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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. § 119 (a)-(d). The certified copy has been filed in parent Application No. EP21194437.6, filed on 09/01/2021.
Claim Objections
Claims 4, 9–14, and 16–18 are objected to because of the following informalities: “and/or” conjunctions prevent Examiner from correctly interpreting the claimed language.1 Examiner determined that the conjunctions render the metes and bounds of the claim unclear as they are grammatically imprecise. If the ambiguity creates a situation where a person of ordinary skill in the art would read the claim with more than one reasonable interpretation, the claim is susceptible to an indefiniteness rejection. 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.
Claims 1, 3–4, 9, 11–14, 16, and 18–20 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.
Claim 1 recites the limitation, “the cell culture process,” “the spatial configuration of cells, cell structures, or groups of cells,” “the progress of a cell state transition process,” and “the outcome of a cell state transition process.” There is insufficient antecedent basis for this limitation in the claim.
Claim 3 recites the limitation, “the efficiency of the cell state transition,” “metrics that are indicative of the quality of the cell population,” “the identification of a stage in a cell state process,” and “the percentage, proportion, or number of cells” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation, “the final stage of the cell state transition” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation, “the number of cells,” “the degree of confluence of the cells,” “the ratio and/or proportion of cells,” “the general structure and morphology of the cell layer,” and “the number and/or size of groups of cells” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation, “the values of one or more process parameters,” “the physical environment of the cells,” “the features of the biochemical environment of the cells,” “the timing of addition,” “the concentration of addition,” and “the cell seeding density” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation, “the values of the label-free image-derived features,” and “the corresponding values of the one or more metrics” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation, “the values of one or more label-free image-derived features,” “the label-free images” “the values are measured values or values or values,” “the values(s) of one or more process parameters,” “the one or more labelled images” “the values of the one or more metrics indicative of a cell transition” “the one or more images of the cell culture,” and “the one or more corresponding labelled images” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites the limitation, “the liquid medium in the cell culture” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation, “the efficiency of the cell state transition” in claim 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 18 recites the limitation, “the presence of the respective marker,” and “the labelled images” in claim 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 19 recites the limitation, “the one or more labelled images,” and “the label-free images” in claim 13. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation, “the end of the cell culture” in claim 1. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1–20 are rejected under 35 U.S.C. § 103 as being unpatentable over Maddah et al. (U.S. 9,619,881 B2) in view of Bharti et al. (U.S. 11,531,844 B2).
Regarding claim 1, Maddah discloses a method for monitoring a cell population in cell culture, the method including the steps of:
obtaining one or more images of the cell population acquired using label-free imaging during the cell culture process, wherein the label-free imaging is an imaging technology that provides information about the spatial configuration of cells, cell structures, or groups of cells, (Per Fig. 4 at step S130, Maddah discloses spatial features of cell populations after processing a set of images. Maddah col. 8 line 50 – col. 9 line 7. [g]enerating an analysis based upon processing the set of images according to a cell graph representation module, which functions to facilitate characterization of geometric and spatial features of the set of cell subpopulations.)
processing the one or more images to obtain one or more label-free image-derived features (label-free image-derived construed as geometric and spatial features). (Per Fig. 4 at step S130, Maddah discloses a cell graph representation where a set of regions in cell population is defined based on geometric and spatial features thereof. [c]omprise any other suitable additional or alternative block configured to facilitate characterization of geometric and spatial features of the set of cell subpopulations.)
However, Maddah fails to specifically disclose predicting one or more metrics indicative of a cell state transition in the cell population using a statistical model that takes the label-free image-derived features as inputs and provides the one or more metrics indicative of a cell state transition in the cell population as outputs, wherein metrics indicative of a cell state transition in the cell population are selected from: metrics that characterize the progress of a cell state transition process occurring in a cell population, and metrics that characterize the outcome of a cell state transition process occurring in a state population, wherein the inputs of the statistical model do not include any feature obtained using an invasive or destructive measurement process.
In related art, Bharti discloses predicting one or more metrics indicative of a cell state transition in the cell population using a statistical model that takes the label-free image-derived features as inputs and provides the one or more metrics indicative of a cell state transition in the cell population as outputs, wherein metrics indicative of a cell state transition in the cell population are selected from: metrics that characterize the progress of a cell state transition process occurring in a cell population, and metrics that characterize the outcome of a cell state transition process occurring in a state population, (Per Fig. 11, Bharti discloses a CNN model where input images are trained with texture metrics such that cell borders are detected correlating to visual parameters. Bharti col. 16 lines 23–46. [b]ased on an understanding of cell borders and visual parameters (e.g., shape, intensity and texture metrics) the deep neural network model 212 is capable of detecting cell borders and performing correlation of visual parameters within similar multispectral absorption images of the new input array 210.) wherein the inputs of the statistical model do not include any feature obtained using an invasive or destructive measurement process. (Per Fig. 13, Bharti discloses a machine learning predictive model 204 wherein a clustering map of analyzed data is represented either with corrected or uncorrected probability thereof. Id. col. 17 lines 4–21. [a]ll numbers labeled by reference numeral 1306 represent the corrected probability of clustering, while the remaining numbers represent the uncorrected probability.)
