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 .
Claim Interpretation
The claims will be read under the broadest reasonable interpretation standard outlined in
MPEP § 2111.01.
Claim Objections
Claim 3 is objected to for the following informalities: “an agglutinate characterized by…” is cited without antecedent/distinguishing basis from the “an agglutinate” of claim 1. Claim 3 further recites “said agglutinated” without antecedent basis, which is presumed to be a typographical error for “said agglutinate”.
Claim 7 is objected to for the following informalities: “thus obtaining a subtraction image:” recites a colon where a semicolon would have been proper.
Claim 12 is objected to for the following informalities: “with serially diluted sample” is grammatically incorrect.
Claim 15 is objected to for the following informalities: “and/or wherein a test of the Widal Wright and Weil Felix type is performed” lacks grammatical correctness with respect to the nested structure of the claim.
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.
Claims 4, 11 and 14-15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
With respect to claim 4, the claim uses the phrase “such as” in multiple instances. The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 4 also recites “should no circular contour be identified as defined by the preceding steps…” in its final limitation. It is unclear whether “no circular contour” includes the “circular contour”, the “second circular contour”, the “single circular contour” previously introduced. The issue is further complicated, as in the limitation above, the “single circular contour” is referred with antecedent basis (possibly erroneously) as “said circular contour”, when “circular contour” was already reserved for “identify a circular contour” in the first limitation.
For the purposes of applying prior art to the claim, interpretations leading to clarity will be analyzed against the prior art.
With respect to claim 11, the claim recites: “cluster said centers based on said coordinates”. The nature of the clustering activity as recited is unclear – whether it involves a mathematical analysis of image data, or a physical activity with respect to the actual “centers”. For the purposes of applying prior art to the claim, both interpretations will be considered.
With respect to claim 14, the claim recites: “the positivity degree of the sample” without antecedent basis.
With respect to claim 15, the claim recites: “and/or wherein a test of the Widal Wright and Weil Felix type is performed, and wherein, when the sample is combined with a specific bacterial suspension, the step of extracting the metric features comprises the step of establishing whether or not there is any agglutinate in the image”. As recited, it is unclear whether the second portion of this recitation, “and wherein, when the sample is combined with a specific bacterial suspension, the step of extracting the metric features comprises the step of establishing whether or not there is any agglutinate in the image” exists within the contingency of the “Widal Wright and Weil Felix type” limitation, or is otherwise a separate limitation outside the same.
Additionally, the usage of multiple and/or clauses creates a separate issue of indefiniteness. The structure of the claim is: “Step 1 comprises: sub-step A, and/or B, and/or C”. As two and/or clauses are used, it is not clear whether the claim should make possible the following cases:
A and B, but not C
B and C, but not A
A and C, but not B
Or instead be read as only including:
A, B, and C
A, or B, or C.
For the purposes of applying prior art, these issues are moot due to the overarching recited contingency.
Claim 15 is further rejected by virtue of its dependency on claim 14.
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 1-6, 8-10, and 13-15 are rejected under 35 U.S.C. 101 because they are directed to ineligible patent subject matter. The claims are directed to the Abstract Idea grouping of mental processes under MPEP § 2106.04(a)(2)(III) and mathematical calculations under MPEP § 2106.04(a)(2)(I). These are judicial exceptions under Step 2A, Prong One of the framework established by the cases of Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 216, 110 USPQ2d 1976, 1980 (2014) and Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012). See MPEP § 2106.04(II).
