beads based on the collected data (see ¶¶ [0013]-[0014], [0040]-[0041] and [0069], i.e., analyzing acquired particle data using software that includes population gating functions for selecting subpopulations).
Li fails to explicitly teach VI) adjusting the acquisition parameters of the equipment based on the calculated gate position.
However, Ortyn teaches calibration beads as known reference population for calibration, diagnostics, and quality metrics in a flow imaging instrument (see ¶¶ [0012]-[0015], [0019], [0284]-[0292]); analyzing calibration-bead-derived signals to identify signal characteristics such as spectral peaks and decision regions and a supervisor/control program that determines boundaries/thresholds based on analyzed bead data (e.g., spectral peak identification and integration limits) (see ¶¶ [0171]-[0175]); and additionally Ortyn teaches automatically adjusting acquisition parameters, including photodetector amplifier gain, decision thresholds, and integration limits, via feedback control based on the analyzed calibration-bead data in order to optimize system performance (see ¶¶ [0171]-[0178]). It would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to modify the flow cytometry system and data acquisition/analysis method of Li to incorporate the calibration-bead-based analysis and feedback control taught by Ortyn because calibration beads provide a stable, known reference population from which signal boundaries (i.e., gate positions or decision regions) can be determined automatically, thereby enabling automated adjustment of acquisition parameters to improve stability, repeatability, and measurement accuracy.
As per claim 2, the combination of Li and Ortyn teach the system as stated above. Ortyn further teaches that the QC beads are the same size (see ¶ [0297], i.e., bead population consisting of 4 µm diameter beads and ¶ [0121], i.e., using 7.9 µm diameter beads (same size)).
As per claim 3, the combination of Li and Ortyn teach the system as stated above. Ortyn further teaches that the size of the QC beads is in the range of 40 nm to 10 pm (see ¶ [0293], i.e., calibration beads with diameters ranging from 20 nanometers to 50 µm) (which encompasses the claimed 40nm to 10 µm).
As per claim 4, the combination of Li and Ortyn teach the system as stated above. Ortyn further teaches that the size of the QC beads is 500 nm, 3 µm, 6 µm or 10 µm (see ¶ [0285], i.e., using 200-500 nm beads for point spread function determination and ¶ [[0285], i.e., using 1-10 µm beads, and “preferably one to ten microns in diameter” which encompasses 3 µm, 6 µm and 10 µm).
As per claim 5, the combination of Li and Ortyn teach the system as stated above. Ortyn further teaches that the QC beads are beads conjugated with a fluorescence agent (see ¶ [0288], i.e., “utilizing a calibration bead set with some distribution of calibration beads having known fluorescent label concentrations, the measured fluorescent image can be compared to the known MESF (molecules of equivalent soluble fluorochrome) to allow for calibration”).
As per claim 6, the combination of Li and Ortyn teach the system as stated above. Ortyn further teaches that the fluorescence agent is configured to generate fluorescence data in one or more fluorescence channels (see ¶ [0297], i.e., “The bead population consisted…FITC labeled beads, ... The system is configured for …, PE fluorescence imagery, FITC fluorescence imagery…”).
As per claim 7, the combination of Li and Ortyn teach the system as stated above. Li further teaches that step II) further includes collecting forward scatter (FSC) data of the QC beads, and wherein the FSC data is determined by the size of the QC beads (see ¶ [0004], i.e., “In addition to fluorescence, two other types of light scatter”).
As per claim 8, the combination of Li and Ortyn teach the system as stated above. Li further teaches that wherein step II) further includes collecting side scatter (SSC) data of the QC beads, and wherein the SSC data is determined by the surface smoothness of the QC beads (see ¶ [0063], i.e., “While forward scatter is detected generally along the propagation path of the laser, side scatter is collected orthogonal to the incident laser beam”).
As per claim 9, the combination of Li and Ortyn teach the system as stated above. Ortyn further teaches that wherein the step II) further includes collecting fluorescence intensity data of the QC beads in each channel. (see ¶¶ [0287]-[0288], i.e., “calibration beads having known fluorescent label concentrations, the measured fluorescent image can be compared to the known MESF”).
As per claim 10, the combination of Li and Ortyn teach the system as stated above. Li further teaches that “device and system provides a 107 dynamic range for signal detection and processing, which can be two orders of magnitude higher than other flow cytometers” (see ¶ [0047]).
