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 .
Priority
Applicant is required to certify that the international application was not withdrawn or considered to be withdrawn, either generally or as to the United States, prior to the filing date of the national application claiming benefit under 35 U.S.C. 120 and 365(c) to such international application (MPEP § 1895.01).
Claim Interpretation
The specification (e.g., see “… the angular positions of the three or more local maxima change along the optical axis … Fig. 8 shows the intensity distribution of the excitation light in the x-y plane for different axial positions …” in the last two paragraphs on pg. 16) serves as a glossary (MPEP § 2111.01) for the claim term “the angular positions of three or more local maxima vary along the optical axis”.
Claim Rejections - 35 USC § 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.
Claim(s) 1, 4-7, and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hell et al. (US 2019/0011367) in view of Kleppe et al. (US 2011/0267688).
In regard to claims 1 and 5, Hell et al. disclose a method for estimating a position of an emitter or reflector in a sample, comprising:
(a) illuminating the sample with excitation light at at least one set of target coordinates, wherein the excitation light has an intensity distribution in the form of a donut (e.g., see “… shall not exclude cases in which the zero point is enclosed by an intensity maximum extending as a ring around the zero point … FIG. 15, for one scan area 7, shows four positions 58 and 59 at which the zero point of the intensity distribution of the light that has an effect on the emission of fluorescence light may be arranged to determine the location of an individual emitting luminescence marker 56, 57 in the scan area 7 …” in Fig. 15 and paragraphs 53 and 108);
(b) detecting fluorescence photons or reflected photons for the individual target coordinates of the set of target coordinates (e.g., see “… luminescence light emitted out of a local area including the zero point is registered and assigned to the respective location at which the zero point was located in the sample when the luminescence light was registered …” in Fig. 15 and paragraph 48);
(c) determining a first estimated position of an emitter or reflector from the fluorescence photons or reflected photons detected for a first subset of the set of target coordinates (e.g., see “… image the object of interest at a high precision. Such a low number of positions of the zero point is sufficient to determine the location of individual luminescence markers in the individual scan areas if the luminescence light registered for each scan area can always be assigned to a certain one of these luminescence markers …” in Fig. 15 and paragraph 60); and
(d) determining a second estimated position of the emitter or reflector from the fluorescence photons or reflected photons detected for a second subset of the set of target coordinates (e.g., see “… scan areas of the sample are, as a rule, repeatedly scanned with the zero point … image the object of interest at a high precision …” in Fig. 15 and paragraph 60).
While Hell et al. also disclose (paragraph 94) that “… methods described here may be supplemented with other measures known in the field of fluorescence microscopy …”, the method of Hell et al. lacks an explicit description of details of the “… measures known in the field of fluorescence microscopy …” such as the first estimated position and the second estimated position are uncalibrated, estimating a position of the emitter or reflector by comparing the first estimated position and the second estimated position, wherein the position estimated by comparing the first estimated position and the second estimated position is calibrated, wherein a difference is determined for the comparison, and wherein the subsets of the set of target coordinates are disjoint. However, “… measures known in the field of fluorescence microscopy …” details are known to one of ordinary skill in the art (e.g., see “… Scanning points which form the basis of both pictures are offset by a step size below the optical resolution limit of the method with regard to each other, and the resulting differences of the pictures are evaluated for obtaining an increased spatial resolution …” in paragraph 21 of Hell et al. and “… Since the illumination pattern as well as the point spread function H are generally well known, it is relatively easy to solve the extremely overdetermined system of equations … STED/RESOLFT, since the PSF in these techniques is already steeper by a factor of 2-3 so that the resolution enhancement generated …” in paragraphs 79 and 120 of Kleppe et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional measure (e.g., comprising details such as “Scanning points which form the basis of both pictures are offset”, in order to “resulting differences of the pictures are evaluated for obtaining an increased spatial resolution” and “solve the extremely overdetermined system of equations”, in order to achieve “resolution enhancement”) for the unspecified “measures” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional measure (e.g., comprising details such as the first estimated position and the second estimated position are uncalibrated, estimating a position of the emitter or reflector by comparing the first estimated position and the second estimated position, wherein the position estimated by comparing the first estimated position and the second estimated position is calibrated, wherein a difference is determined for the comparison, and wherein the subsets of the set of target coordinates are disjoint) as the unspecified “measures” of Hell et al.
