ADETAILED 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 .
Status of the Claims
Currently, claims 1-16 are pending in the application. Claims 1, 15 and 16 are amended.
Continued Examination Under 37 CFR 1.114 1.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/12/2026 has been entered.
Response to Arguments / Amendments
Applicant's arguments filed have been fully considered but they are not persuasive.
Kalkbrenner does not teach or suggest "recording an overview image, in which a sample carrier of the one microscope and/or a sample carrier environment of the one microscope is at least partially visible, evaluating the overview image by way of an image analysis to locate at least one suitable region, . . . based on a type of the manipulation, determining a manipulation position within the at least one suitable region of the one microscope, the manipulation position being suitable for positioning and/or arranging an objective of the one microscope and/or a table of the one microscope," as recited in present claims 1, 15-16.
As to the above argument, Kalkbrenner discloses recording an overview image, in which a sample carrier of the microscope and/or a sample carrier environment is at least partially visible with image data of a specimen are captured or capturable by means of the first objective and the second optical axis (([0021], ) and specimen lies on the first optical axis and at which at least one image of the specimen or of a region of the specimen is captured or can be captured by means of the first objective ([0059).
Kalkbrenner further discloses determining a manipulation position within the at least one suitable region of the one microscope with a specimen is imaged arranged in or on the specimen carrier & the specimen plane extends horizontally, although it also can be provided in other spatial planes in further embodiments of the microscopy arrangement [suitable region] ([0023], [0041]) and manipulation position being suitable for positioning and/or arranging an objective of the one microscope and/or a table of the one microscope positioning the specimen 8 relative to the optical axis 2.1, 4.1 at the respective measuring position P1, P2 and transporting the specimen 8 between the measuring positions P1, P2. Consequently, the specimen 8 never leaves the reference coordinate system of its specimen holder 7. The three-dimensional positioning of the specimen 8, i.e., relative to the axes x, y and z, is facilitated by setting and continuously establishing the reference point 11 ([0068], FIGS. 1a and 1b).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample slide preferably is imaged repeatedly in adjacent areas or is passed in a scanning sweep through the image acquisition as the stage is advanced in the X and Y direction to a position in which an adjacent area ([0084]) and various image collection processes wherein adjacent images are collected to be assembled into a montage or mosaic of strips, tiles or other shapes, wherein the process produces overlapping margins that are optionally useful for aligning and/or stitching together the adjacent images and the one (single) microscope ([0083] FIG. 1; [0130]).
Henderson also teaches subject being imaged is a pathology specimen slide of which a plurality of microscopic digital pictures are taken by snapshot or scanning or similar techniques that produce an overlapping area such as a margin of overlap at adjacent edges and each of the digital pictures corresponds to a respective said limited area. The plurality of microscopic digital pictures together encompass all or at least a predetermined portion of the specimen or specimen slide including the specimen ([0126]).
On the top of the foregoing, Stumpe teaches the one (single) microscope ([0135], a microscope having a stage for holding a slide containing a biological sample, at least one objective lens, and an eyepiece, a digital camera capturing magnified digital images of the sample as seen through the eyepiece of the microscope).
It should be further noted that Applicant has not presented any specific arguments with regards to the rejections of the dependent claims.
Accordingly, Examiner maintains the rejection with regards to above arguments.
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 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, 2, 9-13 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Kalkbrenner et al. (US 20190056579, hereinafter Kalkbrenner) in view of Henderson et al. (US 20110249910, hereinafter Henderson) and Stumpe (US 20210224541, hereinafter Stumpe).
