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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/23/2026 has been entered.
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 Claims 67-68, 70, 75-76, 78 and 84 are withdrawn.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), in view of Carmen et al. (“Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia; Nature Communications; 02/2021; hereinafter Carmen).
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 a focused 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 focused ultrasound beam is applied at a power of at least 5W and that the patient is a human.
Leuthardt discloses a method and system 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.
But, Park and Leuthardt fail to explicitly state the focused ultrasound beam is applied at a power of at least 5W.
Carmen discloses using focused ultrasound for blood brain barrier opening and teaches using low power focused ultrasound of at least 5W (see “primary outcome” on page 2). 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 focused ultrasound of at least 5W in the invention of Park and Leuthardt, as taught by Carmen, to provide focused ultrasound with lower power to open BBB without any ablation or causing any harm.
Regarding claim 2, Park, Leuthardt and Carmen disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the ultrasound beam with MRI guidance (see abstract).
Regarding claim 4, Park, Leuthardt and Carmen 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, Leuthardt and Carmen 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, Leuthardt and Carmen 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, Leuthardt and Carmen disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows a full length antibody (see abstract).
Regarding claim 32, Park, Leuthardt and Carmen 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, Leuthardt and Carmen 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, Leuthardt and Carmen 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, Leuthardt and Carmen 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, Leuthardt and Carmen 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, Leuthardt and Carmen 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), in view of Carmen et al. (“Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia; Nature Communications; 02/2021; hereinafter Carmen) as applied to claim 1 above, and further in view of Peyman (US 2019/0091350).
Regarding claim 20, Park, Leuthardt and Carmen 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, Leuthardt and Carmen, 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), in view of Carmen et al. (“Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia; Nature Communications; 02/2021; hereinafter Carmen) as applied to claim 1 above, and further in view of Ruiz-Opaz et al. (US 2013/0177500; hereinafter Ruiz).
Regarding claim 34, Park, Leuthardt and Carmen 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, Leuthardt and Carmen, 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), in view of Carmen et al. (“Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia; Nature Communications; 02/2021; hereinafter Carmen) as applied to claim 1 above, and further in view of Hiscock et al. (US 2016/0144062; hereinafter Hiscock).
Regarding claim 62, Park, Leuthardt and Carmen 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, Leuthardt and Carmen, 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
Applicant's arguments filed 03/26/2026 have been fully considered but they are not persuasive.
Applicant’s arguments filed on 09/23/2026 with respect to claim limitation “wherein the focused ultrasound beam is applied at a power of at least 5W” have been considered but are moot because the new ground of rejection does not rely on any rejection applied in the prior office action of record for any teaching or matter specifically challenged in the argument. The examiner has provided new prior art Carmen to teach wherein the focused ultrasound beam is applied at a power of at least 5W.
Applicant's arguments filed on 09/23/2026, with respect to prior arts Park and Leuthardt have been fully considered but they are not persuasive.
In response to Applicant’s arguments on pages 12-15, with respect to prior art Park and Leuthardt, the examiner respectfully disagrees. The Applicant argues that a person of ordinary skill in the art would not rely on data presented in Park, and indeed be discouraged to depend on Park’s findings to invent a method of treating a Her2+ metastatic breast tumor by applying of recited ultrasound beam and administering pharmaceutical composition comprising an antibody, the examiner respectfully disagrees. The Applicant provided two exhibits (Huszthy et al. and Wyatt) and further argues that success of treating animal brain tumors in rodents and the failure in a clinical setting is most likely due to several factors such as the tumor models do not reflect the biological properties of the patient tumors, the animals used do not display the same pharmacokinetics as humans, and the tumors established do not reflect the cellular heterogeneity of human tumors. The examiner notes that the exhibits provided by applicants to show evidence the therapeutic efficacy of novel treatment modalities in various animal models does not pertain to current application since Huszthy and Wyatt disclosure are directed to different methods and purpose, and the claim does not limit efficiency of the treatment or the success rate of the treatment. Furthermore, the Applicant argues that prior art Park does not have high success rate or high treatment efficiency, however, the claim 1 does not limit anything regarding the any success rate or treatment efficiency. The examiner notes that claims 1 is directed to a method of treating a human epidermal growth factor receptor 2 (Her2) positive (Her2+) metastatic breast tumor in a brain by perform the steps (a) and (b). The examiner maintains that combined invention of Park and Leuthardt does disclose all the claim limitation required in steps (a) and (b) of claim 1.
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 method and system 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 one of ordinary skill in the art 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 argues on pages 14-15 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 page 14 are not recited in the independent claims.
Conclusion
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.
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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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