But the combination of Li and Ortyn fails to explicitly teach that the fluorescence intensity of the QC beads in each channel is in a concentrated range, and the Log axis coordinate system is adopted, so that the fluorescence channel data is distributed in the Log axis coordinate system in a concentrated area.
However, it would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to adopt logarithmic scaling for fluorescence channels to provide better data visualization because log scaling expands lower-intensity regions while compressing higher-intensity regions, thereby allowing bead population with relatively concentrated intensity ranges to appear as compact, well-resolved clusters. The use of log axes for fluorescence channels was a standard data visualization technique employed to improve interpretability, facilitate gating, and support calibration and quality control workflows.
Accordingly, adopting a log axis coordinate system for displaying QC-bead fluorescence intensity data would have been a predictable use of known data-representation technique to achieve the expected benefit of clearer population visualization and easier gate placement. Such modification involves no change to the underlying measurement hardware or signal acquisition, but merely applies a conventional mathematical transformation to the collected data, and therefore, represent nothing more than the routine optimization of result representation that one having ordinary skill in the art would have implemented as a matter of design choice.
Examiner’s Notes
Claim 11 distinguish over the prior art of record because none of the prior art of
Record teaches or fairly suggests a method of auto gating of quality control (QC) based on population analysis, the method comprising that the QC beads include eight-peak beads which are distributed in one peak for the FSC and SSC, and distributed in eight peaks in fluorescence channels, and the beads of the eighth peak is distributed on the eighth peak or on the peak with the greatest fluorescence value in all fluorescence channels, in combination with the rest of the claim limitations as claimed and defined by the applicant.
Claims 12-20 distinguish over the prior art of record.
Regarding claim 12 none of the prior art of record teaches or fairly suggests a
method of auto gating of quality control (QC) based on population analysis, the method including the steps of: wherein step III) includes performing QC beads population analysis through the following steps: 1) set total QC-bead filter result to all cells; 2) circulate the highest peak analysis for each of one or more fluorescence channels;
3) analyze the peak for FSC or SSC signal based on filter results of the highest peak analysis for the QC beads; and 4) analyze the peak for specific fluorescence channel data based on filter results of auto gating on FSC or SSC.
The examiner notes that claim 12 needs to be amended to overcome the objection made above.
Prior art
The prior art made record and not relied upon is considered pertinent to applicant’s
disclosure:
Rajwa et al. [‘584] disclose methods for determining phenotypic parameters of cell populations and expressing them in terms of tensors that can be compared with one another. Embodiments provide methods for determining phenotypic parameters of cell populations in response to an agent. Embodiments provide methods for comparing effects of an agent on phenotypic parameters to effects of reference standards whose in vivo effects are known. Embodiments provide methods for predicting the effect of an agent by the comparison with the known effects of reference standards. Embodiments provide methods for classifying agents by their effects on phenotypic parameters. Embodiments provide software and computer systems for calculating multiparametric tensors, compressing their complexity and comparing them after compression.
Mohan et al. [‘892] discloses a method for measuring platelet volume. The method may include labeling platelets with a fluorescent dye and measuring the size of the platelets observed; adding beads of known size to the sample; and comparing the observed size of images of the beads to the observed images of the platelets, using the beads as calibration to determine the size of the platelets and to determine the platelet volume in the sample.
Purvis et al. [‘131] discloses a functional, quality control method for flow cytometry or mass spectrometry. It can be used used in diagnosis, prognosis, monitoring therapy, or drug development or other regulated tests and it comprising the steps of providing a microtiter plate; distributing sample cells into wells of the microtiter plate; distributing standard cells into wells of the microtiter plate; distributing rainbow control particles (RCPs) into wells of the microtiter plate; contacting the standard cells and sample cells with at least one modulator; measuring one or more activatable elements and surface markers in the standard cells by flow cytometry or mass spectrometry to create standard cell data; measuring one or more activatable elements in the sample cells by flow cytometry or mass spectrometry to create test data; measuring RCPs by flow cytometry or mass spectrometry to create RCP data; comparing the standard cell data and RCP data to a preset range of acceptable values; and optionally normalizing or excluding the test data based on the standard cell data or RCP data.
Contact information
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to MOHAMED CHARIOUI whose telephone number is (571)272-2213. The examiner can normally be reached Monday through Friday, from 9 am to 6 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Schechter can be reached on (571) 272-2302. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Mohamed Charioui
/MOHAMED CHARIOUI/Primary Examiner, Art Unit 2857