Regarding Claim 1, Kalkbrenner discloses a method for the determination of a manipulation position of
recording an overview image, in which a sample carrier of the microscope and/or a sample carrier environment is at least partially visible ([0021], image data of a specimen are captured or capturable by means of the first objective and the second optical axis; [0059], specimen lies on the first optical axis and at which at least one image of the specimen or of a region of the specimen is captured or can be captured by means of the first objective),
evaluating the overview image by way of an image analysis to locate at least one suitable region in which a manipulation can take place in the sample-the microscope ([0022], receive and hold a specimen carrier is introduced into a specimen plane of the first microscope that is intersected by the first optical axis and onto the optical axis of the first microscope; [0036], capture the images is focused along the optical axis before or during the capture of the image data; [0075] FIG. 2, detection beam paths are superposed on one another and the distances of the measuring positions are selected in such a way that the specimen planes from measurement positions are imaged on a common image plane on the detector by the tube lenses with different focal lengths),
when at the least one suitable region has been located:
based on a type of the manipulation, determining a manipulation position within the at least one suitable region of the ([0021], image data of a specimen are captured or capturable by means of the first objective and the second optical axis is given by the further objective, situated in the working position of the further microscope [0023], [0041], a specimen is imaged arranged in or on the specimen carrier & the specimen plane extends horizontally, although it also can be provided in other spatial planes in further embodiments of the microscopy arrangement [suitable region]), the manipulation position being suitable for positioning and/or arranging an objective of the one microscope and/or a table of the one microscope ([0068], FIGS. 1a and 1b, positioning the specimen 8 relative to the optical axis 2.1, 4.1 at the respective measuring position P1, P2 and transporting the specimen 8 between the measuring positions P1, P2. Consequently, the specimen 8 never leaves the reference coordinate system of its specimen holder 7. The three-dimensional positioning of the specimen 8, i.e., relative to the axes x, y and z, is facilitated by setting and continuously establishing the reference point 11, [0069], a scanning microscope with a manipulation unit for manipulating the specimen 8 by means of beams, by means of acoustic elements and/or by means of mechanical elements)
determining a travel movement of the objective of the ([0024], [0025], the specimen plane is an intrinsic feature of the respective microscope or the currently used objectives and is preferably given by a respective focal plane of the microscope that includes setting a reference point [determining a travel movement]that coincides with the optical axis and establishing coordinates of the set reference point; [0027] the control commands the further delivery movement of the carrier apparatus is controlled such that the carrier apparatus is positioned in such a way that the reference point coincide with the further optical axis),
moving the objective of the one microscope and/or the table of the one microscope movement to the manipulation position based on the previously determined travel ([0027], control commands are generated for the delivery movement of the carrier apparatus [moving the table of the microscope] is controlled such that the carrier apparatus is positioned in such a way that the reference point coincide with the further optical axis depending on the differences established in the comparison between the current coordinates of the reference point and the coordinates of the optical axis of the further microscope) , and
executing the manipulation in the sample([0028], continuously capturing the coordinates of the carrier apparatus and the coordinate of a specimen therewith that ensures the specimen never leaves the reference coordinate system and that each region of the specimen is retrieved and targeted without special markings).
Kalkbrenner disclose manipulation in the sample by receiving and holding a specimen carrier is introduced into a specimen plane of the first microscope that is intersected by the first optical axis and onto the optical axis of the first microscope ([0022]).
However, Kalkbrenner does not explicitly disclose manipulation of in the vicinity or adjacency region of the sample and the one (single) microscope.
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084], slide preferably is imaged repeatedly in adjacent areas or is passed in a scanning sweep through the image acquisition as the stage is advanced in the X and Y direction to a position in which an adjacent area; [0130], various image collection processes wherein adjacent images are collected to be assembled into a montage or mosaic of strips, tiles or other shapes, wherein the process produces overlapping margins that are optionally useful for aligning and/or stitching together the adjacent images) the one (single) microscope ([0083] FIG. 1, a single microscope image acquisition arrangement in digital pathology).
Henderson also teaches subject being imaged is a pathology specimen slide of which a plurality of microscopic digital pictures are taken by snapshot or scanning or similar techniques that produce an overlapping area such as a margin of overlap at adjacent edges and each of the digital pictures corresponds to a respective said limited area. The plurality of microscopic digital pictures together encompass all or at least a predetermined portion of the specimen or specimen slide including the specimen ([0126])
Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of manipulation of in the vicinity or adjacency region of the sample as taught by Henderson ([0130]) into the microscope system of Kalkbrenner in order to provide a system to selectively test the accuracy of focus at two or more Z axis spacings, enabling the device at least once per slide to select an optimal focal distance (Henderson, [0084]).
Furthermore, the teaching of the prior art of one (single) microscope is one of very well-known techniques in the art.
