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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/4/26 has been entered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 19, 23, 45, and 52-53 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (US 2021/0244972; hereinafter Kim).
Kim shows a non-invasive method of reducing cellular senescence (abstract, [0006]) comprising: applying a repetitive low frequency ultrasound treatment to a living cell, wherein the repetitive low frequency ultrasound treatment is applied with a magnitude, frequency, modulation pattern, and duration sufficient to cyclically stretch the living cell (where the action of applying low intensity ultrasound upon the cell is considered to stretch the cell; [0038]-[0041], [0043], [0048]-[0050], [0061]) to reduce cellular senescence of the living cell without killing or causing mechanical or thermal damage to the living cell (low intensity ultrasound avoids damage to living cell, ultrasound stimulation affects cellular senescence including increasing SASP/growth factor in senescent cells, [0093], [0104]-[0106]; [0004]-[0006]).
Kim also shows wherein after receiving the repetitive low frequency ultrasound treatment, the living cell exhibits at least one of, increased cell division, reduced cell size, increased secretion of growth factors, decreased secretion of senescent factors, and increased mitochondrial fission ([0006], [0093]); wherein, after receiving the repetitive low frequency ultrasound treatment, the living cell exhibits at least one of: an extended replicative lifespan of the at least one living cell; and reversion to a more youthful phenotype ([0006]); wherein a wavelength of the low frequency ultrasound treatment is equal to or greater than an average cell diameter (as a variety of wavelengths may be used as described in [0038], and as the ultrasound may be focused on various cells in the patient’s body, at least some of the wavelengths are considered to be equal or greater to at least some cell’s diameter, depending on the patient and the particular cell being treated); wherein the repetitive low frequency ultrasound treatment does not induce a spontaneous cell death in normal cells ([0007]); wherein the frequency of the repetitive low frequency ultrasound treatment is between about 30 kHz and 240 kHz ([0038]); wherein an ultrasound field produced by the repetitive low frequency ultrasound treatment is unfocused and direction-insensitive ([0075], Fig. 2A).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 2021/0244972; hereinafter Kim) in view of Finsterwald (US 2008/0045882).
Kim fails to show wherein the active agent is a supernatant of cells treated with a repetitive low frequency ultrasound treatment.
Finsterwald discloses methods for enhancing uptake of therapeutic biological agents. Finsterwald teaches wherein the active agent is a supernatant of cells treated with a repetitive low frequency ultrasound treatment (where a cell culture is considered to include a supernatant of cells; [0015]-[0018], [0074]-[0076]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kim to utilize an active agent treated with low frequency ultrasound as taught by Finsterwald, as Finsterwald teaches that applying ultrasound to a therapeutic biological agent produces various beneficial effects, such as stimulating the cells, promoting uptake, increasing metabolic activity of cells, increasing production yields, etc. ([0015]-[0018], [0074]-[0076]).
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 2021/0244972; hereinafter Kim) in view of Kenney et al. (US 2022/0047894; hereinafter Kenney).
Kim shows the invention substantially as described in the 102 rejection above.
Kim fails to show further comprising providing a mechanism that at least one of: absorbs or uncouples the repetitive low frequency ultrasound treatment to reduce or deflect a sound wave after patient treatment, is a material that is suitable to at least one of attenuate sound waves or guide the sound waves away from a site or treatment, or includes one or more elements that convert residual sound energy into heat.
Kenney discloses systems and methods for immersion therapy. Kenney teaches providing a mechanism that at least one of: absorbs or uncouples the repetitive low frequency ultrasound treatment to reduce or deflect a sound wave after patient treatment, is a material that is suitable to at least one of attenuate sound waves or guide the sound waves away from a site or treatment, or includes one or more elements that convert residual sound energy into heat ([0088], [0090]).
Kenney additionally teaches an immersion design for the treatment is optimized to treat wounds and ulcers and can include one or more chambers that are generally shallow and suited for full immersion with an absorber shield about a treatment zone, and wherein the one or more one or more ultrasound sources and an absorber can contact a patient or are insulated by an immersion medium ([0062], [0077], [0088], [0095]); providing a mechanism that at least one of: absorbs or uncouples the repetitive low frequency ultrasound treatment to reduce or deflect a sound wave after patient treatment, is a material that is suitable to at least one of attenuate the sound waves or guide the sound waves away from a site or treatment, or includes one or more elements that convert residual sound energy into heat or providing an immersion vessel to treat wounds and ulcers that includes one or more chambers that are partial or full immersion with an absorber shield about a treatment zone, and wherein one or more transducers and one or more absorber can contact a patient or are insulated by an immersion medium ([0062], [0077], [0088], [0090], [0095]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kim to provide an absorber as taught by Kenney, in order to reduce undesired ultrasound waves in regions outside of the treatment area.
Claim(s) 30, 46-47, and 51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 2021/0244972; hereinafter Kim).
Kim shows the invention as described in the 102 rejection above.
Kim also shows low-intensity ultrasound stimulation transmitting a power of 800 mW/cm2 ([0075]).
Kim fails to show wherein applying the repetitive low frequency ultrasound treatment transmits a power of 10, 20, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 1,000, 5,000, or 10,000 mW/cm2; wherein the repetitive low frequency ultrasound treatment transmits a power of less than 500 mW/cm2; wherein cyclically stretching the living cell comprises deforming the living cell by about 1% to about 5%, about 3% to about 8%, or about 5% to about 10%; wherein the repetitive low frequency ultrasound treatment comprises an alternating modulation pattern having an active period of about 1.5 seconds followed by an inactive period of about 1.5 seconds.
