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 .
Specification
The abstract of the disclosure is objected to because the abstract recites "(e.g. for use to determine viability of cells of a sample)"A suggestion would be to delete the phrase within the parenthesis and the phrase ‘e.g.,’. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Drawings
The drawings are objected to because figures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1-7, 9, 13-16, 20-23, and 30-33 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: Claim 1 recites the steps assessing cell mitochondrial morphology. Thus, the claim is a method, which is one the statutory categories of invention. Claim 2-7, 9, 13-16, 20-23, and 30-33 also are dependent on Claim 1.
Step 2A Prong One: Claim 1 recite a judicial exception and identify the abstract idea/law of nature/natural phenomenon. Claim 1 recites “calculating an image parameter” and “assessing morphology”. The mathematical concepts grouping is defined as mathematical relationships, mathematical formulas or equations, and mathematical calculations (See MPEP 2106.04(a)(2)). The "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions (See MPEP 2106(a)(2)(III)). Calculating an image parameter from the general image is a mathematical concept. Assessing the morphology of mitochondria based on an image is an evaluation that can be done by the mind. Claim 5 and 6 both recite “assessing the morphology” which is also an evaluation that can be done by the mind. Claim 7 also recite “assessing the morphology” which is an evaluation done by the mind. Claim 15 and 16 mention calculating which is a mathematical concept. Claim 20 further recites “classifying the cells based of the generated images of the cell mitochondria”. Classifying cells based on images of mitochondria is an evaluation that can be done by the mind, thus a mental evaluation. Claim 21 further recites assigning cell to cluster which is an evaluation that can be done by the mind, thus a mental evaluation. Claim 22 recites “determining” sorting gates which is also an evaluation Thus, both the calculating, assessing, classifying, assigning, and determining steps would fall under the abstract idea groups of mathematical concepts and mental processes. (Step 2A -Prong 1: Yes)
Step 2A Prong Two: The judicial exception is not integrated into a practical application because the claims do not impose any meaningful limits on practicing the abstract idea. Claim 1 recites “measuring” and “generating” steps which are mere data gathering steps. Claim 4 and 16 adds the additional element of calculating image parameter in a high level of generality. Accordingly, this additional element does not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to an abstract idea. (Step 2A -Prong 2: No)
Step 2B: There appears to be no additional steps which are significantly more than the abstract idea. Claims 1 does not have any steps or features which are significantly more, and the steps are well known in the art as taught in the prior art below. Claim 1 is ineligible. Claims 2-7, 9, 13-16, 20-23, and 30-33 do not appear to have ‘significantly’ more. Claim 2-7, 9 and 13-16 and 31-33 merely add parameter for the method for assessing the morphology of mitochondria which are well understood routine and conventional as referenced in the prior art below. Claims 20-23 and 30 merely add steps of sorting the sample to the method for assessing the morphology of mitochondria which are well understood routine and conventional as referenced in the prior art below. Since it is claimed at a high level of generality, there are no meaningful limitation claimed, such as a particular or unconventional machine or transformation of a particular article. (Step 2B: No)
Thus, claim 1 is ineligible. Claims 2-7, 9, 13-16, 20-23, and 30-33 are dependent on claim 1, and are also rejected.
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 1-7, 9, 13-16, 20-23, and 30-33 are 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 “measuring light from cells in a sample”. This limitation is indefinite since it is unclear how this can take place without first providing the sample.
Claims 2-7, 9, 13-16, 20-23, and 30-33 are rejected as being dependent on claim 1.
Claims 3, 4, and 14 recites the limitation "a radial moment”. This limitation is indefinite since it is unclear what the definition of a radial moment. For examination purposes, “a radial moment” will be interpreted as calculated from images generated based on fluorescence measured, light loss measured, forward scattered light measured, side scattered light measured and combinations thereof.
Claim 3 recites the limitation "the flow stream". There is no mention of a flow stream in a previous claim. There is insufficient antecedent basis for this limitation in the claim. The examiner interprets the flow stream as a stream of sample through a flow cytometer (Specification, para 0047).
Claim 3recites the limitation "the flow stream". There is no mention of a flow stream in a previous claim. There is insufficient antecedent basis for this limitation in the claim. The examiner interprets the flow stream as a stream of sample through a flow cytometer (Specification, para 0047).
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 2, 3, 4, 5, 7, 14, 20 21, 31, 32, and 33 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lo et al. (US 20170227466 A1).
