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 .
Election/Restrictions
Applicant’s election without traverse of Species I (claims 1, 2, and 5-11) in the reply filed on 2/19/26 is acknowledged.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/7/24 and 8/20/24 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character “S1” has been used to designate both set sample holder and form spheroids, reference character “S2” has been used to designate both image biological sample and image spheroids by OCT, and “S4” has been used to designate both evaluate condition of biological sample and evaluate condition of spheroids. 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. 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.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because in line 4, “intensity value” should read –an intensity value–. 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).
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because of the following informalities: In Pg. 1, line 5, the related applications paragraph should be numbered “[0000]”.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: In Pg. 1, line 9, “intensity value” should read –an intensity value–. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: In Pg. 3, line 16, “intensity value” should read –an intensity value–. Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “image acquisition unit” and “region extraction unit” in claim 11.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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, 2, and 5-11 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 "the other parts" in Pg. 1, line 3. There is insufficient antecedent basis for this limitation in the claim.
Additionally, the term “unusual” in claim 1 is a relative term which renders the claim indefinite. The term “unusual” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the limitations “unusual part in which a condition of a cell is different from that in the other parts” and “unusual part from the photographic image” has been rendered indefinite.
Claim 2 recites the limitation "intensity value" in Pg. 1, line 16. It is unclear and indefinite if this is the same as the “intensity value” previously recited in the claims.
Additionally, the term “higher than” in claim 2 is a relative term which renders the claim indefinite. The term “higher than” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the limitation “intensity value is higher than a predetermined threshold value in the entire region” has been rendered indefinite.
Also, the term “inner than” in claim 2 is a relative term which renders the claim indefinite. The term “inner than” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the limitation “a region inner than the higher intensity region are excluded from the entire region” has been rendered indefinite.
The term “unusual” in claim 5 is a relative term which renders the claim indefinite. The term “unusual” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the limitation “calculating a size of the unusual part on the basis of the localization region” has been rendered indefinite.
Claim 6 recites the limitation "the entire biological sample" in Pg. 2, line 17. It is unclear and indefinite if this is the same as the biological sample previously recited in the claims, as an “entire” biological sample was not previously recited.
Additionally, the term “unusual” in claim 6 is a relative term which renders the claim indefinite. The term “unusual” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the limitation “calculating a size ratio of the unusual part to the entire biological sample on the basis of the localization region” has been rendered indefinite.
Claims 7-10 depend on claim 1 and are therefore also rejected under 112(b).
Claim 11 recites the limitation "the other parts" in Pg. 3, line 11. There is insufficient antecedent basis for this limitation in the claim.
Additionally, the term “unusual” in claim 11 is a relative term which renders the claim indefinite. The term “unusual” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the limitations “unusual part in which a condition of a cell is different from that in the other parts” and “unusual part from the photographic image” has been rendered indefinite.
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, 2, and 5-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite a method and apparatus for observing a biological sample. With respect to the analysis of Claim 1 (claim 11 recites similar limitations):
Step 1:
With regard to Step 1, the claim is directed to a method; and therefore, the claim is directed to one of the statutory categories of inventions.
Step 2A, Prong One:
With regard to Step 2A, Prong One, the limitations “b) extracting a localization region corresponding to the unusual part from the photographic image, wherein, in the step b), a region of which intensity value satisfies a predetermined requirement in the photographic image is extracted as the localization region” as drafted, recite an abstract idea, such as a process that, under its broadest reasonable interpretation, covers performance of the limitation manually or in the mind by a human. That is, a person (i.e., doctor) can select/extract a region from an image of a cell that looks abnormal, in which the selected/extracted region is determined to be the darkest or brightest region and thus the localization region. This is a concept that falls under the grouping of abstract idea mathematical calculations and mental processes, i.e., a concept performed in the human mind, evaluation, judgment, and/or opinion of a human.