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Step 1: The claims in question are directed to an apparatus and method for “performing serum agglutination tests.” Machines and processes are statutory categories. See MPEP 2106.03(I), “A machine is a "concrete thing, consisting of parts, or of certain devices and combination of devices." Digitech, 758 F.3d at 1348-49, 111 USPQ2d at 1719 (quoting Burr v. Duryee, 68 U.S. 531, 570, 17 L. Ed. 650, 657 (1863)). This category "includes every mechanical device or combination of mechanical powers and devices to perform some function and produce a certain effect or result." Nuijten, 500 F.3d at 1355, 84 USPQ2d at 1501 (quoting Corning v. Burden, 56 U.S. 252, 267, 14 L. Ed. 683, 690 (1854))”; See MPEP 2106.03(I), “NTP, Inc. v. Research in Motion, Ltd., 418 F.3d 1282, 1316, 75 USPQ2d 1763, 1791 (Fed. Cir. 2005) ("[A] process is a series of acts.") (quoting Minton v. Natl. Ass’n. of Securities Dealers, 336 F.3d 1373, 1378, 67 USPQ2d 1614, 1681 (Fed. Cir. 2003)). As defined in 35 U.S.C. 100(b), the term "process" is synonymous with "method."” (Step 1: Yes).
Step 2A, Prong One: As explained in MPEP 2106.04(II), a claim “recites” a judicial
exception when the judicial exception is “set forth” or “described” in the claim. Here, each
claim recites or depends upon the mental processes of controlling an image acquisition, extracting features from an image, verifying formation of agglutinate, identifying contours, taking measurements/recordings, and testing (Claim 1, “control the acquisition of an image…extract metric features…”; Claim 2, “verify that…an agglutinate…is formed”; Claim 4, “identify a…contour…measure a size…assign a numerical index…”; Claim 5, “perform a test…”; Claim 6, “verify…”; Claim 13, “verify…”; Claim 15, “a test…is performed”). The claims further recite or depend upon mathematical calculations (Claim 1, “calculate a numerical index…”; Claim 9, “establish the positivity…if said percentage value is above or below or equal to a pre-fixed threshold)
The claims are recited at a high level of generality and lack any specifics precluding such
an analysis from being interpreted under the mental processes grouping of “practically performed
in the mind” (see also MPEP § 2106.04(a)(2) identifying how e.g. a use of pen and paper, a ruler,
or a computer as a tool (to assist in visually/mentally analyzing/observing acquired
images/video) fails to preclude such an interpretation under the mental processes judicial
exception). Activities such as “the processing unit is configured to” therefore may be performed mentally, even if they may require the additional computer tool. Similarly, image-viewing and feature-extraction components do not elevate these claims past a mental process.
Regarding artificial intelligence (to the extent it is implicated by [0050] of the claimed invention’s specification), the claims are comparable to Claim 2 of Example 47 of the July 2024 PEG regarding subject matter eligibility (https://www.uspto.gov/sites/default/files/documents/2024-AISMEUpdateExamples47-49.pdf). As stated therein, an artificial intelligence’s analyses, detections, and reinforcement learnings may be practically performed in the human mind. To the extent mathematical calculations are required to operate and train the artificial intelligence in image analysis, the separate judicial exception is also implicated.
As such, the usage of a computer to extract features and calculate a determination does not elevate these claims beyond a mental process. (Step 2A, Prong One: Yes).
Step 2A, Prong Two: If Prong One of Step 2A is met, the examiner must consider (1)
whether there are any ‘additional elements’ recited in the claim beyond the judicial exception,
and (2) evaluate those additional elements individually and in combination to determine whether
the claim as a whole integrates the exception into a practical application. See MPEP §
2106.04(d).
Limitations the courts have found indicative of integration include: an improvement in
the functioning of a computer, or an improvement to other technology or technical field, as
discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a); applying or using a judicial exception to
effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in
MPEP § 2106.04(d)(2); implementing a judicial exception with, or using a judicial exception in
conjunction with, a particular machine or manufacture that is integral to the claim, as discussed
in MPEP § 2106.05(b); effecting a transformation or reduction of a particular article to a
different state or thing, as discussed in MPEP § 2106.05(c); and applying or using the judicial
exception in some other meaningful way beyond generally linking the use of the judicial
exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Limitations that the courts have found non-indicative of integration include: merely
reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including
instructions to implement an abstract idea on a computer, or merely using a computer as a tool to
perform an abstract idea, as discussed in MPEP § 2106.05(f); adding insignificant extra-solution
activity to the judicial exception, as discussed in MPEP § 2106.05(g); and generally linking the
use of a judicial exception to a particular technological environment or field of use, as discussed
in MPEP § 2106.05(h).
