Prosecution Insights
Last updated: August 17, 2026
Application No. 18/887,926

LABEL-FREE IDENTIFICATION OF TUMOR TISSUES BY COHERENT NONLINEAR VIBRATIONAL MODE IMAGING

Final Rejection §103
Filed
Sep 17, 2024
Examiner
CHANG, AUDREY Y
Art Unit
2872
Tech Center
2800 — Semiconductors & Electrical Systems
Assignee
The Regents of the University of California
OA Round
2 (Final)
47%
Grant Probability
Moderate
3-4
OA Rounds
1y 6m
Est. Remaining
67%
With Interview

Examiner Intelligence

Grants 47% of resolved cases
47%
Career Allowance Rate
591 granted / 1268 resolved
-21.4% vs TC avg
Strong +20% interview lift
Without
With
+20.2%
Interview Lift
resolved cases with interview
Typical timeline
3y 5m
Avg Prosecution
74 currently pending
Career history
1324
Total Applications
across all art units

Statute-Specific Performance

§101
0.7%
-39.3% vs TC avg
§103
48.6%
+8.6% vs TC avg
§102
9.5%
-30.5% vs TC avg
§112
35.1%
-4.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1268 resolved cases

Office Action

§103
DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claim 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. Claim(s) 1-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over the article “Hyperspectral imaging with laser-scanning sum-frequency generation microscopy” by Hanninen et al (Optical Society America, Biomedical Optics Express, vol. 8, No. 9 pages 4230-4242) in view of the US patent application publication by Zhang et al (US 2018/0088041 A1), US patent application publication by Mueller-Rentz et al (US 2022/0390732 A1) and US patent issued to Quake (PN. 6,002,471). Hanninen et al teaches, with regard to claim 1, a Hyperspectral imaging with laser-scanning sum-frequency generation microscope platform, (please see Figure 1) that is comprised of a pulsed laser, a synchronously-pumped optical parametric oscillator (OPO, please see page 4233) configured to guide the output of the laser beam generating a mid-IR (MIR) beam and a near IR beam (NIR), which through a dichroic mirror (DM2) wherein the MIR beam and the NIR beam are spatially overlapped. Hanninen et al teaches the microscope platform further comprises scan mirrors serves as the resonant beam scanner and an inverted microscope, (please see page 4234) configured to integrate with the beam scanner wherein the MIR beam and the NIR beam are overlapped and directed into the inverted microscope. Hanninen et al teaches the inverted microscope comprises Cassegrain objective (Obj1 and Obj2, please see page 4234) that may be reflective based objectives. Hanninen et al also teaches that the microscope comprise a microscope state for retaining a sample mounted between the first and second objectives (Obj1 and Obj2, please see Figure 1). Hanninen et al teaches that a photomultiplier (PMT, please see Figure 1) serves as the detector coupled to detect and collect the image data. This reference has met all the limitations of the claims. It teaches a synchronously-pumped optical parametric oscillator (OPO, Figure 1) is used to guide the output of the laser beam to generate the MIR beam. It however does not teach explicitly that an optical parametric amplifier to generate the MIR beam and a Fabry-Perot etalon is used to generate the NIR beam. Nevertheless, Hanninen et al indeed teaches that an MIR beam and an NIR beam are generated from the pulsed laser for achieving the hyperspectral VSFG microscopic imaging, such modifications would therefore have been obvious matters of design choices to one skilled in the art since they do not change the operation of the microscope. Hanninen et al teaches a resonant beam scanner is included but does not teach explicitly that it is mounted to an integrated 2-position slider, however such modification is considered to be obvious to one skilled in the art for the benefit of increasing the mobility of the scan mirrors. Hanninen et al teaches to include a reflective based microscope objectives, (Obj1 and Obj2, Figure 1), that may include Cassegrain objective that is an infinite-corrected image objective, but it does not teach explicitly that the objective is a Schwarzschild objective and/or objective based. Zhang et al in the same field of endeavor teaches an inverted microscope wherein the objective may comprise a Schwarzschild objective, (please see paragraph [0012], Figures 1A and 1B). It would then have been obvious to one skilled in the art to apply the teachings of Zhang et al to use art well-known microscope objective for the microscope platform. As shown in Figure 1 of Hanninen et al and Figures 1A to 1C of Zhang et al the objectives seem to be mounted in a vertical arrangement which may implicitly be mounted to a vertical nanopositioning z-axis stage for holding the objectives in proper arrangement and locations. Hanninen et al does not teach explicitly to include a polarizer. Zhang et al in a different embodiment teaches a polarizer, a quarter waveplate and a polarization beamsplitter is used to provide polarization control of the detection and processing of the image signal, (please see Figure 6B). Hanninen et al does teaches a telecentric tube lens arrangement, (please see Figure 1) but it does not teach to include the telecentric tube lens system to guide the image signal for processing and to include a monochromator to magnify the image signal. Muller-Rentz et al teaches a microscope arrangement wherein a