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 .
DETAILED ACTION
This action is a Final Office Action, based on new grounds under 35 U.S.C. §103 over Marcelpoil in view of Hejblum et al., and Bhargav et al., necessitated by Applicants’ amendment to claim 1 and added new claims 15 and 16, filed on 26 November 2025.
Claims 1, 3-8 and 10-16 are pending. Claims 8, 10-14 and 16 are withdrawn.
Claims 1, 3-7 and 15 are rejected.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. §119(e) or under 35 U.S.C. §120, §121, or §365(c) is acknowledged. As noted in the Non-Final Office Action mailed on 28 July 2025, this application is a 371 of PCT/EP2021/059030, filed 04/07/2021. Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. §119 (a)-(d).
Claims 1, 3-7 and 15 have the effective filing date of 07 April 2020.
Information Disclosure Statement
It was noted in the Non-Final Office Action mailed 28 July 2025 that foreign patent document citation WO 2019/063690 A1 was not being considered because no copy had been provided. However, Attorney Michael Gamble had indicated during a telephonic correspondence held on 20 November 2025 that such a copy had been provided. In re-reviewing the IDS references submitted by Applicant, it does appear that this foreign patent document had been provided.
Therefore, the IDS filed on 05 October 2022 as well as this document are being considered.
Claim Interpretations
(1) Applicant's method of determining susceptibility, as recited in claims 1, 3-7 and 15 appear to describe an algorithm to be used in determining a zone of inhibition produced when microorganisms (typically, bacteria) are subjected to antibiotic discs/disks or elements that have been placed on a plate or carrier spread with the bacteria; i.e., a classic antibiotic susceptibility test (AST).
The specification recites: "In the present context, susceptibility may depend on the type of cell/bacteria/microbe in question. Antibiotic susceptibility relates to the effect or efficiency which the antibiotic has on the microbe/bacteria. Antibiotic susceptibility may relate to the amount of antibiotic which will suffice to kill the microbe, such as within a predetermined period of time...Antibiotic susceptibility often is quantified by providing the antibiotic in an element, such as a tablet, disc or wafer, and position it on a growth medium in which the microbe is allowed to grow. A circle will form around the element if the antibiotic has an effect on the microbe. The size of the radius or diameter of the circle will determine or represent the antibiotic susceptibility of the microbe to the antibiotic...The carrier may be any type of carrier,..., such as a Petri dish...The medium preferably is a medium in which the microbe may grow and multiply....A frequently used test method is the Kirby-Bauer method" (originally-filed specification, pg. 2, lines 5-8; 11-15; and 20-26).
That is, without using the typical language/terminology associated with antibiotic susceptibility tests (ASTs), the terms or phrases cited in the instant claims refer to such a test. For example, 'a carrier' = a Petri dish or plate or other receptacle that can hold a bacterial medium (usually containing agar); 'bacteria' = bacteria/microbes/microorganisms; 'a composition affecting the bacteria or cells' = an antibiotic; 'a plurality of elements' = at least one antibiotic disc/disk; 'outline' = the outer circumference or boundary of a zone of inhibition; and 'a plurality of directions from the center of the at least one element' = the measurements taken from the center of the antibiotic disc/disk to some designated point within (or at the outer boundary of) the zone of inhibition, converted into pixel values, acquired by taking an image of the carrier.
Therefore, because the cited prior art uses the terminology associated with classic ASTs, this terminology will be used in the prior art rejections. Again, the instant specification does not refer to an 'antibiotic susceptibility test' or a 'zone of inhibition'.
(2) Claim 1 recites: "...determining the change in pixel value in a number of directions excluding directions toward one or more neighbouring elements, directions toward an edge of the carrier, and directions toward an overlap of a first area...and a second area...around a neighbouring element..."
Claim 1 recites direction conditions that are excluded in determining a change in pixel value. Therefore, prior art which is silent on the inclusion or exclusion of any of the features will be considered to be applicable prior art. That is, prior art which does not show any of the excluded directions will be considered to exclude the cited features.
