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 .
Specification
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 following title is suggested: Cytotoxicity Region Determination Based On Variation of Refractive Index Distribution and Applying A Machine Learning Model Trained Using Cell Death Region Data
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.
Claim 13 is 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.
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Claim 13 recites wherein the cell cluster is a normal cell cluster,” The term “normal” is considered a relative term.
The term “normal” in claim 13 is a relative term which renders the claim indefinite. The term “normal” 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.
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: claim 15 Data acquisition unit and Determination unit which each employ the nonce term “unit”, are recited in purely functional terms without reciting any structural elements and are terms that are not considered to denote structure to one of ordinary skill. Corresponding structure and algorithms have been identified and include the apparatus of Figs. 1-3 and a high-level general-purpose computer; further, the structure of this general-purpose computer is not specially adapted, tuned or designed but instead amounts to “apply-it” type of computer implementation for a determining/analyzing refractive index distribution data. Still further, the data acquisition unit is wholly conventional (see the 102 and 103 rejections as well as the art cited in the 892 form) and corresponding to WURC (well understood routine and conventional) while noting that prior art applied below was filed or published more than a decade before the instant invention. See also the 35 USC 101 rejection in which these findings are hereby incorporated to support lack of substantially more and failure to solve any technological problem.
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 § 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 16 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter as follows:
Claims 16 recites “an information processing program for causing a computer to execute a determination step of determining a region of cells that have undergone programmed cell death in an observation object by the method according to claim 1”. Claim 17 is dependent on claim 16 and also recites a computer program per se.
Claims 16 and 17 do not fall within at least one of the four categories of patent eligible subject matter because these claims are directed to a computer program per se. In more detail, these claims do not positively recite a computer but merely “causing a computer to execute” which is considered mere intended use does not necessarily require a computer, execution on a computer or the inclusion of any structural limitation. Moreover, “a processing program” does not itself indicate or require any structure. As such, these claims have no physical or tangible form and thus do not fall within any statutory category. It is suggested that a standard form of a computer-readable medium claim be utilized to comply with US practice because it recites a statutory category (an article of manufacture).
Claims 1-17 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to a judicial exception, an abstract idea or mental processes, without significantly more.
Specifically, independent claim 1 recites a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object {abstract idea in bold, mental process}.
As such, claim 1 is directed to a method that includes a mental evaluation of refractive index distribution data (an image) to detect apoptosis (programmed cell death) based on refractive index distribution data visually apparent in the image. There is ample evidence that the human mind is well-capable of performing this determination. See the applied art below including Cotte which employs human experts for supervised, unsupervised, and reinforced feedback of a machine learning model in which a human mentally evaluates the refractive index distribution data to detect apoptosis as per [0244]-[0302]. Cotte also discloses that apoptosis of cells results in human-identifiable and visually apparent morphological changes indicative of apoptosis including rounding-up of the cell, nuclear fragmentation, and blebbing of the plasma membrane which are visible in the refractive index distribution data (image), [0087], [0378]. See also Jung applied below in which 3-D voxels of refractive index distribution data also exhibits visually apparent morphological changes that may be mentally evaluated to determine apoptosis on a voxel-3D basis.
Therefore, claim 1 clearly constitutes an abstract idea because it falls within the “Mental process” grouping of abstract ideas. Moreover, as further detailed below, the remaining claims merely automate the mental process using a general-purpose computer (for the determinations) and/or WURC (well-understood routine and conventional) elements for the acquiring of such data as further analyzed below.
As to the remaining claims:
Claim 2 (Original): The method according to claim 1, wherein determination of a region of cells that have undergone programmed cell death is carried out on a basis of an amount of spatial variation of refractive index in pixels or voxels included in the refractive index distribution data {the morphological features indicative of apoptosis are visible via the spatial variations (e.g. edges, structures) of the refractive index in pixels (Cotte) or voxels (Jung)}.