As an additional note, ‘additional elements’ are generally limitations excluded from
interpretation under the Abstract Idea groupings, and may comprise portions of limitations
otherwise identified as falling under those Abstract Idea groupings of the 2019 PEG (e.g. any
‘determination’ that may be made mentally by a user, neural network and/or generic computer hardware is considered under the ‘apply it’ considerations of 2106.05(f)). Any ‘providing’/outputting broadly, and ‘collection/input’ of data (i.e output display, basic gathering of image input, any learning model and/or data/images visually observable/ evaluated by a user/operator), also fail(s) to integrate at least in view of MPEP 2106.05(g) (extra-solution data gathering/output) and/or 2106.05(h) as ‘generally linking’ the exception to a field of use involving machine learning and/or imagery so acquired (e.g. the use of a computer to acquire said image broadly). The same determination holds for dependent claims that serve to limit the collection/output of data/images (by means of what is collected based on recited conditions) and/or introduce limitations generally linking to a field of use.
None of the instant claims appear to explicitly/clearly capture/recite any disclosed
improvement in technology (see MPEP 2106.05(a), with note that ‘functioning of a computer’
concerns functions integral to the way a computer operates and not ‘functions’ that a generic
computer can be programmed/adapted to perform (see also 2106.05(f))) and any ‘additional
elements’, even when considered in combination, fail to integrate at Prong Two of Step 2A
accordingly. Integration in view of subsection (a) requires an identification of the manner in
which the improvement is achieved, to be explicitly and specifically recited in the claims, as
‘additional elements’ precluded from interpretation under any of the Abstract Idea groupings
(since the improvement cannot be to the exception itself). With reference to MPEP 2106.05(a):
It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981))
As applicable here, additional limitations not directed to a judicial exception fail to
integrate at Prong Two of Step 2A. Claim 1 recites a “housing area…a plate…a plurality of wells…a sample…a processing unit…an image detector”. The incorporation of conventional computer and biomedical systems does little more than generally link the judicial exceptions of mental processes and mathematical calculation to a field-of-use and technological environment. See MPEP §§ 2106.05(h); 2106.05(f).
Even when viewed in combination, any additional elements present do not integrate the
recited judicial exception into a practical application (Step 2A, Prong Two: No), and the claims
are directed to the judicial exception. (Revised Step 2A: Yes → Step 2B).
Step 2B: If Prong Two of Step 2A is not met, the examiner must consider whether the
claim as a whole amounts to ‘significantly more’ than the recited exception, i.e., whether any
‘additional element’, or combination of additional elements, adds an inventive concept to the
claim. The considerations of Step 2A Prong 2 and Step 2B overlap, but differ in that 2B also
requires considering whether the claims feature any “specific limitation(s) other than what is
well-understood, routine, conventional activity in the field” (WURC) (MPEP § 2106.05(d)).
Such a limitation if specifically recited however, must still be excluded from interpretation under
any of the Abstract Idea groupings. Limitations not indicative of an inventive concept/‘significantly more’ include those that are not specifically recited (instead recited at a high level of generality), those that are established as WURC (a plurality of cited references serve to evidence the WURC nature of a limitation based at least in part on corroborating/additional ground data), and/or those that are not ‘additional elements’ by nature of their analysis at Prong One of Step 2A (i.e. directed to the exception – see above re. deciding that a second acquisition may be advantageous/desired). The July 2024 PEG describes that an improvement/ inventive concept (for ‘significantly more’ determination(s)) cannot be to the judicial exception itself.
The claims in question recite little beyond those limitations recited at a high level
of generality and falling under e.g. the mental processes Abstract Idea grouping, and would
monopolize the exception accordingly. The additional limitations of computer processing and apparatus structure as recited are WURC, as evidenced by the body of prior art cited by the examiner in this office action. (Step 2B: No).