In regard to claim 4 which is dependent on claim 1, Hell et al. also disclose that the set of target coordinates comprises four or more target coordinates and the subsets of the set of target coordinates each comprise three or more target coordinates (e.g., “… scanned with the zero point of the luminescence inhibiting light in each of its positions extends over a regular hexagon …” in paragraph 104).
In regard to claim 6 which is dependent on claim 1, Hell et al. also disclose that the set of target coordinates comprises six target coordinates arranged in a hexagon (e.g., “… scanned with the zero point of the luminescence inhibiting light in each of its positions extends over a regular hexagon …” in paragraph 104).
In regard to claim 7 which is dependent on claim 6, Hell et al. also disclose that the subsets of the set of target coordinates each comprise three target coordinates arranged in an equilateral triangle (e.g., “… scanned with the zero point of the luminescence inhibiting light in each of its positions extends over a regular hexagon …” in paragraph 104).
In regard to claim 23, Hell et al. disclose a microscope comprising a controller, wherein the controller is configured to estimate a position of an emitter or reflector in a sample by:
(a) illuminating the sample with excitation light at at least one set of target coordinates, wherein the excitation light has an intensity distribution in the form of a donut (e.g., see “… shall not exclude cases in which the zero point is enclosed by an intensity maximum extending as a ring around the zero point … FIG. 15, for one scan area 7, shows four positions 58 and 59 at which the zero point of the intensity distribution of the light that has an effect on the emission of fluorescence light may be arranged to determine the location of an individual emitting luminescence marker 56, 57 in the scan area 7 …” in Fig. 15 and paragraphs 53 and 108);
(b) detecting fluorescence photons or reflected photons for the individual target coordinates of the set of target coordinates (e.g., see “… luminescence light emitted out of a local area including the zero point is registered and assigned to the respective location at which the zero point was located in the sample when the luminescence light was registered …” in Fig. 15 and paragraph 48);
(c) determining a first estimated position of an emitter or reflector from the fluorescence photons or reflected photons detected for a first subset of the set of target coordinates (e.g., see “… image the object of interest at a high precision. Such a low number of positions of the zero point is sufficient to determine the location of individual luminescence markers in the individual scan areas if the luminescence light registered for each scan area can always be assigned to a certain one of these luminescence markers …” in Fig. 15 and paragraph 60); and
(d) determining a second estimated position of the emitter or reflector from the fluorescence photons or reflected photons detected for a second subset of the set of target coordinates (e.g., see “… scan areas of the sample are, as a rule, repeatedly scanned with the zero point … image the object of interest at a high precision …” in Fig. 15 and paragraph 60).
While Hell et al. also disclose (paragraph 94) that “… methods described here may be supplemented with other measures known in the field of fluorescence microscopy …”, the microscope of Hell et al. lacks an explicit description of details of the “… measures known in the field of fluorescence microscopy …” such as estimating a position of the emitter or reflector by comparing the first estimated position and the second estimated position, wherein the first estimated position and the second estimated position are uncalibrated, wherein a difference is determined for the comparing, and wherein the position estimated by comparing the first estimated position and the second estimated position is calibrated. However, “… measures known in the field of fluorescence microscopy …” details are known to one of ordinary skill in the art (e.g., see “… Scanning points which form the basis of both pictures are offset by a step size below the optical resolution limit of the method with regard to each other, and the resulting differences of the pictures are evaluated for obtaining an increased spatial resolution …” in paragraph 21 of Hell et al. and “… Since the illumination pattern as well as the point spread function H are generally well known, it is relatively easy to solve the extremely overdetermined system of equations … STED/RESOLFT, since the PSF in these techniques is already steeper by a factor of 2-3 so that the resolution enhancement generated …” in paragraphs 79 and 120 of Kleppe et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional measure (e.g., comprising details such as “Scanning points which form the basis of both pictures are offset”, in order to “resulting differences of the pictures are evaluated for obtaining an increased spatial resolution” and “solve the extremely overdetermined system of equations”, in order to achieve “resolution enhancement”) for the unspecified “measures” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional measure (e.g., comprising details such as estimating a position of the emitter or reflector by comparing the first estimated position and the second estimated position, wherein the first estimated position and the second estimated position are uncalibrated, wherein a difference is determined for the comparing, and wherein the position estimated by comparing the first estimated position and the second estimated position is calibrated) as the unspecified “measures” of Hell et al.
