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 .
DETAILED ACTION
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.
Claims 1-9, 11-13, 15-16, 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Schettini et al. (US 2015/0301058) and in view of Hynynen et al. (US 2006/0241529).
Addressing claim 11, Schettini discloses a method for releasing extracellular vesicles (EVs) of a subject, comprising:
applying an ultrasound treatment to a target tissue of the subject (see [0167]);
collecting a sample from the subject (see [0122]);
isolating EVs from the sample (see [0093] and [0550]);
analyzing a biomarker in the sample (see [0010] and [0093]).
Schettini does not disclose where the target tissue comprises a brain and/or blood-brain barrier. Hynynen discloses where the target tissue comprises a brain and/or blood-brain barrier (see Fig. 1, [0007-0008] and [0020]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Schettini to have wherein the target tissue comprises a brain and/or blood-brain barrier as taught by Hynynen because this help treat brain cancer (see Schettini’s paragraphs [0010], [0030], [0044], [0095] and [0167]; Hynynen’s [0004]; Schettini disclose diagnose and treat brain tumor; using drug for treatment; Hynynen discloses open blood-brain barrier to help deliver drug for treatment).
Addressing claims 13, 15-16 and 18, Schettini discloses:
addressing claim 13, wherein the sample comprises blood, serum, or a combination thereof (see [0007] and [0019]).
addressing claim 15, wherein the biomarker comprises alpha-synuclein (aSyn), amyloid-beta, tau, or combinations thereof (see [0030], [0281] and [0419]; amyloid-beta).
addressing claim 16, wherein the biomarker comprises an inflammation-related marker, a proliferation-associated gene, an immediate inflammatory response- related protein, a hemoglobin-associated protein, or combinations thereof (see [0282]).
addressing claim 18, wherein the subject has a neurological disorder (see [0113], [0126], [0281], [0287] and [0552]; analyze biomarker to detect neurological disorder or analyze biomarker of a patient suspected of neurological disorder).
Addressing claims 3-5, 9, 12 and 20, Hynynen discloses:
addressing claims 3 and 12, wherein the ultrasound assembly is configured to apply a focused ultrasound (FUS) treatment, a theranostic-ultrasound (ThUS) treatment, or a combination thereof (see [0005]);
addressing claims 4 and 20, wherein the ultrasound treatment has one or more ultrasound parameters, wherein the ultrasound parameters comprise a center frequency, a focal depth, a focal area, one of a peak negative pressure, a stimulation duration, a duty cycle, a pulse repetition frequency (PREF), or combinations thereof (see [0007-0008]; focal region/area);
addressing claim 5, wherein the transducer is configured to apply the ultrasound treatment to a blood-brain barrier (see [0007-0008], [0017], [0020] and claim 1);
addressing claim 9, wherein the ultrasound transducer is configured to apply the FUS treatment at about 0.25 MHz center frequency or the ThUS treatment at about 0.5 MHz center frequency (see [0007-0008], [0017], [0020] and claim 1).
Addressing claims 1-2 and 6-8, the system performs the method therefore claims 1-2 and 6-7 are being rejected for the same reason as method claims 11, 13, 16 and 18. Any ultrasound system is capable of performing pulse-echo therefore any system is pulse-echo ultrasound transducer.
Claims 10 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Schettini et al. (US 2015/0301058), in view of Hynynen et al. (US 2006/0241529) and further in view of Puleo et al. (US 2020/0069975).
Addressing claims 10 and 17, Schettini does not disclose wherein the sample is collected about 1 hour after the ultrasound treatment. However, this is designer choice depend on physician and only require routine skill in the art (applicant specification discloses sample could be collected at many different times after ultrasound treatment (see [0050])). Physician would not the appropriate time to collect the sample. Puleo explicitly disclose wherein the sample is collected about 1 hour after the ultrasound treatment (see [0025] and [0082]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Schettini to collect sample about 1 hour after the ultrasound treatment as taught by Puleo because the sample could be defective if not collect at an appropriate time.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Schettini et al. (US 2015/0301058), in view of Hynynen et al. (US 2006/0241529) and further in view of Goetzl (US 2016/0363599).
Addressing claim 19, Schettini does not disclose applying an effective amount of a therapeutic treatment to a subject based on the biomarker. Goetzl discloses applying an effective amount of a therapeutic treatment to a subject based on the biomarker (see [0015]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Schettini to apply an effective amount of a therapeutic treatment to a subject based on the biomarker as taught by Goetzl because would provide accurate and effective treatment (see [0015]; using biomarker to determine if subject has neurodegenerative disease then administer effective amount of a therapeutic treatment to a subject; if the subject does not has neurodegenerative disease then no reason to administer therapeutic treatment).
Response to Arguments
Applicant's arguments filed 11/19/25 have been fully considered but they are not persuasive. Applicant argues the subject matter of amended claims recites actively stimulating release of EVs from a target tissue. Applicant’s argument is not persuasive because this is not in the claim. Release of EVs is in the pre-ample and does not have weight. There is no “stimulating release of EVs from a target tissue” in the claim. Further, Schettini discloses release of vesicles increase when apply ultrasonic energy (see [0167]). Applicant argues Schettini does not disclose altering physiology to increase EV yield. Applicant’s argument is not persuasive because Schettini discloses release of vesicles increase when apply ultrasonic energy (see [0167]). Applicant argues Hynynen provides a system using focused ultrasound for BBB opening for drug delivery, not for releasing EVs or for diagnostic biomarker enrichment and Hynynen does not measure, collect, or analyze EVs, let alone contemplate that BBB opening would cause biomarker- carrying vesicles to enter circulation, thus, a person skilled in the art would have no motivation to combine Schettini and Hynynen to arrive at the subject matter of amended claim 1. Applicant’s argument is not persuasive because Schettini discloses increase/inrichment vesicles through ultrasound, analyze vesicles and perform treatment while Hynynen disclose opening BBB to help deliver drug for treatment. Examiner does not rely on Hynynen to disclose releasing EVs or for diagnostic biomarker enrichment and measure, collect, or analyze EVs. This is disclosed by Schettini. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Vesicles carry drug, combine Schettini with Hynynen to help deliver drug carrying vesicles to brain tumor.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US 20250263798 (see abstract; BBB and EVs); US 20240358805 (see [0191]; BBB with EVs); US 20210163555 (see [0045]; BBB and EVs) and US 20190323086 (see [0070], [0135] and [0123]; BBB and EVs).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/HIEN N NGUYEN/
Primary Examiner
Art Unit 3793