Step 2A, Prong Two:
The 2019 PEG defines the phrase “integration into a practical application” to require an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception. In the instant case, there are no additional steps/elements/limitations in the claims, with the exception of the following in the claims: “a) imaging the biological sample and acquiring a photographic image in which intensity values are distributed” in claim 1, and “an image acquisition unit configured to image the biological sample and acquire a photographic image in which intensity values are distributed” and “a region extraction unit” in claim 11. The “image acquisition unit” and “region extraction unit” are generic computer components (i.e., part of an imaging device or computer). The imaging/acquiring limitation is just data/image gathering. These limitations are regarded as adding routine and conventional elements to perform the judicial exception, and do not apply into a practical application. Accordingly, the above-mentioned additional elements/limitations do not integrate the abstract idea into a practical application; and therefore, the claims recite an abstract idea.
Step 2B:
Because the claims fail under Step 2A, the claims are further evaluated under Step 2B. The claims herein do not include additional elements that are sufficient to amount to significantly more than the judicial exception, because as discussed above with respect to integration of the abstract idea into practical application, the additional elements/limitations to perform the steps, amount to no more than insignificant routine and conventional elements. Mere instructions to apply an exception using generic components cannot provide an inventive concept. Therefore, independent claims 1 and 11 are not patent eligible.
Furthermore, with regard to dependent Claims 2 and 5-10 viewed individually, these additional steps, under their broadest reasonable interpretation, provide extra-solution activities to cover performance of the limitations as an abstract idea, and do not provide meaningful limitations to transform the abstract idea into a patent eligible application of the abstract idea such that the claims amount to significantly more than the abstract idea itself. Accordingly, they are not patent eligible.
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, 2, 5, and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Matsubara et al. (US 2016/0163049 A1, hereinafter “Matsubara”) in view of Koh et al. (US 2020/0218874 A1, hereinafter “Koh”).
Regarding claim 1, Matsubara teaches, an observation method for a biological sample including an unusual part in which a condition of a cell is different from that in the other parts, the method comprising the steps of (Fig. 1; Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Para. 0137: the degree of malignancy of a cancer cell may be determined; Note: the Examiner interprets stem cells differentiated into cancer/malignant cells as an unusual part in which a condition of a cell is different):
a) imaging the biological sample and acquiring a photographic image in which intensity values are distributed (Fig. 1: imaging device 2 and cell acquisition unit 30; Para. 0051: “The imaging device 2 captures the image of the cell”; Para. 0057: “The cell image acquisition unit 30 acquires the cell image captured by the imaging device 2 and stores the acquired cell image. In addition, the cell image acquisition unit 30 outputs the acquired cell image to the cell evaluation unit 31 and the display control unit 34”; Para. 0092: the distribution of the brightness signal in the stem cell colony is acquired; Para. 0093: “When the brightness signal or the thickness is uniformly distributed, the stem cell is likely to be undifferentiated. When portions with a higher or lower brightness than the surroundings or portions with a larger or smaller thickness than the surroundings are non-uniformly distributed so as to be concentrated, the stem cell is likely to be differentiated”; Note: the Examiner interprets, for example, brightness as an intensity);
and b) extracting a localization region corresponding to the unusual part from the photographic image (Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Para. 0077: “extracting the stem cell colony in the cell image”; Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect as information about the shape of the stem cell colony. In general, when the stem cell is not differentiated, the shape of the stem cell colony is close to a circle. When the differentiation of the stem cell progresses, the stem cell is separated and the circular shape of the stem cell colony is broken. Therefore, the degree of circularity of the outer circumferential shape of the stem cell colony can be evaluated to evaluate the undifferentiation and differentiation of the stem cell colony. In addition, the internal defect of the stem cell colony is, for example, a hole which is formed in the stem cell colony by differentiation”; Para. 0137: the degree of malignancy of a cancer cell may be determined),
Matsubara does not expressly disclose the following limitation: wherein, in the step b), a region of which intensity value satisfies a predetermined requirement in the photographic image is extracted as the localization region.