Claim Rejections - 35 USC § 102
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, 8-9, 11-12, and 14 are rejected under 35 U.S.C. 102(a)(1)(2) and 35 U.S.C. § 102(a)(2) as being anticipated by Patel et. al (WO 2014015194 A3) (Hereinafter, “Patel”)
With respect to claim 1, Patel discloses:
An apparatus for performing serum-agglutination tests ([0076]; [0132]), comprising
a housing area configured to house a plate with a plurality of wells containing a sample to be analyzed ([0116]-[0117]; [0264])
a processing unit adapted to manage the apparatus ([0201])
at least one image detector in communication with the processing unit for acquiring images of the plate located in the housing area ([0015]; [0201] “The computer configured to analyze a set of images to measure the agglutination of the sample may be part of the same apparatus within the system as the camera that is configured to obtain a set of more than one image of the agglutination assay. The computer configured to analyze a set of images to measure agglutination of the same may be embedded within the system”)
wherein the processing unit is configured to ([0201])
control the acquisition of an image containing at least one reaction well ([0021]; [0209]; [0276]; [0306]-[0307])
extract metric features detectable in an agglutinate from said image (Fig. 6A; Fig. 6B; Fig. 8; Fig. 10; [0014]; [0036]; [0045]-[0047] “…the analyzing the image comprises feature extraction from a region of the image comprising imaged information of the mixture comprising visualization particles and agglutinating particles”; [0208]-[0212]; [0225]-[0231]; [0237]-[0240])
based on said metric features, calculate a numerical index indicative of the positivity degree of the sample in the well (Fig. 7; Fig. 9; Fig. 11; Fig. 13; [0033]; [0208]-[0212]; [0231]-[0232]; [0242]-[0244] “A more convenient way of representing the cluster sizes is by a so-called “Association Factor”, defined as…where the normalization is done relative to a minimum value, which may correspond to, for example, a control sample. In an essay involving various dilutions of a given sample, the mean cluster size can be plotted against the dilution factor for all samples to obtain a titer”), said calculation being performed with reference to a mapping wherein a determined numerical index corresponds to a determined metric feature (Fig. 11; Fig. 14; Fig. 19; Fig. 20; [0049]-[0050] “…analyzing the texture of the mixture comprises inputting information obtained from the local binary patterns information from one or more images of a mixture of known agglutination status comprising visualization particles and agglutinating particles”; [0232]; [0243]-[0247]; [0258]; [0327] “The support vector machine classifier was previously trained with information from images of known agglutination status (agglutinated or non-agglutinated)…”)
With respect to claim 8, Patel discloses:
The apparatus according to claim 1, wherein the processing unit is configured to preliminarily binarize the acquired image ([0231] “The dark area formed by red cells or visualization particles can be segmented by region growing methods or adaptive thresholding, generating a binary image containing a region corresponding to cell presence”)
With respect to claim 9, Patel discloses:
The apparatus according to claim 1, wherein the numerical index corresponds to a percentage value, and wherein the processing unit is configured to establish the positivity of a sample if said percentage value is above or below or equal to a pre-fixed threshold ([0211]; [0231]-[0232] “Sixth, when the % of total area of each of the button and teardrop regions (area A/(area A+ area B) and area B/(area A+ area B); Fig. 11, line marked by diamonds and line marked by squares, respectively) is plotted against the extent of agglutination, a clear calibrate-able response is obtained. The ratio of areas (B/A) (Fig. 11, line marked by triangles) may give a more sensitive response to agglutination. Alternatively the total area over threshold may be used as a measure of agglutination. A measure of agglutination may also be obtained by combining shape and intensity information”; Fig. 11)
With respect to claim 11, Patel discloses:
The apparatus according to claim 1, wherein the processing unit is configured to
identify single wells inside the plate by identification of circular contours having a certain radius ([0093]; [0207]-[0211] “Second, the image is oriented using pattern recognition techniques either by reference to fiducial marks on the assay wells or by recognition of the button or teardrop”; [0231] “The area and/or perimeter of the button and/or teardrop are measured. In some embodiments, for each known tube location the segmentation of the image can be initiated in the center of the tube. The dark area formed by red cells or visualization particles can be segmented by region growing methods or adaptive thresholding, generating a binary image containing a region corresponding to cell presence. The shape of the segmented area can be analyzed using the eigenvalues of the distribution, or alternatively by fitting a parametric shape such as an ellipse, or by calculating other shape parameters such as eccentricity or moments of inertia of the region”)