Claim 3 (Original): The method according to claim 2, wherein the determination of a region of cells that have undergone programmed cell death is carried out on a basis of a magnitude relationship between the amount of spatial variation of refractive index and a threshold value {the morphological features indicative of apoptosis are visible via the magnitude relationship between a spatial variation of refractive index and a threshold (e.g. edges, structures) of the refractive index in pixels (Cotte) or voxels (Jung). Further as to threshold, see the color-coded display produced by Cotte in which each color represents a range of refraction indices which are clearly visible to the human eye and usable by the human mind to make the apoptosis determination}.
Claim 4 (Original): The method according to claim 3, wherein the programmed cell death is apoptosis {part of the abstract idea and merely specifies the field of use or input data type for the mental process}.
Claim 5 (Original): The method according to claim 4, wherein the observation object is a cell cluster {part of the abstract idea and merely specifies the field of use or input data type for the mental process while Jung demonstrates that apoptosis of cell clusters is also human-observable and thus a mental process due to the morphological indicators which are visible in the OCT image}.
Claim 6 (Original): The method according to claim 5, wherein the refractive index distribution data is refractive index tomography data in a predetermined direction {mere data gathering elements that gather data (images) of the digital asset and also WURC as per art mappings below}.
Claim 7 (Original): The method according to claim 1, wherein the determination of a region of cells that have undergone programmed cell death is carried out by inputting refractive index distribution data of an observation object into a learning model that has learned using training data including programmed cell death region data of a reference observation object and refractive index distribution data of the reference observation object corresponding to the programmed cell death region data, and a feature quantity utilized by the learning model includes an amount of spatial variation of refractive index in pixels or voxels included in the refractive index distribution data {mere “apply it” generalized method/structure that applies machine learning at a very high level. Also, WURC as per art mapping below}.
Claim 8 (Original): The method according to claim 7, wherein the programmed cell death is apoptosis {part of the abstract idea and merely specifies the field of use or input data type for the mental process}.
Claim 9 (Original): The method according to claim 8, wherein the observation object is a cell cluster {see claim 5 above}.
Claim 10 (Original): The method according to claim 9, wherein the refractive index distribution data is refractive index tomography data in a predetermined direction {see claim 6}.
Claim 11 (Currently Amended): The method according to claim 1 for determining a region of cells that have undergone programmed cell death in observation object, the method further comprising: a step of acquiring the refractive index distribution data of the observation object {mere data gathering and WURC as per art mapping below}; and a step of determining a region of cells that have undergone programmed cell death by the method according to claim 1. {see claim 1}
Claim 12: The method according to claim 1, which is a method for analyzing an effect exerted by a drug on programmed cell death of cells included in a cell cluster, the observation object being a cell cluster, the method further comprising: a step of adding a drug to a cell cluster; a step of acquiring the refractive index distribution data of the cell cluster {this merely describes routine testing of drugs such as chemotherapy drugs and is WURC as per Cotte and Jung below}.
Claim 13 (Original): The method according to claim 12, wherein the cell cluster is a normal cell cluster, and the effect exerted by the drug on the programmed cell death of cells included in the cell cluster is cytotoxicity of the drug {this merely describes routine testing of drugs such as chemotherapy drugs and is WURC as per Cotte and Jung below. Also, cytotoxicity is also human observable and mental process}.
Claim 14 (Original): The method according to claim 12, wherein the cell cluster is a cancer cell cluster, and the effect exerted by the drug on the programmed cell death of cells included in the cell cluster is anticancer activity of the drug {this merely describes routine testing of drugs such as chemotherapy drugs and is WURC as per Cotte and Jung below. Also, anticancer activity is also human observable and mental process}.
Claim 15: An apparatus for determining a region of cells that have
undergone programmed cell death, the apparatus comprising:
a data acquisition unit for acquiring refractive index distribution data of an observation object {mere data gathering and WURC as per below art mapping}; and a
determination unit for determining a region of cells that have undergone programmed cell death in the observation object by the method according to claim 1.
