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 .
Response to Amendment
The amendment filled on 09/03/2025 has been entered. Claims 4-5, 8 and 11-14 remain pending in the application.
Applicant’s arguments, see Page 4, filed 09/03/2025, with respect to claim objection have been fully considered and are persuasive. Accordingly, the claim objection of Claims 11-12 have been withdrawn.
Applicant's arguments under 35 U.S.C § 103:
In page 5, applicant argues that “Schutze is specifically directed to a method of determining transfection of a cell or group of cells. See, e.g., Title and Abstract of Schutze. Applicant notes that it was common technical knowledge in the art that transfection procedures, regardless of the specific method employed, invariably cause significant cellular damage and stress responses. It would be clear to one of ordinary skill in the art that the cellular state changes detected in the method of Schutze represent massive alterations in cellular physiology, including apoptosis, membrane disruption, metabolic stress, etc.”.
In page 5, paragraph, applicant argues that “ “Schutze fails to disclose any specific technical information regarding laser irradiation methods or irradiation pathways. Because Schutze targets the detection of significant cellular damage caused by transfection, there would have been no need for the ordinarily skilled artisan to have developed laser irradiation techniques based on Schutze.”.
In page 5-6, applicant argues that “ In contrast, the methods taught by the present application can distinguish slightly different states of healthy cells, i.e., T cell activation status or hiPS cell colony-forming ability, by the step of "receiving Raman scattered light that is output from a cell as a result of laser light being emitted in an approximately circular manner and in a turning manner to an approximately circular region where the cell exists," as recited in independent claim 4. The present application addresses the significantly more challenging technical problem of detecting subtle cellular state variations in healthy cells, such as T cell activation status or hiPS cell colony-forming ability. These minute physiological differences necessitate the ingenuity of laser irradiation techniques to achieve the requisite sensitivity and specificity for distinguishing between closely related cellular states.
In page 6, applicant argues that “ Huang discloses circular spiral laser irradiation; however, Huang merely addresses general microscopic image acquisition for morphological observation of biological samples and surface examination in materials science. Huang contains no disclosure, teaching, or suggestion regarding spectroscopic analysis for cellular characterization. Applicant respectfully submits that the circular spiral scanning disclosed in Huang, being directed solely to imaging efficiency improvements, would not have suggested or motivated one of ordinary skill in the art to improvement of specialized laser irradiation techniques for detecting subtle physiological differences in healthy cellular states as disclosed in the present application.
Examiner response to arguments under 35 U.S.C § 103:
In response to applicant’s arguments mentioned above regarding (a), the examiner respectfully disagrees since it is noted that the features upon which applicant relies (i.e., (a)) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to applicant’s arguments mentioned above regarding (b), the examiner respectfully disagrees since Schutze teaches a laser-based transfection, also known as photo transfection or optoporation, As a PHOSITA comprehend is a technique that falls under the category of laser irradiation techniques. Additionally, Pavilion et al. discloses in [Page 016007-2, Section 2.2] laser irradiation techniques.
In response to applicant’s arguments mentioned above regarding (c),to newly amended limitations in claim 4 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
In response to applicant’s arguments mentioned above regarding (d), the examiner respectfully disagrees since the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Huang discloses a circular scanning technique comprising analyzing a sample as a biological cell to gather information about the sample, [0060-0061]. Therefore it would be obvious to modified the scanning technique of Pavilion in view of the circular scanning technique of Huang.
Claim Objections
Claim 4 is objected to because of the following informalities:
In claim 4, line 8, there is lack of antecedent basis for the limitation, “the same cell line”. This appears to be due to typographical error. Therefore, In claim 4, line 8, the same cell line” should be changed to —a same cell line —.
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 4, 8, 11-12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Nicolas Pavilion et al., Maximizing Throughput in Label-Free Microspectroscopy with Hybrid Raman Imaging, Journal of Biomedical Optics January 2015, Vol. 20(1), pp. 016007-1-016007- 10. (cited in IDS on 10/12/2023), hereafter Pavilion, in view of Huang et al. (CN 102818797 A) and further in view of Wagner et al. (US 2022/0284574 A1), hereafter Wagner and Hart et al. (US 2019/0250093 A1), hereafter Hart.