Claim Rejections - 35 U.S.C. § 103
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 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 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 of this title, 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, 3-4, 7 and 15 are rejected under 35 U.S.C. §103 as being unpatentable over Marcelpoil (WO 2019/063690 A1) in view of Hejblum et al. (J. Clin. Microbiol. 1993, 31(9): 2396-2401), and Bhargav et al. (IEEE Intl. Conf. Adv. Computing, 2016, pp. 409-414).
Regarding claim 1, pertaining to a method of determining susceptibility, Marcelpoil shows a method in a processor for antibiotic susceptibility testing (pg. 2, para. [0007]).
Further regarding claim 1, pertaining to providing a carrier including a medium comprising cells, and a plurality of porous elements comprising a composition affecting the cells, Marcelpoil shows that a culture plate inoculated with a biological sample is provided. The culture plate has culture media and at least one antibiotic disk disposed thereon (pg. 2, para. [0007] [culture plate = carrier; culture media = medium; biological sample = bacteria or cells; plurality of elements = at least one antibiotic disk]). For example, in the case of agar, after a disk is placed, the antibiotic will migrate away from the disk over time. The migration will diffuse the antibiotic concentration according to the distance from the disk and the rate of diffusion for the antibiotic and medium (pg. 2, para. [0004] [i.e., a porous disk would allow for diffusion of the antibiotic away from the disk]).
Further regarding claim 1, pertaining to an outline formed around at least one porous element of the plurality of porous elements, Marcelpoil shows that the bacterial growth in the area around each antibiotic disk provides an indication of the effect of the particular antibiotic of the disk. For example, an effective antibiotic of a particular disk may have a large area that is free of growth of the tested bacteria (pg. 1, para. [0003] thru pg. 2, cont. para. [0003]). The size of the growth-free zone can provide an indication as to a minimum inhibitory concentration of the antibiotic of a nearby disk (pg. 2, para. [0004] [outline = large area that is free of growth or the growth-free zone]).
Further regarding claim 1, pertaining to providing an image of the carrier with the plurality of porous elements, the image including a plurality of pixels, each pixel of the plurality of pixels having a respective pixel value, Marcelpoil shows that first and second image data of the culture plate is generated with an image sensor. The first and second captured images are taken at separate times using image sensors. The image sensors are controlled to collect the desired image information (i.e., color, intensity, etc.). Pixel characteristic data is generated for pixels of the second image data from a comparison of the first image data and the second image data. The pixel characteristic data is indicative of microbial growth on the culture plate over time (pg. 2, para. [0007] thru pg. 3, cont. para. [0007]). FIG. 8 is a graph mapping growth (e.g., contrast) as a function of radial distance from the antibacterial disk D1 of FIG. 4, determined according to median pixel values (e.g., one or more of intensity, opacity, color, blurring, etc.) (pg. 6, para. [0026]; and Figures 4 and 8).
Further regarding claim 1, pertaining to determining a diameter of the outline formed around the at least one porous element by determining in a plurality of directions of the at least one porous element in the image, a respective distance from the centre to a change in pixel value in each respective direction of the plurality of directions from the centre, Marcelpoil shows that, for each disk, the process may evaluate the growth level modulation as a function of distance to the edge(s) of the antibiotic disk. Contrast information on a pixel by pixel basis, serving as pixel characteristic data, may be derived for the pixels of the second image of the plate relative to the first image of the plate. This characteristic data may include any one or more of intensity value, color value(s), grey value, opacity value and blurring value for each pixel of the evaluated image. These values may also be characterized according to their distance from a particular disk. Such a distance is illustrated in Fig. 9. For example, the pixels may be summarized as a function of distance, such as in a distance map (pg. 11, para. [0054]; and Figure 9). Figure 9 shows an outline of a no-growth zone, wherein the radius "d" is measured from the center of the disk (D1) to the edge of zone.
[It is noted that a diameter (d) may be calculated from a radius (r) (i.e., d = 2r).]