identify coordinates of the centers of said circular contours according to a Cartesian reference system ([0237] “The center-to-center distance of individual erythrocytes can be obtained based on, for example, internal calibration of the image with reference to the size of the red blood cells or visualization particle”; [0274]-[0276] “Upon transfer of the cuvette to the imaging platform, static registration features on the cuvette may interface with mating features on the imaging platform to align the cuvette parallel to the imaging platform's optical axis (X,Y registration)…A microscope stage may be connected to computer-controlled stepper motors to allow translation in the X and Y directions (e.g., horizontal directions). At every location, the desired number of images may be captured and the stage may be moved to the next XY position”)
cluster said centers based on said coordinates (Fig. 12; Fig. 13A; Fig. 13B; Fig. 20; [0035]; [0237]-[0240])
With respect to claim 12, Patel discloses:
The apparatus according to claim 1, wherein the processing unit is configured to acquire and process a plurality of images of a respective plurality of wells, each of said wells corresponding to a specific serial dilution of the sample therein contained ([0196]; [0266]; [0302]-[0304] “The sample was serially diluted by transferring 25 μΐ^ of the sample from the first well to the adjacent well containing 25 μΐ^ PBS/A/BSA. The steps were repeated until the last well in the series. This step is optional and may be replaced with a single dilution level”)
thus producing as output a titration curve in relation to the sample contained in said wells ([0242]-[0244]; [0322]-[0325] “The LOG of the antibody titer for the method of the disclosure samples was plotted against the LOG titer of the traditional method samples”; Fig. 13B; Fig. 17; Fig. 18)
wherein, for each dilution, the processing unit is configured to perform the classification of the sample ([0253]-[0255] “Methods provided herein may be used for both qualitative and quantitative assessment of agglutination status of a sample. For example, in embodiments, methods provided herein may be used to qualitatively classify samples of interest as either agglutinated or not agglutinated. In other embodiments, methods provided herein may be used to quantitatively classify sample of interest, such as by assessing the degree of agglutination of a sample…”)
wherein said processing unit is programmed to automatically identify, inside the plate and based on the instructions therein stored, a series of said wells with serially diluted sample and analyze said wells consecutively ([0199]; [0231]; [0264] “In some embodiments, analysis of sample and the assay reaction products are performed using digital imaging. The assay reaction vessels may be aligned for measurement and scanned or imaged in a single operation. In some embodiments, this is achieved automatically by mechanical components. Assay reaction vessels may be located at defined locations in a cartridge, device, or system and moved to a scanner/camera for imagining and/or analysis. In some embodiments, the orientation of the reaction vessels is kept constant as the reaction vessels are moved to a scanner/camera. In some embodiments, a scanner / camera may be moved to a reaction vessel”; [0276] “A microscope stage may be connected to computer-controlled stepper motors to allow translation in the X and Y directions (e.g., horizontal directions). At every location, the desired number of images may be captured and the stage may be moved to the next XY position”)
With respect to claim 14, it recites a method that captures functional steps of the apparatus of claim 1. As the apparatus of claim 1 is configured to perform the parallel method of claim 14, the claim is rejected as anticipated by Patel in line with the analysis above.
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 2, 4, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Patel in view of Tadashi et. al (WO 2018006050 A1) (Hereinafter, “Tadashi”)
With respect to claim 2, Patel teaches the apparatus of claim 1
Patel does not explicitly teach the further limitations of claim 2
However, Tadashi, in the same field of endeavor of sample analysis, teaches:
wherein the processing unit is configured to perform a test of the Treponema Pallidum Hemagglutination Assay Type ([0034]; [0136] “In other examples, TPHA can be used for detecting anti-Treponema antibody, which has brown color. This can be also detected by the system of the present disclosure in the same or similar manner”)
It would have been obvious to a person of ordinary skill in the art as of the effective filing date of the claimed invention to modify Patel to include the limitations of TPHA-type testing, as taught by Tadashi. Doing so would expand the functionality of the apparatus with respect to detecting anti-Treponema antibody. The systems readily integrate, as both are otherwise configured to analyze fluid samples using image analysis techniques.
