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’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has complied with all conditions for receiving the benefit of an earlier filing date of 07 Aug 2022 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 30 Jan 2025 and 11 Feb 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the Examiner. Examiner further notes that the later submitted IDS is a duplicate of the initially submitted IDS.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites in the preamble “sonothrombolysis mediated with contrast agents” and in the body of the claim the limitation “administering at least one contrast agent into a blood vessel of a patient”. It is unclear whether “contrast agents” recited in the preamble and “at least one contrast agent” recited in the body limitation are the same or different. Claims 2-8 inherit the deficiency by the nature of their dependency on claim 1. For purposes of the examination, “contrast agents” recited in the preamble and “at least one contrast agent” recited in the body limitation are given a broadest reasonable interpretation to be the same.
Claim 5 recites the limitation “the frequency steps range from about 450 kHz to about 650 kHz at 50 kHz intervals”. The antecedent basis for “the frequency steps” in the limitation is unclear. In particular, it is unclear whether “the frequency steps” in the limitation is referring to: a) “a plurality of frequency steps” recited in claim 4, to which claim 5 depends; b) particular frequency steps of “a plurality of frequency steps” recited in claim 4; or c) otherwise. For purposes of the examination, the limitation is being given a broadest reasonable interpretation as “the plurality of frequency steps range from about 450 kHz to about 650 kHz at 50 kHz intervals”.
Claim 10 recites “The device of claim 11 wherein the ultrasound transducer comprises a forward-viewing ultrasound transducer”. The antecedent basis for “the device of claim 11” is unclear. In particular, claim 11 is directed to a system and if claim 10 were to be dependent on the system of claim 11, it would be redundant of claim 20. For purposes of the examination, claim 10 is being given a broadest reasonable interpretation as being dependent on the method of claim 1.
Claim 11 recites in the preamble “sonothrombolysis mediated with contrast agents” and in the body of the claim the limitation “administering at least one contrast agent into a blood vessel of a patient”. It is unclear whether “contrast agents” recited in the preamble and “at least one contrast agent” recited in the body limitation are the same or different. Claims 12-20 inherit the deficiency by the nature of their dependency on claim 1. For purposes of the examination, “contrast agents” recited in the preamble and “at least one contrast agent” recited in the body limitation are given a broadest reasonable interpretation to be the same.
Claim 15 recites the limitation “the frequency steps range from about 450 kHz to about 650 kHz at 50 kHz intervals”. The antecedent basis for “the frequency steps” in the limitation is unclear. In particular, it is unclear whether “the frequency steps” in the limitation is referring to: a) “a plurality of frequency steps” recited in claim 4, to which claim 5 depends; b) particular frequency steps of “a plurality of frequency steps” recited in claim 4; or c) otherwise. For purposes of the examination, the limitation is being given a broadest reasonable interpretation as “the plurality of frequency steps range from about 450 kHz to about 650 kHz at 50 kHz intervals”.
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.
Claims 1-3, 6, 9-13, 16, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jiang et al. (US PG Pub No. 2021/0007759, provided by the Applicant in the IDS of 30 Jan 2025 and 11 Feb 2025) – hereinafter referred to as Jiang.
Regarding claim 1, Jiang discloses a method for sonothrombolysis mediated with contrast agents (see at least Abstract: intravascular thrombolysis using ultrasound transducer; and [0078]: nanodroplets and/or microbubbles supplied intravascular thrombolysis), the method comprising:
administering at least one contrast agent into a blood vessel of a patient (Fig. 6 and [0078]: supply conduit 4 arranged along catheter 3 and configured to supply nanodroplets and/or microbubbles outwardly from the distal end 275 of the catheter; Fig. 9 and [0090]: catheter configured to facilitate local administration of nanodroplets for clot disruption in a blood artery); and
controlling application of ultrasound energy to the at least one contrast agent within the blood vessel (Fig. 9 and [0093]: ultrasound transducer is used to excite the injected microbubble contrast agents (MCA) or nanodroplets to cause enhanced cavitation-induced microstreaming),
wherein controlling the application of the ultrasound energy includes driving an ultrasound transducer with a signal having a first frequency component and a second frequency component different from the first frequency component ([0096]: dual-acoustic excitation at high frequency shock waves and low frequency burst waves applied for thrombolysis).