Claim 16 (Currently Amended): An information processing program for causing a computer to execute a determination step of determining a region of cells that have undergone programmed cell death in an observation object by the method according to claim 1 {“apply it” high-level structure}.
Claim 17 The information processing program according to claim 16, for further causing the computer to execute:
a data acquisition step of acquiring the refractive index distribution data of the observation object {mere data gathering and WURC as per below art mapping}; and
a determination step of determining a region of cells that have undergone programmed cell death in the observation object by the method according to claim 1.
The judicial exceptions are not integrated into a practical application because the additional claim elements merely employ routine and conventional laboratory techniques and generic refractive index distribution data gathering concepts to gather and manipulate information. Specifically, the steps and units for acquiring refractive index distribution data merely generates data that is later subjected to the abstract mental processes of determining programmed cell death (apoptosis). Further, the standard drug testing lab procedures of claims 12-14 are high-level steps which are also considered WURC. In sum, none of these functional activities or high-level structural elements impose any meaningful limits on the abstract idea itself.
The prior art rejections below confirm that various elements and functionality of the remaining claims as identified above are individually and collectively well-understood and conventional (WURC) for at least a decade before the earliest effective filing date of the present application. Indeed, these functionalities and high-level structural elements are recited in the claims using very broad, non-specific and generalized terms.
Furthermore, the claims do not recite any technical improvement to cell biology, determination of programmed cell death, image processing, or computer functionality. Rather, the claims merely apply known concepts such as standard lab testing using very well-known equipment to gather refractive index distribution data and apply high-level WURC machine learning (claim 7) to determine programmed cell death.
The claims also fail to recite any particular implementation, protocol, or technical mechanism for determining programmed cell death. There is no further step of applying the determination in a technologically meaningful manner, such as improving determinations of programmed cell death. Simply implementing the abstract idea of mentally determining programmed cell death based on observations of images (refractive index distribution data) using generic computer hardware or generic machine learning (claim 7) does not constitute a practical application of the abstract idea. The recited data acquisition unit and use of conventional drug testing regimes (e.g. claims 11-13) constitute insignificant extra-solution activities because they merely gather information to be used in the abstract mental process. The claims do not recite any transformation of the data into a therapeutic product, treatment step, or any technological improvement arising from the abstract idea itself.
Enumerated groups of abstract ideas include certain methods of mental processes, mathematical concepts, classification, and information organization, see MPEP 2106.04(a) and 2106.04(a)(2). Limitations that the courts have found not to be enough to quality as 'significantly more' include: Simply appending well-understood, routine, conventional activities, known in the industry, specified at a high level of generality, to the judicial exception, as discussed in Alice Corp., 134 S. Ct. at 2359-60, 110 USPQ2d at 1984; and adding insignificant extra solution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea ... so that the information can be analyzed by an abstract mental process, as discussed in CyberSource v. Retail Decisions, Inc., 654 F.3d 1366, 1375, 99 USPQ2d 1690, 1694 (Fed. Cir. 2011) (MPEP 2106.05 (l)(A)).
As discussed above with respect to integration of the abstract idea into a practical application, the recited additional elements amount to no more than mere instructions to apply the exception using a generic computer component (See MPEP 2106.05(f)) and limits the judicial exception to the particular environment of computers (See MPEP 2106.05(h)). The additional elements of the instant underlying process, when taken in combination, together do not offer substantially more than the sum of the function of the elements when each is taken alone. Mere instructions to apply an exception using a generic computer component cannot provide an inventive concept in Step 2B
Therefore, the claimed subject matter, as individual elements and as a combination of elements, does not recite 'significantly more' than the judicial exception.
The claimed subject matter does not recite patent eligible subject matter under 35 USC § 101.
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 1-4, 7-9, 11, 15-17 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Cotte (US 2021/0271853 A1).