With respect to claim 4, Patel/Tadashi teaches:
The apparatus according to claim 2, wherein the processing unit is configured to:
identify a circular contour having a size, such as for instance the perimeter, beyond a first pre-fixed threshold in the image (Patel, Fig. 6A; Patel, Fig. 6B; Patel, Fig. 8; Patel, Fig. 10; Patel, Fig. 14C; Patel, [0210]; Patel, [0220]; Patel, [0228]-[0231] “Fifth, pattern recognition methods are used to identify areas which correspond to the button, and, when present, the teardrop…The dark area formed by red cells or visualization particles can be segmented by region growing methods or adaptive thresholding, generating a binary image containing a region corresponding to cell presence”; wherein “circular contour” corresponds to initial area)
identify a second circular contour inside said circular contour (Patel, Fig. 6A; Fig. 10, region 1005 within 1000, and more specifically in its “Agglutinated” state in Fig. 6A, defined as a complete mass or a central mass and a tear that does not extend beyond region 610 after tilting; Patel, Fig. 14C; Patel, [0207]-[0208]; Patel, [0228]-[0231])
measure a size, such as the perimeter, of said second circular contour and assign a value proportional to said measured quantity to said numerical index (Patel, Fig. 6A; Patel, Fig. 10; Patel, Fig. 11; Patel, Fig. 14D; Patel, [0014]; Patel, [0065] “FIG. 11 shows a sample graph showing an analysis as in FIG. 10, which depicts the relationship between % area of Area A (1005) and Area B (1010), agglutination extent, and the ratio of Area B to Area A. The line marked by diamonds is Area A, the line marked by squares is Area B, and the line marked by triangles is the ratio of Area B / Area A”; Patel, [0228]-[0232])
should the second circular contour not be identified (i.e., in a case where the agglutinated mass of Fig. 6A is not formed/identified), identify a single circular contour having a size, such as for instance the perimeter, beyond a certain second threshold and, should said circular contour be identified, assign a numerical index equal to zero, said circular contour being representative of a negative sample (Patel, Fig. 6A; Patel, Fig. 9; Patel, Fig. 10, region 1010, indicative of “unagglutinated” at full extent; Fig. 11; Patel, Fig. 14B-14D; Patel, [0094]; Patel, [0213]; Patel, [0231]-[0232] “Sixth, when the % of total area of each of the button and teardrop regions (area A/(area A+ area B) and area B/(area A+ area B); Fig. 11, line marked by diamonds and line marked by squares, respectively) is plotted against the extent of agglutination, a clear calibrate-able response is obtained. The ratio of areas (B/A) (Fig. 11, line marked by triangles) may give a more sensitive response to agglutination. Alternatively the total area over threshold may be used as a measure of agglutination. A measure of agglutination may also be obtained by combining shape and intensity information”)
should no circular contour be identified as defined by the preceding steps, assign a numerical index equal to one hundred, representative of a positive sample (Patel, [0213]; Patel, [0224]; Patel, [0232]; Patel, Fig. 6A, agglutinated; Patel, Fig. 7; Patel, Fig. 9; Patel, Fig. 11; defining the “no circular contour” as the teardrop of Fig. 6A, and the 100% measure as full agglutinization)
With respect to claim 15, Patel/Tadashi teaches:
The method according to claim 14, wherein a test of the Treponema Pallidum Hemagglutination Assay type is performed (refer to analysis of claims 1, 2, and 14)
and wherein, when the sample is combined with treponemal antigens attached to avian erythrocytes, the step of extracting the metric features comprises the step of establishing whether an agglutinate characterized by a circular or semicircular shape is formed in the image of the well, and/or the presence of a circular or semicircular shape within the agglutinate is formed; and/or wherein a test of the Widal Wright and Weil Felix type is performed, and wherein, when the sample is combined with a specific bacterial suspension, the step of extracting the metric features comprises the step of establishing whether or not there is any agglutinate in the image (MPEP § 2111.04 – Contingent Limitations)
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Patel/Tadashi in view of Negash et. al Comparison of RPR and ELISA with TPHA for the Diagnosis of Syphilis: Implication for Updating Syphilis Point-of-Care Tests in Ethiopia (Hereinafter, “Negash”)
With respect to claim 3, Patel/Tadashi teaches:
