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 .
Election/Restrictions
Applicant’s election without traverse of group I (claims 1-2, 4, 7, 11, 20, 29, 32, 34, 49, 55-56 and 62) in the reply filed on 08/15/2025 is acknowledged. Claims 67-68, 70, 75-76, 78 and 84 are withdrawn.
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, 2, 4, 7, 11, 29, 32, 49, 55, 56 and 88-89 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt).
Regarding claim 1, Park discloses ultrasound mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model. Park shows a method of treating epidermal growth factor 2 (Her2) positive Her2+ metastatic breast tumor in a brain (see abstract), comprising:(a) selecting a patient having a Her2+ metastatic breast tumor in the brain (see abstract, “introduction” on page 277, and “material and methods” on page 278) and (b) applying an ultrasound beam to the cranium of the selected patient to cause transient disruption of the blood-brain barrier (BBB) of the selected patient (see “material and methods” on page 278, “ultrasound” on page 279; fig. 2), wherein, the selected patient is receiving: one or more antibodies targeting Her2 during and/or after the application of the ultrasound beam (abstract states “Trastuzumab has showed positive results in many patients with metastatic HER2-positive breast cancer...” see “result” on page 280, see “discussion” on page 281); and one or more microbubble compositions immediately before and/or during the application of the ultrasound beam (see abstract; “study design” on page 278; fig. 2).
But, Park fails to explicitly state that the patient is a human.
Leuthardt discloses a methods and systems for noninvasive and localized brain treatment. Leuthardt teaches a system that can be used to treat brain tumor for mice and human (see par. [0067]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of having the patient being a human, in the invention of Park, as taught by Leuthardt, to be able to non-invasively treat brain tumor of a human patient.
Regarding claim 2, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the ultrasound beam is a focused beam (see abstract).
Regarding claim 4, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the application of the ultrasound beam targets at least one, or two, or three regions or sites of the brain (see fig. 2 and 4).
Regarding claim 7, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the selected human patient: presents with a plurality of lesions (see fig. 2 and 4).
Regarding claim 11, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows where the focused ultrasound beam is applied directly to the selected patient's cranium (see fig. 2 and 4), but Park fails to explicitly state that a helmet-shaped ultrasound transducer.
Leuthardt discloses a methods and systems for noninvasive and localized brain treatment. Leuthardt teaches using a helmet-shaped ultrasound transducer to treat human patient (see par. [0067], [0074]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of a helmet-shaped ultrasound transducer to treat human patient, in the invention of Park, as taught by Leuthardt, to be able to non-invasively treat brain tumor of a human patient, and the helmet provides easier remove and installation of the unit for targeting different brain regions.
Regarding claim 29, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows a full length antibody (see abstract).
Regarding claim 32, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the antibody targeting Her2 is trastuzumab (see abstract).
Regarding claim 49, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the microbubble compositions: are administered by bolus injection (see “ultrasound” on page 279).
Regarding claim 55, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein substantially all of the disrupted BBB closes after the application of the ultrasound beam (“introduction” on page 278 states transiently disrupting the BBB which means the BBB will closes after the treatment).
Regarding claim 56, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein: the transient disruption of the BBB allows for movement of the antibody targeting Her2 across the BBB (see abstract; “study design” on page 278).
Regarding claim 88, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the ultrasound beam is a focused, magnetic resonance-guided ultrasound beam (see abstract).
Regarding claim 89, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the antibody targeting HER2 is administered by systemic infusion (see abstract).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt) as applied to claim 1 above, and further in view of Peyman (US 2019/0091350).
Regarding claim 20, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore Park teaches focused ultrasound beam targets in the brain (see abstract), but fails to explicitly state wherein the focused ultrasound beam targets in temporal lobe.
Peyman discloses HIFU in brain and specially in temporal lobe for cancer treatment (see par. [0064], [0105). Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of focus ultrasound beam targets in temporal lobe in the invention of Park and Leuthardt, as taught by Peyman, to be able to treat cancer in temporal lobe to improve cognitive and motor functions controlled by temporal lobe.
Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt) as applied to claim 1 above, and further in view of Ruiz-Opaz et al. (US 2013/0177500; hereinafter Ruiz).
Regarding claim 34, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park teaches administering an antibody-based anti-tumor combination agent (see abstract), but fails to explicitly state , wherein: the antibody-based anti-tumor combination agent is a full length antibody, which is a monoclonal antibody a bispecific antibody.
Ruiz discloses anti-desper inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and target delivery. Ruiz teaches : the antibody-based anti-tumor combination agent is a full length antibody (see par. [0048], [03331]), which is a monoclonal antibody a bispecific antibody (see par. [0048], [03331]). Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have utilized the teaching of the antibody-based anti-tumor combination agent is a full length antibody, which is a monoclonal antibody a bispecific antibody in the invention of Park and Leuthardt, as taught by Ruiz, to provide a superior serum which contributes to a longer half-life in the body, target and destroy cancerous cells, and provide a more stable antibody.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt) as applied to claim 1 above, and further in view of Hiscock et al. (US 2016/0144062; hereinafter Hiscock).
