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 .
Election/Restrictions
Applicant’s election without traverse of Group VIII (i.e., claims 1, 3, 12-17; claims 1, 3 are linking claims and should not be listed as “withdrawn” but are currently “original” claims) in the reply filed on 11/18/25 is acknowledged.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 12-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schonle et al (EP 4151987 A1; “Schonle”; already of record).
Regarding claim 1, Schonle teaches a method for localizing individual emitters in a sample (e.g., Title; Abstract), comprising a pre-localization comprising the steps [¶s 0002 - 0016: "Prior Art", "PALM", "STORM", "dSTORM", "GSDIM", and ¶ 0067: “a coarse position estimate of the molecule M is obtained, e.g., as described in the prior art”] of:
- illuminating the sample with illumination light, wherein the illumination light induces or modulates light emissions from an individual and stationary emitter in the sample (¶s 0002-0016: "Prior Art", "PALM", "STORM", "dSTORM", "GSDIM"),
- detecting the light emissions from the emitter [¶ 0002: “… light (e.g., fluorescence light) from single emitters in a sparsely labeled sample is detected by a position-specific detector, such as a camera, to image individual point spread functions (PSFs) of the emitters", and ¶ 0003: "In order to detect individual emitters, "];
- estimating the position of the emitter in the sample from the detected light emissions (¶ 0002: "The locations of the individual emitters can then be determined from the positions of the PSF maxima, and an image can be constructed from the determined positions.", and ¶ 0067: “…and a coarse position estimate of the molecule M is obtained…");
; and a subsequent main localization comprising the steps (¶ 0067: "During
MINFLUX localization, ") of
- illuminating the sample with an intensity distribution the illumination light or another illumination light at illumination positions, the intensity distribution comprising a local minimum (¶ 0067: "During MINFLUX localization, to "The local minimum 111 of the light distribution 110 is then moved to positions in the vicinity of the coarse position estimate, ");
- detecting the light emissions of the emitter for the respective illumination positions (¶ 0067: N and a light intensity or photon count of the detection light F is measured by the detector 3 for each position of the local minimum 111");
- determining the position of the emitter in the sample from the light emissions detected for the illumination positions (¶ 0067: "An improved position estimate is then calculated from the light intensities/photon counts and the corresponding positions, e.g., by a least means square algorithm"),
wherein the illumination positions in the main localization are arranged in a first iteration around the position of the emitter estimated in the pre-localization (¶ 0067: "The local minimum 111 of the light distribution 110 is then moved to positions in the vicinity of the coarse position estimate, "), at least one second iteration being carried out after the first iteration [¶ 0067: "This process may be repeated in several iterations to further improve the position estimate, until the estimate converges to an optimal value (influenced by the signal-to-noise ratio) or until the molecule M reversibly or irreversibly switches to the dark state D"], the illumination positions in the at least one second iteration being arranged around the position of the emitter determined in the preceding iteration (¶ 0067: "An improved position estimate is then calculated from the light intensities/photon counts and the corresponding positions,…This process may be repeated in several iterations to further improve the position estimate,… "), [[wherein the illumination positions in the first iteration and the at least one second iteration form a respective illumination pattern comprising a maximum extension, wherein the maximum extension of the illumination pattern is kept constant during the main localization].
Schonle does not explicitly state the illumination positions in the first iteration and the at least one second iteration form a respective illumination pattern comprising a maximum extension, wherein the maximum extension of the illumination pattern is kept constant during the main localization.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to understand that for the sake of simplicity exactly the same procedure is carried out as an iteration step, i.e., the same procedure with the same illumination pattern including illumination positions is repeated so that their shape and size and thus their maximum extension (L) compared to the illumination pattern of the previous iteration is unchanged. It is only the illumination pattern that is repositioned in the direction of the newly estimated position of the emitter (" axial scanning "), so that the center of the illumination pattern is expected to be closer to the real position of the emitter and thus more centric than in the previous iteration step). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention for the illumination positions in the first iteration and the at least one second iteration form a respective illumination pattern comprising a maximum extension, wherein the maximum extension of the illumination pattern is kept constant during the main localization.