However, Koh teaches, wherein, in the step b), a region of which intensity value satisfies a predetermined requirement in the photographic image is extracted as the localization region (Para. 0018: “FIG. 6 shows an example of an image segmentation workflow through the “Spheroid Peeling method”. A number of different methods can be used to perform object segmentation. Given that spheroid peeling is based on brightfield images, segmentation is conducted in the bright field channel where the images are represented as pixels with different intensity levels. In Cell Profiler, identification of primary object is achieved using (1) thresholding and (2) filtering. The thresholding step involves identifying the foreground region from the background region using Maximum correlation threshold”; Para. 0052: cancer tumour spheroids or tumorspheres are spheres of cancer cells; Para. 0093: “Briefly, “Spheroid Peeling” involves repeatedly segmenting the spheroid image from the periphery to the core zone. The entire spheroid was first segmented as an object (hereby referred to as spheroid object) and cropped from the original well image (FIG. 6)”).
It would have been obvious, before the effective filing date of the claimed invention, to one of ordinary skill in the art to combine extracting a region of intensity value that satisfies a predetermined requirement/threshold as taught by Koh with the method of Matsubara in order to assess and screen spheroids (Koh, Para. 0004). Therefore, one of ordinary skill in the art would be capable to have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. It is for at least the aforementioned that the Examiner has reached a conclusion of obviousness with respect to claim 1.
Regarding claim 2, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh further teaches, the observation method according to claim 1 (see claim 1 above), wherein the step b) includes the steps of: b-1) extracting an entire region corresponding to the biological sample from the photographic image (Matsubara, Para. 0077: “extracting the stem cell colony in the cell image”; Koh, Para. 0093: “Briefly, “Spheroid Peeling” involves repeatedly segmenting the spheroid image from the periphery to the core zone. The entire spheroid was first segmented as an object (hereby referred to as spheroid object) and cropped from the original well image (FIG. 6)”; Koh, Para. 0018: “FIG. 6 shows an example of an image segmentation workflow through the “Spheroid Peeling method”. A number of different methods can be used to perform object segmentation. Given that spheroid peeling is based on brightfield images, segmentation is conducted in the bright field channel where the images are represented as pixels with different intensity levels. In Cell Profiler, identification of primary object is achieved using (1) thresholding and (2) filtering. The thresholding step involves identifying the foreground region from the background region using Maximum correlation threshold”; Koh, Para. 0052: cancer tumour spheroids or tumorspheres are spheres of cancer cells);
b-2) extracting a high-intensity region of which intensity value is higher than a predetermined threshold value in the entire region (Koh, Para. 0018: “FIG. 6 shows an example of an image segmentation workflow through the “Spheroid Peeling method”. A number of different methods can be used to perform object segmentation. Given that spheroid peeling is based on brightfield images, segmentation is conducted in the bright field channel where the images are represented as pixels with different intensity levels. In Cell Profiler, identification of primary object is achieved using (1) thresholding and (2) filtering. The thresholding step involves identifying the foreground region from the background region using Maximum correlation threshold”; Koh, Para. 0093: “Briefly, “Spheroid Peeling” involves repeatedly segmenting the spheroid image from the periphery to the core zone. The entire spheroid was first segmented as an object (hereby referred to as spheroid object) and cropped from the original well image (FIG. 6)”; Note: the Examiner interprets the foreground region as the high-intensity region. These paragraphs show that Maximum Correlation thresholding (i.e., thresholding in which the maximum intensity is determined) is used to separate the foreground (high-intensity region) from the background);
and b-3) extracting a region that is left after the high-intensity region and a region inner than the high-intensity region are excluded from the entire region, as the localization region (Koh: Fig. 6; Koh, Para. 0018: “FIG. 6 shows an example of an image segmentation workflow through the “Spheroid Peeling method”; Koh, Para. 0093: “Briefly, "Spheroid Peeling" involves repeatedly segmenting the spheroid image from the periphery to the core zone. The entire spheroid was first segmented as an object (hereby referred to as spheroid object) and cropped from the original well image (FIG. 6). An "inner core" was then identified from the spheroid object, hereby referred to as quiescent object. The proliferating zone was obtained by masking the quiescent object from the spheroid object. Similarly, the necrotic zone was identified as the "inner core" of the quiescent object, and the quiescent zone was obtained by masking the necrotic zone from the quiescent object”; Note: the Examiner interprets masking as an example of excluding).
The proposed combination as well as the motivation for combining the Matsubara and Koh references presented in the rejection of claim 1 apply to claim 2 and are incorporated herein by reference. Thus, the method recited in claim 2 is met by Matsubara and Koh.