Example distance maps that are derived by a growth model may be considered in reference to the example map of FIGs. 10 and 11. In the example of Fig. 10, the distance map provides an estimation of a radial profile that is indicative of bacteria growth as a function of distance from a center of a particular disk. For this particular map, changes in gray value are associated with distances (e.g., pixel distance) from the edge of an antibiotic disk (pg. 13, para. [0059]).
Further regarding claim 1, pertaining to determining a distance from the centre where the most directions have the change in pixel value in the image and determining a susceptibility of the cells to the composition based on the distance, Marcelpoil shows that, with the polar transformation of the pixels of the image, intensity values may be summarized as a function of distance from the disk such as to form a distance map. For example, each column (xc) of n pixels (xc, y0 .. n) may be averaged where X-c represents a fixed pixel distance from the disk center or disk edge. The average for each distance Xc may then collectively provide the distance map. In addition to these intensity distance maps, other such maps may be formed with color value(s), grey values, opacity values and blurring values associated with the pixels of the image (pg. 11, para. [0056] thru pg. 12, cont. para. [0056]).
After a disk is placed, the antibiotic will migrate away from the disk over time. The migration will diffuse the antibiotic concentration according to the distance from the disk and the rate of diffusion for the antibiotic and medium. The antibiotic concentration will be highest near the disk. The concentration will decrease at further distances from the disk. Typically, the minimum inhibitory concentration can be considered the lowest concentration furthest from to the disk that includes an absence of bacterial growth (pg. 2, para. [0004]). Disks with different loads of a given antibiotic may be used and the respective growth patterns may be analyzed for a given susceptible organism (pg. 18, para. [0080]).
Marcelpoil does not specifically show that: 1) the step of determining excludes: a) directions toward one or more neighbouring elements; b) directions towards an edge of the carrier; and c) directions toward an overlap of a first area of pixel values around the at least one element and a second area of pixel values around a neighbouring porous element of the plurality of porous elements [Claim 1].
Hejblum et al. and Bhargav et al. provide information from which one of ordinary skill in the art of acquiring pixel data for antibiotic susceptibility testing, as shown by Marcelpoil, would have excluded the pixel value distances reflecting the directions toward any one of a), b) and/or c) above, by way of addressing the limitations of claim 1.
Hejblum et al. shows automated interpretation of disk diffusion antibiotic susceptibility tests (ASTs) with a radial profile analysis algorithm (pg. 2396, Title [nexus to Marcelpoil- method for performing antibiotic susceptibility testing]). After digitization of the petri plate image, each antibiotic disk is recognized and labeled. Pixels of the local zone around each disk are then used for generating a profile pattern that is subjected to decision rules. The resulting estimate of the inhibition zone diameter is then automatically compared with conventional breakpoints for classifying the tested strain in one of the clinical categories of antibiotic susceptibility (pg. 2396, Abstract [nexus to Marcelpoil- collect pixel values representing distance (radial profile) around the antibiotic disc]).
The estimate of the inhibition zone size is probably the most critical step in the design of a fully automated AST system. A pattern corresponding to each antibiotic disk is tested. The pattern analysis is based on the examination of a profile representing the mean grey-level value as a function of the distance from the disk. The estimate of the inhibition zone size obtained with the profile analysis is finally compared with conventional breakpoints recommended for susceptibility categorization, resulting in an automatic categorization of the organism as susceptible, intermediate, or resistant to the antibiotic tested (pg. 2396, column 1, para. 1 [nexus to Marcelpoil- determine susceptibility of the microorganism (to the composition affecting the microorganism)]).
Regrading claim 1, pertaining to excluding: a) directions toward one or more neighbouring elements, and b) directions towards an edge of the carrier, Hejblum et al. shows that the initial image of the petri plate was split into as many zones of analysis as there were identified disks. Each zone of analysis was composed of the pixels contained in a 35-mm-wide square centered by the disk. The square size was chosen to avoid neighborhood-disk interactions. In order to avoid borderline problems in the case of disks located at the periphery of the plate, only some of the pixels contained in the squares were selected for constituting the region of interest used for the profile building, depending on the disk position, as shown in Fig. 2. Then, for each disk, the radial profile of the corresponding region of interest was built as the calculated grey-level average of the selected pixels located at the same distance from the center of the disk (pg. 2397, column 2, lines 1-13; and Figure 2).