Thus claim 1 is rejected.
Regarding claim 3, Schonle renders as obvious the method according to claim 1 (see above rejection of claim 1). Furthermore, Schonle teaches the illumination light is excitation light that induces the light emissions of the emitter [e.g., as stated in the claim 1 rejection: illuminating the sample with illumination light, wherein the illumination light induces or modulates light emissions from an individual and stationary emitter in the sample; ¶s 0002-0016: "Prior Art", "PALM", "STORM", "dSTORM", "GSDIM"].
Thus claim 3 is rejected.
Regarding claim 12, Schonle renders as obvious the method according to claim 1 (see above rejection of claim 1). Furthermore, Schonle teaches wherein the light emissions from the emitter are detected during the pre-localization [e.g., at ¶ 0067: course position estimate] with a detector 3 comprising a plurality of detector elements (e.g., ¶ 0026: array of APDs).
Thus claim 12 is rejected.
Regarding claim 13, Schonle renders as obvious the method according to claim 12 (see above rejection of claim 12). Furthermore, Schonle teaches the position of the emitter estimated during the pre-localization is determined with a position estimator (e.g., ¶ 0002: "The locations of the individual emitters can then be determined from the positions of the PSF maxima, and an image can be constructed from the determined positions.", and ¶ 0067: “…and a coarse position estimate of the molecule M is obtained…") or by a moment determination based on the light emissions detected by the detector elements.
Thus claim 13 is rejected.
Regarding claim 14, Schonle renders as obvious the method according to claim 12 (see above rejection of claim 12). Furthermore, Schonle teaches wherein a function is fitted to data obtained from light emissions detected by the detector elements, wherein the position estimated during the pre-localization is determined from the fitted function [e.g., ¶ 0002: “… light (e.g., fluorescence light) from single emitters in a sparsely labeled sample is detected by a position-specific detector, such as a camera, to image individual point spread functions (PSFs) of the emitters", and ¶ 0003: "In order to detect individual emitters, "].
Thus claim 14 is rejected.
Regarding claim 15, Schonle renders as obvious the method according to claim 1 (see above rejection of claim 1). Furthermore, Schonle teaches the light emissions of the emitter are detected during the main localization with a detector comprising a plurality of detector elements (e.g., ¶ 0026: array of APDs).
Thus claim 15 is rejected.
Claim(s) 16, 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schonle as applied to claims 12, 15 above with further obviousness evidenced by {OEB} Schmidt et al. (US 20240045190; Schmidt).
Regarding claim 16, Schonle renders as obvious the method according to claim 12 (see above rejection of claim 12).
Schonle does not explicitly state single photons emitted by the emitter and detected by the detector elements of the detector are registered.
However, it was well-known for single photons emitted by the emitter and detected by the detector elements of the detector are registered as evidenced by Schmidt (e.g., Schmidt ¶ 0084). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention for single photons emitted by the emitter and detected by the detector elements of the detector are registered at least for the purpose of efficient localization of emitters in a sample.
Thus claim 16 is rejected.
Regarding claim 17, Schonle renders as obvious the method according to claim 12 (see above rejection of claim 15).
Schonle does not explicitly state single photons emitted by the emitter and detected by the detector elements of the detector are registered.
However, it was well-known for single photons emitted by the emitter and detected by the detector elements of the detector are registered as evidenced by Schmidt (e.g., Schmidt ¶ 0084). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention for single photons emitted by the emitter and detected by the detector elements of the detector are registered at least for the purpose of efficient localization of emitters in a sample.
Thus claim 17 is rejected.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mr. Michael Mooney whose telephone number is 571-272-2422. The examiner can normally be reached during weekdays, M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Uyen-Chau Le can be reached on 571-272-2397. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL P MOONEY/Primary Examiner, Art Unit 2874