Regarding claim 5, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh further teaches, the observation method according to claim 1 (see claim 1 above), further comprising the step of calculating a size of the unusual part on the basis of the localization region, after the step b) (Matsubara, Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Matsubara, Para. 0077: “extracting the stem cell colony in the cell image”; Matsubara, Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect as information about the shape of the stem cell colony. In general, when the stem cell is not differentiated, the shape of the stem cell colony is close to a circle. When the differentiation of the stem cell progresses, the stem cell is separated and the circular shape of the stem cell colony is broken. Therefore, the degree of circularity of the outer circumferential shape of the stem cell colony can be evaluated to evaluate the undifferentiation and differentiation of the stem cell colony. In addition, the internal defect of the stem cell colony is, for example, a hole which is formed in the stem cell colony by differentiation”; Matsubara, Para. 0082: “Then, the cell evaluation unit 31 calculates…an evaluation value related to whether there is an internal defect or the size of the internal defect”; Note: As shown in Matsubara, the size of the internal defect is calculated based on the extracted outer circumferential shape and internal defect (i.e., after the extracting); Koh, Para. 0047: the size or width of each zone (i.e., of the spheroid, or regions of cells of the spheroid) is determined; Koh, Paras. 0018 and 0093: segmentation/ “Spheroid Peeling”; Koh, Para. 0052: cancer tumour spheroids or tumorspheres are spheres of cancer cells).
The proposed combination as well as the motivation for combining the Matsubara and Koh references presented in the rejection of claim 1 apply to claim 5 and are incorporated herein by reference. Thus, the method recited in claim 5 is met by Matsubara and Koh.
Regarding claim 7, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh further teaches, the observation method according to claim 1 (see claim 1 above), wherein the unusual part is a part in which the cell has necrosed (Koh, Para. 0005: a spheroid has necrotic zones; Koh: As shown in Figs. 1, 5, and 6, there are necrotic zones; Koh: “necrosis or cell death”).
The proposed combination as well as the motivation for combining the Matsubara and Koh references presented in the rejection of claim 1 apply to claim 7 and are incorporated herein by reference. Thus, the method recited in claim 7 is met by Matsubara and Koh.
Regarding claim 8, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh further teaches, the observation method according to claim 1 (see claim 1 above), wherein the biological sample includes multiple kinds of cells (Matsubara, Para. 0011: a method has been proposed which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue, such as a cardiac muscle or a skin, or a cancer cell”; Note: the Examiner interprets, for example, cardiac muscle cells, skin cells, and cancer cells as multiple kinds of cells),
and the unusual part is a part in which a specific kind of cells are localized (Matsubara, Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Matsubara, Para. 0077: “extracting the stem cell colony in the cell image”; Matsubara, Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect as information about the shape of the stem cell colony. In general, when the stem cell is not differentiated, the shape of the stem cell colony is close to a circle. When the differentiation of the stem cell progresses, the stem cell is separated and the circular shape of the stem cell colony is broken. Therefore, the degree of circularity of the outer circumferential shape of the stem cell colony can be evaluated to evaluate the undifferentiation and differentiation of the stem cell colony. In addition, the internal defect of the stem cell colony is, for example, a hole which is formed in the stem cell colony by differentiation”; Matsubara, Para. 0137: the degree of malignancy of a cancer cell may be determined; Koh, Para. 0018: “FIG. 6 shows an example of an image segmentation workflow through the “Spheroid Peeling method”. A number of different methods can be used to perform object segmentation. Given that spheroid peeling is based on brightfield images, segmentation is conducted in the bright field channel where the images are represented as pixels with different intensity levels. In Cell Profiler, identification of primary object is achieved using (1) thresholding and (2) filtering. The thresholding step involves identifying the foreground region from the background region using Maximum correlation threshold”; Koh, Para. 0052: cancer tumour spheroids or tumorspheres are spheres of cancer cells; Koh, Para. 0093: “Briefly, “Spheroid Peeling” involves repeatedly segmenting the spheroid image from the periphery to the core zone. The entire spheroid was first segmented as an object (hereby referred to as spheroid object) and cropped from the original well image (FIG. 6)”).