Claim 1
In regards to claim 1, Cotte discloses a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object {see Figs. 1, Fig. 6, [0302]-[0320] illustrating system for observing refractive index of cells and [0375]-[0381] that uses refractive index distribution data to determine apoptosis (programmed cell death)}.
Claim 2
In regards to claim 2, Cotte discloses wherein determination of a region of cells that have undergone programmed cell death is carried out on a basis of an amount of spatial variation of refractive index in pixels or voxels included in the refractive index distribution data {[0375]-[0381] Automated Cell Metrics which employs the spatial variations of refractive index (RI) data to, for example, identify and track cell nucleus size fluctuations and other morphological changes indicative of apoptosis including rounding-up of the cell, nuclear fragmentation, blebbing of the plasma membrane. Further as to “spatial variation” see [0380] which discriminates between different components of the cell using RI gradient values and the digital staining which assigns different colors to each diffraction index range. See also [0384]-[0388]}
Claim 3
In regards to claim 3, Cotte discloses wherein the determination of a region of cells that have undergone programmed cell death is carried out on a basis of a magnitude relationship between the amount of spatial variation of refractive index and a threshold value {[0014]-[0036] which determines and applies thresholds to the 3D/4D refractive index distribution to determine apoptosis. See also [0144]-[0183], [0486]-[0494}.
Claim 4
In regards to claim 4, Cotte discloses wherein the programmed cell death is apoptosis {see mapping for claim 1, see also Fig. 26, [0087] illustrating the 2D map of the refractive index distribution, 3D holographic representation with each color representing a corresponding range of refractive indices and showing the morphological differences for apoptosis including blebbing, loss of cell volume, etc. which are features detected by the disclosed invention}.
Claim 7
In regards to claim 7, Cotte discloses wherein the determination of a region of cells that have undergone programmed cell death is carried out by
inputting refractive index distribution data of an observation object into a learning model that has learned using training data including programmed cell death region data of a reference observation object and refractive index distribution data of the reference observation object corresponding to the programmed cell death region data, and a feature quantity utilized by the learning model includes an amount of spatial variation of refractive index in pixels or voxels included in the refractive index distribution data.
{see machine learning model that ingests refractive index distribution data and which has been trained using training data as recited. See [0017]-[0023], [0040]-[0041], [0125]-[0135], Fig. 10 example, [0136]-[0144], [0281]-[0282]-[0288]}
Claim 8
The rejection of method claims 4 above applies mutatis mutandis to the corresponding limitations of method claims 8. Note that the only difference between these claims is the dependency (upon claim 7 instead of claim 1).
Claim 9
In regards to claim 9, Cotte discloses wherein the refractive index distribution data is refractive index tomography data in a predetermined direction {see [0007] 3D refractive index distribution in which each plane (including a plane of a predetermined direction) may be analyzed. See also Fig. 23, each image in the Z-stack may be analyzed, Fig. 26, [0087]
Claim 11
In regards to claim 11, Cotte discloses a step of acquiring the refractive index distribution data of the observation object {see Fig. 6 illustrating apparatus and steps (e.g. starting step 1 which inputs the data) for acquiring the refractive index distribution data that is then input and used to detect apoptosis, [0301]-[0321]}.
Claim 15
In regards to claim 15, Cotte discloses an apparatus for determining a region of cells that have undergone programmed cell death, the apparatus comprising:
a data acquisition unit for acquiring refractive index distribution data of an observation object {Figs. 6, 7 [0045]-[0050], [0302]-[0320] illustrating system for observing refractive index of cells}; and
a determination unit for determining a region of cells that have undergone programmed cell death in the observation object by the method according to claim 1.
{Figs. 6, 7, including object characterization program 17 and [0375]-[0381] that uses refractive index distribution data to determine apoptosis (programmed cell death)}
Claim 16
In regards to claim 16, Cotte discloses an information processing program for causing a computer to execute a determination step of determining a region of cells that have undergone programmed cell death in an observation object by the method according to claim 1 {see mapping of claim 1. As to the program and computer see Figs. 6, 7, [0045] including computer 5 including local storage 9a and object characterization program 17 and computer-readable medium embodiment in [0057], claim 29}.