Bhargav et al. shows the measurement of the zone of inhibition of an antibiotic. In the Disk Diffusion Antibiotic Sensitivity test (The Kirby-Bauer test) a thin film of bacteria applied on a plate is subjected to various antibiotics. The Zone of inhibition is a circular area around the spot of the antibiotic in which the bacteria colonies do not grow. The zone of inhibition can be used to measure the susceptibility of the bacteria towards the antibiotic. The process of measuring the diameter of this Zone of Inhibition can be automated using Image processing (pg. 409, Title and column 1, Abstract [nexus to Marcelpoil, and Hejblum et al.- using imaging to determine zone of inhibition in an AST]).
Regarding claim 1, pertaining to c) excluding directions toward an overlap of a first area of pixel values around the at least one element and a second area of pixel values around a neighbouring porous element of the plurality of porous elements, Bhargav et al. shows that, as the color of the Zone of Inhibition is different, image processing can be used to detect the various available “circular” zones. Figure 2 shows that the circular areas are well defined. However as seen on the right side of Figure 2 there can be a case of overlap between two different zones (A and B in this case). There needs to be a separate algorithm which has to be used to detect overlapping zones (pg. 410, column 1, para. 1; and Figure 2). Overlapping of the zones is a very common feature in the antibiotic susceptibility test. Due to the addition of many antibiotics, the zones do overlap. The detection of the diameter of these is a little complicated as compared to the other cases. On the point where two or more edges meet, the gradient of the image (in both directions) has a high variation (pg. 412, column 1, para. 1-2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method of determining microbial susceptibility, as shown by Marcelpoil, by excluding: a) directions toward one or more neighbouring elements; and b) directions towards an edge of the carrier [Claim 1], as shown by Hejblum et al., with a reasonable expectation of success, because Hejblum et al. shows and/or suggests that, in building radial profiles for an antibiotic susceptibility test (AST), one should avoid acquiring data that would represent neighboring disk interactions, and shows that for each disk, in order to avoid directions toward the periphery of the plate, only some of the pixels (typically, those that represent the same distance from the center of the disk) are selected for building the radial profile (MPEP 2143 (I)(G)). Hejblum et al. shows interpretation of a disk diffusion AST, which is also shown by Marcelpoil.
In addition, it would have been further obvious to have excluded: c) directions toward an overlap of two areas of neighbouring elements [Claim 1], with a reasonable expectation of success, because Bhargav et al. teaches that this 'overlap' scenario requires a different algorithmic analysis vs the algorithm based on the determination of a measurable diameter representing an unbroken zone of inhibition circumference (e.g., compare Fig. 2I and Fig. 2II in Bhargav et al.). Overlapping zones is described in Bhargav et al. as a 'special case'. Therefore, one of ordinary skill in the art of determining a zone of inhibition in an AST would understand that pixel values representing directions toward an overlap (of two zones) should be avoided, and, therefore, be excluded in the final susceptibility determination analysis (MPEP 2143 (I)(G) and MPEP 2144 (I)).
However, even in the absence of Hejblum et al. and Bhargav et al., it would have been obvious to one of ordinary skill in the art of determining microbial susceptibility using an AST, that directions represented by a), b) and c) above would not be representative of the true diameter of the entire circumference of the zone of inhibition because they would all be shorter (or longer) than the true diameter, and, therefore, should be avoided or excluded. For example, Marcelpoil shows in Figure 9 an example of a radius (from the center of a disk/element to the circumference border/outline of a zone of inhibition) which avoids measuring the distance from the disk center to the edge of the plate- which would necessarily be shorter (or longer) than a radius representing the "true" diameter of the zone (MPEP 2144 (I)).