telecentric lens may be utilized to guide and process the signal image, (please see Figure 1)). It would then have been obvious to one skilled in the art to apply the teachings of Muller-Rentz et al to also use a telecentric tube lens in the microscope to guide the image signal from the sample. Quake in the same field of endeavor to teach a microscope wherein a monochromator (8, Figure 1) may be coupled with a detector to detect the image signal from the sample. It would then have been obvious to one skilled in the art to apply the teachings of Quake to include a monochromator to enhance the detection of the image signal. With regard to claim 2, Hanninen et al teaches that the pulse laser may have a pulse width of about 6 ps (picoseconds, please see page 4233) but it does not teach it is about 100 fs (femtosecond). However, it is within general level skill in the art to select the pulse laser with a desired duration. With regard to claim 3, Hanninen et al teaches that the dichroic mirror (DM2, Figure 1) is transmissive to MIR and reflective to NIR. With regard to claim 4, Hanninen et al in light of Zhang et al teaches that the Schwarzschild objective is reflective and acts as a condenser, (please see Figures 1A and 1B of Zhang et al). With regard to claim 5, it is within general level skilled in the art to make the z-axis position of the refractive based imaging objective is controlled at a 1mm precision. With regard to claim 6, Hanninen et al in light of Mueller-Rentz et al teaches that the telecentric lens may comprise two tube lenses. With regard to claim 7, Hanninen et al teaches a method for detecting a biological tissue sample with the VSFG microscope that is comprised of the steps of mounting the tissue sample on a slide to the microscope stage, subjecting the tissue sample with NIR and MIR beams using objective (Obj1, Figure 1) of the microscope, turning on the beam scan mirrors to raster the laser beams on the tissue samples, collecting a resulting VSFG signal using objective (Obj2) of the microscope, directing the VSFG signal to a spectrometer and a CCD and obtaining VSFG hyperspectral images, whereby the biological tissue sample is detected. Although this reference does not teach explicitly that the biological sample contains a tumor such modification is considered obvious to one skilled in the art since it is considered to be an intended use of the microscope. With regard to claims 8 and 9, it is either implicitly included or obvious modification by one skilled in the art to allow the biological sample to include the claimed features for the benefit of allow the application of the microscope to be expanded. With regard to claim 10, Hanninen et al teaches a method for detecting feature in a biological tissue sample with the VSFG microscope, that is comprised of steps of mounting the tissue sample on a slide of the microscope stage, subjecting the tissue sample with NIR and MIR beams using objective (Obj1) of the microscope, turning on the beam scan mirrors to raster the laser beams on the tissue sample, collecting a resulting VSFG signal using objective (Obj2) of the microscope, directing the VSFG signal to a spectrometer and a CCD and obtaining VSFG hyperspectral images. This reference does not teach explicitly to detect tumor of the biological tissue, however such modification would have been obvious to one skilled in the art since it is considered to be intended use of the microscope. Hanninen et al does not teach explicitly to analyzing spectral signatures for the images of the specific chemical compounds, since this analyzation is specific application for a specific analyzation of a specific tumor of the biological tissue. With regard to claim 12, it is either implicitly included or obvious modification by one skilled in the art to allow the biological sample to include the claimed features for the benefit of allow the application of the microscope to be expanded. With regard to claim 13, these references do not teach explicitly that the biological tissues sample is derived from lung tumor, however such feature is an intended use of the microscope. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Article “Vibrationally resonant sum-frequency generation microscopy with a solid immersion lens” by Lee et al (Optics Society America July 2014, Vol. 5, No. 7, Biomedical Optics Express 2125-2134), discloses a VR-SFG microscope with a NIR beam and MIR beam. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AUDREY Y CHANG whose telephone number is (571)272-2309. The examiner can normally be reached M-TH 9:00AM-4:30PM. 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, Stephone B Allen can be reached at 571-272-2434. 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. AUDREY Y. CHANG Primary Examiner Art Unit 2872 /AUDREY Y CHANG/ Primary Examiner, Art Unit 2872
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Prosecution Timeline

Sep 17, 2024
Application Filed
Jun 08, 2026
Non-Final Rejection mailed — §103
Jul 31, 2026
Response Filed
Aug 14, 2026
Final Rejection mailed — §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
47%
Grant Probability
67%
With Interview (+20.2%)
3y 5m (~1y 6m remaining)
Median Time to Grant
Moderate
PTA Risk
Based on 1268 resolved cases by this examiner. Grant probability derived from career allowance rate.

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