Regarding claim 1, Lo teaches a method comprising measuring light from cells in a sample (‘transmitting a light beam at a fluidic channel carrying a fluid sample’ and ‘detecting the encoded optical signal by an optical detector; and processing the detected optical signal’, para 0005), generating images of the sample from the measured light (para 0005), calculating an image parameter from the generated images (para 0042) and assessing morphology of the sample based on the calculated image parameter (‘the produced image data includes information of a physical characteristic of the particle’, para 0005). Lo further teaches how the method can be applied to structure of particles such as cellular organelles like mitochondria (para 0047). Lo further teaches using fluorescently labeled cellular organelles such as cell nucleus to construct a fluorescently labeled image (para 0042). Fluorescently labeled cellular organelles reads on fluorescently labeled mitochondria because it is an inherent organelle in the cell.
Regarding claim 2, Lo teaches the invention of claim 1. Lo further teaches the image parameter is a quantitative image parameter (para 0042).
Regarding claim 3, Lo teaches the invention of claim 1. Lo further teaches flow cytometry allows for quantification of parameters such as forward scatter, side scatter, and fluorescence which can be used to calculate the radial moment image parameter (para 0089).
Regarding claim 4, Lo teaches the invention of claim 3. Lo further teaches variables needed calculate the radial moment image parameter such as the combination of fluorescence measured, forward scatter and side scatter for the cell mitochondria (para 0089).
Regarding claim 5, Lo teaches the invention of claim 1. Lo further teaches how the method can be applied to structure of particles such as cellular organelles like mitochondria (para 0047). Lo further teaches morphology includes evaluating the size of the cell mitochondria (para 0042).
Regarding claim 7, Lo teaches the invention of claim 1. Lo further teaches how the method can be applied to structure of particles such as cellular organelles like mitochondria (para 0047). Lo further teaches morphology includes evaluating the shape of the cell mitochondria (para 0042).
Regarding claim 14, Lo teaches the invention of claim 1. Lo further teaches flow cytometry allows for quantification of parameters such as forward scatter, side scatter, and fluorescence which can be used to calculate the radial moment image parameter of the fluorophore (para 0089).
Regarding claim 20, Lo teaches the invention of claim 1. Lo further teaches methods include classifying the cells based on the generated images of the cell mitochondria (para 0047).
Regarding claim 21, Lo teaches the invention of claim 20. Lo further teaches classifying the cells includes assigning the cells to one or more particle population clusters (‘the method further includes sorting the particles based on the determined physical characteristic of the particles’, para 0048).
Regarding claim 31, Lo teaches the invention of claim 1. Lo further teaches measuring light from the cell sin the flow stream comprising detecting fluorescence and light absorption (para 0047).
Regarding claim 32, Lo teaches the invention of claim 1. Lo further teaches the image parameter are calculated from the frequency-encoded data used to generate images of the cell mitochondria (para 0071).
Regarding claim 33, Lo teaches the invention of claim 1. Lo further teaches irradiating the sample in the flow steam with a light source (para 0047).
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.
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 6, 15 and 16 is rejected under 35 U.S.C. 103 as being unpatentable over Lo et al. (US 20170227466 A1) as applied to claim 1 above, and further in view of Diebold et al. (US 20210356381 A1).
Regarding claim 6, Lo teaches the invention of claim 1.
Lo does not teach evaluating the degree of punctateness of the cell mitochondria.
Diebold teaches a method of sorting cell in flow cytometry including using optical frequencies and fluorescent radiation to sort cells (Abstract). Diebold further recites cell characteristics may be associated with internal cell organelles (para 0027). Diebold further teaches evaluating the degree of punctateness of the cells for the benefit of using the parameter for sorting cells (para 0207-0208). Thus, it would be obvious to one of ordinary skill the art before the effective filing date to modify Lo with evaluating the degree of punctateness of the cell as taught by Diebold for the benefit of using the parameter for sorting cells (para 0207-0208).
Regarding claim 15, Lo teaches the invention of claim 1.
Lo does not teach calculating pixel density of the generated image of the cell mitochondria.
Diebold further teaches the variables needed to calculate pixel density of the generated image of the cell (para 0154). Thus, it would be obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Lo with calculating pixel density of the generated image of the cell mitochondria as taught by Diebold to construct a one-dimensional fluorescence image (para 0154).
Regarding claim 16, Lo teaches the invention of claim 1.
Lo does not teach the image parameter calculated by determining the sum of the pixels in the generated image weighted by the distance of each pixel from the centroid of the cell mitochondria.
