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 .
Response to Amendment
Applicant’s amendment filed 1/20/2026 is acknowledged.
In light of the applicant’s amendments and remarks the claim objection set forth in the previous office action is withdrawn.
Claims 1-3 and 21-31 remain pending in the current application.
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, 21-24, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (US 20210244972 A1) in view of Khuri-Yakub (US 20240252845 A1).
Regarding claim 1, Kim teaches a method of treating Alzheimer’s disease in a subject, the method comprising administering a therapeutic amount of pulsed or modulated ultrasound to the subject ([0018] promoting cell regeneration, which includes an ultrasound output unit and an instruction, wherein the instruction describes that ultrasound outputted from the ultrasound output unit facilities phagocytosis of senescent cells and cell regeneration by specifically stimulating the senescent cells and that the cell regeneration is caused by migration of normal cells facilitated by the ultrasound outputted from the ultrasound output unit; [0040] ultrasound output unit may have a pulse repetition frequency)
wherein the ultrasound is administered in one or more treatments, each treatment having a duration of 30 to 45 minutes ([0048] In an aspect of the present disclosure, the ultrasound may be irradiated for 1-400 minutes. Specifically, the ultrasound may be irradiated for 1 minute or longer, 2 minutes or longer, 3 minutes or longer, 4 minutes or longer, 5 minutes or longer, 6 minutes or longer, 7 minutes or longer, 8 minutes or longer, 9 minutes or longer, 10 minutes or longer, 11 minutes or longer, 12 minutes or longer, 13 minutes or longer, 14 minutes or longer, 15 minutes or longer, 16 minutes or longer, 17 minutes or longer, 18 minutes or longer, 19 minutes or longer, 20 minutes or longer, 25 minutes or longer, 30 minutes or longer, 35 minutes or longer, 40 minutes or longer, 45 minutes or longer)
and wherein the ultrasound is unfocused and administered with a pulse or modulation pattern, a frequency, and an intensity sufficient for converting senescent cells into phenotypically normal cells ([0053] the ultrasound outputted from the ultrasound output unit may senescent cell-specifically increase the expression of one or more senescent cell-specific cytokine selected from a group consisting of interleukin 6 (IL-6), interleukin 8 (IL-8), matrix metalloproteinase-1 (MMP-1) and interleukin 1β (IL-1β). The senescent cell-specific cytokine is also known as senescence-associated secretory phenotype (SASP). Senescent cells expressing the senescence-associated secretory phenotype secrete high levels of inflammatory cytokines, immune modulators, growth factors and proteases)
Kim fails to teach mechanically stressing the senescent cells without killing the senescent cells.
However, Khuri-Yakub teaches stressing the senescent cells without killing the senescent cells ([0150] EDM 150, 250, and/or 350 can be configured to deliver energy (e.g. ultrasound energy) at a relatively low power density, such as to stimulate tissue without adversely affecting the tissue (e.g. avoiding cell death, such as to stimulate the tissue without adversely affecting the cells of the tissue))
Kim and Khuri-Yakub are considered analogous because both involve application of a therapeutic ultrasound. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the pending application to apply an ultrasound on the senescent cells as disclosed in the Kim reference but with parameters disclosed in the Khuri-Yakub reference in order to achieve the desired therapeutic results while avoiding cell death (Khuri-Yakub [0150])
Regarding claim 2, Kim teaches wherein the ultrasound is low frequency ultrasound ([0038] the ultrasound output unit may be low-intensity ultrasound)
Regarding claim 3, Kim teaches wherein the ultrasound is administered at 30 - 100 kHz ([0038] the ultrasound output unit may be low-intensity ultrasound with a center frequency of 5 kHz to 450 MHz. Specifically, the center frequency of the ultrasound outputted from the ultrasound output unit may be 5 kHz or higher, 10 kHz or higher, 50 kHz or higher, 100 kHz or higher)
Regarding claim 21, Kim teaches the pulse or modulation pattern comprises alternating periods of high and low ultrasound amplitudes ([0041] the ultrasound outputted from the ultrasound output unit may have a duty cycle of 0.1-99.9%; one of ordinary skill in the art would understand that a duty cycle of less than 100% implies alternating between a high and low amplitude where the low amplitude refers to no ultrasound)
Regarding claim 22, Kim teaches the alternating periods of high and low ultrasound amplitudes are of equal duration ([0041] duty cycle of 50%)
Regarding claim 23, Kim teaches the alternating periods of high and low ultrasound amplitudes are of different duration ([0041] the ultrasound outputted from the ultrasound output unit may have a duty cycle of 0.1-99.9%; any duty cycle aside from 50% results in alternating periods of high and low ultrasounds with different durations)
Regarding claim 24, Kim teaches wherein the low ultrasound amplitude is no ultrasound ([0041] the ultrasound outputted from the ultrasound output unit may have a duty cycle of 0.1-99.9%)
Regarding claim 28, Kim teaches wherein mechanically stressing the senescent cells comprises cyclically stressing organelles of the senescent cells without causing permanent damage to the cell organelles (this limitation refers to the target population and not the invention itself, thus it is understood that if the method in Kim is carried out this outcome will occur implicitly)
Regarding claim 29, Kim teaches the organelles that are cyclically stressed comprise cell membranes (this limitation refers to the target population and not the invention itself, thus it is understood that if the method in Kim is carried out this outcome will occur implicitly)
Regarding claim 30, Kim teaches the frequency is 0.44-0.67 MHz ([0038] he ultrasound outputted from the ultrasound output unit may be low-intensity ultrasound with a center frequency of 5 kHz to 450 MHz)
and the intensity comprises a pulse average intensity (IPA) of 0.3-8 W/cm2 and a temporal average intensity (ITA) of 5-50 mW/cm2 ([0078] ultrasound intensity starting from 0 to 7.5, 60 and 800 mW/cm2)
Claims 25 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Khuri-Yakub as applied to claim 1 above, and further in view of Hunziker (US 20100160837 A1).