It can be extrapolated from Applicant's Figures 1 and 2 that directions: a) toward one or more neighboring elements; b) toward an edge of the carrier; and c) toward an overlap region of two neighboring elements would be shorter (or longer) than a direction representing the true diameter of the zone of inhibition (which Applicant refers to as "an outline" or "a circle").
One of ordinary skill in the art would have been motivated to have made those modifications, because, as taught by Hejblum et al. and Bhargav et al. and explained above, excluding directional measurements that would not represent the true diameter of the zone of inhibition in an AST would improve the accuracy of the diameter measurement, thereby allowing a more accurate determination of, for example, the efficacy or minimum inhibitory concentration of the antibiotic(s) used in the AST. Marcelpoil teaches that, typically, the minimum inhibitory concentration can be considered the lowest concentration furthest from the disk that includes an absence of bacterial growth (Marcelpoil, pg. 2, para. [0004]).
Regarding claim 3, Marcelpoil shows Figure 9 which is an image representation of the graph of FIG. 8 for a single disk of a plate (pg. 6, para. [0027]; and Fig. 9). Figure 9 shows an image of a/n (antibiotic) disk that is in a position toward the edge of the carrier/plate. It is clear from the image that the direction toward the edge of the plate, measured as a pixel value, would be lower than a distance representing the "true" radius (and, therefore, diameter) of the zone of inhibition (e.g., radius "d" in Fig. 9).
Regarding claim 7, Marcelpoil shows a method in a processor for antibiotic susceptibility testing. In the method, a culture plate inoculated with a biological sample is provided. The culture plate has culture media and at least one antibiotic disk disposed thereon (pg. 2, para. [0007]).
Regarding claim 15, Marcelpoil shows that a culture plate inoculated with a biological sample is provided. The culture plate has culture media and at least one antibiotic disk disposed thereon (pg. 2, para. [0007] [culture plate = carrier; culture media = medium; biological sample = bacteria or cells; plurality of elements = at least one antibiotic disk]). The bacterial growth in the area around each antibiotic disk provides an indication of the effect of the particular antibiotic of the disk. For example, an effective antibiotic of a particular disk may have a large area that is free of growth of the tested bacteria (pg. 1, para. [0003] thru pg. 2, cont. para. [0003]).
Regarding claim 4, Hejblum et al. shows that in order to avoid borderline problems in the case of disks located at the periphery of the plate, only some of the pixels contained in the squares were selected for constituting the region of interest used for the profile building, depending on the disk position. Then, for each disk, the radial profile of the corresponding region of interest was built as the calculated grey-level average of the selected pixels located at the same distance from the center of the disk (pg. 2397, column 2, lines 5-13). That is, Hejblum et al. shows that the radial profile corresponding to antibiotic disk susceptibility is acquired by repetitively or iteratively excluding grey-level pixel regions which were not located at the same distance from the center of the disk as the majority of the other pixel values measured.
Claims 5 and 6 are rejected under 35 U.S.C. §103 as being unpatentable over Marcelpoil in view of Hejblum et al., and Bhargav et al., as applied to claims 1, 3-4, 7 and 15 above, and further in view of Diab et al. (4th Intl. Conf. Adv. Biomed. Eng., 2017, pp. 1-4), and Wall et al. (Pub. No. GB 2344419A; Date of Pub.: 07.06.2000).
Marcelpoil in view of Hejblum et al., and Bhargav et al. do not show the steps of determining the distance as described in claims 5 and 6.
Diab et al. and Wall et al. provide information that would have motivated one of ordinary skill in the art of determining parameters for determining and interpreting a zone of inhibition in an antibiotic susceptibility test, as shown by Marcelpoil, to determine the distance from the center by ranking adjacent directions with a lower difference with a 'higher weight', by way of addressing claims 5 and 6.