The proposed combination as well as the motivation for combining the Matsubara and Koh references presented in the rejection of claim 1 apply to claim 8 and are incorporated herein by reference. Thus, the method recited in claim 8 is met by Matsubara and Koh.
Regarding claim 9, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh further teaches, the observation method according to claim 1 (see claim 1 above), wherein the unusual part is a part in which the cell is differentiated (Matsubara, Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Matsubara, Para. 0078: differentiation of the stem cell colony is evaluated; Matsubara: Para. 0079).
Regarding claim 10, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh further teaches, the observation method according to claim 1 (see claim 1 above), wherein, in the step a), the biological sample is imaged by optical coherence tomography (Matsubara, Fig. 1; Matsubara, Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Matsubara, Para. 0092: “Furthermore, the feature amount acquisition unit 32 acquires the uniformity of the thickness of the stem cell colony. The thickness of the stem cell colony can be measured by an interferometer such as optical coherence tomography (OCT)”).
Regarding claim 11, Matsubara teaches, an observation apparatus for a biological sample including an unusual part in which a condition of a cell is different from that in the other parts, the apparatus comprising (Fig. 1: imaging device 2 and cell image evaluation device 3; Para. 0003: “The present invention relates to a cell image evaluation device and method and a program which evaluate a captured cell image; Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Para. 0137: the degree of malignancy of a cancer cell may be determined; Note: the Examiner interprets stem cells differentiated into cancer/malignant cells as an unusual part in which a condition of a cell is different):
an image acquisition unit configured to image the biological sample and acquire a photographic image in which intensity values are distributed (Fig. 1: imaging device 2 and cell acquisition unit 30; Para. 0051: “The imaging device 2 captures the image of the cell”; Para. 0057: “The cell image acquisition unit 30 acquires the cell image captured by the imaging device 2 and stores the acquired cell image. In addition, the cell image acquisition unit 30 outputs the acquired cell image to the cell evaluation unit 31 and the display control unit 34”; Para. 0092: the distribution of the brightness signal in the stem cell colony is acquired; Para. 0093: “When the brightness signal or the thickness is uniformly distributed, the stem cell is likely to be undifferentiated. When portions with a higher or lower brightness than the surroundings or portions with a larger or smaller thickness than the surroundings are non-uniformly distributed so as to be concentrated, the stem cell is likely to be differentiated”; Note: the Examiner interprets, for example, brightness as an intensity);
and a region extraction unit configured to extract a localization region corresponding to the unusual part from the photographic image (Fig. 1: cell evaluation unit 31 and feature amount acquisition unit 32; Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Para. 0077: “extracting the stem cell colony in the cell image”; Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect as information about the shape of the stem cell colony. In general, when the stem cell is not differentiated, the shape of the stem cell colony is close to a circle. When the differentiation of the stem cell progresses, the stem cell is separated and the circular shape of the stem cell colony is broken. Therefore, the degree of circularity of the outer circumferential shape of the stem cell colony can be evaluated to evaluate the undifferentiation and differentiation of the stem cell colony. In addition, the internal defect of the stem cell colony is, for example, a hole which is formed in the stem cell colony by differentiation”; Para. 0137: the degree of malignancy of a cancer cell may be determined),
Matsubara does not expressly disclose the following limitation: wherein the region extraction unit extracts a region of which intensity value satisfies a predetermined requirement in the photographic image, as the localization region.
However, Koh teaches, wherein the region extraction unit extracts a region of which intensity value satisfies a predetermined requirement in the photographic image, as the localization region (Abstract: “device configured to perform the methods as disclosed herein”; Para. 0018: “FIG. 6 shows an example of an image segmentation workflow through the “Spheroid Peeling method”. A number of different methods can be used to perform object segmentation. Given that spheroid peeling is based on brightfield images, segmentation is conducted in the bright field channel where the images are represented as pixels with different intensity levels. In Cell Profiler, identification of primary object is achieved using (1) thresholding and (2) filtering. The thresholding step involves identifying the foreground region from the background region using Maximum correlation threshold”; Para. 0052: cancer tumour spheroids or tumorspheres are spheres of cancer cells; Para. 0092: “Bright-field images of the 1,231 spheroids acquired at different time-points and z-planes were computationally segmented”; Para. 0093: “Briefly, “Spheroid Peeling” involves repeatedly segmenting the spheroid image from the periphery to the core zone. The entire spheroid was first segmented as an object (hereby referred to as spheroid object) and cropped from the original well image (FIG. 6)”).