The apparatus according to claim 2, wherein the processing unit is configured to verify that, when the sample is combined with Patel, [0009]; Patel, [0100]; Patel, [0164] “Suitable erythrocytes include, without limitation, avian erythrocytes, such as…”), an agglutinate characterized by a circular or semicircular shape is formed in the image of the well, and/or the presence of a circular or semicircular shape within said agglutinated is formed (Patel, [0206]-[0207]; Patel, [0211]; Patel, [0231])
Patel/Tadashi does not explicitly teach:
treponemal antigens attached to avian erythrocytes
However, Negash, in the same field of endeavor of TPHA, teaches:
treponemal antigens attached to avian erythrocytes ([2.3.3])
It would have been obvious to a person of ordinary skill in the art as of the effective filing date of the claimed invention to modify Patel/Tadashi to include the limitations of treponemal antigen attachment, as taught by Negash. Doing so implements a known method of preparing a reagent for the purpose of a TPHA-type assessment Patel/Tadashi is already configured to perform. The systems readily integrate, as Negash demonstrates that the prepared reagent forms characteristic circular patterns in wells, which complements the existing technique of Patel/Tadashi further.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Patel in view of Ferraz et. al (PT 106871 A) (Hereinafter, “Ferraz”)
With respect to claim 5, Patel teaches the apparatus of claim 1.
Patel does not explicitly teach the further limitations of claim 5
However, Ferraz, in the same field of endeavor of biomedical image analysis, teaches:
wherein the processing unit is configured to perform a test of the Widal Wright and Weil Felix type (Page 4, “These diseases can be detected in this new device and methodology, using also the existing tests 14 for each disease, including: Widal test; Wright test; Weil-Felix test (tick fever); VDRL (Syphilis); mononucleosis; Slidex MRSA and MSSA (nosocomial infections); Slidex Stepto Plus (streptococcus bacteria); Slidex Meningitis-KIT5 (Meningitis) and Slidex pneumotransport Kit (Pneumonia).”)
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify Patel to include the limitations of Widal Wright and Weil Felix testing, as taught by Ferraz. Doing so would increase the versatility of the device in analyzing additional disease information. The systems readily integrate, as Ferraz is also configured to analyze disease information from a well plate using image analysis.
With respect to claim 6, Patel/Ferraz teaches:
The apparatus according to claim 5, wherein the processing unit is configured to verify whether or not there is any agglutinate in the image when the sample is combined with a specific bacterial suspension (Patel, [0161]; Patel, [0296])
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Patel/Ferraz in view of Thomas (US 20130034272 A1) (Hereinafter, “Thomas”)
With respect to claim 7, Patel/Ferraz teaches:
The apparatus according to claim 5, wherein the processing unit is configured to acquire a first image at a first time and a second image at a second time (Patel, [0006]; Patel, [0029]; Patel, [0034])
calculate the numerical index indicative of the positivity degree of the sample Patel, [0015]; Patel, [0090])
Patel/Ferraz does not explicitly teach:
subtract the first image and the second image from each other pixel by pixel, thus obtaining a subtraction image
calculate the sum of the pixels different from zero in said subtraction image
calculate the numerical index indicative of the positivity degree of the sample based on said sum
However, Thomas, in the same field of endeavor of cellular image analysis, teaches:
wherein the processing unit is configured to acquire a first image at a first time and a second image at a second time ([0008])
subtract the first image and the second image from each other pixel by pixel, thus obtaining a subtraction image ([0014]-[0015]; [0038]; [0050]; Fig. 2)
calculate the sum of the pixels different from zero in said subtraction image ([0064] “Cardiomyocyte beat frequency was confirmed mathematically using correlation analysis (FIG. 10) by calculating the sum of absolute differences between the series of mean pixel intensity values over 113 frames (FIG. 8) and the same data series shifted in one frame increments”; noting the phrase “comprising” allows for the inclusion of zero values as well)
calculate the numerical index indicative of the positivity degree of the sample based on said sum ([0058]; [0064])