Claim 17
In regards to claim 17, Cotte discloses causing the computer to execute: a data acquisition step of acquiring the refractive index distribution data of the observation object {See claim 16 for computer implementation. See Figs. 6, 7 [0045]-[0050], [0302]-[0320] illustrating system and method for acquiring the refractive index distribution data of the observation object}
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 5, 6, 10, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Cotte, Jung {Jung Y, Klein OJ, Wang H, Evans CL. Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT. Sci Rep. 2016 Jun 1;6:27017. doi: 10.1038/srep27017. PMID: 27248849; PMCID: PMC4888651} and Jung Supp {Jung Y, Klein OJ, Wang H, Evans CL., Supplementary Information for Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT, Sci Rep. 2016 Jun 1;6:27017}.
Claim 5
In regards to claim 5, Cotte discloses wherein the observation object is a cell cluster {see [0012]-[0015] discussing applications to a broad category of microscopic objects and biological specimens such as cells, [0091] multi-cellular biological samples, [0130]-[0135] discussing biological tissue, bulk tissue, and particularly including Circulating Tumor Cells (CTCs) which may be considered or at least suggests applications to cell clusters [0391]-[0398]}.
Jung teaches a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object wherein the observation object is a cell cluster {see title, abstract, Fig. 1 apparatus, and discussion applying OCT (optical coherence tomograph) to produce a 3D refractive index distribution that is used to detect apoptosis within a cell cluster}.
It 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 to have modified Cotte which already discloses a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object and applies this method to a broad category of microscopic objects and biological specimens such as cells, multi-cellular biological samples, bulk tissue, and Circulating Tumor Cells (CTCs) which may be considered or at least suggests applications to cell clusters such that the method more explicitly applies to cell clusters as taught by Jung because Jung motivates quantitative tracking of 3D tumor cells within clusters to advantageously expand the diagnostic capabilities of the method/device to tumor cell cluster cell death by enabling the monitoring of therapeutic regiments including the efficacy of chemotherapy drugs on cell clusters, because there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Claim 6
In regards to claim 6, Cotte discloses wherein the refractive index distribution data is refractive index tomography data in a predetermined direction {see [0007] 3D refractive index distribution in which each plane (including a plane of a predetermined direction) may be analyzed. See also Fig. 23, each image in the Z-stack may be analyzed, Fig. 26, [0087]
Claim 10
The rejection of method claims 6 above applies mutatis mutandis to the corresponding limitations of method claim 19. Note that the only difference between these claims is the dependency (upon claims 7/8 instead of claim 1).
Claim 12
In regards to claim 12, Cotte discloses which is a method for analyzing an effect exerted by a drug on programmed cell death of cells included in a cell cluster, the observation object being a cell cluster, the method further comprising: a step of adding a drug to a cell cluster; a step of acquiring the refractive index distribution data of the cell cluster {See [0378]-[0382].discussing apoptosis being controlled or otherwise in response to chemicals (drugs). As to cell cluster see [0012]-[0015] discussing applications to a broad category of microscopic objects and biological specimens such as cells, [0091] multi-cellular biological samples, [0130]-[0135] discussing biological tissue, bulk tissue, and particularly including Circulating Tumor Cells (CTCs) which may be considered cell clusters [0391]-[0398]}.