It would have been obvious, before the effective filing date of the claimed invention, to one of ordinary skill in the art to combine extracting a region of intensity value that satisfies a predetermined requirement/threshold as taught by Koh with the apparatus of Matsubara in order to assess and screen spheroids (Koh, Para. 0004). Therefore, one of ordinary skill in the art would be capable to have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. It is for at least the aforementioned that the Examiner has reached a conclusion of obviousness with respect to claim 11.
Claims 6 is rejected under 35 U.S.C. 103 as being unpatentable over Matsubara et al. (US 2016/0163049 A1, hereinafter “Matsubara”) in view of Koh et al. (US 2020/0218874 A1, hereinafter “Koh”) and further in view of Zhou et al. (CN 113066080A, see provided machine translation; hereinafter “Zhou”).
Regarding claim 6, the combination of Matsubara and Koh teaches the limitations as explained above in claim 1.
The combination of Matsubara and Koh does not expressly disclose the following limitation: further comprising the step of calculating a size ratio of the unusual part to the entire biological sample on the basis of the localization region, after the step b).
However, Zhou teaches, further comprising the step of calculating a size ratio of the unusual part to the entire biological sample on the basis of the localization region, after the step b) (Pg. 4 of the entire document: “The method further includes: determining the tissue area containing the diseased cell type in the second image; calculating the ratio of the tissue area of the diseased cell type to all the identified tissue areas”; Pg. 4 of the entire document: extraction/segmenting an image of the tissue area; Pg. 6 of the entire document: a slice image is input into the tissue segmentation model to generate a first image and then a second image is generated; Pg. 9-10 of the entire document; Note: As shown in these paragraphs, the tissue area containing the diseased cell type (.e., unusual part) in the second image is first determined and then the ratio of the tissue area to all the identified tissues is calculated. The second image is generated from the segmentation. The Examiner interprets all the identified tissues as the entire biological sample).
It would have been obvious, before the effective filing date of the claimed invention, to one of ordinary skill in the art to combine calculating a size ratio of the unusual part after extracting (i.e., step b)) as taught by Zhou with the combined method of Matsubara and Koh in order to improve identification efficiency and identification accuracy of the slice tissue (Zhou, Abstract). Therefore, one of ordinary skill in the art would be capable to have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. It is for at least the aforementioned that the Examiner has reached a conclusion of obviousness with respect to claim 6.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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Claims 1, 2, and 5-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18/599,728 in view of Matsubara et al. (US 2016/0163049 A1, hereinafter “Matsubara”).
Regarding claim 1 of the instant application, claim 5 of copending Application No. 18/599,728 teaches, an observation method for a biological sample (claim 5 depends claim 1; claim 1: “An evaluation method for a spheroid”),
the method comprising the steps of: a) imaging the biological sample and acquiring a photographic image (claim 5 depends on claim 1; claim 1: “an image acquisition step of imaging the spheroid by optical coherence tomography and acquiring a photographic image”);
and b) extracting a localization region (claim 5 depends on claim 1; claim 1: “a region extraction step of extracting a localization region in which one kind of cell is localized, from the photographic image”),
wherein, in the step b), a region of which intensity value satisfies a predetermined requirement in the photographic image is extracted as the localization region (claim 5: “wherein the region extraction step includes…extracting a high-intensity region of which intensity value is higher than a predetermined threshold value in the entire region…as the localization region”).
Claim 5 of copending Application No. 18/599,728 does not expressly disclose the following limitations: a biological sample including an unusual part in which a condition of a cell is different from that in the other parts; a photographic image in which intensity values are distributed; extracting a localization region corresponding to the unusual part.