Regarding Claims 4 and 11-12, Pavilion teaches a cell classification method, [abstract] comprising steps of:
receiving Raman scattered light that is outputted from a cell as a result that laser light is emitted in a turning manner (i.e. scanning) to an approximately region where the cell exists, (as shown in Fig. 2 (a), the CW laser images the cell comprising a Raman imaging setup, that also include a dual axis galvanometer. The backscatter light is collected by Czerny-Turner spectrometer and the light dispersed by the grating is then measured with a low-noise CMOS camera [Page 016007-2, Section 2.2]. The setup perform random scanning pattern within a predefined region in the target cell, “The measured region shape is here arbitrarily chosen as a square, but could be adjusted to other shapes by simply changing the scanning pattern”. [page 016007-4, second paragraph], [page 016007-5, second paragraph]),
detecting a Raman spectrum corresponding to the received Raman scattered light, (as shown in Figs 1 and 3, [Page 016007-2, Section 2.3, first paragraph]) [Page 016007-3, Section 3.1, first paragraph]) ; and
classifying the cell based on spectrum data obtained from the detected Raman spectrum, (The device apply principal component analysis (PCA) to the detected data to classified the cell as shown in Figs. 5 and 6 , [page 016007-6, Section 3.3 , first and second paragraph and Section 3.4 “imaging and classification”, first and second paragraph]).
(claim 11) wherein, in the step of receiving Raman scattered light, the laser light is emitted in a turning manner to an approximately a region, (as shown in Fig. 2 (a), the CW laser illuminates the cell comprising a Raman imaging setup, that also include a dual axis galvanometer. [Page 016007-2, Section 2.2]. The setup perform random scanning pattern within a predefined region in the target cell, “The measured region shape is here arbitrarily chosen as a square, but could be adjusted to other shapes by simply changing the scanning pattern”. [page 016007-4, second paragraph], [page 016007-5, second paragraph]).
(claim 12) wherein, in the step of receiving Raman scattered light, the laser light is emitted in a turning manner to a region where plural cells exist. (as shown in Fig. 5 (d) the region comprise cells J774A.1 and Raw264.7, [Fig. 5 caption], (as shown in Fig. 2 (a), the CW laser illuminates the cell comprising a Raman imaging setup, that also include a dual axis galvanometer. [Page 016007-2, Section 2.2]. The setup perform random scanning pattern within a predefined region in the target cell, “The measured region shape is here arbitrarily chosen as a square, but could be adjusted to other shapes by simply changing the scanning pattern”. [page 016007-4, second paragraph], [page 016007-5, second paragraph]).
Pavilion fail to teach:
(claim 1) wherein the classifying step distinguishes among different states of the same cell line selected from activation states of T cells and colony-forming ability of hiPS cells.
(claim 4) a laser light is emitted in an approximately circular manner and in a to an approximately circular region.
(claim 11) the laser light is emitted in a turning manner to an approximately circular region in an individual cell.
(claim 12) the laser light is emitted in a turning manner to an approximately circular region.
However, Huang related to laser scanning devices of biological elements as cell and thus from the same field of endeavor teaches:
(claim 4) a laser light is emitted in an approximately circular manner and in a to an approximately circular region, (as shown in Figs. 5a-d, 10a-b, the device comprise a laser scanning confocal microscope, [0043] for scanning a cell (5a) by a scanning path in a circular manner “helical scan path” (5d), (10a) and (10b), that as shown in Fig. 5d embody a circular region, [0055-0060]).
(claim 11) the laser light is emitted in a turning manner to an approximately circular region in an individual cell, (as shown in Figs. 5a-d, 10a-b, the device comprise a laser scanning confocal microscope, [0043] for scanning a cell (5a) by a scanning path in a circular manner “helical scan path” (5d), (10a) and (10b), that as shown in Fig. 5d embody a circular region, [0055-0060]).
(claim 12) the laser light is emitted in a turning manner to an approximately circular region, (as shown in Figs. 5a-d, 10a-b, the device comprise a laser scanning confocal microscope, [0043] for scanning a cell (5a) by a scanning path in a circular manner “helical scan path” (5d), (10a) and (10b), that as shown in Fig. 5d embody a circular region, [0055-0060]).
Therefore, it would been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Pavilion by including a laser light is emitted in an approximately circular manner and in a to an approximately circular region, the laser light is emitted in a turning manner to an approximately circular region in an individual cell, the laser light is emitted in a turning manner to an approximately circular region, (as taught by Huang) for several advantages such as: allowing to avoids in the prior art line scanning strenuous vibration galvanometer aging galvanometer problems, which is beneficial to prolonging the service life of the vibration mirror, thus increase the efficiency of the device, ([0043], Huang). Also Spiral scanning allows for continuous, efficient acquisition of images across a field of view, particularly useful in microscopy and related imaging techniques. It differs from raster scanning by moving the imaging beam in a spiral path rather than a back-and-forth pattern, leading to faster image acquisition and reduced artifacts.
Pavilion and Huang still lack to teach: (claim 1) wherein the classifying step distinguishes among different states of the same cell line selected from activation states of T cells and colony-forming ability of hiPS cells.
However Wagner related to optical analysis of biological elements as cell and thus from the same field of endeavor teaches wherein the classifying step (Fig. 57A) distinguishes among different states of the same cell line (stem cell) selected from the colony-forming ability of hiPS cells, (the optical measuring system analyze hiPS cell colonies and classified the morphologies of the colonies including centroid trajectory, cell count history, area history, shape factor history, determining the colony proliferation and maturity levels, [0407, 0420, 0437, 0449]).