Regarding claim 25, Kim fails to teach the pulse or modulation pattern comprises a sinusoidal modulation.
However, Hunziker teaches the pulse or modulation pattern comprises a sinusoidal modulation (Fig. 14a)
PNG
media_image1.png
526
601
media_image1.png
Greyscale
Kim and Hunziker are considered analogous because both disclose ultrasonic treatments. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the pending application to use a sinusoidal ultrasound pattern in order to improve homogeneity (Hunziker [0087])
Regarding claim 31, Kim fails to teach generating the ultrasound using beam steering and/or frequency sweeps to homogenize ultrasound fields.
However, Hunziker teaches generating the ultrasound using beam steering and/or frequency sweeps to homogenize ultrasound fields ([0087] FIGS. 14a and 14b depict exemplary embodiments using frequency modulation. FIG. 14a shows a single-element device driven with a frequency-modulated waveform. The waveform may consist of multiple discrete frequency steps, a continuous frequency sweep, or some combination thereof. The frequency steps or sweep may be realized within a single pulse (as shown in waveforms W1 and W2) or a series of pulses. For example, W3 shows a series of 3 single-frequency pulses each having a different frequency. In this case, the improvement in the homogeneity of the exposure is due to the cumulative effect of multiple pulses)
Kim and Hunziker are considered analogous because both disclose ultrasonic treatments. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the pending application to utilize a frequency sweep in order to improve homogeneity of the ultrasound field (Hunziker [0087])
Claims 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Khuri-Yakub as applied to claim 1 above, and further in view of Bonutti (US 20170209717 A1).
Regarding claim 26, Kim fails to teach the pulse or modulation pattern is adjusted over the course of the treatment.
However, Bonutti teaches the pulse or modulation pattern is adjusted over the course of the treatment ([0123] Ultrasound can be used to pick up more infectious agents and these echogenicity patterns could be cataloged and stored. If there is a difference in echogenicity of a fluid area, this would also be an indicator for infection and then device 100 may be configured to initiate treatments. For example, device 100 may be configured to be capable of changing the ultrasonic frequency from a first frequency associated with a diagnostic modality to a second frequency associated with a treatment modality to begin treatment of infection. As set forth above, the ultrasonic treatment may be pulsed or constant. It could be varied through several different frequencies to enhance the removal of biofilm. Since the tissue may be in a three-dimensional location, treatment with ultrasound may be made at varying angles)
Kim and Bonutti are considered analogous because both disclose ultrasound treatments. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date to change an ultrasound pattern as needed in order to account for a difference of echogenicity (Bonutti [0123]).
Regarding claim 27, Kim fails to teach the pulse or modulation pattern is maintained over the course of the treatment.
However, Bonutti teaches the pulse or modulation pattern is maintained over the course of the treatment ([0123] Ultrasound can be used to pick up more infectious agents and these echogenicity patterns could be cataloged and stored. If there is a difference in echogenicity of a fluid area, this would also be an indicator for infection and then device 100 may be configured to initiate treatments. For example, device 100 may be configured to be capable of changing the ultrasonic frequency from a first frequency associated with a diagnostic modality to a second frequency associated with a treatment modality to begin treatment of infection. As set forth above, the ultrasonic treatment may be pulsed or constant. It could be varied through several different frequencies to enhance the removal of biofilm. Since the tissue may be in a three-dimensional location, treatment with ultrasound may be made at varying angles)
Kim and Bonutti are considered analogous because both disclose ultrasound treatments. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date to keep the ultrasound pattern constant if there is no difference in echogenicity (Bonutti [0123]).
Response to Arguments
Applicant’s arguments, see page 5, filed 1/20/2026, with respect to the rejection(s) of claim(s) 1 under 35 USC 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the newly cited Khuri-Yakub reference.
Applicant argues persuasively that the difference between the pending application is that the pending claim as currently amended specifies that the senescent cells are not to be killed while this is not explicitly recited in the primary Kim reference. However, an updated search has uncovered the newly cited Khuri-Yakub reference which explicitly states that the ultrasound is applied at a level that achieves the desired results without inducing cell death and as a result each limitation of the independent claim are obviated by the prior art combination, thus, the claim set remains rejected under 35 USC 103.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GABRIEL VICTOR POPESCU whose telephone number is (571)272-7065. The examiner can normally be reached M-F 8AM-5PM.
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, Anne Kozak can be reached at (571) 270-0552. 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.
/GABRIEL VICTOR POPESCU/Examiner, Art Unit 3797
/SERKAN AKAR/Primary Examiner, Art Unit 3797