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify Patel/Ferraz to include the limitations of subtraction imaging, as taught by Thomas. Doing so would provide a specific means to calculate exact changes over time with regards to cellular motion. The systems readily integrate, as Thomas represents a function which improves the overarching goal of Patel/Ferraz (classification of samples through cellular motion) through a specific implementing technology.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Patel
With respect to claim 10, Patel teaches:
The apparatus according to claim 9, wherein said threshold is adjustable ([0232] “Alternatively the total area over threshold may be used as a measure of agglutination”; MPEP § 2144.04(V)(D), Legal Precedent as Source of Supporting Rationale – “Making Adjustable”, where the advantages of using a different evaluation threshold in accordance with a desired degree of confidence would have been obvious to a person of ordinary skill in the art. Patel does not advocate for any specific threshold value, so any person of ordinary skill in the art seeking to implement Patel’s method would necessarily need to select a user-chosen (adjusted) threshold value)
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Patel in view of European Federation for Immunogenetics Standards for Histocompatibility & Immunogenetics Testing (Hereinafter, “EFI”) and Kasahara (US 20140193038 A1) (Hereinafter, “Kasahara”)
With respect to claim 13, Patel teaches the apparatus of claim 1
Patel does not explicitly teach the further limitations of claim 13
However, EFI, in the same field of endeavor of cell-testing, teaches:
verify the actual presence of the plate (Page 20, maintaining proper orientation necessarily verifies actual presence of the plate)
verify that said plate is the plate associated with a set test (Page 20, “Sample identity and proper plate orientation must be maintained throughout the procedure”)
verify the orientation of the plate (Page 20, “Sample identity and proper plate orientation must be maintained throughout the procedure”)
It would have first been obvious to a person of ordinary skill in the art as of the effective filing date of the claimed invention, to modify Patel to include the limitations of plate verification, as taught by EFI. Doing so would ensure proper stability and identity of the sample to be analyzed, ensuring accuracy of the final output. The systems readily integrate, as EFI relates to the analysis of similar cell plate arrays.
Patel/EFI does not explicitly teach:
wherein, based on an acquired image, the processing unit is configured to:
However, Kasahara, reasonably pertinent to the problem of image analysis, teaches:
wherein, based on an acquired image, the processing unit is configured ([0123]) to:
verify the actual presence ([0087]; Fig. 7; by virtue of confirming orientation)
verify that said ([0087]; Fig. 7)
verify the orientation ([0087] “As one example, the recognition unit 150 may process the input image in keeping with the posture of the template that matches the input image so that the corresponding surface of the object directly faces the image pickup plane and then subject the processed input image to OCR or matching against existing images”; Fig. 7; while not explicitly for confirming the orientation of the object, the underlying method can be utilized to the same effect as shown below)
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It would have been further obvious to a person of ordinary skill in the art as of the effective filing date of the claimed invention to modify Patel/EFI to include the limitations of automation and image analysis, as taught by Kasahara. See MPEP § 2144.04(III) Legal Precedent as Source of Supporting Rationale – “Automating a Manual Activity”. A person of ordinary skill in the art would appreciate the advantages of automation, for ensuring accuracy and reducing the requirements of human labor. The underlying image analysis as recited is conventional and integrates to predictable success.
Additional References
Additionally cited references (see attached PTO-892) otherwise not relied upon above have been made of record in view of the manner in which they evidence the general state of the art.
Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NOAH WILLIAM BOYAR whose telephone number is 571-272-8392. The examiner can normally be reached 10:00 AM – 6:00 PM EST, Monday – Friday.
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/NOAH W BOYAR/Examiner, Art Unit 2669
/CHAN S PARK/Supervisory Patent Examiner, Art Unit 2669