Claim(s) 13, 16, 18, 20-22, 25, 26, and 28-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hell et al. (US 2019/0011367) in view of Antonello et al. (Aberrations in stimulated emission depletion (STED) microscopy, Optics Communications Vol. 404 (Available online June 2017), pp. 203-209).
In regard to claim 13, Hell et al. disclose a method for estimating a position of an emitter or reflector in a sample, comprising:
(a) illuminating the sample with excitation light at at least one set of target coordinates, and wherein the excitation light has an intensity distribution comprising a central minimum and maxima arranged around the central minimum (e.g., see “… intensity maxima may be neighboring the zero point in one, two or three directions … a zero point which is not delimited by the intensity maxima in all directions of main extension of the sample with different orientations of the zero point to maximize the spatial resolution in imaging in dimensions of the scan areas are limited in at least one direction … FIG. 15, for one scan area 7, shows four positions 58 and 59 at which the zero point of the intensity distribution of the light that has an effect on the emission of fluorescence light may be arranged to determine the location of an individual emitting luminescence marker 56, 57 in the scan area 7 …” in Fig. 15 and paragraphs 54 and 108);
(b) detecting fluorescence photons or reflected photons for the individual target coordinates of the set of target coordinates (e.g., see “… luminescence light emitted out of a local area including the zero point is registered and assigned to the respective location at which the zero point was located in the sample when the luminescence light was registered …” in Fig. 15 and paragraph 48); and
(c) estimating a position of an emitter or reflector from the detected fluorescence photons or reflected photons (e.g., see “… image the object of interest at a high precision. Such a low number of positions of the zero point is sufficient to determine the location of individual luminescence markers in the individual scan areas if the luminescence light registered for each scan area can always be assigned to a certain one of these luminescence markers …” in Fig. 15 and paragraph 60),
wherein a depth information for the emitter or reflector is determined from vector sums and/or sums over vectors of the detected fluorescence photons or reflected photons determined for the subsets of the set of target coordinates (e.g., “… one, two or three directions … maximize the spatial resolution in imaging in all directions of main extension of the sample …” in paragraph 54 and one of the “three directions” can also be labeled depth).
The method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the central minimum is extended along an optical axis angular positions of three or more local maxima vary along the optical axis. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… Whilst aberrations affect in general all beams paths (excitation, emission, and depletion) of the STED microscope, for small aberration amplitudes the effects on performance are dominated by the distortion of the depletion beam … integration takes place over a spherical cap described by the coordinates (𝜃, 𝜙), where the upper limit is 𝛼 = arcsin(NA∕𝑛) and NA is the numerical aperture of the objective …” in). (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in sections 1, 2.1, and section 2.3 of Antonello et al. and “… phase and PSF in the 𝑥𝑦 plane are reported below the intensity profiles, along with the magnitude of the aberration in rad …” in Fig. 2 caption of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus” and local maxima “distortion of the depletion beam”, in order to achieve a desired “STED microscope” “performance”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the central minimum is extended along an optical axis angular positions of three or more local maxima vary along the optical axis) as the unspecified “maxima” of Hell et al.
In regard to claim 16 which is dependent on claim 13, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as a combined vortex and trefoil phase is imposed on the excitation light to generate the intensity distribution. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as a combined vortex and trefoil phase is imposed on the excitation light to generate the intensity distribution) as the unspecified “maxima” of Hell et al.
In regard to claim 18 which is dependent on claim 16, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the phase shift of the trefoil phase is between 10% and 200% of the phase shift of the vortex phase. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the phase shift of the trefoil phase is between 10% and 200% of the phase shift of the vortex phase) as the unspecified “maxima” of Hell et al.