Diab et al. teaches that the reading and interpretation of antibiogram tests is a frequently performed task by doctors, researchers and technicians at hospitals and laboratories. An antibiogram is a test of the sensitivity of a microorganism to given antibiotics. There are few automated devices that read and interpret antibiograms. The described study aims to present a prototype that reads and interprets antibiograms. In the study, an algorithm of detection and interpretation using recent image processing techniques is shown. Two principle techniques used for circles detection are the Circular Hough Transform (CHT) technique followed by the Pixel Value Checking (PVC) technique (pg. 1, column 1, Abstract; and column 2, Fig. 1 [nexus to Marcelpoil- determining microbial susceptibility with an AST [AST = antibiogram] using pixel values]).
Regarding claims 5 and 6, in order to detect the center of the inhibition zones, CHT is applied. The antibiotic disks have the same center as the inhibition zones so, once detected, the centers of the inhibition zones are detected too. Once the center of each inhibition zone is determined each pixel value is checked around the center in eight directions: up, down, left, right and diagonally in each of these directions (Figure 4) (pg. 2, column 2, last 2 para. thru pg. 3, column 1, lines 1-2 and Fig. 4).
Where the inhibition zones start and end can be easily detected in this manner. The algorithm allows the users to choose to use either the average of the eight radiuses or the maximum of them. Once the radius (diameter) of each zone is acquired, the calculated data is compared with a previously stored database that contains critical standard values for each antibiotic and bacteria. It is noted that the diameters detected are in pixels and not in mm, so in order to be able to compare them with the database a conversion from pixels to mm was done (pg. 3, column 1, para. 1-2).
The user can choose the threshold of difference between the pixel value and the maximum radius to be detected (Figure 7) (pg. 3, column 1, last line thru column 2, lines 1-2 and Fig. 7). The graphical user interface (GUI) allows the user to select between the average and maximum methods, select the threshold of difference between the pixel value and the maximum radius to be detected, in this way ensuring maximum accuracy and precision (pg. 3, column 1, para. 3).
That is, Diab et al. shows a protocol in which eight radii can be determined, and that either all of the eight adjacent radii can be used (as an average) or adjacent radii representing a desired or "determined" (maximum) distance can be used to calculate the "true" diameter representing the zone of inhibition (for maximum accuracy and precision).
Wall et al. shows examination and analysis of a microbiological test in which locations of a micro-organism in or on a nutrient gel can be differentiated for locations wherein growth is inhibited. Imaging of the surface roughness caused by the microbial growth using a camera produces a pixel map where the pixel values vary according to the surface roughness. The image pixel map is processed to emulate a multiplicity of differently orientated radial scans of a region of the surface, wherein a specified number of pixels in each scan line represents the same physical distance (Abstract [nexus to Marcelpoil, Hejblum et al., and Diab et al.- developing an algorithm for analyzing the results of an AST by determining at least one radius, as a radial scan, converted into pixel values and using distances which have the same pixel value]).
Regarding claims 5 and 6, Wall et al. shows that the basis of the described invention is the extraction of a multiplicity of line samples representing scans substantially along different directions across the region under examination, assembling the line samples to produce a notional image of the region such that the centre of the region is represented by a line and the periphery of the region is represented by a second line separated from the first. The processing may comprise, for example, replacing individual pixel elements by means of a weighted sum of the pixel values in the neighbourhood of the pixel element (pg. 2, lines 1-9). It is accordingly desirable to interpolate between some of the pixels in a line sample, specifically additional pixel elements of the same density as their neighbours, the number of interpolated pixels acquired being determined by a numerical algorithm (pg. 5, lines 2-5).