Regarding claim 2, Jiang discloses all limitations of claim 1, as discussed above, and Jiang further discloses:
inserting the ultrasound transducer into the blood vessel adjacent to the at least one contrast agent before controlling the application of the ultrasound energy (Fig. 9: piezoelectric transducer and laser-generated ultrasound transducer adjacent a blood clot and microbubbles; [0093]: ultrasound transducers used to excite the injected microbubble contrast agents (MCA) or nanodroplets to cause enhanced cavitation-induced microstreaming).
Regarding claim 3, Jiang discloses all limitations of claim 2, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer is housed in a catheter (Fig. 6 and [0078]: first ultrasonic transducer arrangement 1 and third ultrasonic transducer arrangement 7 are at the distal end 275 of catheter 3).
Regarding claim 6, Jiang discloses all limitations of claim 1, as discussed above, and Jiang further discloses:
wherein the at least one contrast agent comprises at least one nanodroplet and/or at least one microbubble (Fig. 6 and [0078]: supply conduit 4 supplies nanodroplets, microbubbles, etc.).
Regarding claim 9, Jiang discloses all limitations of claim 1, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer (Fig. 6: first ultrasonic transducer arrangement 1) comprises at least one piezoelectric element ([0081]: transducer arrangement 1 comprising transducer elements of piezoelectric material).
Regarding claim 10, Jiang discloses all limitations of claim 1, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer (Fig. 6: first and third ultrasonic transducer arrangements 1, 7) comprises a forward-viewing ultrasound transducer (Fig. 6 and [0078]: first and third ultrasonic transducer arrangements 1, 7 are disposed at distal end 275 and oriented with acoustic waves propagating parallel to the longitudinal axis 200 of catheter 3).
Regarding claim 11, Jiang discloses a system for sonothrombolysis mediated with contrast agents (see at least Abstract: intravascular thrombolysis using ultrasound transducer; and [0078]: nanodroplets and/or microbubbles supplied intravascular thrombolysis), the method comprising:
an ultrasound transducer (Fig. 6: first and third ultrasonic transducer arrangements 1, 7); and
a function generator connected to the ultrasound transducer (Fig. 18: function generator connected to piezo-transducer and laser-ultrasound transducer),
the function generator (Fig. 18: function generator connected to power amplifier) configured for controlling application of ultrasound energy to at least one contrast agent within a blood vessel (Fig. 6 and [0078]: supply conduit 4 arranged along catheter 3 and configured to supply nanodroplets and/or microbubbles outwardly from the distal end 275 of the catheter; Fig. 9 and [0090]: catheter configured to facilitate local administration of nanodroplets for clot disruption in a blood artery),
wherein controlling the application of the ultrasound energy includes driving an ultrasound transducer with a signal having a first frequency component and a second frequency component different from the first frequency component ([0096]: dual-acoustic excitation at high frequency shock waves and low frequency burst waves applied for thrombolysis).
Regarding claim 12, Jiang discloses all limitations of claim 11, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer is configured for being inserted into the blood vessel adjacent to the at least one contrast agent (Fig 9: piezoelectric transducer and laser-generated ultrasound transducer adjacent a blood clot and microbubbles).
Regarding claim 13, Jiang discloses all limitations of claim 12, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer is housed in a catheter (Fig. 6 and [0078]: first ultrasonic transducer arrangement 1 and third ultrasonic transducer arrangement 7 are at the distal end 275 of catheter 3).
Regarding claim 16, Jiang discloses all limitations of claim 11, as discussed above, and Jiang further discloses:
wherein the at least one contrast agent comprises at least one nanodroplet and/or at least one microbubble (Fig. 6 and [0078]: supply conduit 4 supplies nanodroplets, microbubbles, etc.).