In regard to claim 20 which is dependent on claim 13, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the angular positions of the three or more local maxima change monotonically along the optical axis. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the angular positions of the three or more local maxima change monotonically along the optical axis) as the unspecified “maxima” of Hell et al.
In regard to claim 21 which is dependent on claim 13, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the three or more local maxima are evenly distributed around the central minimum. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the three or more local maxima are evenly distributed around the central minimum) as the unspecified “maxima” of Hell et al.
In regard to claim 22 which is dependent on claim 21, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the angular positions of the three or more local maxima change along the optical axis by an amount corresponding to 180° divided by the number of maxima. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the angular positions of the three or more local maxima change along the optical axis by an amount corresponding to 180° divided by the number of maxima) as the unspecified “maxima” of Hell et al.
In regard to claim 25, Hell et al. disclose a microscope comprising a controller, wherein the controller is configured to estimate a position of an emitter or reflector in a sample by:
(a) illuminating the sample with excitation light at at least one set of target coordinates, and wherein the excitation light has an intensity distribution comprising a central minimum and maxima arranged around the central minimum (e.g., see “… a zero point which is not delimited by the intensity maxima in all directions of main extension of the sample with different orientations of the zero point to maximize the spatial resolution in imaging in dimensions of the scan areas are limited in at least one direction … FIG. 15, for one scan area 7, shows four positions 58 and 59 at which the zero point of the intensity distribution of the light that has an effect on the emission of fluorescence light may be arranged to determine the location of an individual emitting luminescence marker 56, 57 in the scan area 7 …” in Fig. 15 and paragraphs 54 and 108);
(b) detecting fluorescence photons or reflected photons for the individual target coordinates of the set of target coordinates (e.g., see “… luminescence light emitted out of a local area including the zero point is registered and assigned to the respective location at which the zero point was located in the sample when the luminescence light was registered …” in Fig. 15 and paragraph 48); and
(c) estimating a position of an emitter or reflector from the detected fluorescence photons or reflected photons (e.g., see “… image the object of interest at a high precision. Such a low number of positions of the zero point is sufficient to determine the location of individual luminescence markers in the individual scan areas if the luminescence light registered for each scan area can always be assigned to a certain one of these luminescence markers …” in Fig. 15 and paragraph 60),
wherein a depth information for the emitter or reflector is determined from vector sums and/or sums over vectors of the detected fluorescence photons or reflected photons determined for the subsets of the set of target coordinates (e.g., “… one, two or three directions … maximize the spatial resolution in imaging in all directions of main extension of the sample …” in paragraph 54 and one of the “three directions” can also be labeled depth).
The microscope of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the central minimum is extended along an optical axis angular positions of three or more local maxima vary along the optical axis. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… Whilst aberrations affect in general all beams paths (excitation, emission, and depletion) of the STED microscope, for small aberration amplitudes the effects on performance are dominated by the distortion of the depletion beam … integration takes place over a spherical cap described by the coordinates (𝜃, 𝜙), where the upper limit is 𝛼 = arcsin(NA∕𝑛) and NA is the numerical aperture of the objective …” in). (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in sections 1, 2.1, and section 2.3 of Antonello et al. and “… phase and PSF in the 𝑥𝑦 plane are reported below the intensity profiles, along with the magnitude of the aberration in rad …” in Fig. 2 caption of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus” and local maxima “distortion of the depletion beam”, in order to achieve a desired “STED microscope” “performance”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the central minimum is extended along an optical axis angular positions of three or more local maxima vary along the optical axis) as the unspecified “maxima” of Hell et al.