That is, Wall et al. shows that processing may include the replacing of individual pixels with a weighted sum of pixel values in the neighbourhood of the respective individual pixel (Wall et al., pg. 7, lines 22-24) (i.e., including adjacent directions or distances).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method of determining microbial susceptibility, as shown by Marcelpoil in view of Hejblum et al., and Bhargav et al., as applied to claims 1, 3-4, 7 and 15 above, by: 1) determining the distance by comparing the difference between a (pertaining) direction and an adjacent direction and allocating a higher weight for a lower difference [Claims 5 and 6], with a reasonable expectation of success, because both Diab et al. and Wall et al. show that a multiplicity of directions from the center (of the antibiotic disc/disk) can be determined (via imaging and pixel conversion), and also show that those directions exhibiting the same distance are preferentially included in an algorithmic determination of the overall diameter of the zone of inhibition (or some portion of the zone of inhibition) (MPEP 2143 (I)(G) and MPEP 2144 (I)).
Therefore, it would have been obvious to have preferentially included directions with a lower difference between them in a determination of the "size" of the zone of inhibition, because directions with a lower difference would indicate that they represent a more accurate pixel value of the distance that comprises the zone of inhibition. This is similar to the understanding that adjacent directions having the same pixel value would represent distances that most accurately describe the radius/diameter of the zone of inhibition (whereas anomalous distances would be considered to not be accurate).
For this reason, it would have been further obvious to have allocated a higher weight for a lower difference between adjacent directions, as shown by Wall et al., with a reasonable expectation of success, with the understanding that those directions which most accurately predict the radius/diameter should be given a 'higher weight' or attributed greater importance, because they most accurately predict the size of the zone of inhibition (MPEP 2143 (I)(G) and MPEP 2144 (I)).
However, even in the absence of Diab et al. and Wall et al., it would have been obvious to one of ordinary skill in the art of determining the zone of inhibition of an AST to have preferentially selected radius/diameter measurements which are the same pixel value (or which exhibited a small subtractive difference between pixel values) with the understanding that these measurement/direction/distance values would more accurately represent the actual radius/diameter of the zone of inhibition. For this same reason, it would have been obvious to have given such measurements a higher weight or assigned them a more favorable priority in their use to determine the size of the zone of inhibition (MPEP 2144 (I)).
One of ordinary skill in the art would have been motivated to have made that modification, because Wall et al. shows that one form of image improvement which may be employed is the conversion of each pixel element into a replacement element which is a weighted sum of the element and its immediate neighbours (Wall et al., pg. 5, lines 20-23).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s arguments, pp. 23-29, filed on 26 November 2025, with respect to the prior art references cited in the 35 U.S.C. §103 rejections, have been fully considered but they are either not persuasive or are moot because the arguments do not apply to the references as they are applied in the context of the current rejection, or as new grounds necessitated by Applicant’s amendment, in which claims 1 was amended, and new claims 15 and 16 were added.
1. Applicant remarks (pg. 24, para. 1) that with regard to FIG. 9 of Marcelpoil (reproduced below), Marcelpoil illustrates that directions from the centre of the at least one porous element toward: a) one or more neighboring porous elements; b) an edge of the alleged carrier in the image; and c) an overlap of a first area of pixel values and second area of pixel values give wrong distances, but Marcelpoil does not notice this or describe this and thus does not exclude these directions when determining the distance. Applicants submit that Marcelpoil does not give one having ordinary skill in the art any hints relating to excluding these directions. There is no teaching or suggestion in Marcelpoil to exclude such directions in the determination of the diameter of an outline formed around the at least one porous element that includes determining the change in pixel value in a number of directions.
However, in response to Applicant, it appears that Applicant's statement (that Marcelpoil illustrates that directions that give wrong distances) is considered to be so-called "opinion evidence". It is well known that to be of probative value, any objective evidence should be supported by actual proof. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) (MPEP 716.01(c)(I)(II)). In addition, the limitations of claim 1 which describe the various excluded directions or distances are not addressed by Marcelpoil, but by the references of Hejblum et al. and Bhargav et al. (see 103 rejection above).