Regarding claim 19, Jiang discloses all limitations of claim 11, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer (Fig. 6: first ultrasonic transducer arrangement 1) comprises at least one piezoelectric element ([0081]: transducer arrangement 1 comprising transducer elements of piezoelectric material).
Regarding claim 20, Jiang discloses all limitations of claim 11, as discussed above, and Jiang further discloses:
wherein the ultrasound transducer (Fig. 6: first and third ultrasonic transducer arrangements 1, 7) comprises a forward-viewing ultrasound transducer (Fig. 6 and [0078]: first and third ultrasonic transducer arrangements 1, 7 are disposed at distal end 275 and oriented with acoustic waves propagating parallel to the longitudinal axis 200 of catheter 3).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 4 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang, as applied to claims 1 and 11, respectively above, and further in view of Patil et al. (Patil et al. Dual Frequency Method for Simultaneous Translation and Real-Time Imaging of Ultrasound Contrast Agents Within Large Blood Vessels, Ultrasound in Medicine & Biology, Volume 35, Issue 12, 2009, Pages 2021-2030, ISSN 0301-5629, doi:10.1016/j.ultrasmedbio.2009.07.003. A copy attached to this Office action.) – hereinafter referred to as Patil.
Regarding claim 4, Jiang discloses all limitations of claim 1, as discussed above, and Jiang does not disclose:
wherein the first frequency component is a constant frequency component and
the second frequency component includes a plurality of frequency steps within a range of frequencies.
In the same field of sonothrombolysis, Patil, however, discloses:
driving an ultrasound transducer at a first frequency of a constant frequency components and at a second frequency of a plurality of frequency steps within a range of frequencies (pg. 2024: Phantom experiments: As illustrated in Table 1, the radiation force pulse frequency was varied from 1.6 to 10 MHz (second frequency) while keeping the imaging frequency constant at 8 MHz (first frequency)).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Jiang’s method to include Patil’s method of driving an ultrasound transducer at different frequencies. One of ordinary skill in the art would have combined the elements as claimed by known methods (i.e., driving the ultrasound transducer at different frequencies for imaging vs. thrombolysis, as disclosed by Patil), and the combination would have yielded a reasonable expectation of success since both Jiang and Patil are directed to sonothrombolysis using an ultrasound transducer. The motivation for the combination would have been to “optimiz[ing] the effect of targeted imaging and modulating drug delivery in large blood vessels with high flow velocities”, as taught by Patil (Abstract).
Regarding claim 14, Jiang discloses all limitations of claim 11, as discussed above, and Jiang does not disclose:
wherein the first frequency component is a constant frequency component and
the second frequency component includes a plurality of frequency steps within a range of frequencies.
In the same field of sonothrombolysis, Patil, however, discloses:
driving an ultrasound transducer at a first frequency of a constant frequency components and at a second frequency of a plurality of frequency steps within a range of frequencies (pg. 2024: Phantom experiments: As illustrated in Table 1, the radiation force pulse frequency was varied from 1.6 to 10 MHz (second frequency) while keeping the imaging frequency constant at 8 MHz (first frequency)).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Jiang’s system to include Patil’s method of driving an ultrasound transducer at different frequencies. One of ordinary skill in the art would have combined the elements as claimed by known methods (i.e., driving the ultrasound transducer at different frequencies for imaging vs. thrombolysis, as disclosed by Patil), and the combination would have yielded a reasonable expectation of success since both Jiang and Patil are directed to sonothrombolysis using an ultrasound transducer. The motivation for the combination would have been to “optimiz[ing] the effect of targeted imaging and modulating drug delivery in large blood vessels with high flow velocities”, as taught by Patil (Abstract).
Claims 5 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang in view of Patil, as applied to claims 4 and 14, respectively above, and further in view of De Picciotto et al. (US PG Pub No. 2021/0146156) – hereinafter referred to as De Picciotto.