In regard to claim 26 which is dependent on claim 25, the microscope of Hell et al. lacks an explicit description of details of the “… measures known in the field of fluorescence microscopy …” such as estimating the position of the emitter or reflector comprises comparing estimated positions for the emitter or reflector determined from fluorescence photons or reflected photons detected for subsets of the set of target coordinates. However, “… measures known in the field of fluorescence microscopy …” details are known to one of ordinary skill in the art (e.g., see “… Scanning points which form the basis of both pictures are offset by a step size below the optical resolution limit of the method with regard to each other, and the resulting differences of the pictures are evaluated for obtaining an increased spatial resolution …” in paragraph 21 of Hell et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional measure (e.g., comprising details such as “Scanning points which form the basis of both pictures are offset”, in order to “resulting differences of the pictures are evaluated for obtaining an increased spatial resolution”) for the unspecified “measures” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional measure (e.g., comprising details such as estimating the position of the emitter or reflector comprises comparing estimated positions for the emitter or reflector determined from fluorescence photons or reflected photons detected for subsets of the set of target coordinates) as the unspecified “measures” of Hell et al.
In regard to claim 28 which is dependent on claim 16, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the phase shift of the trefoil phase is between 20% and 150% of the phase shift of the vortex phase. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the phase shift of the trefoil phase is between 20% and 150% of the phase shift of the vortex phase) as the unspecified “maxima” of Hell et al.
In regard to claim 29 which is dependent on claim 16, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the phase shift of the trefoil phase is between 30% and 120% of the phase shift of the vortex phase. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the phase shift of the trefoil phase is between 30% and 120% of the phase shift of the vortex phase) as the unspecified “maxima” of Hell et al.
In regard to claim 30 which is dependent on claim 16, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the phase shift of the trefoil phase is between 80% and 110% of the phase shift of the vortex phase. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the phase shift of the trefoil phase is between 80% and 110% of the phase shift of the vortex phase) as the unspecified “maxima” of Hell et al.
In regard to claim 31 which is dependent on claim 16, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the phase shift of the trefoil phase is 100% of the phase shift of the vortex phase. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the phase shift of the trefoil phase is 100% of the phase shift of the vortex phase) as the unspecified “maxima” of Hell et al.
In regard to claim 32 which is dependent on claim 13, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the angular positions of the three or more local maxima change strictly monotonically along the optical axis. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the angular positions of the three or more local maxima change strictly monotonically along the optical axis) as the unspecified “maxima” of Hell et al.
In regard to claim 33 which is dependent on claim 13, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the angular positions of the three or more local maxima change proportional to an axial position along the optical axis. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… 2D and 3D STED configurations require different phase masks 𝑇 (𝜃, 𝜙) to create the depletion foci. For 2D STED we consider the helicoidal phase pattern described by 𝑇2(𝜙) = 𝑒𝑖𝜙, (9) which results in the depletion pattern depicted on the left column in Fig. 1. For 3D STED, we use the pi-step phase mask defined by
T
3
θ
=
-
-
1
θ
≤
β
1
θ
>
β
where 𝛽 is chosen to ensure destructive interference at the centre of the focus. In practice, 𝛽 depends upon the illumination profile 𝐴(𝜃) and is often tuned empirically …” in section 2.3 of Antonello et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “phase masks 𝑇 (𝜃, 𝜙)” “often tuned empirically”, in order to achieve a desired “destructive interference at the centre of the focus”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the angular positions of the three or more local maxima change proportional to an axial position along the optical axis) as the unspecified “maxima” of Hell et al.
Claim(s) 17 and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hell et al. in view of Antonello et al. as applied to claim(s) 16 and 25 above, and further in view of Zhu et al. (Compact three-dimensional super-resolution system based on fluorescence emission difference microscopy, Optics Communications Vol. 405 (Available online August 2017), pp. 157-163).
In regard to claim 17 which is dependent on claim 16, the method of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as the combined vortex and trefoil phase is imposed on the excitation light by means of an adjustable spatial light modulator. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… methods based on a classic confocal system, include stimulated emission depletion (STED) microscopy [1] and fluorescence emission difference (FED) microscopy [2] … spatial light modulator (SLM) to generate a negative focal spot. The negative spot can also be generated using a specific phase plate. One of the limitations of using a phase plate is that the phase retardation distribution is fixed. In contrast, the SLM is more flexible owing to the user-defined phase modulation pattern. Because of this, the usage of SLM is preferred, especially in the case where phase modulation of the incident light is required. Additionally, the similar utilization of SLM has been working well in STED systems [13–15]. Furthermore, based on SLM, one can apply adaptive optics and wavefront optimiza-tion to correct system aberrations [14,16,17] …” in section 1 of Zhu et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “SLM is more flexible owing to the user-defined phase modulation pattern”, in order to achieve a desired “phase modulation of the incident light”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as the combined vortex and trefoil phase is imposed on the excitation light by means of an adjustable spatial light modulator) as the unspecified “maxima” of Hell et al.