2. Applicant's remark (pg. 25, para. 2 thru pg. 26) that Applicants note that Hejblum relates to a method of determining the diameter of a profile where the mean pixel value in a diameter around the tablet centre is plotted. Hejblum neither describes nor explains overlap between zones or with the disc edge. The image analysis of Hejblum consists of dividing the image into squares which is used to avoid interactions between neighbouring tablets and where pixels representing are deleted when representing the surroundings of the disc and the disc edge. Hejblum does not propose excluding the change in pixel values in these directions when determining the change in pixel value in multiple directions to determine the diameter of the outlet around the porous element- not using the portions of the image which represent the disc edge and the surroundings.
However, in response to Applicant, Hejblum et al. shows a templated approach to antibiotic disk testing by using a square size which was chosen to avoid neighborhood disk interactions. The porous elements were placed on this template and diffusion circles were formed around each (round) porous element (i.e., antibiotic disk). Therefore, Hejblum et al. teaches to the method of Marcelpoil that neighboring disk interactions can be excluded- while maintaining an accurate measurement of antibiotic disk efficacy.
3. Applicant remarks (pg. 27, para. 1) that Bhargav determines the tablet diameter by determining the area around the tablet and determines the diameter from said area. This has the advantage that uneven contours are not problematic. Bhargav describes that overlaps are seen and that these are handled by finding the corners (the intersections of the two circles) and completing the circles using a straight line between these intersections. Thus, the directions (a), (b), and (c) as required by claim 1 are not excluded but the contour is deliberately given a shape which would not conform to the circle. Therefore, Bhargav is aware that overlaps take place but deliberately does NOT exclude the directions to these overlaps. Instead another solution is chosen which is completely different from what is required by claim 1.
However, in response to Applicant, Bhargav et al. is cited to address the "third" (or (c)) excluded measurement. Hejblum et al. addresses exclusions (a) and (b). Bhargav et al. teaches that there can be a case of overlap between two different zones; however, Bhargav et al. also teaches that a separate algorithm needs to be used to detect overlapping zones and concedes that the detection of the diameter of overlapping zones is a little complicated as compared to the other cases. That is, because Bhargav et al. teaches that an algorithm is required to detect overlapping zones (e.g., in order to eliminate them from any antibiotic efficacy assessment) and that overlapping zones present a complication, Bhargav et al. provides motivation for excluding pixel values representing an overlapping area around neighboring porous elements.
4. Applicant remarks (pg. 27, para. 2 thru pg. 28) that Applicants submit that even a modification of Marcelpoil in view of Hejblum and Bhargav would not teach or suggest a determination of a diameter of the outline formed around the at least one porous element that includes determining the change in pixel value in a number of directions excluding directions: (a) towards one or more neighboring porous elements; (b) toward an edge of the carrier; and (c) towards an overlap between a first area and a second area of pixel values of neighboring porous elements. Applicants submit that there is no teaching or suggestion of the specific exclusion of the directions as required by claim 1.
However, in response to Applicant, it is clear from the cited prior art with regard to antibiotic susceptibility testing (specifically, via use of the disk diffusion method) that there are diffusion results that (may) pose a problem in analyzing the susceptibility data with regard to the zones of inhibition surrounding each of the disks. Therefore, it would have been obvious to have to have excluded these scenarios from the determination of antibiotic efficacy. MPEP 2143 (I)(G) states: Examples of rationales that may support a conclusion of obviousness include:...(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention." That is, limitations intended to be excluded would be supported by prior art which disparages said limitations.
5. Applicant remarks (pg. 28, para. 3 thru pg. 29), with regard to the rejection of claims 5 and 6 in view of Diab et al., that claims 5 and 6 depend from claim 1. As indicated above, Applicants submit that claim 1 is patentable over Marcelpoil in view of Hejblum and Bhargav. Applicants submit further that the Office does not show how claim 1 is unpatentable over Marcelpoil in view of Hejblum and Bhargav and further in view of Diab. Applicants submit that claims 5 and 6 are patentable at least by virtue of dependence from claim 1.
However, in response to Applicant, the limitations of claims 5 and 6 were addressed by both Diab et al. and Wall et al. Applicant does not argue that these prior art references did not address the limitations of claims 5 and 6.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/SMP/Examiner, Art Unit 1657
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