Regarding claim 5, Jiang in view of Patil discloses all limitations of claim 4, as discussed above, and Jiang in view of Patil does not explicitly disclose:
wherein the first frequency component has a center frequency of about 750 kHz and the frequency steps range from about 450 kHz to about 650 kHz at 50 kHz intervals.
As noted above in claim 4, Patil discloses driving an ultrasound transducer at a first frequency of a constant frequency components and at a second frequency of a plurality of frequency steps within a range of frequencies (pg. 2024 of Patil: Phantom experiments: As illustrated in Table 1, the radiation force pulse frequency was varied from 1.6 to 10 MHz (second frequency) while keeping the imaging frequency constant at 8 MHz (first frequency)). However, Patil does not explicitly disclose the claimed frequencies in claim 5.
In the same field of sonothrombolysis, De Picciotto, however, discloses:
applying a range of ultrasound frequency between 100 kHz and 1.0 MHz at various step intervals ([0027]: applying a range of frequencies suitable for ultrasound treatments, 0,1 MHz (or 100 kHz) to 10 MHz at small and large frequency intervals in kHz).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Jiang’s method to include Yang’s method of applying a range of ultrasound frequencies between 100 kHz and 1.0 MHz at various step intervals. One of ordinary skill in the art would have combined the elements as claimed by known methods (i.e., applying a range of acoustic frequency at varying step intervals, as disclosed by De Picciotto), and the combination would have yielded a reasonable expectation of success since both Jiang and De Picciotto are directed to sonothrombolysis using an ultrasound transducer. The motivation for the combination would have been to “optimiz[ing] the ultrasound frequency (for sonothrombolysis)”, as taught by De Picciotto ([0027]-[0028]).
Regarding claim 15, Jiang in view of Patil discloses all limitations of claim 14, as discussed above, and Jiang in view of Patil does not explicitly disclose:
wherein the first frequency component has a center frequency of about 750 kHz and the frequency steps range from about 450 kHz to about 650 kHz at 50 kHz intervals.
As noted above in claim 14, Patil discloses driving an ultrasound transducer at a first frequency of a constant frequency components and at a second frequency of a plurality of frequency steps within a range of frequencies (pg. 2024 of Patil: Phantom experiments: As illustrated in Table 1, the radiation force pulse frequency was varied from 1.6 to 10 MHz (second frequency) while keeping the imaging frequency constant at 8 MHz (first frequency)). However, Patil does not explicitly disclose the claimed frequencies in claim 5.
In the same field of sonothrombolysis, De Picciotto, however, discloses:
applying a range of ultrasound frequency between 100 kHz and 1.0 MHz at various step intervals ([0027]: applying a range of frequencies suitable for ultrasound treatments, 0,1 MHz (or 100 kHz) to 10 MHz at small and large frequency intervals in kHz).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Jiang’s system to include Yang’s method of applying a range of ultrasound frequencies between 100 kHz and 1.0 MHz at various step intervals. One of ordinary skill in the art would have combined the elements as claimed by known methods (i.e., applying a range of acoustic frequency at varying step intervals, as disclosed by De Picciotto), and the combination would have yielded a reasonable expectation of success since both Jiang and De Picciotto are directed to sonothrombolysis using an ultrasound transducer. The motivation for the combination would have been to “optimiz[ing] the ultrasound frequency (for sonothrombolysis)”, as taught by De Picciotto ([0027]-[0028]).
Claims 7-8 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang, as applied to claims 1 and 11, respectively above, and further in view of Robinson et al. (US PG Pub No. 2022/0409169, priority date of 21 Oct 2019) – hereinafter referred to as Robinson.
Regarding claims 7-8, Jiang discloses all limitations of claim 1, as discussed above, and Jiang does not disclose:
wherein a strength of the signal is adjusted according to each frequency component (claims 7-8); and
wherein the strength of the signal is adjusted to provide approximately equal levels of ultrasound energy by the first frequency component and the second frequency component of the signal (claim 8).