For instance Stumpe teaches the one (single) microscope ([0135], a microscope having a stage for holding a slide containing a biological sample, at least one objective lens, and an eyepiece, a digital camera capturing magnified digital images of the sample as seen through the eyepiece of the microscope).
A person of ordinary skill in the art would have recognized that applying the known technique of one (single) microscope would have yielded predictable results of an improved microscope system and method for assisting a pathologist in classifying biological samples such as blood or tissue (Stumpe, [0002]).
Regarding Claim 2, Kalkbrenner view of Henderson and Stumpe and Stumpe discloses the method as claimed in claim 1,
Kalkbrenner discloses wherein a manipulation in the sample([0075],a dedicated microscope 1, which does not allow, or only allows to restricted extent, conventional microscopy method steps such as objective interchange, recording of an overview image, alternative contrasts (DIC (differential interference contrast), phase contrast, polarization contrast, etc.), is situated at the measuring position P1).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084]; [0130]) and the same reason or rational of obviousness motivation applied as used above in claim 1.
Regarding Claim 9, Kalkbrenner view of Henderson and Stumpe discloses the method as claimed in claim 1,
Kalkbrenner discloses wherein for locating at least one suitable region, for assessing multiple located regions, and/or for determining the manipulation position, one or more of the following items of context information the presence or absence of exchangeable components of the microscope, the type and size of exchangeable components of the microscope, the presence or absence of an incubator, the type of the stand, the type of an immersion medium, the type of the manipulation tool, the type and parameters of the observation task, the quality of the workspace, the illumination conditions at the workspace, the examined type of sample, a microscopic image from the experiment, the type and quality of the table, and/or the following items of user information the handedness of a user, an ascertained preference of a user, a prior correction and/or selection of a user with respect to a determined travel movement are taken into consideration ([0034], the coordinates of the reference point are compared to setpoint coordinates of a target point to be targeted on the optical axis of the further microscope. Depending on the differences established by means of the comparison between the current coordinates of the reference point and the coordinates of the target point, control commands are generated and the further delivery movement of the carrier apparatus is controlled by means of the control commands such that the carrier apparatus is positioned in such a way that the reference point coincides with the target point).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084]; [0130]) and the same reason or rational of obviousness motivation applied as used above in claim 1.
Regarding Claim 10, Kalkbrenner view of Henderson and Stumpe discloses the method as claimed in claim 1,
Kalkbrenner discloses wherein the movement of the objective and/or the table of the microscope is carried out automatically based on the previously determined travel movement, or the travel movement is output to a user for the manual adjustment of the objective and/or the table of the microscope ([0034], the coordinates of the reference point are compared to setpoint coordinates of a target point to be targeted on the optical axis of the further microscope. Depending on the differences established by means of the comparison between the current coordinates of the reference point and the coordinates of the target point, control commands are generated and the further delivery movement of the carrier apparatus is controlled by means of the control commands such that the carrier apparatus is positioned in such a way that the reference point coincides with the target point).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084]; [0130]) and the same reason or rational of obviousness motivation applied as used above in claim 1.
Regarding Claim 11, Kalkbrenner view of Henderson and Stumpe discloses the method as claimed in claim 1,
Kalkbrenner discloses wherein the determination of a travel movement includes a movement of a motorized component which is in contact or is to be brought into contact with the sample ([0078] use filter devices for both beam paths together, said filter devices being able to be introduced into, or removed from, the respective beam paths in a manual or motor-driven manner).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084]; [0130]) and the same reason or rational of obviousness motivation applied as used above in claim 1.
Regarding Claim 12, Kalkbrenner view of Henderson and Stumpe discloses the method as claimed in claim 1,
Kalkbrenner discloses wherein before the movement of the objective, a table, and/or a motorized component in contact or to be brought into contact with the sample, the resulting position of the objective, the table, and/or a motorized component is compared to stored permitted position ranges and a warning is output if the resulting position of the objective, the table, and/or a motorized component is outside the permitted position range ([0079], the specimen 8 is moved between the measuring positions P1 and P2 by means of the common transporting apparatus that allows both the change in position in the x-direction and the fine positioning of the specimen 8 at the respective measuring positions P1, P2 in the x-, y- and z-direction . It also includes focusing (z-direction), and so, for example, two dedicated measuring positions P1, P2 can be linked to one another by means of the solution according to the invention and it is possible to dispense with the z-drive, for example for focusing the objectives 2, 4 or an objective interchange device; [0027]).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084]; [0130]) and the same reason or rational of obviousness motivation applied as used above in claim 1.