Jung also teaches applications to cell clusters including analyzing an effect exerted by a drug on programmed cell death of cells included in a cell cluster, the observation object being a cell cluster, the method further comprising: a step of adding a drug to a cell cluster; a step of acquiring the refractive index distribution data of the cell cluster {see title, abstract, Fig. 1 apparatus, and discussion applying OCT (optical coherence tomograph) to produce a 3D refractive index distribution that is used to detect apoptosis within cell clusters in response to therapeutic regimens including chemotherapy drugs}
It 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 to have modified Cotte which already discloses a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object and applies this method to a broad category of microscopic objects and biological specimens such as cells, multi-cellular biological samples, bulk tissue, and Circulating Tumor Cells (CTCs) which may be considered cell clusters and also discloses tracking the apoptotic response to the application of chemicals (drugs) such that the method more explicitly applies to cell clusters and chemotherapy drugs applies to cell clusters as taught by Jung because Jung motivates quantitative tracking of 3D tumors cell clusters to advantageously expand the diagnostic capabilities of the method/device to tumor cell cluster cell death by enabling the monitoring of therapeutic regiments including the efficacy of chemotherapy drugs on cell clusters, because there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Claim 13
In regards to claim 13, Cotte is not relied upon to disclose but Jung teaches
wherein the cell cluster is a normal cell cluster, and the effect exerted by the drug on the programmed cell death of cells included in the cell cluster is cytotoxicity of the drug {see abstract and discussion including pg. 9 measuring cytotoxicity of carboplatin following a 72-hour incubation. It is noted that this claim broadly recites “normal cell cluster” which may include but does not necessarily require healthy cells that have been tested by another technique to ensure they are “normal” and that the claim does not require such validation of “normal” cell cluster before applying the disclosed methods to determine apoptosis of the cell. See also the 112(b) rejection in which “normal” is considered a relative term that renders the claim indefinite.}.
It 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 to have modified Cotte which already discloses a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object and applies this method to a broad category of microscopic objects and biological specimens such as cells, multi-cellular biological samples, bulk tissue, and Circulating Tumor Cells (CTCs) which may be considered cell clusters and also discloses tracking the apoptotic response to the application of chemicals (drugs) such that the method more explicitly applies to cell clusters and chemotherapy drugs as taught by Jung and such that wherein the cell cluster is a normal cell cluster, and the effect exerted by the drug on the programmed cell death of cells included in the cell cluster is cytotoxicity of the drug as also taught by Jung because Jung motivates quantitative tracking of 3D cell clusters to advantageously expand the diagnostic capabilities of the method/device to tumor cell cluster cell death and drug toxicity by enabling the monitoring of therapeutic regiments including the efficacy and toxicity of chemotherapy drugs on cell clusters, because there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Claim 14
In regards to claim 14, Cotte is not relied upon to disclose but Jung teaches wherein the cell cluster is a cancer cell cluster, and the effect exerted by the drug on the programmed cell death of cells included in the cell cluster is anticancer activity of the drug. {see abstract and discussion including pg. 9 measuring cytotoxicity of carboplatin following a 72-hour incubation. Further as to anticancer activity see the determination of apoptosis which is the effect hopefully exerted by the drug on the cancer}.
It 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 to have modified Cotte which already discloses a method for determining a region of cells that have undergone programmed cell death in an observation object, using refractive index distribution data of the observation object and applies this method to a broad category of microscopic objects and biological specimens such as cells, multi-cellular biological samples, bulk tissue, and Circulating Tumor Cells (CTCs) which may be considered cell clusters and also discloses tracking the apoptotic response to the application of chemicals (drugs) such that the method more explicitly applies to cell clusters and chemotherapy drugs as taught by Jung and such that wherein the cell cluster is a cancer cell cluster, and the effect exerted by the drug on the programmed cell death of cells included in the cell cluster is anticancer activity of the drug as also taught by Jung because Jung motivates quantitative tracking of 3D cell clusters to advantageously expand the diagnostic capabilities of the method/device to tumor cell cluster cell death and drug toxicity by enabling the monitoring of therapeutic regiments including the efficacy and toxicity of chemotherapy drugs on cell clusters, because there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Conclusion
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/MICHAEL ROBERT CAMMARATA/Primary Examiner, Art Unit 2667
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