Diebold further teaches the image parameter is calculated by determining the sum of the pixels in the generated image weighted by the distance of each pixel from the centroid of the cell (para 0236). Thus, it would be obvious to one of ordinary skill the art before the effective filing date to modify Lo with the image parameter calculated by determining the sum of the pixels in the generated image weighted by the distance of each pixel from the centroid of the cell mitochondria as taught by Diebold for the benefit obtaining different information about the distribution of signal (para 0237).
Claims 9 and 13 is rejected under 35 U.S.C. 103 as being unpatentable over Lo et al. (US 20170227466 A1) as applied to claim 1 above, and further in view of Pande et al. (US 20100062460 A1).
Regarding claim 9, Lo teaches the invention of claim 1.
Lo does not teach the mitochondria are labelled with one or more lipophilic cationic fluorophores.
Pande teaches a method of identifying cell organelles using detection reagents (Abstract). Pande further teaches fluorophores can be useful in visualizing mitochondria (para 0010) and taking images of the mitochondria for fluorescent signals (para 0133). Pande further teaches the mitochondria are labelled with one or more lipophilic cationic fluorophores (para 0066). Thus, it would be obvious to one of ordinary skill in the art before the effective filing date to the mitochondria are labelled with one or more lipophilic cationic fluorophores as taught by Pande for the benefit of the positive charge interacting with electric potential of the mitochondrial membrane (para 0066).
Regarding claim 13, Lo teaches the invention of claim 1.
Lo does not teach the mitochondria are labelled with a fluorophore that stains the inner mitochondrial membrane.
Pande teaches the mitochondria are labelled with a fluorophore that stains the inner mitochondrial membrane for the benefit of the strong electric potential allowing for the positively charged fluorophore to interact with the inner membrane (para 0066). Thus, it would be obvious to one of ordinary skill in the art before the effect filing date to modify Lo with the mitochondria are labelled with a fluorophore that stains the inner mitochondrial membrane as taught by Pande for the benefit of the strong electric potential allowing for the positively charged fluorophore to interact with the inner membrane (para 0066).
Claims 22, 23, and 30 is rejected under 35 U.S.C. 103 as being unpatentable over Lo et al. (US 20170227466 A1), and further in view of St-Pierre et al. (US 20230031708 A1).
Regarding claim 22, Lo teaches the invention of claim 20.
Lo does not teach determining one or more sorting gates for the classified cells of
the sample.
St-Pierre teaches a method for screening subcellular structure and tagging targeted structure to isolate the targeted structure (Abstract) and the subcellular structure includes mitochondria (para 0039). St-Pierre further teaches the embodiment including imaging and detecting fluorescence (para 0013). St-Pierre further teaches determining one or more sorting gates for the classified cells of the sample (para 0067). Thus, it would be obvious to one of ordinary skill in the art before the effective filing date to modify Lo with determining one or more sorting gates for the classified cells of the sample as taught by St-Pierre for the benefit of distinguishing between tagged and untagged structures (para 0067).
Regarding claim 23, Lo teaches the invention of claim 22.
Lo does not teach that one or more sorting gates capture cells having mitochondria of a target particle population cluster and exclude particles of a non-target particle population cluster.
St-Pierre teaches one or more sorting gates capture cells having mitochondria of a target particle population cluster and exclude particles of a non-target particle population cluster (para 0069). Thus, it would be obvious to one of ordinary skill in the art before the effective filing date to modify Lo with one or more sorting gates capture cells having mitochondria of a target particle population cluster and exclude particles of a non-target particle population cluster as taught by St-Pierre for the benefit of isolating the structures with various morphologies (para 0069).
Regarding claim 30, Lo teaches the invention of claim 1.
Lo does not teach sorting cells of the sample into a plurality of sample containers.
St-Pierre further teaches sorting cells of the sample into a plurality of sample containers (para 0069). Thus, it would be obvious to one of ordinary skill that art before the effective filing date to modify Lo with sorting cells of the sample into a plurality of sample containers as taught by St-Pierre for the benefit of separating the tagged and non-tagged cellular structures for analysis (para 0069).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENA BERA whose telephone number is (571)272-9964. The examiner can normally be reached Mon-Fri 8:00-5:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at (571) 270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H.R.B./ Examiner, Art Unit 1798
/CHARLES CAPOZZI/ Supervisory Patent Examiner, Art Unit 1798
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