In regard to claim 27 which is dependent on claim 25, the microscope of Hell et al. lacks an explicit description of details of the “… zero point which is not delimited by the intensity maxima in all directions …” such as an adjustable spatial light modulator for imposing a combined vortex and trefoil phase on the excitation light. However, “… zero point which is not delimited by the intensity maxima in all directions …” details are known to one of ordinary skill in the art (e.g., see “… methods based on a classic confocal system, include stimulated emission depletion (STED) microscopy [1] and fluorescence emission difference (FED) microscopy [2] … spatial light modulator (SLM) to generate a negative focal spot. The negative spot can also be generated using a specific phase plate. One of the limitations of using a phase plate is that the phase retardation distribution is fixed. In contrast, the SLM is more flexible owing to the user-defined phase modulation pattern. Because of this, the usage of SLM is preferred, especially in the case where phase modulation of the incident light is required. Additionally, the similar utilization of SLM has been working well in STED systems [13–15]. Furthermore, based on SLM, one can apply adaptive optics and wavefront optimiza-tion to correct system aberrations [14,16,17] …” in section 1 of Zhu et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional maxima (e.g., comprising details such as “SLM is more flexible owing to the user-defined phase modulation pattern”, in order to achieve a desired “phase modulation of the incident light”) for the unspecified “maxima” of Hell et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional maxima (e.g., comprising details such as an adjustable spatial light modulator for imposing a combined vortex and trefoil phase on the excitation light) as the unspecified “maxima” of Hell et al.
Response to Arguments
Applicant’s arguments with respect to the amended and new claims have been fully considered but some are moot in view of the new ground(s) of rejection. Applicant's remaining arguments filed 6 March 2026 have been fully considered but they are not persuasive.
Applicant argues that Hell et al. only teaches a “set” but not a “subset” because the cited portion of paragraph 60 states“… image the object of interest at a high precision. Such a low number of positions of the zero point is sufficient to determine the location of individual luminescence markers in the individual scan areas if the luminescence light registered for each scan area can always be assigned to a certain one of these luminescence markers …” refers to MINFLUX, and specifically to the implementation in which exactly four scanning positions are used to determine the position of an emitter in a plane. Examiner respectfully disagrees. The complete paragraph 60 states “In the method according to the invention, the scan areas of the sample are, as a rule, repeatedly scanned with the zero point to measure the reactions of the object of interest to the varying surrounding conditions. At least during a repetition of scanning the scan areas of the sample, it is preferred to arrange the zero point at not more than 3n or even not more than 2n positions per scan area, n being the number of spatial dimensions in which the scan areas of the sample are scanned, to image the object of interest at a high precision. Such a low number of positions of the zero point is sufficient to determine the location of individual luminescence markers in the individual scan areas if the luminescence light registered for each scan area can always be assigned to a certain one of these luminescence markers. Such an assignment is possible, if at each point in time only one of the luminescence markers emits the luminescence light, so that a temporal differentiation is possible, or if the luminescence light can be assigned to individual luminescence markers due to its wavelength, for example. Thus, this embodiment of the method according to the invention may make use of the method known as MINFLUX. In MINFLUX, a zero point of a light intensity distribution of excitation light is positioned at four different positions in the sample, and the intensity of the luminescence light from an individual luminescence marker is registered for these four positions to determine the location of the individual luminescence marker in a sample plane”. Thus Hell et al. teach or suggest at least during a repetition of scanning the scan areas of the sample, it is preferred to arrange the zero point at not more than 3n or even not more than 2n positions per scan area, n being the number of spatial dimensions in which the scan areas of the sample are scanned, to image the object of interest at a high precision. Hell et al. also teach or suggest this embodiment of the method according to the invention may make use of the method known as MINFLUX. Therefore, applicant's arguments are not persuasive.