Regarding claim 62, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein: the therapeutic delivery is quantified to determine an effect of improved therapeutic delivery across the BBB specific to the treatment agent being delivered (see abstract; see “result” on page 280, see “discussion” on page 281; fig. 3, 4, 5 and 6) and the effect of ultrasound beam (see abstract; see “result” on page 280, see “discussion” on page 281; fig. 3, 4, 5 and 6).
But, Park and Leuthardt fail to explicitly state the one or more antibodies targeting Her2 are labeled with a tracer label, to permit tracking of the transit of the treatment agent.
Hiscock discloses the uses of HER2 binders. Hiscock teaches the one or more antibodies targeting Her2 are labeled with a tracer label, to permit tracking of the transit of the treatment agent (see par. [0017], [0049]). Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of the one or more antibodies targeting Her2 are labeled with a tracer label, to permit tracking of the transit of the treatment agent in the invention of Park and Leuthardt, as taught by Hiscock, to be able to track, visualize and treat cancer with high precision by directly treating tumor while minizine damage to healthy tissue.
Response to Arguments
Previous claim objections have been withdrawn in view of Applicant’s amendments to the claims.
Previous rejections under 35 USC 112 (b) have been withdrawn in view of Applicant’s amendments to the claim.
Applicant's arguments filed 03/26/2026 have been fully considered but they are not persuasive.
In response to Applicant’s arguments on pages 14-18, with respect to prior art rejection, the examiner respectfully disagrees. The Applicant argues that combined invention of prior art Park and Leuthardt does not teach the treating a human epidermal grown factor receptor 2 (Her2) positive (Her2+) by applying an ultrasound beam to the human patient causing transient disruption of a blood-brain barrier of the human patient, and prior art Leuthardt has data primarily with rodent skulls and some data with healthy pig skulls, but nothing in Park or Leuthardt would suggest to a person of ordinary skill in the art that the disclosure would be feasible and safe in human patients, the examiner respectfully disagrees.
The examiner maintains that prior art Park does show a method of treating epidermal growth factor 2 (Her2) positive Her2+ metastatic breast tumor in a brain (see abstract), comprising:(a) selecting a patient having a Her2+ metastatic breast tumor in the brain (see abstract, “introduction” on page 277, and “material and methods” on page 278) and (b) applying an ultrasound beam to the cranium of the selected patient to cause transient disruption of the blood-brain barrier (BBB) of the selected patient (see “material and methods” on page 278, “ultrasound” on page 279; fig. 2). The examiner has relied on prior art Leuthardt discloses a methods and systems for noninvasive and localized brain treatment. Leuthardt teaches a system that can be used to treat brain tumor for mice and human and cause transient disruption of the blood-brain barrier (BBB) using HIFU (par. [0011] states using high focused ultrasound frequency to disrupt BBB; par. [0067], [0068], [0074] state how a helmet with ultrasound transducer can be used to treat a human patient by causing disruption of the BBB of the human patient).
Therefore, the examiner maintains that would have found it obvious to have utilized the teaching of using high focused ultrasound frequency to disrupt BBB of a human patient, in the invention of Park, as taught by Leuthardt, to be able to non-invasively treat brain tumor of a human patient.
The Applicant further agues that prior art Leuthardt does not provide any guidance regarding application of the ultrasound human skull, however, the examiner notes that the prior art does not explicitly provide specific guidance to show applying of the ultrasound to the human skull. Leuthardt teaches using specific ultrasound frequency and pressure for human and using helmet comprising ultrasound transducer to apply focused ultrasound to the human skull (see par. [0067], [0068], [0074]).
The Applicant further argues on pages 17-18 that a person of ordinary skill in the art would not have predicted specific results based on the teaching of the prior arts in record, however, the examiner notes that the specific results listed on pages 17-18 are not recited in the independent claims.
Furthermore, the Applicant further provided and cited arts as evidence to show that applying ultrasound to human skull can be dangerous, but the examiner notes that prior art Leuthardt teaches using specific ultrasound frequency and pressure for human and using helmet comprising ultrasound transducer to apply focused ultrasound to the human skull (see par. [0067], [0068], [0074]), and combined invention of Park and Leuthardt does read on the claim limitations set forth in claim 1.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Nagel et al. (US 2023/0017864) discloses using a helmet with ultrasound transducer to teach human patient and applying focused ultrasound to huma skull (see fig. 2 and par. [0053]).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHAHDEEP MOHAMMED whose telephone number is (571)270-3134. The examiner can normally be reached Monday to Friday, 9am to 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 M 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.
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/SHAHDEEP MOHAMMED/Primary Examiner, Art Unit 3797
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