However, Matsubara teaches, a biological sample including an unusual part in which a condition of a cell is different from that in the other parts (Fig. 1; Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Para. 0137: the degree of malignancy of a cancer cell may be determined; Note: the Examiner interprets stem cells differentiated into cancer/malignant cells as an unusual part in which a condition of a cell is different);
a photographic image in which intensity values are distributed (Fig. 1: imaging device 2 and cell acquisition unit 30; Para. 0051: “The imaging device 2 captures the image of the cell”; Para. 0057: “The cell image acquisition unit 30 acquires the cell image captured by the imaging device 2 and stores the acquired cell image. In addition, the cell image acquisition unit 30 outputs the acquired cell image to the cell evaluation unit 31 and the display control unit 34”; Para. 0092: the distribution of the brightness signal in the stem cell colony is acquired; Para. 0093: “When the brightness signal or the thickness is uniformly distributed, the stem cell is likely to be undifferentiated. When portions with a higher or lower brightness than the surroundings or portions with a larger or smaller thickness than the surroundings are non-uniformly distributed so as to be concentrated, the stem cell is likely to be differentiated”; Note: the Examiner interprets, for example, brightness as an intensity);
extracting a localization region corresponding to the unusual part (Para. 0011: a method which captures an image of a cell obtained by inducing a stem cell to be differentiated to a target tissue such as a cancer cell; Para. 0077: “extracting the stem cell colony in the cell image”; Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect as information about the shape of the stem cell colony. In general, when the stem cell is not differentiated, the shape of the stem cell colony is close to a circle. When the differentiation of the stem cell progresses, the stem cell is separated and the circular shape of the stem cell colony is broken. Therefore, the degree of circularity of the outer circumferential shape of the stem cell colony can be evaluated to evaluate the undifferentiation and differentiation of the stem cell colony. In addition, the internal defect of the stem cell colony is, for example, a hole which is formed in the stem cell colony by differentiation”; Para. 0137: the degree of malignancy of a cancer cell may be determined).
It would have been obvious, before the effective filing date of the claimed invention, to one of ordinary skill in the art to combine a biological sample including an unusual part in which a condition of a cell is different from that in the other parts, a photographic image having distributed intensity values, and extracting a localization region corresponding to the unusual part as taught by Matsubara with claim 5 of copending Application No. 18/599,728 in order to evaluate the cell image on the basis of the information related to maturity (Matsubara, Abstract) and accurately evaluate undifferentiation and differentiation (Matsubara, Para. 0084). Therefore, one of ordinary skill in the art would be capable to have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately.
Claims 2 and 5-10 of the instant application depend on claim 1. The dependent claims are therefore also provisionally rejected under obviousness type nonstatutory double patenting for the same reasons as above.
Independent claim 11 of the instant application recites an apparatus with elements corresponding to the steps recited in claim 1. Therefore, the recited elements of this claim are mapped to the proposed combination in the same manner as the corresponding steps in its corresponding method claim. Additionally, the rationale and motivation to combine claim 5 of copending Application No. 18/599,728 and Matsubara, represented in the double patenting rejection of claim 1, apply to this claim. Finally, the combination of claim 5 of copending Application No. 18/599,728 and Matsubara, discloses an apparatus, image acquisition unit, and region extraction unit (for example, see Matsubara, Fig. 1: imaging device 2, cell image evaluation device 3, cell evaluation unit 31, and feature acquisition unit 32; Para. 0003: “The present invention relates to a cell image evaluation device and method and a program which evaluate a captured cell image; Para. 0051: “The imaging device 2 captures the image of the cell”; Para. 0057: “The cell image acquisition unit 30 acquires the cell image captured by the imaging device 2 and stores the acquired cell image. In addition, the cell image acquisition unit 30 outputs the acquired cell image to the cell evaluation unit 31 and the display control unit 34”; Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect…”). Therefore, claim 11 is also provisionally rejected under obviousness type nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, and 5-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18/599,334 in view of Matsubara et al. (US 2016/0163049 A1, hereinafter “Matsubara”).