Applicant argues that amended claim 1 (amended to include claim 3) is not anticipated by Hell et al. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that amended claim 1 is patentable over Hell et al. and Kleppe et al., whether considered individually or in any permissible combination, if any, because Kleppe et al. do not determine any position at all. Examiner respectfully disagrees. Kleppe et al. teach (paragraphs 70, 77, 79, 80, and 120) that “… additional scanning of the excitation over the detection spot … method for reconstructing specimen information that has a dimension below the diffraction limit … Since the illumination pattern as well as the point spread function H are generally well known, it is relatively easy to solve the extremely overdetermined system of equations … signal-to-noise ratio of the overscan region limits the possible resolution … STED/RESOLFT, since the PSF in these techniques is already steeper by a factor of 2-3 so that the resolution enhancement generated …”. Thus Kleppe et al. determine position wherein “signal-to-noise ratio of the overscan region limits the possible resolution”. Therefore, the combination of the cited prior art teaches or suggests all limitations as arranged in the claims.
Applicant argues that amended claim 1 is patentable over Hell et al. and Kleppe et al., whether considered individually or in any permissible combination, if any, because the present claims do not solve any system of equations. Examiner respectfully disagrees. MPEP § 2111.01 states that “… Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms …”. Thus under a broadest reasonable interpretation, the greatest clarity is obtained when the specification (e.g., see “… For a target coordinate pattern with m beam positions bi(i=0 … m-1) and associated photon counts pi the position u can be estimated, for example, using an uncalibrated symmetric estimator as follows:
u
→
x
→
,
b
→
i
=
u
→
p
i
x
→
,
b
→
i
=
∑
i
=
0
m
-
1
p
i
∙
b
→
i
∑
i
=
0
m
-
1
p
i
(1) …” on pg. 2) serves as a glossary for the claim term “estimating a position”. Therefore, the combination of the cited prior art teaches or suggests all limitations as arranged in the claims.
Applicant argues that independent claim 23 is believed to be patentable for at least the same reasons as discussed above in connection with claim 1. Examiner respectfully disagrees for the reasons discussed above.
Applicant argues that claims 4-7 depend from independent claim 1 are submitted to be patentable for at least the same reasons. Examiner respectfully disagrees for the reasons discussed above.
Applicant argues that independent claim 13 is patentable over Hell et al. and Antonello et al. because Antonello et al. relate to aberrations, i.e., disturbances, in connection with STED microscopy. Examiner respectfully disagrees. In response to applicant's argument, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In response to applicant's argument that the references fail to show certain features of applicant’s invention, it is noted that the features upon which applicant relies (i.e., MINFLUX) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that independent claim 13 is patentable over Hell et al. and Antonello et al. because Hell et al. do something completely different from the solution as presently claimed, where the central minimum is extended along an optical axis, i.e., where in the depth direction there are no intensity maxima neighboring the zero point. In response to applicant's argument that the references fail to show certain features of applicant’s invention, it is noted that the features upon which applicant relies (i.e., in the depth direction there are no intensity maxima neighboring the zero point) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further it is important to recognize a standard donut have properties such as in the depth direction there are no intensity maxima neighboring the zero point.
Applicant argues that independent claim 25 is believed to be patentable for at least the same reasons as discussed above in connection with claim 13. Examiner respectfully disagrees for the reasons discussed above.
Applicant argues that claims 16, 18, 20-22, and 26 depend from either independent claims 13 and 25 are submitted to be patentable for at least the same reasons. Examiner respectfully disagrees for the reasons discussed above.
Applicant argues that claims 17 and 27 depend from either independent claims 13 and 25 are submitted to be patentable for at least the same reasons. Examiner respectfully disagrees for the reasons discussed above.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 2021/0190691 teaches a microscope.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shun Lee whose telephone number is (571)272-2439. The examiner can normally be reached Monday-Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Uzma Alam can be reached at (571)272-3995. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SL/
Examiner, Art Unit 2884
/UZMA ALAM/Supervisory Patent Examiner, Art Unit 2884
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