It would have been an obvious design choice to one of ordinary skill in the art, to transmit at a power less than 500 mW/cm2, as Kim shows transmitting at a particular power of 800 mW/cm2 for the demonstration experiment to illustrate the effects of ultrasound on cellular senescence. Kim also specifically recognizes using “low” intensity levels ([0075]), and it would be within the level of one of ordinary skill in the art, without undue experimentation, to operate the ultrasound transducer at other low intensity levels, including levels less than 500 mW/cm2 in order to effectuate the desired low intensity ultrasound treatment. It is noted that known ultrasound treatment transducers are capable of being operated at a variety of low power levels.
Furthermore, it would have been an obvious design choice to one of ordinary skill in the art operating the transducer to perform the desired ultrasound treatment, without undue experimentation, to perform cyclically stretching the living cell comprises deforming the living cell by about 1% to about 5%, about 3% to about 8%, or about 5% to about 10% in order to accomplish the desired cellular affects described by Kim to treat age related diseases ([0006]). The examiner notes that Kim describes operating the transducer over a range of different operating parameters ([0038]-[0041]) and describes optimizing ultrasound parameters such as center frequency, sound pressure, pulse repetition frequency, and duty cycle ([0043]), where control over these ultrasound system parameters will control the functional changes occurring within the patient’s cells such as the amount of deformation, to perform the desired effects of prolonging life, defeating aging, treating age-related disease ([0006]).
Furthermore, it would be an obvious design choice, without undue experimentation, to utilize an alternating modulation pattern having an active period of about 1.5 seconds followed by an inactive period of about 1.5 seconds, in order to effectuate the desired treatment protocol according to the desired optimized duty cycle of Kim, where it would be within the level of one of ordinary skill in the art to control the length of time of the period in relation to the optimized duty and where a 50% duty cycle is associated with the active and inactive period of the transducer being equal ([0041], [0043]).
The examiner maintains that it would be within the level of one of ordinary skill in the art, performing the ultrasound treatment protocol to reduce cellular senescence of Kim, to control and vary the ultrasound treatment parameters depending on various conditions including the user’s preference and the patient’s disease state.
Claim(s) 48-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 2021/0244972; hereinafter Kim) in view of Owen et al. (US 2018/0264266; hereinafter Owen).
Kim shows the invention as described in the 102 rejection above.
Kim fails to show wherein the repetitive low frequency ultrasound treatment comprises a ramp-up phase during which the magnitude of the ultrasound is gradually increased; wherein the repetitive low frequency ultrasound treatment comprises a ramp-down phase during which the magnitude of the ultrasound is gradually decreased; wherein the repetitive low frequency ultrasound treatment comprises: a ramp-up phase during which the magnitude of the repetitive low frequency ultrasound treatment is gradually increased; and a ramp-down phase during which the magnitude of the repetitive low frequency ultrasound treatment is gradually decreased;
Owen discloses systems and methods for treating vestibular conditions using vibratory devices. Owen teaches wherein the repetitive low frequency ultrasound treatment comprises a ramp-up phase during which the magnitude of the ultrasound is gradually increased; wherein the repetitive low frequency ultrasound treatment comprises a ramp-down phase during which the magnitude of the ultrasound is gradually decreased; wherein the repetitive low frequency ultrasound treatment comprises: a ramp-up phase during which the magnitude of the repetitive low frequency ultrasound treatment is gradually increased; and a ramp-down phase during which the magnitude of the repetitive low frequency ultrasound treatment is gradually decreased.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the invention of Kim to utilize a ramp-up and ramp-down phase as taught by Owen, as Owen teaches that the rate of increase/decrease may be specified depending on various conditions, and that the ramp may reduce sudden/jarring effects caused by transitioning the device on and off ([0119]).
Response to Arguments
Applicant's arguments filed 5/4/26 have been fully considered but they are not persuasive.
First, it is noted that the claim language uses the term “or”, in the phrase “without killing or causing mechanical or thermal damage to the living cell”. The prior art only requires one of without “killing”, “mechanical damage”, or “thermal damage” to meet the claim limitation.
Additionally, Kim does teach “applying a repetitive low frequency ultrasound treatment…without killing”. As noted in the rejection above, Kim teaches using low intensity ultrasound. The physical action of the low intensity ultrasound treatment does not directly kill the living cell as compared to an ultrasound treatment technology such as HIFU which acts to thermally ablate cells ([0007]), but rather low intensity ultrasound may act to stimulate senescent cells ([0051]-[0055]) and promote secretion of SASP factors, leading to enhanced immune cell migration ([0107]). That is, low intensity ultrasound may achieve a variety of different effects on the cell, including effects which do not directly kill the cells, depending on the ultrasound treatment parameters. Additionally, the ultrasound treatment may act to stimulate the patient’s immune system, where the patient’s immune system may then kill the cells through phagocytosis.
The examiner notes that Kim is similarly directed to applying a low frequency ultrasound treatment to a living cell to reduce cellular senescence. The examiner maintains that similar effects related to cyclically stretching the cells will be achieved at various timepoints throughout the ultrasound treatment. While applicant claims that the final function of the treatment is distinct, it is unclear how the low-frequency ultrasound treatment itself is differentiated from the prior art of record. The examiner maintains that application of low frequency ultrasound treatment will produce similar effects. Furthermore Kim teaches utilizing a variety of different ultrasound treatment parameters ([0038]-[0041], [0048]-[0050]).
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 JONATHAN CWERN whose telephone number is (571)270-1560. The examiner can normally be reached Monday - Friday, 8:00 am - 5:00 pm.
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, Christopher Koharski can be reached at (571) 272-7230. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONATHAN CWERN/Primary Examiner, Art Unit 3797
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