Regarding claim 1 of the instant application, claim 2 of copending Application No. 18/599,334 teaches, an observation method for a biological sample including an unusual part in which a condition of a cell is different from that in the other parts (claim 2 depends claim 1; claim 1: “An evaluation method for a biological sample…a fibrotic region in which a cell is fibrosed”; Note: the Examiner interprets a fibrotic region as a condition of a cell that is different from other parts),
the method comprising the steps of: a) imaging the biological sample and acquiring a photographic image (claim 2 depends on claim 1; claim 1: “an image acquisition step of imaging the biological sample by optical coherence tomography and acquiring an image”);
and b) extracting a localization region corresponding to the unusual part from the photographic image (claim 2 depends on claim 1; “a region extraction step of extracting a fibrotic region in which a cell is fibrosed, from the taken image”),
wherein, in the step b), a region of which intensity value satisfies a predetermined requirement in the photographic image is extracted as the localization region (claim 2: “wherein the region extraction step includes…extracting a high-intensity region of which intensity value is higher than a predetermined threshold value in the entire region…as the fibrotic region”).
Claim 2 of copending Application 18/599,334 does not expressly disclose the following limitation: a photographic image in which intensity values are distributed.
However, Matsubara teaches, a photographic image in which intensity values are distributed (Fig. 1: imaging device 2 and cell acquisition unit 30; Para. 0051: “The imaging device 2 captures the image of the cell”; Para. 0057: “The cell image acquisition unit 30 acquires the cell image captured by the imaging device 2 and stores the acquired cell image. In addition, the cell image acquisition unit 30 outputs the acquired cell image to the cell evaluation unit 31 and the display control unit 34”; Para. 0092: the distribution of the brightness signal in the stem cell colony is acquired; Para. 0093: “When the brightness signal or the thickness is uniformly distributed, the stem cell is likely to be undifferentiated. When portions with a higher or lower brightness than the surroundings or portions with a larger or smaller thickness than the surroundings are non-uniformly distributed so as to be concentrated, the stem cell is likely to be differentiated”; Note: the Examiner interprets, for example, brightness as an intensity).
It would have been obvious, before the effective filing date of the claimed invention, to one of ordinary skill in the art to combine a photographic image having distributed intensity values as taught by Matsubara with claim 2 of copending Application No. 18/599,334 in order to evaluate the cell image on the basis of the information related to maturity (Matsubara, Abstract) and accurately evaluate undifferentiation and differentiation (Matsubara, Para. 0084). Therefore, one of ordinary skill in the art would be capable to have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately.
Claims 2 and 5-10 of the instant application depend on claim 1. The dependent claims are therefore also provisionally rejected under obviousness type nonstatutory double patenting for the same reasons as above.
Independent claim 11 of the instant application recites an apparatus with elements corresponding to the steps recited in claim 1. Therefore, the recited elements of this claim are mapped to the proposed combination in the same manner as the corresponding steps in its corresponding method claim. Additionally, the rationale and motivation to combine claim 2 of copending Application 18/599,334 and Matsubara, represented in the double patenting rejection of claim 1, apply to this claim. Finally, the combination of claim 2 of copending Application No. 18/599,334 and Matsubara, discloses an apparatus, image acquisition unit, and region extraction unit (for example, see Matsubara, Fig. 1: imaging device 2, cell image evaluation device 3, cell evaluation unit 31, and feature acquisition unit 32; Para. 0003: “The present invention relates to a cell image evaluation device and method and a program which evaluate a captured cell image; Para. 0051: “The imaging device 2 captures the image of the cell”; Para. 0057: “The cell image acquisition unit 30 acquires the cell image captured by the imaging device 2 and stores the acquired cell image. In addition, the cell image acquisition unit 30 outputs the acquired cell image to the cell evaluation unit 31 and the display control unit 34”; Para. 0079: “Specifically, the feature amount acquisition unit 32 extracts an outer circumferential shape and an internal defect…”). Therefore, claim 11 is also provisionally rejected under obviousness type nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Senda et al. (US 2019/0244349 A1)
Mei et al. (US 2021/0319551 A1)
Contact Information
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/Daniella M. DiGuglielmo/Examiner, Art Unit 2666
/EMILY C TERRELL/Supervisory Patent Examiner, Art Unit 2666