Therefore, it would been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the modified method of Pavilion by including wherein the classifying step distinguishes among different states of the same cell line selected from the colony-forming ability of hiPS cells, (as taught by Wagner) for several advantages such as: the automated nature of the system allows to removes the need for manual human intervention at many stages of cell culture development, thus reducing the time and cost of making output cell products, ([0147, Wagner).
The modified device of Pavilion still lack to teach about wherein the classifying step distinguishes among different states of the same cell line selected from activation states of T cells.
However, Hart related to optical analysis of biological elements as cell and thus from the same field of endeavor teaches: (claim 1) wherein the classifying step distinguishes among different states of the same cell line selected from activation states of T cells, (determining and classifying the activation state of stem cells as T cells, [0070-71]).
Therefore, it would been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the modified method of Pavilion by including wherein the classifying step distinguishes among different states of the same cell line selected from activation states of T cells (as taught by Hart) for several advantages such as: the methods herein allow for the optimization of cell-based immunotherapy by enabling the selection, enrichment and differentiation of cells, assessment of cell interaction with other agents and technologies, production of consistent cGMP cell products at commercial scale in a cost-effective manner., ([0072, Hart).
Regarding Claim 8, Pavilion in the combination outlined above teaches the cell classification method as recited in claim 4.
Pavilion further teaches wherein the step of classifying the cell is performed by using machine learning, (the classification of the cells as shown in Fig. 5 “by multivariate analysis, as shown by PCA decomposition of data sets composed of J774A.1 and Raw 264.7 cell lines”, [Fig. 5 caption] and [Page 016007-6, Section Imaging and classification, Second paragraph] to [page016007-7, first paragraph]. Examiners note: The specification of the application indicate PCA as an unsupervised learning method in [0090] “For examining discrimination of respective cell types, spectra that have been obtained as multivariate data for principal component analysis (PCA), that is an unsupervised machine learning method”).
Regarding claim 14, Pavilion in the combination outlined above teaches the cell classification method as recited in claim 4, circular region (Fig. 5d, Huang).
Pavilion further teaches wherein the approximately region covers a nucleus and a cytoplasm of the cell, (as shown in Fig. 1(b), [page 016007-4, first paragraph]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Pavilion, in view of Huang, Wagner, Hart and further in view of Schutze et al. (US 2019/0226994 A1).
Regarding Claim 5, Pavilion in the combination outlined above teaches the cell classification method as recited in claim 4.
The modified device of Pavilion fail to teach:
(claim 5) wherein the step of classifying the cell comprises comparing the obtained spectrum data with standard spectrum data.
However, Schutze related to optical analysis of biological elements as cell and thus from the same field of endeavor teaches wherein the step of classifying the cell comprises comparing the obtained spectrum data with standard spectrum data, (“optionally by comparing measured values with reference values”, [0083]).
Therefore, it would been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the modified method of Pavilion by including wherein the step of classifying the cell comprises comparing the obtained spectrum data with standard spectrum data. , (as taught by Schutze) for several advantages such as: the morphological determination allows to confirm or verify information about the vitality of the cells which indicate that a cell is dead cells or that cells start to decay or become apoptotic or necrotic thereby be confirmed or corrected by said morphological determination, thus increase accuracy of the device, ([0083], Schutze).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Pavilion, in view of Huang, Wagner, Hart and further in view of Jalali et al. (US 2018/0286038 A1), hereafter Jalali.
Regarding claim 13, Pavilion in the combination outlined above teaches the cell classification method as recited in in Claim 4.
The modified device of Pavilion is silent about wherein the cell is in an approximately spherical shape.
However, Jalali related to optical analysis of biological elements as cell and thus from the same field of endeavor teaches the cell is in an approximately spherical shape, [0066].
Therefore, it would been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Pavilion by including a laser light is emitted in an approximately circular manner and in a to an approximately circular region (as taught by Jalali) for several advantages such as: the device determiner feature extraction that operates on optical phase and loss images simultaneously. That allows to use the average refractive index, as a measure of protein concentration, that is obtained by dividing the integral of the optical path length by the cell volume. Since cells in suspension relax to a spherical shape (due to surface tension), an independent measure of cell diameter can be obtained from its lateral dimension for volume estimation, ([0066], Jalali).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 CARLOS G PEREZ-GUZMAN whose telephone number is (571)272-3904. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tarifur Chowdhury can be reached at (571) 272-2287. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TARIFUR R CHOWDHURY/ Supervisory Patent Examiner, Art Unit 2877
/CARLOS PEREZ-GUZMAN/ Examiner, Art Unit 2877