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to incorporate the teachings of Bharti into the teachings of Maddah to resolve difficulty in terms of causation, correlation of visual data and sampling bias when predicting certain types of cells. Id. col. 2 lines 10–23.
Regarding claim 2, Maddah as modified by Bharti, discloses the method, wherein the cell state transition is a differentiation, a dedifferentiation, a transition from non-mobile to mobile, a cell activation, a change in the physiological processing capacity, a maturation, or a transition from non-senescent cell to senescent cell, optionally wherein the cell population is a population of pluripotent cells and the cell state transition is a differentiation. (Per Fig. 1A, Maddah discloses a method where a cell subpopulation is assessed corresponding to suitable portions of number of cell cultures. Maddah col. 2 line 66 – col. 3 line 23. [t]he method 100 can additionally or alternatively facilitate characterization of any suitable portion(s) (e.g., a single cell population) of any number of cell cultures. The method 100 can allow responses of cell populations to experimentally applied conditions (e.g., exposure to doses of therapeutic substances) to be assessed at a subpopulation level.)
Regarding claim 3, Maddah as modified by Bharti, discloses the method, wherein the metrics that are indicative of the outcome of a cell state transition are selected from: metrics that are indicative of the efficiency of the cell state transition, and metrics that are indicative of the quality of the cell population for a particular purpose; and the metrics that are indicative of the progress of a cell state transition are selected from the identification of a stage in a cell state transition process, the percentage, proportion or number of cells in each of one or more stages of a cell state transition process, and the percentage, proportion or number of cells in each of one different cell state transition processes. (Per Fig. 13, Bharti discloses a machine learning predictive model 204 wherein a clustering map of analyzed data is represented either with corrected or uncorrected probability thereof. Id. col. 17 lines 4–21. [a]ll numbers labeled by reference numeral 1306 represent the corrected probability of clustering, while the remaining numbers represent the uncorrected probability.)
Regarding claim 4, Maddah as modified by Bharti, discloses the method, wherein the one or more metrics indicative of a cell state transition in the cell population are associated with the final stage of the cell state transition and/or the end of the cell culture, and/or wherein the one or more label-free image- derived features are obtained by processing label-free images acquired prior to the end of the cell culture, and/or wherein the one or more label-free image-derived features are obtained by processing label-free images acquired at a single time point or a plurality of time points. (Per Fig. 11, Bharti discloses a CNN model where input images are trained with texture metrics such that cell borders are detected correlating to visual parameters. Bharti col. 16 lines 23–46. [b]ased on an understanding of cell borders and visual parameters (e.g., shape, intensity and texture metrics) the deep neural network model 212 is capable of detecting cell borders and performing correlation of visual parameters within similar multispectral absorption images of the new input array 210.)
Regarding claim 5, it has been rejected in the same manner as claim 2.
Regarding claim 6, it has been rejected in the same manner as claim 3.
Regarding claim 7, it has been rejected in the same manner as claim 6.
Regarding claim 8, it has been rejected in the same manner as claim 3.
Regarding claim 9, it has been rejected in the same manner as claim 3.
Regarding claim 10, it has been rejected in the same manner as claim 3.
Regarding claim 11, it has been rejected in the same manner as claim 6.
Regarding claim 12, it has been rejected in the same manner as claim 3.
Regarding claim 13, it has been rejected in the same manner as claim 1.
Regarding claim 14, it has been rejected in the same manner as claim 2.
Regarding claim 15, Maddah as modified by Bharti, discloses a system for monitoring a cell culture, the system comprising: at least one processor; and at least one non-transitory computer readable medium containing instructions that, when executed by the at least one processor, cause the at least one processor to perform the method of claim 1; wherein the system further comprises one or more of: a cell culture environment, optionally, one or more sensors, optionally one or more label-free imaging devices, and one or more effectors, optionally one or more liquid handling systems. (See his Fig. 10. Maddah col. 21 lines 27–44.)
Regarding claim 16, it has been rejected in the same manner as claim 3.
Regarding claim 17, it has been rejected in the same manner as claim 13.
Regarding claim 18, it has been rejected in the same manner as claim 17.
Regarding claim 19, it has been rejected in the same manner as claim 17.
Regarding claim 20, it has been rejected in the same manner as claim 17.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chander et al. (U.S. 2018/0239949 A1) discloses methods for evaluating the status of cells in a sample.
Contact
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENEDICT LEE whose telephone number is (571)270-0390. The examiner can normally be reached 10:00-16:00 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Stephen R. Koziol can be reached at (408) 918-7630. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENEDICT E LEE/Examiner, Art Unit 2665
/Stephen R Koziol/Supervisory Patent Examiner, Art Unit 2665
1 See MPEP § 2173.02, I. CLAIMS UNDER EXAMINATION ARE CONSTRUED DIFFERENTLY THAN PATENTED CLAIMS. During examination, after applying the broadest reasonable interpretation consistent with the specification to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected.
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