Regarding Claim 13, Kalkbrenner view of Henderson and Stumpe discloses the method as claimed in claim 1,
Kalkbrenner discloses wherein the execution of the manipulation, in particular an immersion, is carried out automatically ([0027], control commands are generated for the delivery movement of the carrier apparatus [moving the table of the microscope] is controlled such that the carrier apparatus is positioned in such a way that the reference point coincide with the further optical axis depending on the differences established in the comparison between the current coordinates of the reference point and the coordinates of the optical axis of the further microscope).
Henderson teaches wherein manipulation of in the vicinity or adjacency region of the sample ([0084]; [0130]) and the same reason or rational of obviousness motivation applied as used above in claim 1.
Regarding Claims 15, microscopy system claim 15 of using the corresponding method claimed in claims 1, and the rejections of which are incorporated herein for the same reasons of obviousness as used above.
Regarding Claims 16, computer program claim 16 of using the corresponding method claimed in claims 1, and the rejections of which are incorporated herein for the same reasons of obviousness as used above.
Claims 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over Kalkbrenner et al. (US 20190056579, hereinafter Kalkbrenner) view of Henderson , Stumpe and Finkbeiner et al. (US 20150278625, hereinafter Finkbeiner).
Regarding Claim 3, Kalkbrenner view of Henderson and Stumpe disclose the method he method as claimed in claim 1, but does not explicitly disclose wherein the image analysis is carried out by a machine learning model of a computer program, which locates the at least one region suitable for a manipulation in the sample
Finkbeiner teaches wherein the image analysis is carried out by a machine learning model of a computer program, which locates the at least one region suitable for a manipulation in the sample([0171], automated robotic microscopy systems having individual results from the individual pipelines are combined using any convenient method, such as absolute classification (e.g., requiring positive identification of an area as a neuron by all pipelines for the object to be classified as a neuron), or fuzzy classification (e.g., via voting and/or a weighted combination of the results of the individual pipelines). Such combinations and classifications may involve applying one or more statistical or learning machine algorithms, such as genetic algorithms, neural networks, hidden Markov models, Bayesian networks, support vector machines, and the like )
Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of the image analysis is carried out by a machine learning model as taught by Finkbeiner ([0171]) into the microscope system of Kalkbrenner in order to provide automated robotic microscopy systems that facilitate high throughput and high content analysis of samples, including biological samples such as living cells and/or tissues (Finkbeiner, [0003]).
Regarding Claim 4 and 5, Analogous rejection as the rejection of Claim 3 applies.
Finkbeiner teaches automated robotic microscopy systems having individual results from the individual pipelines are combined using any convenient method, such as absolute classification (e.g., requiring positive identification of an area as a neuron by all pipelines for the object to be classified as a neuron), or fuzzy classification (e.g., via voting and/or a weighted combination of the results of the individual pipelines). Such combinations and classifications may involve applying one or more statistical or learning machine algorithms, such as genetic algorithms, neural networks, hidden Markov models, Bayesian networks, support vector machines, and the like ( [0171] )
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Finkbeiner further teaches sample imaging subsystem, which includes an imaging device 206 (optical scanner or microscope), robotic arm 204 of the sample transport subsystem returning the sample to the incubator 201 of the bulk sample storage subsystem, placing the sample back on the holder contained in the sample identification subsystem [0078] and the image processor 207 includes a processor configured to execute instructions from software modules to organize the images taken of the sample; stitch the images together; align the images; identify objects (e.g., cells, such as neurons) within the images; track an object (e.g., a cell, such as a neuron) through a temporal series of images; extract data (e.g., fluorescence data) from objects identified within an image; and/or analyze the resulting images ([0079]).
Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of the image analysis is carried out by a machine learning model as taught by Finkbeiner ([0171]) into the microscope system of Kalkbrenner in order to provide automated robotic microscopy systems that facilitate high throughput and high content analysis of samples, including biological samples such as living cells and/or tissues (Finkbeiner, [0003]).
Regarding Claim 6, Analogous rejection as the rejection of Claim 3 applies.
Finkbeiner teaches automated robotic microscopy systems having individual results from the individual pipelines are combined using any convenient method, such as absolute classification (e.g., requiring positive identification of an area as a neuron by all pipelines for the object to be classified as a neuron), or fuzzy classification (e.g., via voting and/or a weighted combination of the results of the individual pipelines). Such combinations and classifications may involve applying one or more statistical or learning machine algorithms, such as genetic algorithms, neural networks, hidden Markov models, Bayesian networks, support vector machines, and the like ([0171]).
Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of the image analysis is carried out by a machine learning model as taught by Finkbeiner ([0171]) into the microscope system of Kalkbrenner in order to provide automated robotic microscopy systems that facilitate high throughput and high content analysis of samples, including biological samples such as living cells and/or tissues (Finkbeiner, [0003]).
Regarding Claim 7 and 8, Analogous rejection as the rejection of Claim 3 applies.
Finkbeiner teaches automated robotic microscopy systems having individual results from the individual pipelines are combined using any convenient method, such as absolute classification (e.g., requiring positive identification of an area as a neuron by all pipelines for the object to be classified as a neuron), or fuzzy classification (e.g., via voting and/or a weighted combination of the results of the individual pipelines). Such combinations and classifications may involve applying one or more statistical or learning machine algorithms, such as genetic algorithms, neural networks, hidden Markov models, Bayesian networks, support vector machines, and the like ([0171]).
Finkbeiner further teaches sample imaging subsystem, which includes an imaging device 206 (optical scanner or microscope), robotic arm 204 of the sample transport subsystem returning the sample to the incubator 201 of the bulk sample storage subsystem, placing the sample back on the holder contained in the sample identification subsystem [0078] and the image processor 207 includes a processor configured to execute instructions from software modules to organize the images taken of the sample; stitch the images together; align the images; identify objects (e.g., cells, such as neurons) within the images; track an object (e.g., a cell, such as a neuron) through a temporal series of images; extract data (e.g., fluorescence data) from objects identified within an image; and/or analyze the resulting images ([0079]).
Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of the image analysis is carried out by a machine learning model as taught by Finkbeiner ([0171]) into the microscope system of Kalkbrenner in order to provide automated robotic microscopy systems that facilitate high throughput and high content analysis of samples, including biological samples such as living cells and/or tissues (Finkbeiner, [0003]).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Kalkbrenner et al. (US 20190056579, hereinafter Kalkbrenner) view of Henderson, Stumpe and Ominami et al. (US 20160203944, hereinafter Ominami).
Regarding Claim 14, Kalkbrenner view of Henderson and Stumpe disclose the method he method as claimed in claim 1, but does not explicitly disclose wherein a warning message is transmitted to a user if a region suitable for a manipulation in the sample-adjacent region cannot be located.
Ominami teaches wherein a warning message is transmitted to a user if a region suitable for a manipulation in the sample-adjacent region cannot be located ([0087], If a monitoring message that the parameter reaches the threshold is displayed on the monitor 33, the user easily grasps the message. For example, a predetermined threshold is set and a process that a warring is issued to the user or moving of the sample stage is limited if the signal attenuation distance L is less than the threshold, and the like may be performed. Setting of the threshold and the display of the warning are performed by the computer 35. Finally, the observation is executed (step 810).)
Therefore, it would have been obvious to one ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of the warning message as taught by Ominami ([0087]) into the microscope system of Kalkbrenner in order to adjust the distance between the membrane and the sample without contacting the sample disposed under atmospheric pressure, or an atmosphere of a substantially equal pressure, with the membrane since the distance between the sample disposed just below the membrane and the membrane can be monitored (Ominami, [0008]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samuel D Fereja whose telephone number is (469)295-9243. The examiner can normally be reached 8AM-5PM.
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/SAMUEL D FEREJA/Primary Examiner, Art Unit 2487
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