In the same field of ultrasound treatment, Slayton, however, teaches:
adjusting a strength of an ultrasound drive signal according to a frequency component ([0040]: power to transducer elements are adjusted to achieve the peak negative pressure of ~20 MPa or greater); and
wherein the strength of the signal is adjusted to provide approximately equal levels of ultrasound energy by different frequency components of the signal ([0040]: operating frequencies of therapeutic transducer element ranging from 0.5 MHz to 2.0MHz, and power to transducer elements are adjusted to achieve the peak negative pressure of ~20 MPa or greater).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Jiang’s method to include Robinson’s method of adjusting a strength of a signal according to a frequency. One of ordinary skill in the art would have combined the elements as claimed by known methods (i.e., adjusting the signal strength for a frequency to maintain an equal level of ultrasound energy, as disclosed by Robinson), and the combination would have yielded a reasonable expectation of success since both Jiang and Robinson are directed to sonothrombolysis using an ultrasound transducer. The motivation for the combination would have been to provide “a (constant) pulse wave characterized by approximately 10 megapascals (MPa) of pressure in order to affect the calcification (or for thrombolysis)”, as taught by Robinson ([0048]).
Regarding claims 17-18, Jiang discloses all limitations of claim 11, as discussed above, and Jiang does not disclose:
wherein a strength of the signal is adjusted according to each frequency component (claims 17-18); and
wherein the strength of the signal is adjusted to provide approximately equal levels of ultrasound energy by the first frequency component and the second frequency component of the signal (claim 18).
In the same field of ultrasound treatment, Slayton, however, teaches:
adjusting a strength of an ultrasound drive signal according to a frequency component ([0040]: power to transducer elements are adjusted to achieve the peak negative pressure of ~20 MPa or greater); and
wherein the strength of the signal is adjusted to provide approximately equal levels of ultrasound energy by different frequency components of the signal ([0040]: operating frequencies of therapeutic transducer element ranging from 0.5 MHz to 2.0MHz, and power to transducer elements are adjusted to achieve the peak negative pressure of ~20 MPa or greater).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Jiang’s method to include Robinson’s method of adjusting a strength of a signal according to a frequency. One of ordinary skill in the art would have combined the elements as claimed by known methods (i.e., adjusting the signal strength for a frequency to maintain an equal level of ultrasound energy, as disclosed by Robinson), and the combination would have yielded a reasonable expectation of success since both Jiang and Robinson are directed to sonothrombolysis using an ultrasound transducer. The motivation for the combination would have been to provide “a (constant) pulse wave characterized by approximately 10 megapascals (MPa) of pressure in order to affect the calcification (or for thrombolysis)”, as taught by Robinson ([0048]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wu et al. (Wu et al. Dual-Frequency Intravascular Sonothrombolysis: An In Vitro Study. IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Dec;68(12):3599-3607. doi: 10.1109/TUFFC.2021.3103409. Epub 2021 Nov 23. PMID: 34370663; PMCID: PMC8645157. Applicant’s published research paper.) discloses applying two different ultrasound frequencies for sonothrombolysis (at least Abstract);
Auboire et al. (Auboire et al. Microbubbles combined with ultrasound therapy in ischemic stroke: A systematic review of in-vivo preclinical studies. PLoS One. 2018 Feb 8;13(2):e0191788. doi: 10.1371/journal.pone.0191788.) discloses a range of ultrasound frequencies used for imaging and treatment (see Table 5);
Yang et al. (US PG Pub No. 2022/0071705) discloses an ultrasound frequency of 750 kHz for sonothrombolysis (see [0038]); and
Galluzzo et al. (US PG Pub No. 2012/0267986) discloses an ultrasound transducer configured for two frequency components (see Abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Younhee Choi whose telephone number is (571)272-7013. The examiner can normally be reached M-F 9AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anhtuan Nguyen can be reached at 571-272-4963. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Y.C./Examiner, Art Unit 3797
/ANH TUAN T NGUYEN/Supervisory Patent Examiner, Art Unit 3795
1/12/26